The liver sieve and atherosclerosis.

PubMed

Fraser, Robin; Cogger, Victoria C; Dobbs, Bruce; Jamieson, Hamish; Warren, Alessandra; Hilmer, Sarah N; Le Couteur, David G

2012-04-01

The 'liver sieve' is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins. The liver sieve is a very efficient exchange system, however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus and old age, there is defenestration of the liver sieve. Such defenestration has been shown to influence the hepatic uptake of various substrates including lipoproteins. In the future, pharmacological manipulation of the liver sieve may play a number of therapeutic roles including the management of dyslipidaemia; increasing the efficiency of liver-targeted gene therapy; and improving regeneration of old livers. (C) 2012 Royal College of Pathologists of Australasia.

Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases

PubMed Central

Movsesyan, Nina; Platt, Frances M.

2017-01-01

In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters. PMID:29119141

Direct-Acting Antiviral Therapy for Chronic HCV Infection Results in Liver Stiffness Regression Over 12 Months Post-treatment.

PubMed

Chan, Justin; Gogela, Neliswa; Zheng, Hui; Lammert, Sara; Ajayi, Tokunbo; Fricker, Zachary; Kim, Arthur Y; Robbins, Gregory K; Chung, Raymond T

2018-02-01

Liver fibrosis stage determines risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. Prior data have shown long-term reversal of liver fibrosis, measured by vibration-controlled transient elastography (VCTE), in patients successfully treated with interferon-based therapies. Our study sought to determine the effect of treatment with modern HCV direct-acting antiviral (DAA) therapy on noninvasive liver fibrosis measurements. A total of 70 patients had VCTE-based liver stiffness measurement (LSM) taken before treatment, directly after treatment completion, and at least 12 months after completion of DAA therapy. Our primary outcome was a >30% improvement in VCTE score at the end of follow-up, relative to baseline. The sustained virologic response rate in our cohort was 95.7%. In our cohort, 34 (48.6%) met the primary outcome. Those who had baseline elevated alanine aminotransferase (OR 3.27; 95% CI 1.13-9.47) and genotype 1 (OR 14.63; 95% CI 1.70-125.83) had higher odds of meeting that outcome, and this remained significant after adjusting for age, baseline body mass index, gender, baseline elevated alkaline phosphatase levels, treatment experience, liver transplant status, smoking, and baseline liver stiffness. Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion.

Morphometric analysis of abdominal organs and rib cage: Implication for risk of solid organ injuries in children.

PubMed

Harbaugh, Calista M; Shlykov, Maksim A; Tsuchida, Ryan E; Holcombe, Sven A; Hirschl, Jake; Wang, Stewart C; Ehrlich, Peter F

2015-06-01

Motor vehicle crashes are the leading cause of injury-related mortality in children, with a higher rate of multiorgan injuries than in adults. This may be related to increased solid organ volume relative to abdominal cavity and decreased protection of an underdeveloped cartilaginous rib cage in young children. To date, these anatomic relationships have not been fully described. Our study used analytic morphomics to obtain precise measures of the pediatric liver, spleen, kidneys, and ribs. This pilot study included 215 trauma patients (aged 0-18 years) with anonymized computed tomography (CT) scans. Liver, spleen, and kidney volumes were modeled using semiautomatic algorithms (MATLAB 2013a, MathWorks Inc., Natick, MA). Thirty-one scans were adequate to model the rib cage. Pearson's r was used to correlate absolute organ volume, fractional organ volume, and organ exposure with age and weight. Spleen, right and left kidney, and liver volumes increased with age and weight (p < 0.01). Right/left kidney and liver fractional volumes decreased with age (p < 0.01), whereas spleen fractional volume remained relatively constant. Exposed surface area of the liver only significantly decreased with age in the anterior (p < 0.01), right (p < 0.01), and posterior views (p = 0.02). With this study, we have demonstrated the ability to model solid organ and rib cage anatomy of children using cross-sectional imaging. In younger children, there may be a decrease in fractional organ volume and increase in liver surface exposure, although analysis of a larger sample size is warranted. In the future, this information may be used to improve the design of safety restraints in motor vehicles.

Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice.

PubMed

Bell-Anderson, K S; Aouad, L; Williams, H; Sanz, F R; Phuyal, J; Larter, C Z; Farrell, G C; Caterson, I D

2011-12-01

Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice. Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age. Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice. The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.

How important is donor age in liver transplantation?

PubMed

Lué, Alberto; Solanas, Estela; Baptista, Pedro; Lorente, Sara; Araiz, Juan J; Garcia-Gil, Agustin; Serrano, M Trinidad

2016-06-07

The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed.

How important is donor age in liver transplantation?

PubMed Central

Lué, Alberto; Solanas, Estela; Baptista, Pedro; Lorente, Sara; Araiz, Juan J; Garcia-Gil, Agustin; Serrano, M Trinidad

2016-01-01

The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed. PMID:27275089

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

PubMed

La Fata, G; van Vliet, N; Barnhoorn, S; Brandt, R M C; Etheve, S; Chenal, E; Grunenwald, C; Seifert, N; Weber, P; Hoeijmakers, J H J; Mohajeri, M H; Vermeij, W P

2017-01-01

Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Predictors of liver donation without kidney recovery in a cohort of expanded criteria donors: identifying opportunities to improve expanded criteria donor kidney utilization.

PubMed

White, S L; Leichtman, A B; O'Connor, K; Lipkowitz, G; Pietroski, R; Stoff, J S; Luskin, R S; Belcher, J; Meyer, K; Merion, R M; Port, F K; Delmonico, F L

2012-09-01

To maximize deceased donation, it is necessary to facilitate organ recovery from expanded criteria donors (ECDs). Utilization of donors meeting the kidney definition for ECDs increases access to kidney transplantation and reduces waiting times; however, ECDs often do not proceed to kidney recovery. Based on a prospective study of three Organ Procurement Organizations in the United States, we describe the characteristics of donors meeting the Organ Procurement and Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60 years with two of the following: final serum creatinine > 1.5 mg/dL, history of hypertension, or death from cerebral vascular accident) who donated a liver without kidney recovery. ECDs with organs recovered between February 2003 and September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice Donor Services were studied (n = 324). All donors were declared dead by neurological criteria. Data on a wide range of donor characteristics were collected, including donor demographics, medical history, cause of death, donor status during hospitalization, serological status, and donor kidney quality. Logistic regression models were used to identify donor characteristics predictive of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD definition for kidneys donated a liver alone (23%). History of diabetes, final serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were associated with liver-alone donation in univariate models. On multivariate analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently predictive of liver donation alone. Older age and elevated serum creatinine may be perceived as stronger contraindications to kidney donation than the remaining elements of the ECD definition. It is likely that at least a proportion of these liver-alone donors represent missed opportunities for kidney transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in survival patterns in urban Chinese patients with liver cancer

PubMed Central

Hao, Xi-Shan; Chen, Ke-Xin; Wang, Peizhong Peter; Rohan, Tom

2003-01-01

AIM: To examine the survival patterns and determinants of primary liver cancer in a geographically defined Chinese population. METHODS: Primary liver cancer cases (n = 13685) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-adjusted and age-specific incidence rates were examined in both males and females. Proportional hazards (Cox) regression was utilized to explore the effects of time of diagnosis, sex, age, occupation, residence, and hospital of diagnosis on survival. RESULTS: Crude and age-adjusted incidence rates in the study period were: 27.4/100000 and 26.3/100000 in males; and 11.5/100000 and 10.4/100000 in females, respectively. Cox regression analyses indicated that there was a significant improvement in survival rates over time. Industrial workers and older people had relatively poor survival rates. The hospital in which the liver cancer was diagnosed was a statistically significant predictor of survival; patients diagnosed in city hospitals were more likely to have better survival than those diagnosed in community/district hospitals. CONCLUSION: Patients diagnosed in recent years appeared to have a better outcome than those diagnosed in early times. There were also significant survival disparities with respect to occupation and hospital of diagnosis, which suggest that socioeconomic status may play an important role in determining prognosis. PMID:12800226

Vitamin D Deficiency and Its Relationship with Child-Pugh Class in Patients with Chronic Liver Disease

PubMed Central

Jamil, Zubia; Arif, Sharmin; Khan, Anum; Durrani, Asghar Aurangzeb; Yaqoob, Nayyar

2018-01-01

Abstract Background and Aims: Skeletal manifestation in liver diseases represents the minimally scrutinized part of the disease spectrum. Vitamin D deficiency has a central role in developing hepatic osteodystrophy in patients with chronic liver disease. This study aimed to investigate vitamin D levels and their relationship with disease advancement in these patients. Methods: Vitamin D levels were checked in 125 chronic liver disease patients. The patients were classified in three stages according to Child-Pugh score: A, B and C. The relationship of vitamin D levels with Child-Pugh score and other variables in the study was assessed by the contingency coefficient. Correlation and logistic regression analyses were also carried out to find additional predictors of low vitamin D levels. Results: Among the patients, 88% had either insufficient or deficient stores of vitamin D, while only 12% had sufficient vitamin D levels (p >0.05). Vitamin D levels were notably related to Child-Pugh class (contingency coefficient = 0.5, p <0.05). On univariate and multinomial regression analyses, age, female sex, MELD and Child-Pugh class were predictors of low vitamin D levels. Age, model of end-stage liver disease score and Child-Pugh score were negatively correlated to vitamin D levels (p <0.05). Conclusions: Vitamin D deficiency is notably related to age, female sex and model of end-stage liver disease score, in addition to Child-Pugh class of liver cirrhosis. Vitamin D levels should be routinely checked in patients with advanced liver cirrhosis (Child-Pugh class B and C) and this deficiency must be addressed in a timely manner to improve general well-being of cirrhotic patients.

Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis.

PubMed

Togo, Shinji; Tanaka, Kuniya; Morioka, Daisuke; Sugita, Mitsutaka; Ueda, Michio; Miura, Yasuhiko; Kubota, Toru; Nagano, Yasuhiko; Matsuo, Kenichi; Endo, Itaru; Sekido, Hitoshi; Shimada, Hiroshi

2005-04-01

Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional state.

The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age-associated inflammation and oxidative stress in healthy rats.

PubMed

Niu, Yucun; Na, Lixin; Feng, Rennan; Gong, Liya; Zhao, Yue; Li, Qiang; Li, Ying; Sun, Changhao

2013-12-01

It is known that phytochemicals have many potential health benefits in humans. The aim of this study was to investigate the effects of long-term consumption of the phytochemical, epigallocatechin gallate (EGCG), on body growth, disease protection, and lifespan in healthy rats. 68 male weaning Wistar rats were randomly divided into the control and EGCG groups. Variables influencing lifespan such as blood pressure, serum glucose and lipids, inflammation, and oxidative stress were dynamically determined from weaning to death. The median lifespan of controls was 92.5 weeks. EGCG increased median lifespan to 105.0 weeks and delayed death by approximately 8-12 weeks. Blood pressure and serum glucose and lipids significantly increased with age in both groups compared with the levels at 0 week. However, there were no differences in these variables between the two groups during the whole lifespan. Inflammation and oxidative stress significantly increased with age in both groups compared with 0 week and were significantly lower in serum and liver and kidney tissues in the EGCG group. Damage to liver and kidney function was significantly alleviated in the EGCG group. In addition, EGCG decreased the mRNA and protein expressions of transcription factor NF-κB and increased the upstream protein expressions of silent mating type information regulation two homolog one (SIRT1) and forkhead box class O 3a (FOXO3a). In conclusion, EGCG extends lifespan in healthy rats by reducing liver and kidney damage and improving age-associated inflammation and oxidative stress through the inhibition of NF-κB signaling by activating the longevity factors FoxO3a and SIRT1. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study.

PubMed

Jones, Simon A; Rojas-Caro, Sandra; Quinn, Anthony G; Friedman, Mark; Marulkar, Sachin; Ezgu, Fatih; Zaki, Osama; Gargus, J Jay; Hughes, Joanne; Plantaz, Dominique; Vara, Roshni; Eckert, Stephen; Arnoux, Jean-Baptiste; Brassier, Anais; Le Quan Sang, Kim-Hanh; Valayannopoulos, Vassili

2017-02-08

Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age. Nine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious. Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011.

Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis.

PubMed

Wahlin, Staffan; Aschan, Johan; Björnstedt, Mikael; Broomé, Ulrika; Harper, Pauline

2007-01-01

We report the case of a middle-age patient presenting with severe progressive protoporphyric cholestasis. To halt further progression of liver disease, medical treatment was given aimed at different mechanisms possibly causing cholestasis in erythropoietic protoporphyria. Within eighty days, liver biochemistry completely normalized and liver histology markedly improved. Bone marrow transplantation was performed to prevent relapse of cholestatic liver disease by correcting the main site of protoporphyrin overproduction. Thirty-three months after cholestatic presentation and ten months after bone marrow transplantation, liver and porphyrin biochemistry remains normal. The patient is in excellent condition and photosensitivity is absent. The theoretical role of each treatment used to successfully reverse cholestasis and the role of bone marrow transplantation in erythropoietic protoporphyria are discussed. Medical treatment can resolve hepatic abnormalities in protoporphyric cholestasis. Bone marrow transplantation achieves phenotypic reversal and may offer protection from future protoporphyric liver disease.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

PubMed

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-06-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan

PubMed Central

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-01-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females. PMID:28553763

Organ allocation for chronic liver disease: model for end-stage liver disease and beyond.

PubMed

Asrani, Sumeet K; Kim, W Ray

2010-05-01

Implementation of the model for end-stage liver disease (MELD) score has led to a reduction in waiting list registration and waitlist mortality. Prognostic models have been proposed to either refine or improve the current MELD-based liver allocation. The model for end-stage liver disease - sodium (MELDNa) incorporates serum sodium and has been shown to improve the predictive accuracy of the MELD score. However, laboratory variation and manipulation of serum sodium is a concern. Organ allocation in the United Kingdom is now based on a model that includes serum sodium. An updated MELD score is associated with a lower relative weight for serum creatinine coefficient and a higher relative weight for bilirubin coefficient, although the contribution of reweighting coefficients as compared with addition of variables is unclear. The D-MELD, the arithmetic product of donor age and preoperative MELD, proposes donor-recipient matching; however, inappropriate transplantation of high-risk donors is a concern. Finally, the net benefit model ranks patients according to the net survival benefit that they would derive from the transplant. However, complex statistical models are required and unmeasured characteristics may unduly affect the model. Despite their limitations, efforts to improve the current MELD-based organ allocation are encouraging.

Nutritional risk and anthropometric evaluation in pediatric liver transplantation.

PubMed

Zamberlan, Patrícia; Leone, Cláudio; Tannuri, Uenis; Carvalho, Werther Brunow de; Delgado, Artur Figueiredo

2012-12-01

To analyze the nutritional status of pediatric patients after orthotopic liver transplantation and the relationship with short-term clinical outcome. Anthropometric evaluations of 60 children and adolescents after orthotopic liver transplantation, during the first 24 hours in a tertiary pediatric intensive care unit. Nutritional status was determined from the Z score for the following indices: weight/age height/age or length/age, weight/height or weight/length, body mass index/age, arm circumference/age and triceps skinfold/age. The severity of liver disease was evaluated using one of the two models which was adequated to the patients' age: 1. Pediatric End-stage Liver Disease, 2. Model for End-Stage Liver Disease. We found 50.0% undernutrition by height/age; 27.3% by weight/age; 11.1% by weight/height or weight/ length; 10.0% by body mass index/age; 61.6% by arm circumference/age and 51.0% by triceps skinfold/age. There was no correlation between nutritional status and Pediatric End-stage Liver Disease or mortality. We found a negative correlation between arm circumference/age and length of hospitalization. Children with chronic liver diseases experience a significant degree of undernutrition, which makes nutritional support an important aspect of therapy. Despite the difficulties in assessment, anthropometric evaluation of the upper limbs is useful to evaluate nutritional status of children before or after liver transplantation.

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

PubMed

Bertrais, Sandrine; Boursier, Jérôme; Ducancelle, Alexandra; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Moal, Valérie; Calès, Paul

2017-06-01

There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeter V2G . Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and <6 months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeter V2G with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeter V2G or LSM alone for all-cause mortality and FibroMeter V2G alone for liver-related mortality. The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

First liver transplant in Qatar: an evolving program facing many challenges.

PubMed

Khalaf, Hatem; Derballa, Moataz; Elmasry, Mohammed; Khalil, Ahmed; Yakoob, Rafie; Almohannadi, Muneera; Almaslamani, Muna; Fadhil, Riadh; Al-Kaabi, Saad; Al-Ansari, Abdulla; Almaslamani, Yousuf

2013-10-01

Beginning to do liver transplants in a developing country is challenging. We report on the first few liver transplants performed in Qatar and discuss future exceptions and challenges facing our program. The first liver transplant was performed in Qatar on December 6, 2011. Since starting the program, 4 deceased-donor liver transplants have been performed in Qatar. All recipients underwent a standard deceased-donor liver transplant procedure, which included a duct-to-duct biliary anastomosis without a veno-venous bypass. All liver transplants were performed at the Hamad Medical Corporation by a local team of surgeons without external assistance. The 4 patients were all men, with a median age of 56 years (age range, 46-63 y). Indications for liver transplant included hepatitis C cirrhosis in 2 patients, and 1 patient with hepatitis B cirrhosis with hepatocellular carcinoma, and the other patient with cryptogenic liver cirrhosis. Median amount of blood transfused was 6 units (range, 0-10 U); median time spent in the intensive care unit was 2 days (range, 2-5 d); median amount of time spent in the hospital was 10 days (range, 9-16 d). All 4 recipients have survived after a median follow-up of 438 days (range, 33-602 d) and are enjoying a healthy life, with no significant posttransplant complications. A deceased-donor liver transplant can be performed in Qatar with no external assistance. However, a severe organ shortage remains the biggest obstacle facing us. Efforts should be directed toward improving the number and quality of available deceased donors in Qatar. Meanwhile, live-donor liver transplant may be the only way for us, going forward, to prevent deaths on the waiting list.

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

PubMed

Mitchell, Sarah J; Madrigal-Matute, Julio; Scheibye-Knudsen, Morten; Fang, Evandro; Aon, Miguel; González-Reyes, José A; Cortassa, Sonia; Kaushik, Susmita; Gonzalez-Freire, Marta; Patel, Bindi; Wahl, Devin; Ali, Ahmed; Calvo-Rubio, Miguel; Burón, María I; Guiterrez, Vincent; Ward, Theresa M; Palacios, Hector H; Cai, Huan; Frederick, David W; Hine, Christopher; Broeskamp, Filomena; Habering, Lukas; Dawson, John; Beasley, T Mark; Wan, Junxiang; Ikeno, Yuji; Hubbard, Gene; Becker, Kevin G; Zhang, Yongqing; Bohr, Vilhelm A; Longo, Dan L; Navas, Placido; Ferrucci, Luigi; Sinclair, David A; Cohen, Pinchas; Egan, Josephine M; Mitchell, James R; Baur, Joseph A; Allison, David B; Anson, R Michael; Villalba, José M; Madeo, Frank; Cuervo, Ana Maria; Pearson, Kevin J; Ingram, Donald K; Bernier, Michel; de Cabo, Rafael

2016-06-14

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. Published by Elsevier Inc.

The Impact of a Hepatobiliary Multidisciplinary Team Assessment in Patients with Colorectal Cancer Liver Metastases: A Population-Based Study.

PubMed

Engstrand, Jennie; Kartalis, Nikolaos; Strömberg, Cecilia; Broberg, Mats; Stillström, Anna; Lekberg, Tobias; Jonas, Eduard; Freedman, Jacob; Nilsson, Henrik

2017-09-01

Assessing patients with colorectal cancer liver metastases (CRCLM) by a liver multidisciplinary team (MDT) results in higher resection rates and improved survival. The aim of this study was to evaluate the potentially improved resection rate in a defined cohort if all patients with CRCLM were evaluated by a liver MDT. A retrospective analysis of patients diagnosed with colorectal cancer during 2008 in the greater Stockholm region was conducted. All patients with liver metastases (LM), detected during 5-year follow-up, were re-evaluated at a fictive liver MDT in which previous imaging studies, tumor characteristics, medical history, and patients' own treatment preferences were presented. Treatment decisions for each patient were compared to the original management. Odds ratios (ORs) and 95% confidence intervals were estimated for factors associated with referral to the liver MDT. Of 272 patients diagnosed with LM, 102 patients were discussed at an original liver MDT and 69 patients were eventually resected. At the fictive liver MDT, a further 22 patients were considered as resectable/potentially resectable, none previously assessed by a hepatobiliary surgeon. Factors influencing referral to liver MDT were age (OR 3.12, 1.72-5.65), American Society of Anaesthesiologists (ASA) score (OR 0.34, 0.18-0.63; ASA 2 vs. ASA 3), and number of LM (OR 0.10, 0.04-0.22; 1-5 LM vs. >10 LM), while gender ( p  = .194) and treatment at a teaching hospital ( p  = .838) were not. A meaningful number of patients with liver metastases are not managed according to best available evidence and the potential for higher resection rates is substantial. Patients with liver metastatic colorectal cancer who are assessed at a hepatobiliary multidisciplinary meeting achieve higher resection rates and improved survival. Unfortunately, patients who may benefit from resection are not always properly referred. In this study, the potential improved resection rate was assessed by re-evaluating all patients with liver metastases from a population-based cohort, including patients with extrahepatic metastases and accounting for comorbidity and patients' own preferences towards treatment. An additional 12.9% of the patients were found to be potentially resectable. The results highlight the importance of all patients being evaluated in the setting of a hepatobiliary multidisciplinary meeting. © AlphaMed Press 2017.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Long-lasting improvements in liver fat and metabolism despite body weight regain after dietary weight loss.

PubMed

Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan

2013-11-01

Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17-36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions.

Dihydrocapsiate improved age-associated impairments in mice by increasing energy expenditure.

PubMed

Ohyama, Kana; Suzuki, Katsuya

2017-11-01

Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in nonpungent peppers and increase whole body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated. In this study, we investigated whether DCT supplementation in aged mice improves age-associated impairments. We obtained 5-wk-old and 1-yr-old male C57BL/6J mice and randomly assigned the aged mice to two groups, resulting in a total of three groups: 1 ) young mice, 2 ) old mice, and 3 ) old mice supplemented with 0.3% DCT. After 12 wk of supplementation, blood and tissue samples were collected and analyzed. DCT significantly suppressed age-associated fat accumulation, adipocyte hypertrophy, and liver steatosis. In addition, the DCT treatment dramatically suppressed age-associated increases in hepatic inflammation, immune cell infiltration, and oxidative stress. DCT exerted these suppression effects by increasing energy expenditure linked to upregulation of both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that DCT efficiently improves age-associated impairments, including liver steatosis and inflammation, in part by increasing energy expenditure via activation of the fat oxidation pathway in skeletal muscle. Copyright © 2017 the American Physiological Society.

The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition.

PubMed

Crespo, Gonzalo; Trota, Núria; Londoño, Maria-Carlota; Mauro, Ezequiel; Baliellas, Carme; Castells, Lluís; Castellote, Jose; Tort, Jaume; Forns, Xavier; Navasa, Miquel

2018-07-01

The efficacy of direct-acting antivirals (DAAs) has dramatically changed the prognosis of patients with chronic hepatitis C. We aimed to evaluate the impact of DAA therapy on the composition of the liver transplant (LT) waiting list and the early post-transplant survival. We evaluated all patients admitted to the waiting list for a primary LT between 1st January 2008 and 31st of December 2016 in Catalonia, Spain. Time span was divided into two periods according to the availability of different antiviral therapies: 2008-2013 (interferon-based therapies) and 2014-2016 (DAA). Changes in the indications of LT and the aetiology of liver disease, as well as post-LT patient survival, were evaluated according to the year of inclusion and transplantation, respectively. We included 1,483 patients. Admissions in the waiting list for hepatitis C virus (HCV)-related liver disease decreased significantly, from 47% in 2008-2013 to 35% in 2014-2016 (p <0.001), particularly because of a reduction in patients with decompensated cirrhosis. In contrast, NASH-related inclusions increased from 4% to 7% (p = 0.003). Three-year post-LT patient survival increased significantly in the second period in the whole cohort (82% vs. 91%, p = 0.002), because of better survival in anti-HCV positive patients (76% vs. 91%, p = 0.001), but not in anti-HCV negative patients (88% vs. 91% p = 0.359). Anti-HCV positive serology, the time period of 2008-2013 and higher donor age were independently associated with post-LT mortality in the whole cohort; while time period and donor age were independently associated with post-LT mortality in anti-HCV positive recipients. The high efficacy of DAAs is associated with significant changes in the composition of the LT waiting list and, more importantly, results in improved post-transplant survival. The efficacy of the new direct-acting antivirals is associated with a significant improvement in survival of patients undergoing liver transplantation because of hepatitis C virus-related liver disease. In addition, it has decreased the number of patients with hepatitis C that need a liver transplant. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

THE IMPACT OF THE MELD SCORE ON LIVER TRANSPLANT ALLOCATION AND RESULTS: AN INTEGRATIVE REVIEW

PubMed Central

de MORAES, Ana Claudia Oliveira; de OLIVEIRA, Priscilla Caroliny; da FONSECA-NETO, Olival Cirilo Lucena

2017-01-01

ABSTRACT Introduction: Liver transplantation is intended to increase the survival of patients with chronic liver disease in terminal phase, as well as improved quality of life. Since the first transplant until today many changes have occurred in the organ allocation system. Objective: To review the literature on the Model for End-stage Liver Disease (MELD) and analyze its correlation with survival after liver transplantation. Method: An integrative literature review in Lilacs, SciELO, and Pubmed in October 2015, was realized. Were included eight studies related to the MELD score and its impact on liver transplant. Results: There was predominance of transplants in male between 45-55 y. The main indications were hepatitis C, hepatocellular carcinoma and alcoholic cirrhosis. The most important factors post-surgery were related to the MELD score, the recipient age, expanded donor criteria and hemotransfusion. Conclusion: The MELD system reduced the death rate in patients waiting for a liver transplant. However, this score by itself is not a good predictor of survival after liver transplantation. PMID:28489174

The role of birth cohorts in long-term trends in liver cirrhosis mortality across eight European countries.

PubMed

Trias-Llimós, Sergi; Bijlsma, Maarten J; Janssen, Fanny

2017-02-01

Understanding why inequalities in alcohol-related mortality trends by sex and country exist is essential for developing health policies. Birth cohort effects, indicative of differences by generation in drinking, have rarely been studied. This study estimated the relative contributions of birth cohorts to liver cirrhosis mortality trends and compared sex- and country-specific cohort patterns across eight European countries. Time-series analysis of population-level mortality data. Austria, Finland, Hungary, Italy, the Netherlands, Poland, Spain and Sweden; 1950-2011. National populations aged 15-94 years. We modelled country- and sex-specific liver cirrhosis mortality (from national vital registers) adjusting for age, period and birth cohort. Birth cohorts (adjusted for age and period) made statistically significant contributions to liver cirrhosis mortality in all countries and for both sexes (P < 0.001), and more so among women (average contribution to deviance reduction of 38.8%) than among men (17.4%). The observed cohort patterns were statistically different between all but two country pairs (P < 0.001). Sex differences existed overall (P < 0.001), but not in the majority of countries (P > 0.999). Visual inspection of birth cohort patterns reveals birth cohorts at higher risk of liver cirrhosis mortality. The inclusion of the birth cohort dimension improves the understanding of alcohol-attributable mortality trends in Europe. Birth cohorts at higher risk of liver cirrhosis mortality were born during 1935-49 in Sweden and Finland, around 1950 in Austria and the Netherlands and 1960 or later in Hungary, Italy, Poland and Spain. © 2016 Society for the Study of Addiction.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents

PubMed Central

Antunes, Barbara de Moura M.; Monteiro, Paula Alves; Silveira, Loreana Sanches; Cayres, Suziane Ungari; da Silva, Camila Buonani; F., Ismael Forte

2013-01-01

OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate. PMID:24142321

Outcomes after liver transplantation of patients with Indo-Asian ethnicity.

PubMed

Rocha, Chiara; Perera, M Thamara; Roberts, Keith; Bonney, Glenn; Gunson, Bridget; Nightingale, Peter; Bramhall, Simon R; Isaac, John; Muiesan, Paolo; Mirza, Darius F

2015-04-01

The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.

The influence of donor age on liver regeneration and hepatic progenitor cell populations.

PubMed

Ono, Yoshihiro; Kawachi, Shigeyuki; Hayashida, Tetsu; Wakui, Masatoshi; Tanabe, Minoru; Itano, Osamu; Obara, Hideaki; Shinoda, Masahiro; Hibi, Taizo; Oshima, Go; Tani, Noriyuki; Mihara, Kisyo; Kitagawa, Yuko

2011-08-01

Recent reports suggest that donor age might have a major impact on recipient outcome in adult living donor liver transplantation (LDLT), but the reasons underlying this effect remain unclear. The aims of this study were to compare liver regeneration between young and aged living donors and to evaluate the number of Thy-1+ cells, which have been reported to be human hepatic progenitor cells. LDLT donors were divided into 2 groups (Group O, donor age ≥ 50 years, n = 6 and Group Y, donor age ≤ 30 years, n = 9). The remnant liver regeneration rates were calculated on the basis of computed tomography volumetry on postoperative days 7 and 30. Liver tissue samples were obtained from donors undergoing routine liver biopsy or patients undergoing partial hepatectomy for metastatic liver tumors. Thy-1+ cells were isolated and counted using immunomagnetic activated cell sorting (MACS) technique. Donor liver regeneration rates were significantly higher in young donors compared to old donors (P = .042) on postoperative day 7. Regeneration rates were significantly higher after right lobe resection compared to rates after left lobe resection. The MACS findings showed that the number of Thy-1+ cells in the human liver consistently tended to decline with age. Our study revealed that liver regeneration is impaired with age after donor hepatectomy, especially after right lobe resection. The declining hepatic progenitor cell population might be one of the reasons for impaired liver regeneration in aged donors. Copyright © 2011 Mosby, Inc. All rights reserved.

Text Messaging Improves Participation in Laboratory Testing in Adolescent Liver Transplant Patients.

PubMed

McKenzie, Rebecca B; Berquist, William E; Foley, Megan A; Park, K T; Windsheimer, Jered E; Litt, Iris F

In solid organ transplant patients, non-participation in all aspects of the medical regimen is a prevalent problem associated with adverse consequences particularly in the adolescent and young adult (AYA) age group. This study is the first to evaluate the feasibility, utility and impact of a text messaging (TM) intervention to improve participation in laboratory testing in adolescent liver transplant patients. AYA patients, aged 12 to 21 years, were recruited for a prospective pilot trial evaluating a TM intervention delivered over a 1-year period. The intervention involved automated TM reminders with feedback administered according to a prescribed laboratory testing frequency. Participation rate in laboratory testing after the intervention was compared to the year prior. Patient responses and feedback by text and survey were used to assess feasibility, acceptability and use of the intervention. Forty-two patients were recruited and 33 patients remained enrolled for the study duration. Recipients of the TM intervention demonstrated a significant improvement in participation rate in laboratory testing from 58% to 78% (P<.001). This rate was also significantly higher than in non-intervention controls (P=.003). There was a high acceptability, response rate and a significant correlation with reported versus actual completion of laboratory tests by TM. TM reminders significantly improved participation in laboratory testing in AYA liver transplant patients. The intervention demonstrated feasibility, acceptability, and use with a high proportion of patients who engaged in and perceived a benefit from using this technology.

Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

PubMed

Chen, Hanbei; Li, Yakui; Zhu, Yemin; Wu, Lifang; Meng, Jian; Lin, Ning; Yang, Dianqiang; Li, Minle; Ding, WenJin; Tong, Xuemei; Su, Qing

2017-08-01

The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

Hyperemesis gravidarum presenting as jaundice and transient hyperthyroidism complicated with acute pancreatitis.

PubMed

Weng, Meng Tzu; Wei, Shu Chen; Wong, Jau Min; Chang, Tien Chun

2005-03-01

Hyperemesis gravidarum is an extreme form of nausea and vomiting during pregnancy. Its presenting symptoms include vomiting, disturbed nutrition, electrolyte imbalance, ketosis, extreme weight loss, renal and/or liver damage. It is rare for a hyperemesis gravidarum patient to present with jaundice, hyperthyroidism and idiopathic acute pancreatitis during the same hospitalization period. Here, we report such a case. A 25-year-old pregnant woman without underlying liver or thyroid disease was admitted due to jaundice noted for 2 days at 8 weeks of gestational age. Hyperthyroidism symptoms of tachycardia and finger tremor also bothered her. After treatment with parenteral fluid and antithyroid agents, her clinical condition improved. However, an episode of idiopathic pancreatitis occurred after nausea and vomiting subsided. Bowel rest with parenteral fluid and nutrition supplement was given and the increased pancreatic enzyme level gradually subsided. Follow-up liver and thyroid function were normal after gestational age of 26 weeks. She delivered a healthy female baby without low birth body weight at gestational age of 39 weeks. Rapid diagnosis and supportive care are important for the hyperemesis gravidarum patient with the complication of acute pancreatitis.

Improvement of liver function and non-invasive fibrosis markers in hepatitis B virus-associated cirrhosis: 2 years of entecavir treatment.

PubMed

Shin, Seung Kak; Kim, Jeong Han; Park, Hyeonsu; Kwon, Oh Sang; Lee, Hyun Jung; Yeon, Jong Eun; Byun, Kwan Soo; Suh, Sang Jun; Yim, Hyung Joon; Kim, Yun Soo; Kim, Ju Hyun

2015-12-01

Entecavir (ETV) induces biochemical and histologic improvement of the liver in patients with chronic hepatitis B. This study aimed to confirm that 2 years of ETV treatment improves liver function and non-invasive fibrosis markers in patients with hepatitis B virus (HBV)-associated cirrhosis. A total 472 naïve patients with HBV-associated cirrhosis was treated with ETV for at least 2 years, between March 2007 and December 2012. Model for end-stage liver disease and Child-Pugh (CP) score were used to evaluate the improvement of liver function. Aspartate transaminase to platelet ratio index, FIB-4 index, and fibrosis index were used to evaluate the improvement of fibrosis. The final 370 of 472 patients with HBV-associated cirrhosis were enrolled. Mean age was 51 ± 10 years, and 240 patients (64.9%) were men. The distribution of CP class was 71.1% in A, 24.6% in B, and 4.3% in C. Mean end-stage liver disease and CP score changed over the study period from 8.5 ± 4.6 to 6.2 ± 4.2 (P < 0.001) and from 6.2 ± 1.6 to 5.6 ± 0.9 (P < 0.001), respectively. Aspartate transaminase to platelet ratio index, FIB-4 index, and fibrosis index changed from 3.6 ± 4.5 to 1.5 ± 1.5 (P < 0.001), from 7.0 ± 6.2 to 3.9 ± 2.8 (P < 0.001), and from 3.3 ± 0.9 to 2.5 ± 1.1 (P < 0.001), respectively. After 2 years of treatment, ETV improves liver function and non-invasive fibrosis markers in patients with HBV-associated cirrhosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

PubMed

Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

2018-03-15

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

MRI artifact reduction and quality improvement in the upper abdomen with PROPELLER and prospective acquisition correction (PACE) technique.

PubMed

Hirokawa, Yuusuke; Isoda, Hiroyoshi; Maetani, Yoji S; Arizono, Shigeki; Shimada, Kotaro; Togashi, Kaori

2008-10-01

The purpose of this study was to evaluate the effectiveness of the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER [BLADE in the MR systems from Siemens Medical Solutions]) with a respiratory compensation technique for motion correction, image noise reduction, improved sharpness of liver edge, and image quality of the upper abdomen. Twenty healthy adult volunteers with a mean age of 28 years (age range, 23-42 years) underwent upper abdominal MRI with a 1.5-T scanner. For each subject, fat-saturated T2-weighted turbo spin-echo (TSE) sequences with respiratory compensation (prospective acquisition correction [PACE]) were performed with and without the BLADE technique. Ghosting artifact, artifacts except ghosting artifact such as respiratory motion and bowel movement, sharpness of liver edge, image noise, and overall image quality were evaluated visually by three radiologists using a 5-point scale for qualitative analysis. The Wilcoxon's signed rank test was used to determine whether a significant difference existed between images with and without BLADE. A p value less than 0.05 was considered to be statistically significant. In the BLADE images, image artifacts, sharpness of liver edge, image noise, and overall image quality were significantly improved (p < 0.001). With the BLADE technique, T2-weighted TSE images of the upper abdomen could provide reduced image artifacts including ghosting artifact and image noise and provide better image quality.

Clinical significance of liver histology on outcomes in biliary atresia.

PubMed

Webb, Nicholas L; Jiwane, Ashish; Ooi, Chee Y; Nightinghale, Scott; Adams, Susan E; Krishnan, Usha

2017-03-01

Biliary atresia (BA) literature has focussed on the relationship between age at Kasai procedure (KP) and post-KP outcomes. This study primarily examines post-KP outcomes including, 6-month normalisation of bilirubin, 5-year native liver survival (NLS), development of portal hypertension (PHT) and incidence of ascending cholangitis at a single tertiary paediatric centre in Australia. The study also evaluated prognostic factors which may influence these aforementioned outcomes. Retrospective chart review of all BA cases between 1999 and 2014. Age at KP, liver biopsy results, use of ursodeoxycholic acid or prophylactic antibiotics and occurrence of PHT and ascending cholangitis post-KP were recorded and related to the primary post-KP outcome measures. BA was diagnosed in 29 patients. Twenty-four of 29 patients underwent KP. Median age at KP was 68 days (29-104). Fourteen of 24 (58.3%) had bridging fibrosis and 5 of 24 (20.8%) had cirrhosis at time of KP. Median follow-up was 8.4 years (2.08-15.58 years). Bilirubin normalisation within 6 months occurred in 7 of 24 (29.2%) patients and 5-year NLS was 45.8% (11/24). Fourteen of 24 (58.3%) had PHT and 18 of 24 (75%) patients had ascending cholangitis post-KP. Absence of bridging fibrosis in liver histology at KP was the only factor to be significantly associated with improved 5-year NLS. None of the other variables examined had a significant association with either 5-year NLS or bilirubin normalisation by 6 months. Five-year NLS in this series was 45.8%. Absence of bridging fibrosis at time of KP was the only factor significantly associated with improved 5-year NLS. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Long-Lasting Improvements in Liver Fat and Metabolism Despite Body Weight Regain After Dietary Weight Loss

PubMed Central

Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L.; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C.; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan

2013-01-01

OBJECTIVE Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. RESEARCH DESIGN AND METHODS We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17–36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. RESULTS Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. CONCLUSIONS A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions. PMID:23963894

Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1β for steatohepatitis

PubMed Central

Chung, Ki Wung; Lee, Eun Kyeong; Kim, Dae Hyun; An, Hye Jin; Kim, Nam Deuk; Im, Dong Soon; Lee, Jaewon; Yu, Byung Pal; Chung, Hae Young

2015-01-01

Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/IL-1β pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged rats. To monitor the effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg−1) to young (6-month old) and aged (24-month old) rats and found abnormal lipid metabolism in only aged rats with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of PPARα and SREBP1c. We also observed severe liver inflammation in aged rats as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many inflammation-associated factors, the aged rat liver showed chronically increased IL-1β production. Increased levels of IL-1β were caused by the upregulation of caspase-1 activity and inflammasome activation. In vitro studies with HepG2 cells demonstrated that treatment with IL-1β significantly induced lipid accumulation in hepatocytes through the regulation of PPARα and SREBP1c. In summary, we demonstrated that LPS-induced liver inflammation and lipid accumulation were associated with a chronically overactive inflammasome/IL-1β pathway in aged rat livers. Based on the present findings, we propose a mechanism of aging-associated progression of steatohepatitis induced by endotoxin, delineating a pathogenic role of the inflammasome/IL-1β pathway involved in lipid accumulation in the liver. PMID:25847140

Computational Modeling in Liver Surgery

PubMed Central

Christ, Bruno; Dahmen, Uta; Herrmann, Karl-Heinz; König, Matthias; Reichenbach, Jürgen R.; Ricken, Tim; Schleicher, Jana; Ole Schwen, Lars; Vlaic, Sebastian; Waschinsky, Navina

2017-01-01

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery. PMID:29249974

Liver cancer mortality rate model in Thailand

NASA Astrophysics Data System (ADS)

Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

2013-09-01

Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse.

PubMed

Liu, Benny; Turley, Stephen D; Burns, Dennis K; Miller, Anna M; Repa, Joyce J; Dietschy, John M

2009-02-17

Niemann-Pick type C disease is largely attributable to an inactivating mutation of NPC1 protein, which normally aids movement of unesterified cholesterol (C) from the endosomal/lysosomal (E/L) compartment to the cytosolic compartment of cells throughout the body. This defect results in activation of macrophages in many tissues, progressive liver disease, and neurodegeneration. In the npc1(-/-) mouse, a model of this disease, the whole-animal C pool expands from 2,082 to 4,925 mg/kg body weight (bw) and the hepatic C pool increases from 132 to 1,485 mg/kg bw between birth and 49 days of age. A single dose of 2-hydroxypropyl-beta-cyclodextrin (CYCLO) administered at 7 days of age immediately caused this sequestered C to flow from the lysosomes to the cytosolic pool in many organs, resulting in a marked increase in cholesteryl esters, suppression of C but not fatty acid synthesis, down-regulation of genes controlled by sterol regulatory element 2, and up-regulation of many liver X receptor target genes. There was also decreased expression of proinflammatory proteins in the liver and brain. In the liver, where the rate of C sequestration equaled 79 mg x d(-1) x kg(-1), treatment with CYCLO within 24 h increased C movement out of the E/L compartment from near 0 to 233 mg x d(-1) x kg(-1). By 49 days of age, this single injection of CYCLO resulted in a reduction in whole-body C burden of >900 mg/kg, marked improvement in liver function tests, much less neurodegeneration, and, ultimately, significant prolongation of life. These findings suggest that CYCLO acutely reverses the lysosomal transport defect seen in NPC disease.

Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior.

PubMed

Ansari, Shahla; Azarkeivan, Azita; Miri-Aliabad, Ghasem; Yousefian, Saeed; Rostami, Tahereh

2017-01-01

Cardiac complications due to iron overload are the most common cause of death in patients with thalassemia major. The aim of this study was to compare iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on cardiac and liver iron load measured by T2* MRI. In this study, 108 patients with thalassemia major aged over 10 years who had iron overload in cardiac T2* MRI were studied in terms of iron chelators efficacy on the reduction of myocardial siderosis. The first group received deferoxamine, the second group only deferasirox, and the third group, a combination of deferoxamine and deferiprone. Myocardial iron was measured at baseline and 12 months later through T2* MRI technique. The three groups were similar in terms of age, gender, ferritin level, and mean myocardial T2* at baseline. In the deferoxamine group, myocardial T2* was increased from 12.0±4.1 ms at baseline to 13.5±8.4 ms at 12 months (p=0.10). Significant improvement was observed in myocardial T2* of the deferasirox group (p<0.001). In the combined treatment group, myocardial T2* was significantly increased (p<0.001). These differences among the three groups were not significant at the 12 months. A significant improvement was observed in liver T2* at 12 months compared to baseline in the deferasirox and the combination group. In comparison to deferoxamine monotherapy, combination therapy and deferasirox monotherapy have a significant impact on reducing iron overload and improvement of myocardial and liver T2* MRI.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme.

PubMed

Detry, O; Deroover, A; Meurisse, N; Hans, M F; Delwaide, J; Lauwick, S; Kaba, A; Joris, J; Meurisse, M; Honoré, P

2014-06-01

Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Liver spots

MedlinePlus

Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

Dark adaptation in vitamin A-deficient adults awaiting liver transplantation: improvement with intramuscular vitamin A treatment.

PubMed

Abbott-Johnson, Winsome J; Kerlin, Paul; Abiad, Ghassan; Clague, Alan E; Cuneo, Ross C

2011-04-01

Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A. This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month. Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05). Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

Hepatocyte Transplantation Improves Phenotype and Extends Survival in a Murine Model of Intermediate Maple Syrup Urine Disease

PubMed Central

Skvorak, Kristen J; Paul, Harbhajan S; Dorko, Kenneth; Marongiu, Fabio; Ellis, Ewa; Chace, Donald; Ferguson, Carolyn; Gibson, K Michael; Homanics, Gregg E; Strom, Stephen C

2009-01-01

Maple syrup urine disease (MSUD; OMIM 248600) is an inborn error of metabolism of the branched chain α-ketoacid dehydrogenase (BCKDH) complex that is treated primarily by dietary manipulation of branched-chain amino acids (BCAA). Dietary restriction is lifelong and compliance is difficult. Liver transplantation significantly improves outcomes; however, alternative therapies are needed. To test novel therapies such as hepatocyte transplantation (HTx), we previously created a murine model of intermediate MSUD (iMSUD), which closely mimics human iMSUD. LacZ-positive murine donor hepatocytes were harvested and directly injected (105 cells/50 µl) into liver of iMSUD mice (two injections at 1–10 days of age). Donor hepatocytes engrafted into iMSUD recipient liver, increased liver BCKDH activity, improved blood total BCAA/alanine ratio, increased body weight at weaning, and extended the lifespan of HTx-treated iMSUD mice compared to phosphate-buffered saline (PBS)–treated and untreated iMSUD mice. Based on these data demonstrating partial metabolic correction of iMSUD in a murine model, coupled to the fact that multiple transplants are possible to enhance these results, we suggest that HTx represents a promising therapeutic intervention for MSUD that warrants further investigation. PMID:19436271

Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic, and Statistical Study.

PubMed

Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Mila-Kierzenkowska, Celestyna; Elminowska-Wenda, Gabriela; Dombek, Małgorzata; Szpinda, Anna; Badura, Mateusz

2015-01-01

Using anatomical, hydrostatic, and statistical methods, liver volumes were assessed in 69 human fetuses of both sexes aged 18-30 weeks. No sex differences were found. The median of liver volume achieved by hydrostatic measurements increased from 6.57 cm(3) at 18-21 weeks through 14.36 cm(3) at 22-25 weeks to 20.77 cm(3) at 26-30 weeks, according to the following regression: y = -26.95 + 1.74 × age ± Z × (-3.15 + 0.27 × age). The median of liver volume calculated indirectly according to the formula liver volume = 0.55 × liver length × liver transverse diameter × liver sagittal diameter increased from 12.41 cm(3) at 18-21 weeks through 28.21 cm(3) at 22-25 weeks to 49.69 cm(3) at 26-30 weeks. There was a strong relationship (r = 0.91, p < 0.001) between the liver volumes achieved by hydrostatic (x) and indirect (y) methods, expressed by y = -0.05 + 2.16x ± 7.26. The liver volume should be calculated as follows liver volume = 0.26 × liver length × liver transverse diameter × liver sagittal diameter. The age-specific liver volumes are of great relevance in the evaluation of the normal hepatic growth and the early diagnosis of fetal micro- and macrosomias.

Age-associated change of C/EBP family proteins causes severe liver injury and acceleration of liver proliferation after CCl4 treatments.

PubMed

Hong, Il-Hwa; Lewis, Kyle; Iakova, Polina; Jin, Jingling; Sullivan, Emily; Jawanmardi, Nicole; Timchenko, Lubov; Timchenko, Nikolai

2014-01-10

The aged liver is more sensitive to the drug treatments and has a high probability of developing liver disorders such as fibrosis, cirrhosis, and cancer. Here we present mechanisms underlying age-associated severe liver injury and acceleration of liver proliferation after CCl4 treatments. We have examined liver response to CCl4 treatments using old WT mice and young C/EBPα-S193D knockin mice, which express an aged-like isoform of C/EBPα. Both animal models have altered chromatin structure as well as increased liver injury and proliferation after acute CCl4 treatments. We found that these age-related changes are associated with the repression of key regulators of liver biology: C/EBPα, Farnesoid X Receptor (FXR) and telomere reverse transcriptase (TERT). In quiescent livers of old WT and young S193D mice, the inhibition of TERT is mediated by HDAC1-C/EBPα complexes. After CCl4 treatments, TERT, C/EBPα and FXR are repressed by different mechanisms. These mechanisms include the increase of a dominant negative isoform, C/EBPβ-LIP, and subsequent repression of C/EBPα, FXR, and TERT promoters. C/EBPβ-LIP also disrupts Rb-E2F1 complexes in C/EBPα-S193D mice after CCl4 treatments. To examine if these alterations are involved in drug-mediated liver diseases, we performed chronic treatments of mice with CCl4. We found that C/EBPα-S193D mice developed fibrosis much more rapidly than WT mice. Thus, our data show that the age-associated alterations of C/EBP proteins create favorable conditions for the increased liver proliferation after CCl4 treatments and for development of drug-mediated liver diseases.

Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments*

PubMed Central

Hong, Il-Hwa; Lewis, Kyle; Iakova, Polina; Jin, Jingling; Sullivan, Emily; Jawanmardi, Nicole; Timchenko, Lubov; Timchenko, Nikolai

2014-01-01

The aged liver is more sensitive to the drug treatments and has a high probability of developing liver disorders such as fibrosis, cirrhosis, and cancer. Here we present mechanisms underlying age-associated severe liver injury and acceleration of liver proliferation after CCl4 treatments. We have examined liver response to CCl4 treatments using old WT mice and young C/EBPα-S193D knockin mice, which express an aged-like isoform of C/EBPα. Both animal models have altered chromatin structure as well as increased liver injury and proliferation after acute CCl4 treatments. We found that these age-related changes are associated with the repression of key regulators of liver biology: C/EBPα, Farnesoid X Receptor (FXR) and telomere reverse transcriptase (TERT). In quiescent livers of old WT and young S193D mice, the inhibition of TERT is mediated by HDAC1-C/EBPα complexes. After CCl4 treatments, TERT, C/EBPα and FXR are repressed by different mechanisms. These mechanisms include the increase of a dominant negative isoform, C/EBPβ-LIP, and subsequent repression of C/EBPα, FXR, and TERT promoters. C/EBPβ-LIP also disrupts Rb-E2F1 complexes in C/EBPα-S193D mice after CCl4 treatments. To examine if these alterations are involved in drug-mediated liver diseases, we performed chronic treatments of mice with CCl4. We found that C/EBPα-S193D mice developed fibrosis much more rapidly than WT mice. Thus, our data show that the age-associated alterations of C/EBP proteins create favorable conditions for the increased liver proliferation after CCl4 treatments and for development of drug-mediated liver diseases. PMID:24273171

Effect of nanosilicon dioxide on growth performance, egg quality, liver histopathology and concentration of calcium, phosphorus and silicon in egg, liver and bone in laying quails

NASA Astrophysics Data System (ADS)

Faryadi, Samira; Sheikhahmadi, Ardashir

2017-11-01

This experiment was conducted to evaluate the effects of different levels of nanosilicon dioxide (nSiO2) on performance, egg quality, liver histopathology and concentration of calcium (Ca), phosphorus and silicon (Si) in egg, liver and bone in laying quails. The experiment was administered using 60 laying quails at 16-26 weeks of age with five treatments [0 (control), 500, 1000, 2000 and 4000 mg nSiO2 per kg of diet] and four replicates in a completely randomized design. During the experiment, the amount of feed intake was recorded weekly and performance parameters were measured. During the last 3 days of the experiment, all of the eggs in each replicate were collected and egg quality parameters were measured. At the end of 26 weeks of age, the birds were sacrificed and blood samples were collected. Liver samples from each treatment were fixed in 10% buffered formalin for histopathological assessment. The right thigh bone and a portion of liver were inserted in plastic bags and stored at - 20. The results showed that nSiO2 supplementation significantly affected egg weight and egg mass ( P < 0.05). Also, dietary nSiO2 supplementation decreased the yolk weight and increased the shell weight ( P < 0.05). Moreover, nSiO2 increased bone ash content, Ca and Si concentration in the bone ( P < 0.05). The liver enzymes in plasma and the liver tissue histopathology were not significantly affected ( P > 0.05) by dietary treatments. In conclusion, the results indicated that dietary supplementation of nSiO2 could improve bone density and performance without any adverse effect on the health of laying quails.

Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

PubMed

Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

2017-01-01

The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by PPARγ modulation.

Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle.

PubMed

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam; Nielsen, Louise Aas; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-12-30

Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss. ClinicalTrials.gov registration number: NCT00928473 , the Danish Childhood Obesity Biobank. Registered June 25, 2009.

Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection

PubMed Central

Maeba, Shinji; Hasegawa, Shunji; Shimomura, Maiko; Ichimura, Takuya; Takahashi, Kazumasa; Motoyama, Masashi; Fukunaga, Shinnosuke; Ito, Yoshinori; Ichiyama, Takashi; Ohga, Shouichi

2015-01-01

Background Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination. PMID:26495160

Do older patients utilize excess health care resources after liver transplantation?

PubMed

Shankar, Neil; AlBasheer, Mamoun; Marotta, Paul; Wall, William; McAlister, Vivian; Chandok, Natasha

2011-01-01

Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age ≥ 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure. To determine if patients ≥ 60 years of age utilize more health resources following liver transplantation compared with younger patients. Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age ≥ 60 years (n = 51) and < 60 years (n = 157). The Chi-Square Test, Mantel-Haenszel Test, 2-sample test and odds ratios were calculated to ascertain associations between age and resource utilization parameters. Regression analyses were adjusted for model for end-stage liver disease score, location before surgery, diabetes mellitus, donor age, cold ischemia time, albumin, and diagnosis of hepatitis C. Recipients ≥ 60 years of age have similar lengths of hospitalization, re-operative rates, need for consultative services and readmission rates following liver transplantation, but have longer lengths of stay in the intensive care (hazard ratio 1.97, p = 0.03). Overall, liver transplant recipients ≥ 60 years of age utilize comparable resources following LT vs. younger recipients. Our findings have implications on cost-containment policies for liver transplantation.

Effects of testosterone administration on liver structure and function in aging rats.

PubMed

Nucci, Ricardo Aparecido Baptista; Teodoro, Ana Caroline de Souza; Krause Neto, Walter; Silva, Wellington de Assis; de Souza, Romeu Rodrigues; Anaruma, Carlos Alberto; Gama, Eliane Florencio

2017-06-01

Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver. This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals. Wistar rats were divided into three groups: 20 months' group (G20), 24 months' group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months. Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals' liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores. Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals' liver.

Transjugular Intrahepatic Porto-Systemic Shunt in Patients with Liver Cirrhosis and Model for End-Stage Liver Disease ≥15.

PubMed

Ascha, Mona; Hanouneh, Mohamad; S Ascha, Mustafa; Zein, Nizar N; Sands, Mark; Lopez, Rocio; Hanouneh, Ibrahim A

2017-02-01

It is not known whether transjugular intrahepatic porto-systemic shunt (TIPS) is safe in patients with advanced liver cirrhosis. The aim of our study was to evaluate the impact of TIPS on transplant-free survival in patients with liver cirrhosis and MELD score ≥15. All adult patients who underwent TIPS at our institution between 2004 and 2011 were identified (N = 470). A total of 144 patients had MELD ≥15 at the time of TIPS. These patients were matched 1:1 to patients with liver cirrhosis who did not undergo TIPS based on age and MELD score using the greedy algorithm. Patients were followed up until time of death or liver transplantation. Kaplan-Meier curves and log-rank tests were used to test for differences in survival outcome between the two groups. A total of 288 patients with liver cirrhosis were included, of whom 144 underwent TIPS and 144 did not. The two groups were matched based on age and MELD score and were comparable with regard to gender and ethnicity. Mean MELD and Child-Pugh scores in the study population were 20.9 ± 6.5 and 10.5 ± 1.8, respectively. The most common indication for TIPS was varices (49 %), followed by refractory ascites (42 %). In the first 2 months post-TIPS, there was increased mortality or liver transplantation in patients who had TIPS compared to those who did not, but this did not reach statistical significance (p = 0.07). However, after 2 months, TIPS is associated with 56 % lower risk of dying or needing liver transplantation (p < 0.01) than cirrhotic patients who did not undergo TIPS. In patients with liver cirrhosis and MELD ≥15, TIPS might improve transplant-free survival for patients who live for at least 2 months after the procedure.

How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

PubMed

Uemura, Tadahiro; Nikkel, Lucas E; Hollenbeak, Christopher S; Ramprasad, Varun; Schaefer, Eric; Kadry, Zakiyah

2012-06-01

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

PubMed

Marcos, Ricardo; Correia-Gomes, Carla

2016-12-01

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

Association of age dependent liver injury and fibrosis with immune cell populations

PubMed Central

Collins, Bradley H.; Holzknecht, Zoie E.; Lynn, Kellie A.; Sempowski, Gregory D.; Smith, Cathy Choy; Liu, Songling; Parker, William; Rockey, Don C.

2014-01-01

Background/Aim The liver’s response to injury is fibrosis, and when chronic, cirrhosis. Age is a critical factor impacting many immune-mediated processes, potentially including the liver’s wounding response to injury. Methods The effects of age on acute and chronic liver injury were evaluated using a carbon tetrachloride model in mice. Lymphocyte and macrophage populations were assessed by flow cytometry and immunohistochemical analysis. Results Acute liver injury was greater in 18-month old (old) mice than in 9-month old (middle aged) mice as judged by changes in aminotransferases. Similarly, 18-month old livers had a significantly greater fibrogenic response to injury than did 9-month old livers after chronic injury (assessed by col1α1 mRNA expression, morphometric analysis and hydroxyproline measurement). Interestingly, livers from young mice (6 weeks old) also exhibited an increase in fibrogenesis compared to 9-month old mice, albeit not to the same degree as in old mice. Consistent with a role for macrophages in fibrogenesis, the number of liver macrophages in young and 9-month old mice increased, while in chronically injured 18-month old livers, the number of macrophages was reduced, and was less than in the livers of young and 9-month old injured livers. Conclusions Our data indicate that the fibrogenic response to injury varies substantially with age, and moreover that macrophage recruitment and dynamics may be an important component in differential age-associated fibrotic disease. PMID:23710620

Polycystic liver disease with right pleural effusion

NASA Astrophysics Data System (ADS)

Anggreini, A. Y.; Dairi, L. B.

2018-03-01

Polycystic liver disease (PCLD) is a condition in which multiple cysts form in the hepatic parenchyma. The polycystic liver disease is also an autosomal dominant disorder (ADPLD) caused by a mutation in a gene that encodes a protein hepatocystin. PCLD has a prevalence count of 1:200,000 people in the people of America. PCLD occurs ± 24% of patients in the third decade of age to 80% by the sixth decade. Women tend to get larger cysts and more and correlated with the number of pregnancies. The following case report of a woman, 51-years-old who was treated at Haji Adam Malik hospital Medan with a diagnosis of polycystic liver disease with right pleural effusion. Some literature has reported complications of the polycystic liver disease but rarely reported with pleural effusion presentation. The patient had already undergone a puncture of pleural fluid and after three weeks of treatment condition of the patient improved and permitted to be outgoing patient.

Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long-term outcomes from a single center.

PubMed

Foley, David P; Fernandez, Luis A; Leverson, Glen; Anderson, Michael; Mezrich, Joshua; Sollinger, Hans W; D'Alessandro, Anthony

2011-04-01

This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from "donation after cardiac death" (DCD) donors. Recent enthusiasm toward increased use of DCD donors' livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined. We performed a retrospective review of 1157 "donation after brain death" (DBD) and 87 DCD liver transplants performed between January 1, 1993, and December 31, 2008. Patient and graft survivals and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors. Patient survival was significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 84%, 68%, 54%, and 54% vs DBD: 91%, 81%, 67%, and 58%; P < 0.01). Graft survival was also significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 69%, 56%, 43%, 43% vs DBD: 86%, 76%, 60%, 51%; P < 0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs DBD: 26%; P < 0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs DBD: 1%; P < 0.01) were significantly higher in the DCD group. Donor age [hazard ratio (HR): 1.04; P < 0.01] and donor age greater than 40 years (HR: 3.13; P < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed that cold ischemic time (CIT) greater than 8 hours (HR: 2.46; P = 0.05) and donor age greater than 40 years (HR: 2.90; P < 0.01) significantly increased the risk of IC. Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared with DBD liver transplantations. Donor age and CIT greater than 8 hours are the strongest predictors for the development of IC. Careful selection of younger DCD donors and minimization of CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donors' livers.

Biliary Complications after Liver Transplantation from Donation after Cardiac Death Donors: An Analysis of Risk Factors and Long Term Outcomes from a Single Center

PubMed Central

Foley, David P.; Fernandez, Luis A.; Leverson, Glen; Anderson, Michael; Mezrich, Joshua; Sollinger, Hans W.; D’Alessandro, Anthony

2011-01-01

Objective This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from donation after cardiac death (DCD) donors. Summary Background Data Recent enthusiasm toward increased use of DCD donor livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined. Methods We performed a retrospective review of 1157 donation after brain death (DBD) and 87 DCD liver transplants performed between January 1, 1993 and December 31, 2008. Patient and graft survivals, and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors. Results Patient survival was significantly lower in the DCD group compared to the DBD group at 1, 5, 10 and 15 years (DCD: 84%, 68%, 54%, 54% vs. DBD: 91%, 81%, 67%, 58%, p<0.01). Graft survival was also significantly lower in the DCD group compared to the DBD group at 1, 5, 10 and 15 years (DCD: 69%, 56%, 43%, 43% vs. DBD: 86%, 76%, 60%, 51%, p<0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs. DBD: 26%, p<0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs. DBD: 1%, p<0.01) were significantly higher in the DCD group. Donor age (HR: 1.04, p<0.01) and donor age >40 years (HR: 3.13, p < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed cold ischemic time (CIT) >8 hours (HR: 2.46, p=0.05), donor age >40 (HR: 2.90, p< 0.01) significantly increased the risk of IC. Conclusions Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared to DBD liver transplants. Donor age and CIT >8 hours are the strongest predictors for the development of ischemic cholangiopathy. Careful selection of younger DCD donors and minimizing CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donor livers. PMID:21475025

Long-Term Telbivudine Treatment Results in Resolution of Liver Inflammation and Fibrosis in Patients with Chronic Hepatitis B.

PubMed

Hou, Jin-Lin; Xu, Daozheng; Shi, Guangfeng; Wan, Mobin; Goodman, Zachary; Tan, Deming; Xie, Qing; Chen, Chengwei; Wei, Lai; Niu, Junqi; Wang, Qinhuan; Ren, Hong; Wang, Yuming; Jia, Jidong; Bao, Weibin; Dong, Yuhong; Trylesinski, Aldo; Naoumov, Nikolai V

2015-08-01

The long-term goal of chronic hepatitis B (CHB) treatment is improvement of liver disease and prevention of cirrhosis. The aim of this study was to assess whether prolonged telbivudine treatment improves liver inflammation and fibrosis. The primary objective was to evaluate the proportion of patients with absence/minimal inflammation (Knodell necroinflammatory score ≤3) on liver biopsy at Year 5. Fifty-seven patients aged 16-70 years with a clinical history of CHB and active viral replication (38 hepatitis B e antigen [HBeAg] positive and 19 HBeAg negative) were followed for 6 years: 33 received telbivudine 600 mg/day continuously for 5 years; 24 received lamivudine 100 mg/day for 2 years and then telbivudine for 3 years. Liver biopsies were taken pre-treatment and after 5 years of treatment. At baseline, mean (standard deviation) serum hepatitis B virus (HBV) DNA load was 8.5 (1.7) log10 copies/mL, Knodell necroinflammatory score was 7.6 (2.9), and Ishak fibrosis score was 2.2 (1.1). After antiviral treatment (median duration: 261 weeks), liver histology improved with increased proportions of patients with absence/minimal liver inflammation (Knodell necroinflammatory score ≤3), from 16% (9/57) at baseline to 98% (56/57), and absence/minimal fibrosis (Ishak score ≤1), from 25% (14/57) at baseline to 84% (48/57). At Year 5, HBV DNA load was <300 copies/mL for all patients; cumulative HBeAg loss and seroconversion rates were 88% and 77%, respectively. At Year 6, 95% of patients with abnormal baseline glomerular filtration rate (60-90 mL/min/1.73 m(2)) improved to normal GFR (>90 mL/min/1.73 m(2)). Long-term telbivudine treatment with profound and durable viral suppression significantly improved liver histology, thus achieving the long-term goals of CHB treatment. FibroScan(®) results after 5 and 6 years of treatment (in almost 20% of patients) were consistent with this information. Novartis and National Science and Technology Major Project (2012ZX10002003). ClinicalTrials.gov # NCT00877149.

Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic, and Statistical Study

PubMed Central

Szpinda, Michał; Paruszewska-Achtel, Monika; Mila-Kierzenkowska, Celestyna; Elminowska-Wenda, Gabriela; Dombek, Małgorzata; Szpinda, Anna; Badura, Mateusz

2015-01-01

Using anatomical, hydrostatic, and statistical methods, liver volumes were assessed in 69 human fetuses of both sexes aged 18–30 weeks. No sex differences were found. The median of liver volume achieved by hydrostatic measurements increased from 6.57 cm3 at 18–21 weeks through 14.36 cm3 at 22–25 weeks to 20.77 cm3 at 26–30 weeks, according to the following regression: y = −26.95 + 1.74 × age ± Z  × (−3.15 + 0.27 × age). The median of liver volume calculated indirectly according to the formula liver volume = 0.55 × liver length × liver transverse diameter × liver sagittal diameter increased from 12.41 cm3 at 18–21 weeks through 28.21 cm3 at 22–25 weeks to 49.69 cm3 at 26–30 weeks. There was a strong relationship (r = 0.91, p < 0.001) between the liver volumes achieved by hydrostatic (x) and indirect (y) methods, expressed by y = −0.05 + 2.16x  ± 7.26. The liver volume should be calculated as follows liver volume = 0.26 × liver length × liver transverse diameter × liver sagittal diameter. The age-specific liver volumes are of great relevance in the evaluation of the normal hepatic growth and the early diagnosis of fetal micro- and macrosomias. PMID:26413551

Marine collagen peptides protect against early alcoholic liver injury in rats.

PubMed

Lin, Bing; Zhang, Feng; Yu, Yongchao; Jiang, Qinghao; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

2012-04-01

Marine collagen peptides (MCP) have been reported to exhibit antioxidative activity, which is the common property of numerous hepatoprotective agents. Previous studies have shown that MCP have biological functions including anti-hypertension, anti-ulcer, anti-skin ageing and extending the life span. However, its role in alcoholic liver injury remains unknown. The present study aimed to investigate the effects of MCP on early alcoholic liver injury in rats. Rats were administered with alcohol at a dose of 6 g/kg body weight intragastrically per d to induce early liver injury, which was then evaluated by serum markers and histopathological examination. Treatment with MCP could reverse the increased level of serum aminotransferase and reduce hepatic histological damage. In addition, MCP attenuated the alteration in serum superoxide dismutase and malondialdehyde levels. MCP also counteracted the increased levels of total cholesterol and TAG. However, no significant difference was observed in the contents of alcohol dehydrogenase both in liver and serum protein of rats. These findings suggest that MCP have a protective effect on early alcoholic liver injury in rats by their antioxidative activity and improving lipid metabolism.

Three-dimensional growth dynamics of the liver in the human fetus.

PubMed

Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Badura, Mateusz; Mila-Kierzenkowska, Celestyna; Wiśniewski, Marcin

2015-07-01

The fetal liver is indubitably the earliest and the most severely affected organ by abnormal fetal growth. The size of the fetal liver assessed by three-dimensional ultrasonography is indispensable in determining the status of fetal growth, nutrition and maturity, and in the early recognition and monitoring fetal micro- and macrosomias. The aim of the present study was to measure the human fetal liver length, transverse and sagittal diameters to establish their age-specific reference intervals, the 3rd, 10th, 50th, 90th, and 97th smoothed centile curves, and the relative growth of the liver calculated for the 50th centile. Using anatomical, digital (NIS-Elements AR 3.0, Nikon) and statistical methods (one-way ANOVA test for paired data and post hoc RIR Tukey test, Shapiro-Wilk test, Fisher's test, Student's t test, the Altman-Chitty method), length, transverse and sagittal diameters of the liver for the 3rd, 10th, 50th, 90th, and 97th centiles were assessed in 69 human fetuses of both sexes (32 males and 37 females) aged 18-30 weeks, derived from spontaneous abortions or stillbirths. No male-female differences (P > 0.05) concerning the three parameters studied were found. During the study period, the fetal liver increased tri-dimensionally: in length from 19.51 ± 1.02 to 39.65 ± 7.05 mm, in transverse diameter from 29.44 ± 3.73 to 53.13 ± 5.31 mm, and in sagittal diameter from 22.97 ± 3.79 to 43.22 ± 5.49 mm. The natural logarithmic models were found to fit the data with gestational age (P < 0.001) in the following five cutoff points: 3rd, 10th, 50th, 90th and 97th centiles. The values of liver parameters in relation to gestational age in weeks were calculated by the following logarithmic regressions: y = -82.778 + 35.752 × ln(age) ± Z × (-2.778 + 0.308 × age) for liver length, y = -123.06 + 52.668 × ln(age) ± Z × (3.156 + 0.049 × age) for liver transverse diameter, and y = -108.94 + 46.052 × ln(age) ± Z × (-0.541 + 0.188 × age) for liver sagittal diameter. For the 50th centile, at the range of 18-30 weeks, the growth rates per week were gradually decreasing from 1.93 to 1.21 mm for length, from 2.85 to 1.79 mm for transverse diameter, and from 2.49 to 1.56 mm for sagittal diameter of the liver (P < 0.05). During the study period both the length-to-transverse diameter ratio and the sagittal-to-transverse diameter ratio of the liver changed little, attaining the values of 0.71 ± 0.11 and 0.87 ± 0.12, respectively. The fetal liver does not reveal sex differences in its length, transverse and sagittal diameters. The fetal liver length, transverse and sagittal diameters grow logarithmically. The regression equations for the estimation of the mean and standard deviation of liver length, transverse and sagittal diameters allow for calculating any desired centiles according to gestational age. The three-dimensional evolution of the fetal liver follows proportionately. The age-specific reference intervals for evolving liver length, transverse and sagittal diameters constitute the normative values of potential relevance in monitoring normal fetal development and screening for disturbances in fetal growth.

Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

PubMed

Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

2016-06-01

Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Zebrafish: An Important Tool for Liver Disease Research

PubMed Central

Goessling, Wolfram; Sadler, Kirsten C.

2016-01-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

Improving National Results in Liver Transplantation Using Grafts From Donation After Cardiac Death Donors.

PubMed

Croome, Kristopher P; Lee, David D; Keaveny, Andrew P; Taner, C Burcin

2016-12-01

Published reports describing the national experience with liver grafts from donation after cardiac death (DCD) donors have resulted in reservations with their widespread utilization. The present study aimed to investigate if temporal improvements in outcomes have been observed on a national level and to determine if donor and recipient selection have been modified in a fashion consistent with published data on DCD use in liver transplantation (LT). Patients undergoing DCD LT between 2003 and 2014 were obtained from the United Network of Organ Sharing Standard Transplant Analysis and Research file and divided into 3 equal eras based on the date of DCD LT: era 1 (2003-2006), era 2 (2007-2010), and era 3 (2011-2014). Improvement in graft survival was seen between era 1 and era 2 (P = 0.001) and between era 2 and era 3 (P < 0.001). Concurrently, an increase in the proportion of patients with hepatocellular carcinoma and a decrease in critically ill patients, retransplant recipients, donor age, warm ischemia time greater than 30 minutes and cold ischemic time also occurred over the same period. On multivariate analysis, significant predictors of graft survival included: recipient age, biologic MELD score, recipient on ventilator, recipient hepatitis C virus + serology, donor age and cold ischemic time. In addition, even after adjustment for all of the aforementioned variables, both era 2 (hazard ratio, 0.81; confidence interval, 0.69-0.94; P = 0.007), and era 3 (hazard ratio, 0.61; confidence interval, 0.5-0.73; P < 0.001) had a protective effect compared to era 1. The national outcomes for DCD LT have improved over the last 12 years. This change was associated with modifications in both recipient and donor selection. Furthermore, an era effect was observed, even after adjustment for all recipient and donor variables on multivariate analysis.

Anthocyanins Delay Ageing-Related Degenerative Changes in the Liver.

PubMed

Wei, Jie; Zhang, Guokun; Zhang, Xiao; Xu, Dexin; Gao, Jun; Fan, Jungang

2017-12-01

Liver ageing is a significant risk factor for chronic liver diseases. Anthocyanin is a food additive that has previously shown efficacy in increasing longevity. Here, we tested whether anthocyanins could protect young mice from accelerated ageing of the liver. Kunming mice were injected with D-galactose to accelerate ageing and were given 20 or 40 mg/kg anthocyanins as an intervention. After eight weeks, whole liver function and structure were evaluated, and the expression levels of genes involved in the DNA damage signalling pathway were assessed by Western blot analysis. Anthocyanins delayed the reduction of the liver index (p < 0.05), hepatic tissue injury and fibrosis. Anthocyanins also maintained the stability of the redox system (GSH-PX, T-SOD and MDA) in plasma and liver structures (p < 0.001) and reduced the levels of inflammatory factors (IL-1, IL-6 and TNF-α) in the liver (p < 0.05). Moreover, the expression levels of sensors (ATM and ATR), mediators (H2AX and γ-H2AX) and effectors (Chk1, Chk2, p53 and p-p53) in the DNA damage signalling pathway were all reduced. Anthocyanins could be widely used in the field of health products to slow ageing-related deterioration of liver function and structure by inhibiting DNA damage.

Role of liver-directed local tumor therapy in the management of hepatocellular carcinoma with extrahepatic metastases: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2017-02-01

This study assessed the prognostic impact of the liver-directed local tumor therapy in the management of hepatocellular carcinoma (HCC) with extrahepatic metastases. Metastatic HCC patients diagnosed between 2004 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TNM stage, site of metastases, fibrosis score and alpha fetoprotein). A total of 2529 patients were identified. The median age was 65 years, and 151 patients received liver-directed local treatment (either surgical treatment or local destructive treatment). Both before and after propensity score matching, cancer-specific and overall survival (p < 0.0001 for all) were better in the liver-directed local therapy group. When the overall survival was stratified by the type of local treatment (surgical resection versus destructive treatment), both types of treatment improved overall survival (p < 0.0001 for both). In multivariate analysis of the matched population, the only factor correlated with better survival receiving is local therapy (p < 0.0001). This analysis suggests that liver-directed local treatment may play a role -in addition to systemic treatment- in the management of selected patients with metastatic HCC. Further prospective randomized controlled trials are needed to confirm or deny this hypothesis.

Comparative factor analysis of the effect of postoperative peripheral parenteral nutrition on recovery of right lobe liver donors.

PubMed

Hsieh, Chia-En; Lin, Kuo-Hua; Lin, Chia-Cheng; Hwu, Yueh-Juen; Lin, Ping-Yi; Lin, Hui-Chuan; Ko, Chih-Jan; Wang, Su-Han; Chen, Yao-Li

2015-04-01

Intensive nutritional support can reduce the catabolic response, improve protein synthesis, and promote liver regeneration. This study examined whether postoperative peripheral parenteral nutrition may improve recovery and reduce the length of hospital stay in right lobe liver donors. In this retrospective study, we enrolled liver donors with residual liver volume < 50%. Donors were classified into 2 groups: donors who received (n = 44) or did not receive (n = 40) postoperative peripheral parenteral nutrition. Liver function tests included alanine aminotransferase and total bilirubin levels, and postoperative complications included pleural effusion, atelectasis, and wound complications. Hospital length of stay was included as a potential risk factor for the evaluation of the effect of postoperative peripheral parenteral nutrition on recovery of right lobe liver donors. Male sex (β, 22.04; 95% confidence interval: 6.22 - 37.86) was a significant predictor of changes in postoperative alanine aminotransferase level. Male sex (β, 0.045; 95% confidence interval: 0.16 - 37.86) and receipt of peripheral parenteral nutrition (β, -0.045; 95% confidence interval: -0.72 - 0.17) were significant predictors of changes in total bilirubin level. Postoperative atelectasis (P < .001), pleural effusion (P < .011), and total complications (P = .015) had significantly lower incidence in the peripheral parenteral nutrition than control group. Multivariate logistic regression showed that recipients of peripheral parenteral nutrition (odds ratio, 0.161; 95% confidence interval: 0.043 - 0.598) and age (odds ratio, 0.870; 95% confidence interval: 0.782 - 0.968) were significant preoperative risk factors for postoperative complications. Postoperative peripheral parenteral nutrition is associated with a lower incidence of pleural effusion and atelectasis, a more rapid recovery of hyperbilirubinemia, and shorter length of stay in right lobe liver donors.

Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging.

PubMed

Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai

2007-11-01

Administration of an orally active agonist (MK-0677) of the growth hormone secretagogue receptor (GHS-R1a) to elderly subjects restored the amplitude of endogenous episodic growth hormone (GH) release to that of young adults. Functional benefits include increased lean mass and bone density and modest improvements in strength. In old mice, a similar agonist partially restored function to the thymus and reduced tumor cell growth and metastasis. Treatment of old mice with the endogenous GHS-R1a agonist ghrelin restored a young liver phenotype. The mechanism involves inhibition of cyclin D3:cdk4/cdk6 activity and increased protein phosphatase-2A (PP2A) activity in liver nuclei, which stabilizes the dephosphorylated form of the transcription factor C/EBPalpha preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear complex. By inhibiting formation of this complex, repression of E2F target genes is de-repressed and C/EBPalpha regulated expression of Pepck, a regulator of gluconeogenesis, is normalized, thereby restoring a young liver phenotype. In the brain, aging is associated with decline in dopamine function. We investigated the potential neuromodulatory role of GHS-R1a on dopamine action. Neurons were identified in the hippocampus, cortex, substantia nigra, and ventral tegmental areas that coexpressed GHS-R1a and dopamine receptor subtype-1 (D1R). Cell culture studies showed that, in the presence of ghrelin and dopamine, GHS-R and D1R form heterodimers, which modified G-protein signal transduction resulting in amplification of dopamine signaling. We speculate that aging is associated with deficient endogenous ghrelin signaling that can be rescued by intervention with GHS-R1a agonists to improve quality of life and maintain independence.

Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1

PubMed Central

Shabalina, Irina G.; Vyssokikh, Mikhail Yu.; Gibanova, Natalia; Csikasz, Robert I.; Edgar, Daniel; Hallden-Waldemarson, Anne; Rozhdestvenskaya, Zinaida; Bakeeva, Lora E.; Vays, Valeria B.; Pustovidko, Antonina V.; Skulachev, Maxim V.; Cannon, Barbara; Skulachev, Vladimir P.; Nedergaard, Jan

2017-01-01

MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions. SkQ1 counteracts this as it scavenges mitochondrial ROS. As the results, the normal mitochondrial ultrastructure is preserved in liver and heart; the phosphorylation capacity of skeletal muscle mitochondria as well as the thermogenic capacity of brown adipose tissue is also improved. The SkQ1-treated mice live significantly longer (335 versus 290 days). These data may be relevant in relation to treatment of mitochondrial diseases particularly and the process of aging in general. PMID:28209927

Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

PubMed Central

Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

2015-01-01

Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers.

PubMed

Scalea, Joseph R; Redfield, Robert R; Foley, David P

2016-09-01

Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation from donation after brain death (DBD) donors. We hypothesized that carefully selected, underutilized DCD livers recovered from younger donors have excellent outcomes. We performed a retrospective study of the United Network for Organ Sharing database to determine graft survivals for patients who received liver transplants from DBD donors of age ≥ 60 years, DBD donors < 60 years, and DCD donors < 50 years of age. Between January 2002 and December 2014, 52,271 liver transplants were performed in the United States. Of these, 41,181 (78.8%) underwent transplantation with livers from DBD donors of age < 60 years, 8905 (17.0%) from DBD donors ≥ 60 years old, and 2195 (4.2%) livers from DCD donors < 50 years of age. DCD livers of age < 50 years with < 6 hours of cold ischemia time (CIT) had superior graft survival when compared with DBD livers ≥ age 60 years (P < 0.001). In 2014, there were 133 discarded DCD livers; of these, 111 (83.4%) were from donors < age 50 years old. Young DCD donor livers (age < 50 years old) with short CITs yield results better than that seen with DBD livers > 60 years old. Careful donor organ and recipient selection can lead to excellent results, despite previous reports suggesting otherwise. Increased acceptance of these DCD livers would lead to shorter wait list times and increased national liver transplant rates. Liver Transplantation 22 1197-1204 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

[The incidence differences among sex, geographical areas and mean age of diagnosis for liver cancer in China, 1989-2008].

PubMed

Zhang, Siwei; Zheng, Rongshou; Zeng, Hongmei; Chen, Wanqing

2014-05-01

Using the incidence data from 1989 to 2008 of liver cancer from population in cancer registration areas in China, the differences and changes of gender, urban and rural areas for liver cancer incidence in different years were studied, and the mean age of incidence was analyzed. The incidence data of liver cancer from National Cancer Registration database were sorted and checked. A total of 181 097 new liver cancer cases were collected, covering 711 843 051 person years from 1989 to 2008.Using Poisson regression model, Stratified by gender and areas, changes of incidence gender ratio, ratio of urban and rural, and mean age were analyzed. After adjusting the age, the liver cancer incidence in male was about 3 times higher than that in females (ranging from 2.64-3.54), and the ratio change between male and female for the 20 years did not have statistically significant (P = 0.150). The incidence ratio between urban and rural areas has increased from 0.51 in 1989 to 0.61 in 2008 (P < 0.01). The mean ages of diagnosis for male and female increased from 57.14 years to 60.34 years, 61.69 years to 66.47 years, respectively from 1989 to 2008. The mean age of liver cancer diagnosis has increased in the 20 years (P < 0.01). The liver cancer incidence between male and female did not change significantly among 20 years. The difference of liver cancer incidence between urban and rural areas has reduced, and the mean age of diagnosis was deferred.

Identification of miR-31-5p, miR-141-3p, miR-200c-3p, and GLT1 as human liver aging markers sensitive to donor-recipient age-mismatch in transplants.

PubMed

Capri, Miriam; Olivieri, Fabiola; Lanzarini, Catia; Remondini, Daniel; Borelli, Vincenzo; Lazzarini, Raffaella; Graciotti, Laura; Albertini, Maria Cristina; Bellavista, Elena; Santoro, Aurelia; Biondi, Fiammetta; Tagliafico, Enrico; Tenedini, Elena; Morsiani, Cristina; Pizza, Grazia; Vasuri, Francesco; D'Errico, Antonietta; Dazzi, Alessandro; Pellegrini, Sara; Magenta, Alessandra; D'Agostino, Marco; Capogrossi, Maurizio C; Cescon, Matteo; Rippo, Maria Rita; Procopio, Antonio Domenico; Franceschi, Claudio; Grazi, Gian Luca

2017-04-01

To understand why livers from aged donors are successfully used for transplants, we looked for markers of liver aging in 71 biopsies from donors aged 12-92 years before transplants and in 11 biopsies after transplants with high donor-recipient age-mismatch. We also assessed liver function in 36 age-mismatched recipients. The major findings were the following: (i) miR-31-5p, miR-141-3p, and miR-200c-3p increased with age, as assessed by microRNAs (miRs) and mRNA transcript profiling in 12 biopsies and results were validated by RT-qPCR in a total of 58 biopsies; (ii) telomere length measured by qPCR in 45 samples showed a significant age-dependent shortage; (iii) a bioinformatic approach combining transcriptome and miRs data identified putative miRs targets, the most informative being GLT1, a glutamate transporter expressed in hepatocytes. GLT1 was demonstrated by luciferase assay to be a target of miR-31-5p and miR-200c-3p, and both its mRNA (RT-qPCR) and protein (immunohistochemistry) significantly decreased with age in liver biopsies and in hepatic centrilobular zone, respectively; (iv) miR-31-5p, miR-141-3p and miR-200c-3p expression was significantly affected by recipient age (older environment) as assessed in eleven cases of donor-recipient extreme age-mismatch; (v) the analysis of recipients plasma by N-glycans profiling, capable of assessing liver functions and biological age, showed that liver function recovered after transplants, independently of age-mismatch, and recipients apparently 'rejuvenated' according to their glycomic age. In conclusion, we identified new markers of aging in human liver, their relevance in donor-recipient age-mismatches in transplantation, and offered positive evidence for the use of organs from old donors. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases.

PubMed

Poinsot, Pierre; Collardeau Frachon, Sophie; Restier, Lioara; Sérusclat, André; Di Filippo, Mathilde; Charrière, Sybil; Moulin, Philippe; Lachaux, Alain; Peretti, Noel

The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity. To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin. Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data (LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment. The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm). Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the importance of having a global metabolic view and to evaluate the cardiovascular impact of the new enzymatic treatment. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Impact of sequential proton density fat fraction for quantification of hepatic steatosis in nonalcoholic fatty liver disease.

PubMed

Idilman, Ilkay S; Keskin, Onur; Elhan, Atilla Halil; Idilman, Ramazan; Karcaaltincaba, Musturay

2014-05-01

To determine the utility of sequential MRI-estimated proton density fat fraction (MRI-PDFF) for quantification of the longitudinal changes in liver fat content in individuals with nonalcoholic fatty liver disease (NAFLD). A total of 18 consecutive individuals (M/F: 10/8, mean age: 47.7±9.8 years) diagnosed with NAFLD, who underwent sequential PDFF calculations for the quantification of hepatic steatosis at two different time points, were included in the study. All patients underwent T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling. A close correlation for quantification of hepatic steatosis between the initial MRI-PDFF and liver biopsy was observed (rs=0.758, p<0.001). The median interval between two sequential MRI-PDFF measurements was 184 days. From baseline to the end of the follow-up period, serum GGT level and homeostasis model assessment score were significantly improved (p=0.015, p=0.006, respectively), whereas BMI, serum AST, and ALT levels were slightly decreased. MRI-PDFFs were significantly improved (p=0.004). A good correlation between two sequential MRI-PDFF calculations was observed (rs=0.714, p=0.001). With linear regression analyses, only delta serum ALT levels had a significant effect on delta MRI-PDFF calculations (r2=38.6%, p=0.006). At least 5.9% improvement in MRI-PDFF is needed to achieve a normalized abnormal ALT level. The improvement of MRI-PDFF score was associated with the improvement of biochemical parameters in patients who had improvement in delta MRI-PDFF (p<0.05). MRI-PDFF can be used for the quantification of the longitudinal changes of hepatic steatosis. The changes in serum ALT levels significantly reflected changes in MRI-PDFF in patients with NAFLD.

Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation.

PubMed

Sorensen, Lisa G; Neighbors, Katie; Martz, Karen; Zelko, Frank; Bucuvalas, John C; Alonso, Estella M

2014-07-01

To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Vegetarian diet, food substitution, and nonalcoholic fatty liver.

PubMed

Chiu, Tina H; Lin, Ming-Nan; Pan, Wen-Harn; Chen, Yen-Ching; Lin, Chin-Lon

2018-01-01

Vegetarian diets have been shown to improve insulin resistance and reduce body weight, but the effects on nonalcoholic fatty liver require further confirmation. We aim to investigate the association between vegetarian diets, major food groups, and nonalcoholic fatty liver, and to compare the degree of liver fibrosis between vegetarians and nonvegetarians in those with fatty liver. We analyzed cross-sectional data from the Tzu Chi Health Study which included 2127 nonvegetarians and 1273 vegetarians who did not smoke or habitually drink alcohol and had no hepatitis B or hepatitis C. Fatty liver and liver fibrosis were determined using ultrasonography and the nonalcoholic fatty liver disease fibrosis score, respectively. Diet was assessed through a validated food frequency questionnaire. Vegetarian diets were associated with lower odds of fatty liver (odds ratio = 0.79, 95% confidence interval: 0.68-0.91) after adjusting for age, gender, education, history of smoking and alcohol drinking. Adjustment for body mass index (BMI) attenuated the protective association. Vegetarians had less severe fibrosis than nonvegetarians. Replacing a serving of soy with a serving of meat or fish was associated with 12%-13% increased risk, and replacing a serving of whole grains with a serving of refined grains, fruits, and fruit juice was associated with 3%-12% increased the risk of fatty liver. Vegetarian diets, replacing meat and fish with soy, and replacing refined carbohydrates with whole grains, may be inversely associated with nonalcoholic fatty liver related to BMI.

Vegetarian diet, food substitution, and nonalcoholic fatty liver

PubMed Central

Chiu, Tina H.; Lin, Ming-Nan; Pan, Wen-Harn; Chen, Yen-Ching; Lin, Chin-Lon

2018-01-01

Objectives: Vegetarian diets have been shown to improve insulin resistance and reduce body weight, but the effects on nonalcoholic fatty liver require further confirmation. We aim to investigate the association between vegetarian diets, major food groups, and nonalcoholic fatty liver, and to compare the degree of liver fibrosis between vegetarians and nonvegetarians in those with fatty liver. Materials and Methods: We analyzed cross-sectional data from the Tzu Chi Health Study which included 2127 nonvegetarians and 1273 vegetarians who did not smoke or habitually drink alcohol and had no hepatitis B or hepatitis C. Fatty liver and liver fibrosis were determined using ultrasonography and the nonalcoholic fatty liver disease fibrosis score, respectively. Diet was assessed through a validated food frequency questionnaire. Results: Vegetarian diets were associated with lower odds of fatty liver (odds ratio = 0.79, 95% confidence interval: 0.68–0.91) after adjusting for age, gender, education, history of smoking and alcohol drinking. Adjustment for body mass index (BMI) attenuated the protective association. Vegetarians had less severe fibrosis than nonvegetarians. Replacing a serving of soy with a serving of meat or fish was associated with 12%–13% increased risk, and replacing a serving of whole grains with a serving of refined grains, fruits, and fruit juice was associated with 3%–12% increased the risk of fatty liver. Conclusion: Vegetarian diets, replacing meat and fish with soy, and replacing refined carbohydrates with whole grains, may be inversely associated with nonalcoholic fatty liver related to BMI. PMID:29875591

Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways.

PubMed

Uebanso, Takashi; Taketani, Yutaka; Fukaya, Makiko; Sato, Kazusa; Takei, Yuichiro; Sato, Tadatoshi; Sawada, Naoki; Amo, Kikuko; Harada, Nagakatsu; Arai, Hidekazu; Yamamoto, Hironori; Takeda, Eiji

2009-07-01

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice

PubMed Central

Yang, Hao; Wang, Shu Pei; Mitchell, Grant A.

2017-01-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency. PMID:29232702

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

PubMed

Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujisawa, Koichi; Terai, Shuji, E-mail: terais@yamaguchi-u.ac.jp; Hirose, Yoshikazu

2011-10-22

Highlights: {yields} Zebrafish SMP30/RGN mRNA expression decreases with aging. {yields} Decreased expression was observed in liver tumors as compared to the surrounding area. {yields} SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish bymore » administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.« less

Effects of Silicon vs. Hydroxytyrosol-Enriched Restructured Pork on Liver Oxidation Status of Aged Rats Fed High-Saturated/High-Cholesterol Diets.

PubMed

Santos-López, Jorge A; Garcimartín, Alba; Merino, Pinar; López-Oliva, M Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J

2016-01-01

Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH.

Liver transplantation in children with Alagille syndrome--a study of twelve cases.

PubMed

Cardona, J; Houssin, D; Gauthier, F; Devictor, D; Losay, J; Hadchouel, M; Bernard, O

1995-08-27

Cholestasis associated with Alagille syndrome may, in a few cases, be extremely severe and result in major impairment in the quality of life during early childhood and end up in cirrhosis eventually. We report the results of liver transplantation in 12 children with a severe hepatic form of Alagille syndrome. All children presented with cholestatic jaundice from birth, peculiar facies, stenosis of the peripheral pulmonary artery, and posterior embryotoxon; butterfly-like vertebrae were present in 9 children. At the time of transplantation (mean age 7 years 10 months) refractory pruritus was present in 9 children, xanthoma in 11, and height and weight retardation in 11. Total serum bilirubin ranged from 116 to 322 mumol/L and total serum cholesterol from 3.5 to 29 mmol/L. Systolic right ventricular pressure was moderately raised (36 to 48 mmHg) in 5 children; mean creatinine clearance was 99 ml/min/1.73 m2. Histologic examination of the removed livers showed cirrhosis, severe annular fibrosis, and moderate portal fibrosis in 4 children each. Follow-up in the 11 survivors has ranged from 14 months to 5 1/2 years. All lead normal lives. Pruritus and xanthomas disappeared. Increase in height was observed in 8 of the 10 survivors who had growth retardation prior to transplantation. School level is normal in 4 (median age at LT: 5 yr 9 mo) and below normal in 6 (median age at OLT: 9 yr 9 mo). Liver function tests are normal in 10 children. Mean creatinine clearance is 101 ml/min/1.73 m2. These results indicate that the quality of life can be considerably improved after liver transplantation in children with a severe hepatic form of Alagille syndrome and suggest that it could be carried out before these children attend elementary school.

Effects of Silicon vs. Hydroxytyrosol-Enriched Restructured Pork on Liver Oxidation Status of Aged Rats Fed High-Saturated/High-Cholesterol Diets

PubMed Central

Merino, Pinar; López-Oliva, M. Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.

2016-01-01

Background Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. Objective This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Methods Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Results Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Conclusions Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH. PMID:26807847

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

PubMed

Schall, Joan I; Mascarenhas, Maria R; Maqbool, Asim; Dougherty, Kelly A; Elci, Okan; Wang, Dah-Jyuu; Altes, Talissa A; Hommel, Kevin A; Shaw, Walter; Moore, Jeff; Stallings, Virginia A

2016-04-01

Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. A total of 110 subjects were enrolled (age 10.4 ± 3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.

PubMed

Halac, Ugur; Lacaille, Florence; Joly, Francisca; Hugot, Jean-Pierre; Talbotec, Cécile; Colomb, Virginie; Ruemmele, Frank M; Goulet, Olivier

2011-04-01

Microvillous inclusion disease (MVID) is a rare congenital enterocyte disorder causing severe diarrhea and intestinal failure. The objective of this study was to analyze clinical evolution and the most frequent complications of MVID in children receiving parenteral nutrition (PN) and after small-bowel transplantation (SBTx) with the aim to improve treatment strategies and prognosis. From 1995 to 2009, 24 patients (16 boys, median follow-up 4.7 years, range: from birth to 23.5 years) with MVID were admitted to our unit. The recorded parameters included growth, neurological development, liver and renal functions, bone disease, and outcome. Almost half of the children were from consanguineous families from the Mediterranean area. All of the patients completely depended on PN. Four children died of PN complications before 4 years of age. Before or without SBTx, growth failure was common (mean height -2.5 standard deviations [SD]), as was developmental delay (12/24), liver (20/22 with fibrosis) or kidney disease (3/23 with moderate renal insufficiency), and osteoporosis (6/24). Thirteen children underwent SBTx (9 isolated, 4 combined with liver Tx) at a median age of 3.5 years. Follow-up after SBTx was 0.4 to 14 years. Patient survival rates were 63% without SBTx and 77% with SBTx. After SBTx, 4 children experienced catch-up growth. PN in MVID is difficult to manage and requires expertise. Despite improved results in expert centers, the risk of death or irreversible sequelae is higher with PN than after Tx. SBTx, despite being complicated, remains the only hope to improve the quality of life and long-term prognosis of these children.

Choline Supplementation with a Structured Lipid in Children with Cystic Fibrosis: A Randomized Placebo-Controlled Trial

PubMed Central

Schall, Joan I.; Mascarenhas, Maria R.; Maqbool, Asim; Dougherty, Kelly A.; Elci, Okan; Wang, Dah-Jyuu; Altes, Talissa A.; Hommel, Kevin A.; Shaw, Walter; Moore, Jeff; Stallings, Virginia A.

2015-01-01

Background Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency (PI) in spite of enzyme treatment and may result in liver, fatty acid and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. Methods Children with CF and PI were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption (CFA), pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared to a healthy comparison group matched for age, sex and body size. Results 110 subjects were enrolled (age 10.4±3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P=0.007). Plasma lysophosphatidylcholine and phosphatidylcholine (PC) increased and fecal PC/phosphatidylethanolamine ratio decreased (P≤0.05) in LXS only, accompanied by a 6% CFA increase (P=0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. Conclusions LXS had improved choline intake, plasma choline status and muscle choline stores, compared with placebo. The choline-rich supplement was safe, accepted by participants and improved choline status in children with CF. PMID:26465792

Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

PubMed

Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

2012-01-01

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study.

PubMed

Acciuffi, Sara; Meyer, Frank; Bauschke, Astrid; Settmacher, Utz; Lippert, Hans; Croner, Roland; Altendorf-Hofmann, Annelore

2018-03-01

The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.

Is ability to hepatic steatosis influenced by age at the beginning of the overfeeding period in Muscovy and Pekin ducks?

PubMed

Chartrin, P; Bernadet, M D; Sannier, M; Baéza, E

2013-04-01

The aim of this study was to analyse the effects of species (Muscovy and Pekin ducks) and age at the beginning of the overfeeding period on fatty liver production, carcass composition and lipid and moisture content of the liver and breast muscle. We reared four groups of 40 ducks per species for the study, starting at 2-week intervals in order to have four different ages together at the beginning of the overfeeding period (10, 12, 14 and 16 weeks). At the end of the overfeeding period, all ducks were slaughtered. Our results confirmed the high levels of difference in carcass composition and lipid content in the plasma, liver and breast muscle between Muscovy and Pekin ducks at all ages. Pekin ducks were not able to develop a high degree of hepatic steatosis, but had increased lipid storage in peripheral adipose and muscle tissues than Muscovy ducks. However, the fatty liver weight of Pekin ducks increased with age, with lipid deposition in the liver and peripheral tissues. The ability of Muscovy ducks to produce fatty livers remained unchanged with age in line, with lipid deposition in the liver and peripheral tissues. The sites of lipid deposition thus depend on species and not on the physiological maturity of ducks.

Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis.

PubMed

Bajaj, Jasmohan S; Fagan, Andrew; Sikaroodi, Masoumeh; White, Melanie B; Sterling, Richard K; Gilles, HoChong; Heuman, Douglas; Stravitz, Richard T; Matherly, Scott C; Siddiqui, Mohammed S; Puri, Puneet; Sanyal, Arun J; Luketic, Velimir; John, Binu; Fuchs, Michael; Ahluwalia, Vishwadeep; Gillevet, Patrick M

2017-07-01

Liver transplantation (LT) improves daily function and cognition in patients with cirrhosis, but a subset of patients can remain impaired. Unfavorable microbiota or dysbiosis is observed in patients with cirrhosis, but the effect of LT on microbial composition, especially with poor post-LT cognition, is unclear. The aims were to determine the effect of LT on gut microbiota and to determine whether gut microbiota are associated with cognitive dysfunction after LT. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Cognition (Psychometric Hepatic Encephalopathy score [PHES]), health-related quality of life (HRQOL), and stool microbiota (multitagged sequencing for diversity and taxa) tests were performed at both visits. Persistent cognitive impairment was defined as a stable/worsening PHES. Both pre-/post-LT data were compared with age-matched healthy controls. We enrolled 45 patients (56 ± 7 years, Model for End-Stage Liver Disease score 26 ± 8). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 2 months after LT with a stable course. A significantly improved HRQOL, PHES, with increase in microbial diversity, increase in autochthonous, and decrease in potentially pathogenic taxa were seen after LT compared with baseline. However, there was continued dysbiosis and HRQOL/cognitive impairment after LT compared with controls in 29% who did not improve PHES after LT. In these, Proteobacteria relative abundance was significantly higher and Firmicutes were lower after LT, whereas the reverse occurred in the group that improved. Delta PHES was negatively correlated with delta Proteobacteria and positively with delta Firmicutes. In conclusion, LT improves gut microbiota diversity and dysbiosis compared with pre-LT baseline but residual dysbiosis remains compared with controls. There is cognitive and HRQOL enhancement in general after LT, but a higher Proteobacteria relative abundance change is associated with posttransplant cognitive impairment. Liver Transplantation 23 907-914 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Health-related quality of life and employment status of liver transplant patients.

PubMed

Aberg, Fredrik; Rissanen, Anne M; Sintonen, Harri; Roine, Risto P; Höckerstedt, Krister; Isoniemi, Helena

2009-01-01

Health-related quality of life (HRQoL) is one preferable outcome measure of medical interventions such as liver transplantation (LT). The aim of this study was to compare HRQoL of LT patients with that of the general population and to assess the employment status of LT patients. HRQoL was measured with the 15D instrument, a validated, non-disease-specific, 15-dimensional, self-administered HRQoL instrument. The questionnaire was sent to all adult LT patients in Finland (401 patients) alive in June 2007. The response rate was 89% (353 patients). The results were compared to those of 6050 age-standardized and gender-standardized controls from the general population. LT patients (mean age, 55 years; range, 20-82) had slightly worse HRQoL scores than the general population (mean 15D score, 0.889 versus 0.907; P < 0.002). Survival time and retransplantation did not affect HRQoL significantly in age-adjusted and gender-adjusted analyses. HRQoL decreased with increasing age (P < 0.0001). Patients transplanted for acute liver failure (ALF) or chronic liver disease (CLD) had significantly worse HRQoL than the general population (P = 0.014 and P = 0.040). Forty-four percent of working-age patients were employed at the time of the study. Persons that were employed had significantly better HRQoL than those unemployed (15D scores, 0.934 versus 0.859; P < 0.0001). Eighty-seven percent of patients experienced improved working capacity after LT. Early retirement was the most common cause of unemployment (56% of unemployed patients), and those patients presented with worse HRQoL than patients unemployed for other reasons. In conclusion, HRQoL of LT patients is very close to that of the general population. Older age, CLD, and ALF impair HRQoL. Employment is an indicator of HRQoL. Copyright 2008 AASLD.

Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

PubMed

Kim, Seong Min; Lee, Bonggi; An, Hye Jin; Kim, Dae Hyun; Park, Kyung Chul; Noh, Sang-Gyun; Chung, Ki Wung; Lee, Eun Kyeong; Kim, Kyung Mok; Kim, Do Hyun; Kim, Su Jeong; Chun, Pusoon; Lee, Ho Jeong; Moon, Hyung Ryong; Chung, Hae Young

2017-07-11

Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

Tissue-specific time courses of spontaneous mutation frequency and deviations in mutation pattern are observed in middle to late adulthood in Big Blue mice.

PubMed

Hill, Kathleen A; Halangoda, Asanga; Heinmoeller, Petra W; Gonzalez, Kelly; Chitaphan, Chaniga; Longmate, Jeffrey; Scaringe, William A; Wang, Ji-Cheng; Sommer, Steve S

2005-06-01

To better define the time course of spontaneous mutation frequency in middle to late adulthood of the mouse, measurements were made at 10, 14, 17, 23, 25, and 30 months of age in samples of adipose tissue, liver, cerebellum (90% neurons), and the male germline (95% germ cells). A total of 46 million plaque-forming units (pfus) were screened at the six time points and 1,450 circular blue plaques were harvested and sequenced. These data improve resolution and confirm the previously observed occurrence of at least two tissue-specific profiles of spontaneous mutation frequency (elevation with age in adipose tissue and liver, and constancy with age in neurons and male germ cells), a low mutation frequency in the male germline, and a mutation pattern unchanged with age within a tissue. These findings appear to extend to very old age (30 months). Additional findings include interanimal variation in spontaneous mutation frequency is larger in adipose tissues and liver compared with neurons and male germ cells, and subtle but significant differences in the mutation pattern among tissues, consistent with a minor effect of tissue-specific metabolism. The presumptive unaltered balance of DNA damage and repair with age in the male germline has evolutionary consequences. It is of particular interest given the controversy over whether or not increasing germline mutation frequency with paternal age underlies the reports associating older males with a higher incidence of some types of genetic disease. These most detailed measurements available to date regarding the time course of spontaneous mutation frequency and pattern in individual tissues help to constrain hypotheses regarding the role of mutational mechanisms in DNA repair and aging.

Manuka honey protects middle-aged rats from oxidative damage

PubMed Central

Jubri, Zakiah; Rahim, Noor Baitee Abdul; Aan, Goon Jo

2013-01-01

OBJECTIVE: This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. METHOD: Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. RESULTS: Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. CONCLUSIONS: Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status. PMID:24270958

Manuka honey protects middle-aged rats from oxidative damage.

PubMed

Jubri, Zakiah; Rahim, Noor Baitee Abdul; Aan, Goon Jo

2013-11-01

This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status.

Glycogen Storage Disease Type Ia: Linkage of Glucose, Glycogen, Lactic Acid, Triglyceride, and Uric Acid Metabolism

PubMed Central

Sever, Sakine; Weinstein, David A.; Wolfsdorf, Joseph I.; Gedik, Reyhan; Schaefer, Ernst J.

2013-01-01

Case Summary A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides > 5,000 mg/dl. The diagnosis of type 1A glycogen storage disease (GSD) was made by liver biopsy that showed increased glycogen and absent glucose-6-phosphatase enzyme activity. She was treated with dextrose feeding, which was replaced by frequent cornstarch feeding, with improvement of her metabolic parameters. At age 18 years she had marked hypertriglyceridemia (3,860 mg/dl) and eruptive xanthomas, and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels > 75 mg/dl and lactate levels < 2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dl) off all medications were: total cholesterol 222, triglycerides 179, high density lipoprotein cholesterol 32, and calculated low density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m2. Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels > 75 mg/dl is critical in the management of this disease. PMID:23312056

Matching donor to recipient in liver transplantation: Relevance in clinical practice

PubMed Central

Reddy, Mettu Srinivas; Varghese, Joy; Venkataraman, Jayanthi; Rela, Mohamed

2013-01-01

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’ clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down. PMID:24303088

Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

PubMed

Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

2016-01-01

De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. To describe the overall pattern of de novo cancers in liver transplant recipients. Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

Liver Transplantation Results by Donor Age.

PubMed

Rabelo, A V; Bastante, M D; Raya, A M; Méndez, C S M; Ramirez, A R G; Suarez, Y F

2016-11-01

The objective of this study was to compare liver transplantation outcomes as a function of donor age. We performed 212 liver transplantations between 2008 and 2014. We described a prospective cohort study and grouped the patients by liver donor age. We compared quantitative and categorical variables using statistical analysis. No statistically significant differences were found among any graft age groups in gender (always more males), time on waiting list, age, height, Child Pugh Turcotte (CHILD) score, Model for End-stage Liver Disease (MELD) score, need for intraoperative blood products, or intensive care unit stay. The most frequent etiology of liver failure was alcohol. A brain-dead donor was the most frequent type in all groups. The whole graft was used except in 4 cases. No statistically significant differences were found among groups in the surgical technique, postreperfusion syndrome, arterial complications, biliary complications, venous complications, acute rejection, and retransplantation. The 3-year patient survival rate was 64% in the <60-year graft age group, 48% in the 60- to 69-year group, 64% in the 70- to 79-year group, and 40% in the ≥80-year group (P = .264). The 3-year graft survival rate was 62% in the <60-year graft age group, 47% in the 60- to 69-year group, 65% in the 70- to 79-year group, and 40% in the ≥80-year group (P = .295). Given the need to increase the pool of liver donors, older donors should be considered as a source for liver transplantation, although careful selection is required. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparing the efficiency of Fib-4, Egy-score, APRI, and GUCI in liver fibrosis staging in Egyptians with chronic hepatitis C.

PubMed

Cordie, Ahmed; Salama, Ahmed; El-Sharkawy, Marwa; El-Nahaas, Saeed M; Khairy, Marwa; Elsharkawy, Aisha; Hassany, Mohamed; Esmat, Gamal

2018-06-01

Assessment of hepatic fibrosis in chronic hepatitis C virus patients by liver biopsy is not widely accepted despite its accuracy, being invasive, carrying complications, and adding cost. This paved the way to development and use of non-invasive markers of fibrosis in diagnosis of hepatic fibrosis. We aimed at evaluating the efficiency of Fib-4, Egy-score, Aspartate-to-platelet ratio index (APRI), and Göteborg University Cirrhosis Index (GUCI) in comparison to liver biopsy, in the assessment of hepatic fibrosis in chronic hepatitis C patients. This was a cross sectional study including 200 chronic HCV patients were divided into two groups according to stage of fibrosis (Metavir score) into non-significant fibrosis (1.27, APRI >0.48, Egy-score >0.73, and GUCI >0.57 significantly predict significant fibrosis (P < 0.01). Fib-4 carries the best performance and significant reliability with AUROC 0.783, sensitivity 74%, specificity 69%, PPV 0.55, and NPV 0.86. The addition of BMI to Fib-4 improved the significant fibrosis AUROC curve performance but did not reach statistical significant improvement. We concluded that age and BMI are good predictors of hepatic fibrosis. Fib-4 (>1.27) is the best method of prediction of significant fibrosis compared to Egy-score, APRI, and GUCI. Addition of BMI to Fib-4 did not improve diagnostic value of Fib-4. © 2018 Wiley Periodicals, Inc.

Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease.

PubMed

Pervez, Muhammad Amjad; Khan, Dishad Ahmet; Ijaz, Aamir; Khan, Shamrez

2018-03-01

Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and is associated with increased morbidity and mortality. Currently, there is no definitive treatment for this disease. δ-Tocotrienol has potent anti-inflammatory and antioxidant properties and may reduce liver injury in NAFLD. The present study aims to evaluate the efficacy and safety of δ-tocotrienol in the treatment of NAFLD. The present study was a randomized, double-blind, placebo-controlled pilot study conducted in patients aged > 20 years, belonging to both sexes, having ultrasound-proven fatty liver disease, having a fatty liver index (FLI) of ≥ 60, and persistent elevation of alanine transaminase. A total of 71 patients were assigned to receive either oral δ-tocotrienol (n=35, 300 mg twice daily) or placebo (n=36) for 12 weeks. At the baseline and at the end of the study, clinical and biochemical parameters, including lipid profile, liver function tests, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. Body mass index and FLI were calculated, and ultrasound grading of hepatic steatosis was performed. Out of 71 enrolled patients, 64 patients, 31 in the δ-tocotrienol group and 33 in the placebo group, completed the study. After 12 weeks of supplementation, δ-tocotrienol showed greater efficacy than placebo by decreasing serum aminotransferases, hs-CRP, MDA, and FLI score (p<0.001). However, it did not improve hepatic steatosis on ultrasound examination. No adverse effects were reported. δ-Tocotrienol was safe, and it effectively improved aminotransferase levels and inflammatory and oxidative stress markers in patients with NAFLD. Large-scale randomized clinical trials are warranted to further support these findings.

The value of "liver windows" settings in the detection of small renal cell carcinomas on unenhanced computed tomography.

PubMed

Sahi, Kamal; Jackson, Stuart; Wiebe, Edward; Armstrong, Gavin; Winters, Sean; Moore, Ronald; Low, Gavin

2014-02-01

To assess if "liver window" settings improve the conspicuity of small renal cell carcinomas (RCC). Patients were analysed from our institution's pathology-confirmed RCC database that included the following: (1) stage T1a RCCs, (2) an unenhanced computed tomography (CT) abdomen performed ≤ 6 months before histologic diagnosis, and (3) age ≥ 17 years. Patients with multiple tumours, prior nephrectomy, von Hippel-Lindau disease, and polycystic kidney disease were excluded. The unenhanced CT was analysed, and the tumour locations were confirmed by using corresponding contrast-enhanced CT or magnetic resonance imaging studies. Representative single-slice axial, coronal, and sagittal unenhanced CT images were acquired in "soft tissue windows" (width, 400 Hounsfield unit (HU); level, 40 HU) and liver windows (width, 150 HU; level, 88 HU). In addition, single-slice axial, coronal, and sagittal unenhanced CT images of nontumourous renal tissue (obtained from the same cases) were acquired in soft tissue windows and liver windows. These data sets were randomized, unpaired, and were presented independently to 3 blinded radiologists for analysis. The presence or absence of suspicious findings for tumour was scored on a 5-point confidence scale. Eighty-three of 415 patients met the study criteria. Receiver operating characteristics (ROC) analysis, t test analysis, and kappa analysis were used. ROC analysis showed statistically superior diagnostic performance for liver windows compared with soft tissue windows (area under the curve of 0.923 vs 0.879; P = .0002). Kappa statistics showed "good" vs "moderate" agreement between readers for liver windows compared with soft tissue windows. Use of liver windows settings improves the detection of small RCCs on the unenhanced CT. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

PubMed

Yi, Haiqing; Zhang, Quan; Brooks, Elizabeth D; Yang, Chunyu; Thurberg, Beth L; Kishnani, Priya S; Sun, Baodong

2017-03-01

Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1 ys/ys ). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1 ys/ys mice at a dose of 5 × 10 11 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1 ys/ys mice.

Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age.

PubMed

Rusli, Fenni; Boekschoten, Mark V; Borelli, Vincenzo; Sun, Chen; Lute, Carolien; Menke, Aswin L; van den Heuvel, Joost; Salvioli, Stefano; Franceschi, Claudio; Müller, Michael; Steegenga, Wilma T

2018-04-01

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR, or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitumMF feeding (CR-MF). The mice were sacrificed at the age of 28 months, and then, biochemical and molecular analyses were performed. Our results showed that, despite the long-term exposure to the CR regimen, mice in the CR-MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR-improved survival was observed in the diet switch group. The liver transcriptomic profile of CR-MF mice largely shifted to a profile similar to the MF-fed animals but leaving ~22% of the 1,578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the lifelong CR group. Therefore, although the diet switch was performed at an old age, the CR-MF-exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Inverse Association between Hepatitis B Virus Infection and Fatty Liver Disease: A Large-Scale Study in Populations Seeking for Check-Up

PubMed Central

Cheng, Yuan-Lung; Wang, Yuan-Jen; Kao, Wei-Yu; Chen, Ping-Hsien; Huo, Teh-Ia; Huang, Yi-Hsiang; Lan, Keng-Hsin; Su, Chien-Wei; Chan, Wan-Leong; Lin, Han-Chieh; Lee, Fa-Yauh; Wu, Jaw-Ching

2013-01-01

Background Although many studies have attempted to clarify the association between hepatitis B virus (HBV) infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI). Aim To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI. Methods We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association. Results Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT) levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg) positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m2 and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI. Conclusions Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease. PMID:23991037

Quality of life following liver transplantation: a comparative study between Familial Amyloid Neuropathy and liver disease patients

PubMed Central

2009-01-01

Background It has been demonstrated in many studies that quality of life can be improved after liver transplantation in patients with liver disease. Nevertherless quality of life improvement in specific groups of transplantated patients such as those with Familial Amyloid Polineuropathy hasn't yet been explored. The present study aimed to compare the change in quality of life following liver transplantation between patients with Familial Amyloid Polineuropathy (FAP) and patients with liver disease. Results Patient's mental quality of life showed an improvement in all liver disease patients, and a worsening in FAP patients, resulting in a significant difference between the two groups. Regarding physical quality of life, although a similar improvement was seen in both groups, FAP patients had significantly less improvement than the sub-group of decompensated liver disease (Child-Pugh B and C). Conclusion It is concluded that liver transplantation has a less beneficial impact in FAP patient's physical quality of life, probably because they are not so much disabled by their disease at the moment of liver transplantation. The lesser improvement in mental quality of life of FAP patients may be due to their particular psychological profile and greater expectations towards transplantation. PMID:19604387

Grape Juice Concentrate Protects Rat Liver Against Cadmium Intoxication: Histopathology, Cytochrome C and Metalloproteinases Expression.

PubMed

de Moura, C F G; Ribeiro, F A P; Handan, B A; Aguiar, O; Oshima, C T F; Ribeiro, D A

2016-07-01

The aim of this study was to investigate if grape juice concentrate is able to protect rat liver against cadmium toxicity. For this purpose, histopathological analysis, cytochrome C expression and immunoexpresssion of metalloproteinases (MMP) 2 and 9 were investigated. A total of 15 Wistar rats weighing 250 g on the average, and 8 weeks age were distributed into 3 groups (n=5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and grape juice concentrate group (Cd+GJ). Histopathological analysis revealed that liver from animals treated with grape juice concentrate improved tissue degeneration induced by cadmium intoxication. Animals intoxicated with cadmium and treated with grape juice concentrate showed higher cytochrome C gene expression in liver cells. No significant statistically differences (p>0.05) were found to MMP 2 and 9 immunoexpression between groups. Taken together, our results demonstrate that grape juice concentrate is able to prevent tissue degeneration in rat liver as a result of increasing apoptosis. © Georg Thieme Verlag KG Stuttgart · New York.

Postsurgical complications in living-related liver donors.

PubMed

Sevmis, S; Karakayali, H; Karakayali, F; Savas, N A; Akkoc, H; Haberal, M

2008-01-01

From September 2001 until March 2007, we performed 127 living-donor liver transplantations in our transplantation center. Of 127 donors, 74 were men and 53 women, of overall mean donor age of 35.2 +/- 9.3 years (range, 20-56 years). Ninety-six (75.6%) were first-degree relatives, 18 (14.1%) were second-degree relatives, and 13 (10.3%) were spouses. We performed 34 (26.7%) left hepatic lobectomies, 33 (25.3%) left lateral segmentectomies, and 60 (48%) right hepatic lobectomies. The mean percentages of remnant to donor total liver volume for the right, left, and left-lateral lobectomies were 41.7%, 67.8%, and 75.1%, respectively. The mean length of patient postoperative hospital stay was 7.4 +/- 3.1 days (range, 3-33 days). There was no postoperative mortality. Ten complications occurred in 7 of the 127 donors (5.5%). Most complications were treated with radiologic interventions. In conclusion, donor safety should be the primary focus in living-donor liver transplantation. More experience, improved surgical techniques, and meticulous donor evaluation will help to minimize morbidity and mortality for living liver donors.

[The effectiveness of the spa and health resort-based treatment with the application of Essentuki-type drinking mineral waters for the management of non-alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus].

PubMed

Efimenko, N V; Kaĭsinova, A S; Fedorova, T E; Botvineva, L A

2015-01-01

The objective of the present study was to estimate the effectiveness of the spa and health resort-based treatment of non-alcoholic fatty liver disease in 40 patients at the mean age of 48,8 ± 5.7 years suffering from type 2 diabetes mellitus. All of them received combined therapy including the application of potable Essentuki-Novaya mineral water (20 patients) or Essentuki No 4 water (20 patients). This therapeutic modality resulted in positive dynamics of clinical symptoms of the disease, the functional liver tests, and parameters of intra-hepatic hemodynamics, lipid peroxidation homeostasis, and the hormonal status. It is concluded that the spa and health resort-based treatment with the application of local drinking Essentuki-type mineral waters for the management of non-alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus leads to the improvement of the main functions of the liver, stabilizes carbohydrate and lipid metabolism, and prevents progression of the pathological process.

Zebrafish: an important tool for liver disease research.

PubMed

Goessling, Wolfram; Sadler, Kirsten C

2015-11-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Capability of different non-nutritive feed additives on improving productive and physiological traits of broiler chicks fed diets with or without aflatoxin during the first 3 weeks of life.

PubMed

Attia, Y A; Allakany, H F; Abd Al-Hamid, A E; Al-Saffar, A A; Hassan, R A; Mohamed, N A

2013-08-01

An experiment was conducted to determine whether some non-nutritive feed additives (NNFA) could block the adverse effects of aflatoxin (AF) on growth performance and physiological parameters of Cobb broilers throughout the period from 1 to 21 day of age. There were eight treatments consisting of two levels of AF at 0 and 200 ppb and four NNFA within each AF level. These additives included mannan oligosaccharides (MOS) at 2 g/kg diet, hydrated sodium calcium aluminosilicate (HSCAS) at 2 g/kg diet and Lactobacillus acidophilus (Lac) at 2 g/kg diet. At 21 day of age, five chickens of each treatment were slaughtered to study dressing percentage and relative weight of inner organs and glands. AF had a significant negative effect on body weight gain (BWG), and feed intake, while impairing feed conversion ratio (FCR). Aflatoxin significantly increased percentage liver, lymphocyte (%), monocyte (%), serum triglyceride level, and the aspartate aminotransferase (AST), and alanine aminotransferase (ALT), concentrations while decreasing dressing percentage, intestinal percentage, white blood cells (WBCs), red blood cells (RBCs), haemoglobin (Hgb), packed cell volume (PCV), heterophil (%), heterophil/lymphocyte ratio, total serum protein and serum albumin. Aflatoxin adversely affected the morphology of the liver, bursa and the thymus. There was a significant interaction between AF and NNFA on the relative weights of liver, heart and intestine. Lac completely blocked the negative effects of AF on the percentage liver and the heart and partially on the intestine. In conclusion, Lac was most effective in reversing the adverse effects of AF on growth and FCR and on the percentage, functions and morphology of the liver. Hydrated sodium calcium aluminosilicate also improved the economic traits of broilers but was less effective than Lac and more effective than MOS. © 2012 Blackwell Verlag GmbH.

Predicting the discharge status after liver transplantation at a single center: a new approach for a new era.

PubMed

Kelly, Dympna M; Bennett, Renee; Brown, Nancy; McCoy, Judy; Boerner, Derek; Yu, Changhong; Eghtesad, Bijan; Barsoum, Wael; Fung, John J; Kattan, Michael W

2012-07-01

The aim of this study was to develop a tool for preoperatively predicting the need of a patient to attend an extended care facility after orthotopic liver transplantation (OLT). A multidisciplinary group, which included 2 transplant surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case manager, 1 home health care professional, 1 rehabilitation physician, and 1 statistician, met to identify preoperative factors relevant to discharge planning. The parameters that were examined as potential predictors of the discharge status were as follows: age, sex, language, Karnofsky score, OLT alone (versus a combined procedure), creatinine, bilirubin, international normalized ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical Model for End-Stage Liver Disease score, renal dialysis, location before transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and right ventricular systolic pressure, sex and availability of the primary caregiver, donor risk index, and donor characteristics. Between January 2004 and April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and 47 patients (6%) underwent combined procedures. Five hundred nineteen patients (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%) died early after OLT. A multivariate logistic regression analysis identified the following parameters as significantly influencing the discharge status: a low Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of 2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI, and renal dialysis before OLT. The nomogram was prospectively validated with a population of 126 OLT recipients with a concordance index of 0.813. In conclusion, a new approach to improving the efficiency of hospital care is essential. We believe that this tool will aid in reducing lengths of stay and improving the experience of patients by facilitating early discharge planning. Copyright © 2012 American Association for the Study of Liver Diseases.

Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease.

PubMed

Lens, Sabela; Fernández, Inmaculada; Rodríguez-Tajes, Sergio; Hontangas, Vanessa; Vergara, Mercedes; Forné, Montserrat; Calleja, Jose Luis; Diago, Moisés; Llaneras, Jordi; Llerena, Susana; Torras, Xavier; Sacristán, Begoña; Roget, Merce; Fernández-Rodríguez, Conrado Manuel; Navascués, Mari Carmen; Fuentes, Javier; Sánchez-Ruano, Juan-José; Simón, Miguel-Ángel; Sáez-Royuela, Federico; Baliellas, Carmen; Morillas, Rosa; Forns, Xavier

2017-09-01

Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15-0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16-5.83); P =0.02) and albumin ≤3.5 (17 (6.3-47); P <0.01). SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children.

PubMed

Ramon-Krauel, Marta; Salsberg, Sandra L; Ebbeling, Cara B; Voss, Stephan D; Mulkern, Robert V; Apura, Margaret M; Cooke, Emily A; Sarao, Karen; Jonas, Maureen M; Ludwig, David S

2013-06-01

Fatty liver is highly prevalent among obese children and represents a major risk factor for chronic liver diseases and severe metabolic complications. We randomly assigned 17 obese children 8-17 years of age with fatty liver to either an experimental low-glycemic-load or conventional low-fat diet for 6 months. Participants in both groups received nutrition education and behavioral counseling of equal intensity. The primary outcome was hepatic lipid content measured by proton magnetic resonance spectroscopy. Secondary outcomes included change in visceral fat, BMI, anthropometrics, alanine aminotransferase (ALT), and insulin resistance. A total of 16 participants completed the study. Reported glycemic load decreased in the low-glycemic-load group and reported dietary fat decreased in the low-fat group. At baseline, liver fat was 23.8% [standard deviation (SD) 12.2] in the low-glycemic-load group and 29.3% (14.1) in the low-fat group. Liver fat decreased substantially in both groups at 6 months expressed as absolute percentage change, with no between-group differences [-8.8 (standard error (SE) 4.1) vs. -10.5 (3.7)%, respectively, p=0.76 for group×time interaction]. Secondary outcomes also improved on both diets, with no between-group differences. Baseline and change in ALT were strongly associated with hepatic fat content. Weight-reducing diets focused either on glycemic load or dietary fat improved hepatic steatosis over 6 months. Additional research is needed to determine whether these diets differ in effectiveness over the long term. clinicaltrials.gov Identifier: NCT00480922.

Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3 p.I148M and TM6SF2 p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study.

PubMed

Krawczyk, Marcin; Stachowska, Ewa; Milkiewicz, Piotr; Lammert, Frank; Milkiewicz, Malgorzata

2016-01-01

The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent risk factors for non-alcoholic fatty liver disease (NAFLD). In this study, we assessed the effects of caloric restriction on liver phenotypes in NAFLD patients in relation to the PNPLA3 and TM6SF2 genotypes. We genotyped both variants in 143 individuals with NAFLD (55 females, age 18-74 years) and 180 controls (85 females, age 33-66 years). Liver steatosis was assessed using the ultrasound-based Hamaguchi score. A 4-month dietetic intervention, consisting of restriction of daily caloric intake without changes in physical activity, was performed. Both PNPLA3 (p = 0.002) and TM6SF2 (p = 0.041) variants were associated with NAFLD before intervention. Overall, 88 patients completed the intervention, which led to a significant decrease of steatosis, ALT activities, body mass index, hip and waist circumferences, and waist-hip ratio (all p < 0.0001). Hepatic steatosis and anthropometric traits improved significantly (p < 0.05) in carriers of either PNPLA3 or TM6SF2 risk genotype. The improvement of phenotypic traits, apart from WHR (p = 0.02), was not modified by the presence of PNPLA3 or TM6SF2 variants. The PNPLA3 and TM6SF2 polymorphisms are associated with NAFLD assessed by the Hamaguchi score. Neither PNPLA3 nor TM6SF2 risk alleles impair the response to dietetic intervention in NAFLD. © 2016 S. Karger AG, Basel.

Home-Based Screening for Biliary Atresia Using Infant Stool Color Cards in Canada: Quebec Feasibility Study.

PubMed

Morinville, Véronique; Ahmed, Najma; Ibberson, Cindy; Kovacs, Lajos; Kaczorowski, Janusz; Bryan, Stirling; Collet, Jean-Paul; Schreiber, Richard

2016-04-01

Biliary atresia (BA) is a leading cause of liver failure and liver transplantation in pediatrics. BA manifests by 3 weeks of life with jaundice and pale stools. Delayed diagnosis and surgical intervention with Kasai portoenterostomy after 3 months of age is significantly associated with poor prognosis for native liver survival. A national Taiwan infant stool color card (SCC) screening program has entirely eliminated late Kasai portoenterostomy >90 days of age and improved native liver survival. A recent large-scale prospective cohort study in British Columbia, Canada, indicated that distribution of SCC on the maternity ward was feasible, led to high utilization rate, and was cost-effective. The aim of the present study was to assess the generalizability of this screening strategy in another Canadian jurisdiction with a different sociodemographic profile. An SCC was distributed to families of newborns discharged at St Mary's Hospital Center, Montreal, Quebec. Families were instructed to monitor their infant's stool color for 21 days and then complete and mail the SCC to the study center. Phone surveys to families who did not return cards were used to estimate total card utilization rate. Two thousand two hundred forty-six infants were eligible for inclusion; 99.9% were enrolled. Mail SCC return rate was 63.3%. No cases of BA were identified. All of the 118 families who completed the phone survey reported that they had utilized the SCC. Conservative and optimistic estimates for total card utilization rates were 82% and 100%, respectively. The high enrollment and utilization rates in this screening study strongly support the feasibility of implementing a Canadian SCC screening program to improve outcomes of children with BA.

GSK3β and aging liver

PubMed Central

Jin, Jingling; Wang, Guo-Li; Timchenko, Lubov; Timchenko, and Nikolai A

2009-01-01

The loss of regenerative capacity of tissues is one of the major characteristics of aging. Liver represents a powerful system for investigations of mechanisms by which aging reduces regenerative capacity of tissues. The studies within last five years revealed critical role of epigenetic silencing in the inhibition of liver proliferation in old mice. These studies have shown that a number of cell cycle proteins are silenced in livers of old mice by C/EBPα-HDAC1-Brm complex and that old liver fails to reduce the complex and activate these genes in response to proliferative stimulus such as partial hepatectomy. The complex modifies histone H3 on the promoters of c-myc and FoxM1B in the manner which prevents expression of these genes. Despite this progress, little is known about mechanisms by which aging causes this epigenetic silencing. We have recently discovered signal transduction pathways which operate upstream of the C/EBPα-HDAC1-Brm complex. These pathways involve communications of growth hormone, GSK3β and cyclin D3. In addition to the liver, GH-GSK3β-cyclin D3 pathway is also changed with age in lung, brain and adipose tissues. We suggest that other age-associated alterations in these tissues might be mediated by the reduced levels of GSK3β and by elevation of cyclin D3. In this review, we summarize these new data and discuss the role of such alterations in the development of aging phenotype in the liver and in other tissues. PMID:20157540

Influence of age and gender before and after liver transplantation.

PubMed

Burra, Patrizia; De Martin, Eleonora; Gitto, Stefano; Villa, Erica

2013-02-01

Women constitute a particular group among patients with chronic liver disease and in the post-liver transplantation (LT) setting: they are set apart not only by traditional differences with respect to men (ie, body mass index, different etiologies of liver disease, and accessibility to transplantation) but also in increasingly evident ways related to hormonal changes that characterize first the fertile age and subsequently the postmenopausal period (eg, disease course variability and responses to therapy). The aim of this review is, therefore, to evaluate the role of the interplay of factors such as age, gender, and hormones in influencing the natural history of chronic liver disease before and after LT and their importance in determining outcomes after LT. As the population requiring LT ages and the mean age at transplantation increases, older females are being considered for transplantation. Older patients are at greater risk for nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral therapy. Female gender per se is associated with a greater risk for osteoporosis because of metabolic changes after menopause, the bodily structure of females, and, in the population of patients with chronic liver disease, the greater prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall of protective estrogen levels can lead to increased fibrosis progression, and this represents a negative turning point for women with chronic liver disease and especially for patients with hepatitis C. Therefore, the notion of gender as a binary female/male factor is now giving way to the awareness of more complex disease processes within the female gender that follow hormonal, social, and age patterns and need to be addressed directly and specifically. Copyright © 2012 American Association for the Study of Liver Diseases.

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

PubMed

Zheng, Jian-Ping; Miao, Hai-Xiong; Zheng, Shao-Wei; Liu, Wei-le; Chen, Chu-Qun; Zhong, Hao-Bo; Li, Sheng-Fa; Fang, Yong-Ping; Sun, Chun-Han

2018-05-01

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ± 10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ± 9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea.

PubMed

Kheirandish-Gozal, Leila; Sans Capdevila, Oscar; Kheirandish, Ebrahim; Gozal, David

2008-01-01

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

[Anti-aging action of the total lactones of ginkgo on aging mice].

PubMed

Dong, Liu-yi; Fan, Li; Li, Gui-fang; Guo, Yan; Pan, Jian; Chen, Zhi-wu

2004-03-01

To investigate the effects of total lactones of ginkgo on aging by using D-galactose induced aging mice and natural aging mice. By using D-galactose induced aging mice, to detect the LF content in heart and liver, the Hyp content in liver, the MAO, GSH-Px activities and the NO content in cerebrum. The apoptosis of cerebral cell was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling (Tunel) in natural aging mice. TLG was shown to increase the GSH-Px activities, reduce the NO content and decrease the MAO activity in cerebrum. Meanwhile, TLG was found to reduce the LF content in liver and heart and raise the Hyp content in liver. TLG was shown to inhibit apoptosis of cerebral cell and decrease the number of apoptotic cells in the brain. TLG possesses effect on antiaging via attenuating lipid peroxidation and NO and apoptosis of cerebral cells.

Hepatic lesions: improved image quality and detection with the periodically rotated overlapping parallel lines with enhanced reconstruction technique--evaluation of SPIO-enhanced T2-weighted MR images.

PubMed

Hirokawa, Yuusuke; Isoda, Hiroyoshi; Maetani, Yoji S; Arizono, Shigeki; Shimada, Kotaro; Okada, Tomohisa; Shibata, Toshiya; Togashi, Kaori

2009-05-01

To evaluate the effectiveness of the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique for superparamagnetic iron oxide (SPIO)-enhanced T2-weighted magnetic resonance (MR) imaging with respiratory compensation with the prospective acquisition correction (PACE) technique in the detection of hepatic lesions. The institutional human research committee approved this prospective study, and all patients provided written informed consent. Eighty-one patients (mean age, 58 years) underwent hepatic 1.5-T MR imaging. Fat-saturated T2-weighted turbo spin-echo images were acquired with the PACE technique and with and without the PROPELLER method after administration of SPIO. Images were qualitatively evaluated for image artifacts, depiction of liver edge and intrahepatic vessels, overall image quality, and presence of lesions. Three radiologists independently assessed these characteristics with a five-point confidence scale. Diagnostic performance was assessed with receiver operating characteristic (ROC) curve analysis. Quantitative analysis was conducted by measuring the liver signal-to-noise ratio (SNR) and the lesion-to-liver contrast-to-noise ratio (CNR). The Wilcoxon signed rank test and two-tailed Student t test were used, and P < .05 indicated a significant difference. MR imaging with the PROPELLER and PACE techniques resulted in significantly improved image quality, higher sensitivity, and greater area under the ROC curve for hepatic lesion detection than did MR imaging with the PACE technique alone (P < .001). The mean liver SNR and the lesion-to-liver CNR were higher with the PROPELLER technique than without it (P < .001). T2-weighted MR imaging with the PROPELLER and PACE technique and SPIO enhancement is a promising method with which to improve the detection of hepatic lesions. (c) RSNA, 2009.

Combination Iron Chelation Therapy with Deferiprone and Deferasirox in Iron-Overloaded Patients with Transfusion-Dependent β-Thalassemia Major.

PubMed

Karami, Hossein; Kosaryan, Mehrnoush; Amree, Arash Hadian; Darvishi-Khezri, Hadi; Mousavi, Masoomeh

2017-01-11

There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms) before and after treatment, respectively ( p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading.

Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

PubMed

Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

2015-12-01

Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

The long-term outcomes of cirrhotic patients with pleural effusion.

PubMed

Hung, Tsung-Hsing; Tseng, Chih-Wei; Tsai, Chih-Chun; Tsai, Chen-Chi; Tseng, Kuo-Chih; Hsieh, Yu-Hsi

2018-01-01

A pleural effusion is an abnormal collection of fluid in the pleural space and may cause related morbidity or mortality in cirrhotic patients. Currently, there are insufficient data to support the long-term prognosis for cirrhotic patients with pleural effusion. In this study, we investigated the short- and long-term effects of pleural effusion on mortality in cirrhotic patients and evaluated the benefit of liver transplantation in these patients. The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic patients with pleural effusion requiring drainage between January 1, 2007 and December 31, 2010. The proportional hazards Cox regression model was used to control for possible confounding factors. The 30-day, 90-day, 1-year, and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the cirrhotic patients with pleural effusion. After Cox proportional hazard regression analysis adjusted by patient gender, age, complications of cirrhosis and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and without liver transplantation conferred higher risks for 3-year mortality in the cirrhotic patients with pleura effusion. Liver transplantation is the most important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11- 0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the non-liver transplantation group. In cirrhotic patients, the presence of pleural effusion predicts poor long-term outcomes. Liver transplantation could dramatically improve the survival and should be suggested as soon as possible.

Assessment of liver size by ultrasonography.

PubMed

Patzak, Monika; Porzner, Marc; Oeztuerk, Suemeyra; Mason, Richard Andrew; Wilhelm, Manfred; Graeter, Tilmann; Kratzer, Wolfgang; Haenle, Mark Martin; Akinli, Atilla Serif

2014-09-01

To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size. A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire. The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence. Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span. © 2014 Wiley Periodicals, Inc.

Trends in cancer of the liver, gall bladder, bile duct, and pancreas in elderly in Denmark, 1980-2012.

PubMed

Bjerregaard, Jon Kroll; Mortensen, Michael Bau; Pfeiffer, Per

2016-01-01

Cancers of the liver, bile duct, gall bladder and pancreas (HPB-c) are a heterogeneous group, united almost exclusively by a poor prognosis. As the number of elderly in the Western world continues to rise and HPB-c are associated with age, we wanted to examine changes in incidence, mortality, prevalence and relative survival for these cancers. HBP-c was defined as ICD-10 codes C22 (liver), C23-24 (gall bladder), and C25 (pancreas). Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. The incidence and mortality rates of cancer of the liver and pancreas increased over time while the rates of cancer of the gall bladder and bile duct decreased. All HBP-c were more frequent in persons over the age of 70 than in younger persons. The relative one- and five-year survival rose in most HPB-c, but mainly occurring in the younger population of 0-69 years with only small to no gains in the 80 + group. As the number of persons aged 80 years or more will increase dramatically in the following years, and our results show a gap in relative survival, it is important to continue to study this population in order to improve management and outcome.

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

PubMed

Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

2017-01-01

This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

Early markers of reperfusion injury after liver transplantation: association with primary dysfunction.

PubMed

Bruns, Helge; Heil, Jan; Schultze, Daniel; Al Saeedi, Mohammed; Schemmer, Peter

2015-06-01

In patients with end-stage liver disease, liver transplantation is the only available curative treatment. Although the outcome and quality of life in the patients have improved over the past decades, primary dys- or nonfunction (PDF/PNF) can occur. Early detection of PDF and PNF is crucial and could lead to individual therapies. This study was designed to identify early markers of reperfusion injury and PDF in liver biopsies taken during the first hour after reperfusion. Biopsies from donor livers were prospectively taken as a routine during the first hour after reperfusion. Recipient data, transaminases and outcome were routinely monitored. In total, 10 biopsy specimens taken from patients with 90-day mortality and PDF, and patients with long-term survival but without PDF were used for DNA microarrays. Markers that were significantly up- or down-regulated in the microarray were verified using quantitative real-time PCR. Age, indications and labMELD score were similar in both groups. Peak-transaminases during the first week after transplantation were significantly different in the two groups. In total, 20 differentially regulated markers that correlated to PDF were identified using microarray analysis and verified with quantitative real-time PCR. The markers identified in this study could predict PDF at a very early time point and might point to interventions that ameliorate reperfusion injury and thus prevent PDF. Identification of patients and organs at risk might lead to individualized therapies and could ultimately improve outcome.

Assessment of biochemical liver function tests in relation to age among steady state sickle cell anemia patients.

PubMed

Akuyam, S A; Abubakar, A; Lawal, N; Yusuf, R; Aminu, S M; Hassan, A; Musa, A; Bello, A K; Yahaya, I A; Okafor, P A

2017-11-01

Multiorgan failure including liver dysfunction is a common finding in sickle cell anemia (SCA) patients, the cause of which is multifactorial with advancing age said to be a major determinant. There is a paucity of data on liver function among SCA patients in relation to age in northern Nigerian hospitals, including Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. This study was to assess the biochemical liver function tests (LFTs) as they relate to age among SCA patients in steady state, with a view to improving the overall monitoring of these patients. This study was carried out in ABUTH, Zaria, Northern Nigeria. LFTs were carried out in 100 SCA and 100 apparently healthy participants (controls). The SCA group was made up of fifty adults and fifty children diagnosed of SCA, whereas the control group was made up of fifty adults and fifty children who were apparently healthy and had hemoglobin AA. Paired two-tailed Student's t-test for matched samples and Pearson's linear correlation statistical methods were employed for the data analysis using Microsoft Office Excel 2007. A P ≤ 0.05 was considered as statistically significant. The serum concentrations of total bilirubin (TB), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and AST/ALT ratio were significantly higher in SCA patients compared to the controls (P = 0.001, P = 0.001, P = 0.05, P = 0.05 and P = 0.001, respectively). Serum total protein (TP) and ALB were significantly lower (P = 0.01 and P < 0.05, respectively) in SCA patients compared with the controls. The levels of TB, ALT, AST, ALP, and AST/ALT were significantly lower in SCA adults compared to SCA children, whereas TP and ALB were higher in SCA adults compared to the SCA children. There were significant negative correlations between age and each of TB, ALT, AST, ALP, and AST/ALT, and significant positive correlations between age and each of TP and ALB in SCA patients. There are mild LFTs derangements in SCA patients even in steady state with the extent of the abnormalities decreasing with advancing age of the patients.

Deep learning for staging liver fibrosis on CT: a pilot study.

PubMed

Yasaka, Koichiro; Akai, Hiroyuki; Kunimatsu, Akira; Abe, Osamu; Kiryu, Shigeru

2018-05-14

To investigate whether liver fibrosis can be staged by deep learning techniques based on CT images. This clinical retrospective study, approved by our institutional review board, included 496 CT examinations of 286 patients who underwent dynamic contrast-enhanced CT for evaluations of the liver and for whom histopathological information regarding liver fibrosis stage was available. The 396 portal phase images with age and sex data of patients (F0/F1/F2/F3/F4 = 113/36/56/66/125) were used for training a deep convolutional neural network (DCNN); the data for the other 100 (F0/F1/F2/F3/F4 = 29/9/14/16/32) were utilised for testing the trained network, with the histopathological fibrosis stage used as reference. To improve robustness, additional images for training data were generated by rotating or parallel shifting the images, or adding Gaussian noise. Supervised training was used to minimise the difference between the liver fibrosis stage and the fibrosis score obtained from deep learning based on CT images (F DLCT score) output by the model. Testing data were input into the trained DCNNs to evaluate their performance. The F DLCT scores showed a significant correlation with liver fibrosis stage (Spearman's correlation coefficient = 0.48, p < 0.001). The areas under the receiver operating characteristic curves (with 95% confidence intervals) for diagnosing significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) by using F DLCT scores were 0.74 (0.64-0.85), 0.76 (0.66-0.85) and 0.73 (0.62-0.84), respectively. Liver fibrosis can be staged by using a deep learning model based on CT images, with moderate performance. • Liver fibrosis can be staged by a deep learning model based on magnified CT images including the liver surface, with moderate performance. • Scores from a trained deep learning model showed moderate correlation with histopathological liver fibrosis staging. • Further improvement are necessary before utilisation in clinical settings.

Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging.

PubMed

Sato, Shogo; Solanas, Guiomar; Peixoto, Francisca Oliveira; Bee, Leonardo; Symeonidi, Aikaterini; Schmidt, Mark S; Brenner, Charles; Masri, Selma; Benitah, Salvador Aznar; Sassone-Corsi, Paolo

2017-08-10

The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and rewires circadian metabolism. Using young versus old mice, fed ad libitum or under CR, we reveal reprogramming of the circadian transcriptome in the liver. These age-dependent changes occur in a highly tissue-specific manner, as demonstrated by comparing circadian gene expression in the liver versus epidermal and skeletal muscle stem cells. Moreover, de novo oscillating genes under CR show an enrichment in SIRT1 targets in the liver. This is accompanied by distinct circadian hepatic signatures in NAD + -related metabolites and cyclic global protein acetylation. Strikingly, this oscillation in acetylation is absent in old mice while CR robustly rescues global protein acetylation. Our findings indicate that the clock operates at the crossroad between protein acetylation, liver metabolism, and aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD

PubMed Central

Takeuchi, Masayoshi; Takino, Jun-ichi; Sakasai-Sakai, Akiko; Takata, Takanobu; Tsutsumi, Mikihiro

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively) in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE) and a related novel theory for preventing the onset/progression of NAFLD and ALD. PMID:28632197

Assessment of School Readiness in Chronic Cholestatic Liver Disease: A Pilot Study Examining Children with and without Liver Transplantation.

PubMed

Gold, Anna; Rogers, Alaine; Cruchley, Elizabeth; Rankin, Stephanie; Parmar, Arpita; Kamath, Binita M; Avitzur, Yaron; Ng, Vicky Lee

2017-01-01

Background. Assessment of school readiness evaluates physical, social-emotional, and neuropsychological domains essential for educational success. Cognitive testing of preschool aged children with chronic liver disease may guide more timely interventions and focused efforts by health care providers. Patients and Methods. Children with chronic cholestatic liver disease diagnosed as an infant and still with their native liver (NL) and children who received a liver transplant (LT) before age of 2 years underwent testing with a battery of well-validated pediatric psychometric measures. Results. Eighteen (13 LT, 5 NL) patients (median age of 4.45 and 4.05 years, resp.) were tested. Median Full-Scale IQ was 98 (range 102-116) for LT and 116 [(range 90-106), p = 0.35, NS] for NL subjects. LT recipients had significantly greater visual based difficulties, poorer caregiver rated daily living skills ( p = 0.04), and higher levels of executive function based difficulties (e.g., inattention, inhibition). Conclusion. This pilot study highlights the risk of neuropsychological difficulties in early school age children who were under 2 years of age at time of LT. Comprehensive early school age assessment should integrate psychometric measures to identify children at greatest risk, thus allowing for proactive educational intervention.

Age- and sex-related differences of organic anion-transporting polypeptide gene expression in livers of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Wei-Yu; Xu, Shang-Fu; Zhu, Qiong-Ni

Organic anion-transporting polypeptides (Oatps) play important roles in transporting endogenous substances and xenobiotics into the liver and are implicated in drug-drug interactions. Many factors could influence their expression and result in alterations in drug disposition, efficacy and toxicity. This study was aimed to examine the development-, aging-, and sex-dependent Oatps expression in livers of rats. The livers from SD rats during development (− 2, 1, 7, 14, 21, 28, 35, and 60 d) and aging (60, 180, 540 and/or 800 d) were collected and total RNAs were extracted, purified, and subjected to real-time PCR analysis. Total proteins were extracted formore » western-blot analysis. Results showed that Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 were all hardly detectable in fetal rat livers, low at birth, rapidly increased after weaning (21 d), and reached the peak at 60 d. The Oatps remained stable during the age between 60–180 d, and decreased at elderly (540 and/or 800 d). After birth, Oatp1a1, Oatp1a4, and Oatp1b2 were all highly expressed in liver, in contrast, Oatp1a5 expression was low. Oatp expressions are male-predominant in rat livers. In the livers of aged rats, the Oatp expression decreased and shared a consistent ontogeny pattern at the mRNA and protein level. In conclusion, this study showed that in rat liver, Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 gene expressions are influenced by age and gender, which could provide a basis of individual variation in drug transport, metabolism and toxicity in children, elderly and women. - Highlights: • Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 expression in livers of rats. • Ontogenic changes of Oatps at − 2, 1, 7, 14, 21, 28, 35, and 60 days. • Age-related changes of Oatps at 60, 180, 540, and 800 days. • Sex-difference of Oatps at the both mRNA and protein levels.« less

Steroid use in acute liver failure.

PubMed

Karkhanis, Jamuna; Verna, Elizabeth C; Chang, Matthew S; Stravitz, R Todd; Schilsky, Michael; Lee, William M; Brown, Robert S

2014-02-01

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%, P = 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P = 0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH < 7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%, P = 0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores. © 2013 by the American Association for the Study of Liver Diseases.

Aging-associated oxidative stress inhibits liver progenitor cell activation in mice.

PubMed

Cheng, Yiji; Wang, Xue; Wang, Bei; Zhou, Hong; Dang, Shipeng; Shi, Yufang; Hao, Li; Luo, Qingquan; Jin, Min; Zhou, Qianjun; Zhang, Yanyun

2017-04-29

Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging.

[Effect of age, different light conditions, melatonin, and epitalon on lysosomal proteinase activity in the liver and kidneys of rats].

PubMed

Rendakov, N L; Tiutiunnik, N N; Vinogradova, I A

2006-01-01

Ageing, melatonin, epithalon (tetrapeptide Ala-Glu-Asp-Gly) and different light conditions effects on protein content and cathepsins B and D activities in rat liver and kidneys lysosomal fractions were studied. Ageing leads to decrease of cathepsins activity in rat liver lysosomal fractions. Constant light and darkness conditions result in earlier age decline of cathepsins activity. Absence of day and night succession in comparison with alternating light conditions causes decline of both general and specific cathepsin D activity. Melatonin and epithalon administration resulted in decrease of cathepsin D activity in liver only under control interchangeable light conditions. Cathepsin B activity in liver and kidneys lysosomal fractions declined in all experimental light conditions. Cathepsins activity decrease under the influence of epiphysial factors is evidently connected with their inhibitory effect on protein and general metabolism.

Breath-hold black-blood T1rho mapping improves liver T1rho quantification in healthy volunteers.

PubMed

Wáng, Yì Xiáng J; Deng, Min; Lo, Gladys G; Liang, Dong; Yuan, Jing; Chen, Weitian

2018-03-01

Background Recent researches suggest that T1rho may be a non-invasive and quantitative technique for detecting and grading liver fibrosis. Purpose To compare a multi-breath-hold bright-blood fast gradient echo (GRE) imaging and a single breath-hold single-shot fast spin echo (FSE) imaging with black-blood effect for liver parenchyma T1rho measurement and to study liver physiological T1rho value in healthy volunteers. Material and Methods The institutional Ethics Committee approved this study. 28 healthy participants (18 men, 10 women; age = 29.6 ± 5.1 years) underwent GRE liver T1rho imaging, and 20 healthy participants (10 men, 10 women; age = 36.9 ± 10.3 years) underwent novel black-blood FSE liver T1rho imaging, both at 3T with spin-lock frequency of 500 Hz. The FSE technique allows simultaneous acquisition of four spin lock times (TSLs; 1 ms, 10 ms, 30 ms, 50msec) in 10 s. Results For FSE technique the intra-scan repeatability intraclass correlation coefficient (ICC) was 0.98; while the inter-scan reproducibility ICC was 0.82 which is better than GRE technique's 0.76. Liver T1rho value in women tended to have a higher value than T1rho values in men (FSE: 42.28 ± 4.06 ms for women and 39.13 ± 2.12 ms for men; GRE: 44.44 ± 1.62 ms for women and 42.36 ± 2.00 ms for men) and FSE technique showed liver T1rho value decreased slightly as age increased. Conclusion Single breath-hold black-blood FSE sequence has better scan-rescan reproducibility than multi-breath-hold bright-blood GRE sequence. Gender and age dependence of liver T1rho in healthy participants is observed, with young women tending to have a higher T1rho measurement.

Post-transplant outcomes of patients with and without hepatitis C virus infection according to donor age and gender matching.

PubMed

Grąt, Michał; Kornasiewicz, Oskar; Lewandowski, Zbigniew; Ligocka, Joanna; Grąt, Karolina; Wronka, Karolina Maria; Zieniewicz, Krzysztof; Krawczyk, Marek

2013-12-23

The purpose of this study was to evaluate the impact of donor age and donor-recipient gender matching on liver transplantation outcomes, focusing on differences between patients with and without hepatitis C virus (HCV) infection. This retrospective cohort study evaluated 622 liver transplantation recipients. HCV (n=164) and non-HCV (n=458) patients were subdivided by donor age (≤ 30, 31-50, and >50 years) and donor-recipient gender configurations. Five-year patient survival (PS) and graft survival (GS) were set as outcome measures. Five-year PS was 83.1% for HCV-positive and 81.6% for HCV-negative patients (p=0.614), with the corresponding GS rates of 81.2% and 79.3% (p=0.538), respectively. In HCV patients, transplantations from donors older than 50 years were associated with lower PS (p=0.035) and GS (p=0.006) than those from donors aged 31-50 years. This difference was not observed among non-HCV recipients (PS, p=0.994; GS, p=0.878). Regarding donor-recipient gender configurations, outcomes were similar in HCV (PS, p=0.751; GS, p=0.592) and non-HCV patients (PS, p=0.217; GS, p=0.249), except for a tendency toward lower PS for male-to-female transplantations than female-to-female transplantations in non-HCV patients (p=0.064). Outcomes of HCV patients were superior to those of non-HCV patients after transplantation from donors aged 31-50 years (PS, p=0.080; GS, p=0.026). Avoiding the transplantation of grafts from donors aged over 50 years to patients with HCV infection might improve the general outcomes of liver transplantation programs. There is no specific rationale for gender matching with respect to HCV status.

Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets.

PubMed

Zhang, Hao; Li, Yue; Hou, Xiang; Zhang, Lili; Wang, Tian

2016-05-01

We previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets' biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

Liver cirrhosis: a risk factor for gallstone disease in chronic hepatitis C patients in China.

PubMed

Li, Xu; Wang, Zhongfeng; Wang, Le; Pan, Meng; Gao, Pujun

2017-06-01

We investigated the possible link between liver cirrhosis and gallstone risk in chronic hepatitis C (CHC) patients in China.To analyze the association between liver cirrhosis and gallstone development, we compared outcomes of 133 Chinese CHC patients with gallstones and an age-, sex-, and hepatitis C virus RNA level-matched control group of 431 CHC patients without gallstones.We found that liver cirrhosis was more prevalent in gallstone patients (40.6%) than in the control group (24.4%). Logistic regression analyses adjusting for demographic features and other gallstone risk factors revealed that liver cirrhosis increased the risk of gallstone development 2-fold (adjusted odds ratio [AOR]: 2.122; 95% confidence interval [CI]: 1.408-3.198). Moreover, multivariate analyses comparing the risk of gallstone development in liver cirrhosis patients with decompensated or compensated liver cirrhosis yielded an estimated AOR (95% CI) of 2.869 (1.277-6.450) in patients with decompensated liver cirrhosis. Gallstone risk also increased significantly with older age (>60 years) (AOR: 2.019; 95% CI: 1.017-4.009).Liver cirrhosis significantly correlates with increased risk of gallstone development in CHC patients in China. Decompensated liver cirrhosis and older age further heighten this risk in patients diagnosed with hepatitis C-related cirrhosis.

Effect of age increase on metabolism and toxicity of ethanol in female rats.

PubMed

Kim, Young C; Kim, Sung Y; Sohn, Young R

2003-12-12

Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

Donor age as a predictor of risk for short-term outcomes after liver transplant.

PubMed

Macedo, Francisco Igor B; Miranda, Luiz Eduardo C; Fernandes, Jordão L; Pádua, Tiago C; Figueroa, José N; Neto, Olival Lucena F; Lacerda, Cláudio M

2010-09-01

To investigate an association between short-term mortality and donor age-associated worst outcomes in liver transplant. A total of 178 consecutive patients underwent a liver transplant between 1999 and 2007. Among these patients, there were 172 liver transplants (donor age, 32.04 +/- 16.66; range, 2-65 years) and 167 recipients. Mean recipient age was 39.16 +/- 21.61 years (range, 6 months to 71 years), and 90 were males (53.8%). Among 172 transplants, 32.9% recipients died during follow-up (mean, 34.37 +/- 20.50 months). A lower mean recipient and graft survival occurred in donors older than 50 years (P = .01) and 30 years (P = .02) at 7-year patient survival. At 6- month and 1-year recipient survival, cutoffs were 50 and 55 years (P < .05). Log-rank test showed no statistical difference among recipients, and graft survival from donors older/younger 50 and 30 years 1.5 years after liver transplant (P < .565 and P < .259). Donor age is a key factor in liver transplant that carries prognostic impact in the recipients. Our data suggest that its harmful effects are exclusively elicited during the short-term, postoperative phase. We recommend careful and distinct management of recipients receiving grafts from elderly donors up to 1.5 years after liver transplant. Changes in the current early postoperative management of this selected group are encouraged.

Anti-ageing effects of protocatechuic acid from Alpinia on spleen and liver antioxidative system of senescent mice.

PubMed

Zhang, Xiuli; Shi, Gui-Fang; Liu, Xiu-zhen; An, Li-jia; Guan, Shui

2011-06-01

The effects of Alpinia protocatechuic acid (PCA) on spleen and liver antioxidant system in aged rats have been studied. Alpinia PCA, a phenolic compound, was first isolated from the dried fruits of Alpinia Oxyphylla Miq. in our laboratory. Young and aged rats were injected intraperitoneally with Alpinia PCA at single doses of 5 mg kg(-1) (low dose) or 10 mg kg(-1) (high dose) per day for 7 days. The activities of endogenous antioxidants and the content of lipid peroxide in spleen and liver were assayed. Compared with young group, aged rats had significantly lower splenic weights, lower activities of glutathione peroxidase (GSH-PX) and catalase (CAT), higher level of malondialdehyde (MDA) in spleen and liver. The results proved that Alpinia PCA significantly elevated the splenic weights, increased the activities of GSH-PX and CAT and decreased the MDA level of aged rats. All these suggested that Alpinia PCA was a potential anti-ageing agent, and its effects on spleen and liver were achieved at least partly by promoting endogenous antioxidant enzymatic activities and normalizing age-associated alterations. It may be therapeutically useful to minimize age-associated disorders where oxidative damage is the major cause. Copyright © 2011 John Wiley & Sons, Ltd.

Self-Management in Liver Transplant Recipients: A Narrative Review.

PubMed

Ko, Dami; Muehrer, Rebecca J; Bratzke, Lisa C

2018-06-01

Although self-management is essential for liver transplant recipients, there is no review that has synthesized findings related to self-management in this population. This narrative review aimed to synthesize the current findings and identify the gaps in knowledge about self-management in liver recipients. A search of PubMed, CINAHL Plus, PsychINFO, ProQuest, and Web of Science was conducted using the following terms: [Self-care OR Self-management OR Health behavior] AND [Liver transplantation]. Peer-reviewed published research articles focusing on self-management of adult recipients were selected. A total of 23 articles were included for review. Two reviewers independently reviewed the full text of selected articles and extracted the data about definitions, measurements, and findings regarding self-management. Three areas of self-management were identified, including medication nonadherence (n = 11), alcohol recidivism (n = 11), and health maintenance (n = 5). Reported rates of medication nonadherence ranged from 8% to 66%. Medication nonadherence was related to recipients' demographic (eg, age or sex), transplant-related (eg, time since transplant), and pretransplant variables (eg, history of substance/alcohol abuse). Reported alcohol recidivism rates ranged from 3% to 95%. Age, pretransplant variables (eg, abstinent time before transplant), and personality disorder were identified to be related to alcohol recidivism after transplant. The health maintenance studies discussed behaviors such as smoking, clinic appointment attendance, or vaccination/health screening behaviors of recipients. Self-management studies in liver recipients have been narrowly focused on medication nonadherence and alcohol recidivism. To improve self-management in recipients, self-management beyond medication nonadherence and alcohol recidivism should be comprehensively examined.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PubMed

Paul, Shashi B; Das, Prasenjit; Mahanta, Mousumi; Sreenivas, Vishnubhatla; Kedia, Saurabh; Kalra, Nancy; Kaur, Harpreet; Vijayvargiya, Maneesh; Ghosh, Shouriyo; Gamanagatti, Shivanand R; Shalimar; Gupta, Siddhartha Dutta; Acharya, Subrat K

2017-12-01

To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

The incompatibility of healthcare services and end-of-life needs in advanced liver disease: A qualitative interview study of patients and bereaved carers.

PubMed

Hudson, Benjamin; Hunt, Victoria; Waylen, Andrea; McCune, Catherine Anne; Verne, Julia; Forbes, Karen

2018-05-01

Liver disease represents the third commonest cause of death in adults of working age and is associated with an extensive illness burden towards the end of life. Despite this, patients rarely receive palliative care and are unlikely to be involved in advance care planning discussions. Evidence addressing how existing services meet end-of-life needs, and exploring attitudes of patients and carers towards palliative care, is lacking. To explore the needs of patients and carers with liver disease towards the end of life, evaluate how existing services meet need, and examine patient and carer attitudes towards palliative care. Qualitative study - semi-structured interviews analysed using thematic analysis. Settings/participants: A total of 17 participants (12 patients, 5 bereaved carers) recruited from University Hospitals Bristol. Participants described escalating physical, psychological and social needs as liver disease progressed, including disabling symptoms, emotional distress and uncertainty, addiction, financial hardship and social isolation. End-of-life needs were incompatible with the healthcare services available to address them; these were heavily centred in secondary care, focussed on disease modification at the expense of symptom control and provided limited support after curative options were exhausted. Attitudes towards palliative care were mixed, however, participants valued opportunities to express future care preferences (particularly relating to avoidance of hospital admission towards the end of life) and an increased focus on symptomatic and logistical aspects of care. The needs of patients with liver disease and their carers are frequently incompatible with the healthcare services available to them towards the end of life. Novel strategies, which recognise the life-limiting nature of liver disease explicitly and improve coordination with community services, are required if end-of-life care is to improve.

ARFI cut-off values and significance of standard deviation for liver fibrosis staging in patients with chronic liver disease.

PubMed

Goertz, Ruediger S; Sturm, Joerg; Pfeifer, Lukas; Wildner, Dane; Wachter, David L; Neurath, Markus F; Strobel, Deike

2013-01-01

Acoustic radiation force impulse (ARFI) elastometry quantifies hepatic stiffness, and thus degree of fibrosis, non-invasively. Our aim was to analyse the diagnostic accuracy of ARFI cut-off values, and the significance of a defined limit of standard deviation (SD) as a potential quality parameter for liver fibrosis staging in patients with chronic liver diseases (CLD). 153 patients with CLD (various aetiologies) undergoing liver biopsy, and an additional 25 patients with known liver cirrhosis, were investigated. ARFI measurements were performed in the right hepatic lobe, and correlated with the histopathological Ludwig fibrosis score (inclusion criteria: at least 6 portal tracts). The diagnostic accuracy of cut-off values was analysed with respect to an SD limit of 30% of the mean ARFI value. The mean ARFI elastometry showed 1.95 ± 0.87 m/s (range 0.79-4.40) in 178 patients (80 female, 98 male, mean age: 52 years). The cut-offs were 1.25 m/s for F ≥ 2, 1.72 m/s for F ≥ 3 and 1.75 m/s for F = 4, and the corresponding AUROC 80.7%, 86.2% and 88.7%, respectively. Exclusion of 31 patients (17.4%) with an SD higher than 30% of the mean ARFI improved the diagnostic accuracy: The AUROC for F ≥ 2, F ≥ 3 and F = 4 were 86.1%, 91.2% and 91.5%, respectively. The diagnostic accuracy of ARFI can be improved by applying a maximum SD of 30% of the mean ARFI as a quality parameter--which however leads to an exclusion of a relevant number of patients. ARFI results with a high SD should be interpreted with caution.

A Low-Glycemic-Load versus Low-Fat Diet in the Treatment of Fatty Liver in Obese Children

PubMed Central

Ramon-Krauel, Marta; Salsberg, Sandra L.; Ebbeling, Cara B.; Voss, Stephan D.; Mulkern, Robert V.; Apura, Margaret M.; Cooke, Emily A.; Sarao, Karen; Jonas, Maureen M.

2013-01-01

Abstract Background Fatty liver is highly prevalent among obese children and represents a major risk factor for chronic liver diseases and severe metabolic complications. Methods We randomly assigned 17 obese children 8–17 years of age with fatty liver to either an experimental low-glycemic-load or conventional low-fat diet for 6 months. Participants in both groups received nutrition education and behavioral counseling of equal intensity. The primary outcome was hepatic lipid content measured by proton magnetic resonance spectroscopy. Secondary outcomes included change in visceral fat, BMI, anthropometrics, alanine aminotransferase (ALT), and insulin resistance. Results A total of 16 participants completed the study. Reported glycemic load decreased in the low-glycemic-load group and reported dietary fat decreased in the low-fat group. At baseline, liver fat was 23.8% [standard deviation (SD) 12.2] in the low-glycemic-load group and 29.3% (14.1) in the low-fat group. Liver fat decreased substantially in both groups at 6 months expressed as absolute percentage change, with no between-group differences [−8.8 (standard error (SE) 4.1) vs. −10.5 (3.7)%, respectively, p=0.76 for group×time interaction]. Secondary outcomes also improved on both diets, with no between-group differences. Baseline and change in ALT were strongly associated with hepatic fat content. Conclusions Weight-reducing diets focused either on glycemic load or dietary fat improved hepatic steatosis over 6 months. Additional research is needed to determine whether these diets differ in effectiveness over the long term. Trial Registration clinicaltrials.gov Identifier: NCT00480922 PMID:23705885

Hepatocyte polyploidization and its association with pathophysiological processes.

PubMed

Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping

2017-05-18

A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered.

Hepatocyte polyploidization and its association with pathophysiological processes

PubMed Central

Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping

2017-01-01

A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered. PMID:28518148

Quantification of total mercury in liver and heart tissue of Harbor Seals (Phoca vitulina) from Alaska USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marino, Kady B.; Hoover-Miller, Anne; Conlon, Suzanne

This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results of this study indicate liver and heart tissues' Hg ppm dw concentrations significantly increase with age. Male Harbor Seals bioaccumulated Hg in both their liver and heart tissues at a significantly faster rate than females. The liver Hg bioaccumulation rates between the harvest locationsmore » Kodiak Island and Prince William Sound were not found to be significantly different. On adsorption Hg is transported throughout the Harbor Seal's body with the partition coefficient higher for the liver than the heart. No significant differences in the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with respect to either age, sex or geographic harvest location. In this study the age at which Hg liver and heart bioaccumulation levels become significantly distinct in male and female Harbor Seals were identified through a Tukey's analysis. Of notably concern to human health was a male Harbor Seal's liver tissue harvested from Kodiak Island region. Mercury accumulation in this sample tissue was determined through a Q-test to be an outlier, having far higher Hg concentrarion (liver 392 Hg ppm dw) than the general population sampled. - Highlights: Black-Right-Pointing-Pointer Mercury accumulation in the liver and heart of seals exceed food safety guidelines. Black-Right-Pointing-Pointer Accumulation rate is greater in males than females with age. Black-Right-Pointing-Pointer Liver mercury accumulation is greater than in the heart tissues. Black-Right-Pointing-Pointer Mercury determination by USA EPA Method 7473 using thermal decomposition.« less

[Viral and drug-induced liver damage in children with tuberculosis: prevalence, clinical features].

PubMed

Borzakova, S N; Aksenova, V A; Reĭzis, A R

2013-01-01

THE AIM OF THE RESEARCH: Improving the effectiveness of diagnostics and treatment of viral and drug-induced lesions of the liver (DILL) at a tuberculosis in children by identifying the frequency of their distribution, peculiarities of diagnostics and clinics. We examined 242 children in the age from 2 months to 17 years, the patients with different forms of tuberculosis. The prevalence of hepatitis in children with tuberculosis: B - 1,2%, C-0.4%, G - 4,6%, TT - 8,7%. DILL was diagnosed in 67.5% of children - TB patients, in 48% of the children with DILL an asymptomatic course of the disease was noted, however, in 54.4% of the children with DILL cytolitic syndrome was expressed (ALT> standards). The prevalence of viral hepatitis B and C among children with TB is low. The infection with viruses of hepatitis G and TT is more often, but has no significant impact as on the course of tuberculosis, and on the severity of the liver damage. Drug-induced liver damage is a dominant view of pathology of the liver in children - TB patients and is mostly asymptomatic, but with a pronounced cytolitic syndrome.

Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.

PubMed

Palma-Duran, Susana A; Kontogianni, Meropi D; Vlassopoulos, Antonis; Zhao, Shudong; Margariti, Aikaterini; Georgoulis, Michael; Papatheodoridis, George; Combet, Emilie

2018-06-01

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Early and advanced glycation end-products, except N ε -carboxymethyl-L-lysine (CML), were 10-30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD. Copyright © 2018 Elsevier Inc. All rights reserved.

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet

PubMed Central

Mitchell, Sarah J.; Martin-Montalvo, Alejandro; Mercken, Evi M.; Palacios, Hector H.; Ward, Theresa M.; Abulwerdi, Gelareh; Minor, Robin K.; Vlasuk, George P.; Ellis, James L.; Sinclair, David A.; Dawson, John; Allison, David B.; Zhang, Yongqing; Becker, Kevin G.; Bernier, Michel; de Cabo, Rafael

2014-01-01

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+ deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of pro-inflammatory gene expression both in the liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. PMID:24582957

Long-term natural history of liver disease in patients with chronic hepatitis B virus infection: an analysis using the Markov chain model.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Ohisa, Masayuki; Akita, Tomoyuki; Tanaka, Junko

2018-04-19

The relationship between the hepatitis B e antigen (HBeAg) seroconversion and the long-term natural history of liver disease has not been sufficiently investigated. A total of 408 [4352 person-year (PY) units] patients with chronic hepatitis B virus (HBV) without antiviral therapy were enrolled. The study patients were divided into three groups, as follows: Group A (2666 PY units), seroconverted of HBeAg at age < 40; Group B (413 PY units), seroconverted of HBeAg at age ≥ 40; Group C (1273 PY units), persistently HBeAg positive. Yearly transition probabilities from each liver state [chronic HBV infection, chronic hepatitis B, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) negativity] were calculated using the Markov chain model. In the analysis of 1 year liver disease state transition probabilities, the liver states remained almost the same in Group A. In Groups B and C, each liver state tended to progress to a worse state. Assuming a chronic hepatitis B state at age 40 as the starting condition for simulation over the next 40 years, the chronic hepatitis B state accounted for approximately 60% of males aged ≥ 50 and approximately 40% of females aged ≥ 60 in Group A, and the HBsAg-negative state accounted for approximately 30-40% of males and females aged ≥ 60. In Groups B and C, the probabilities of patients with cirrhosis and HCC gradually increased with age. Not only patients with persistent HBeAg positive, but also patients with delayed HBeAg seroconversion showed poor prognosis of liver-related natural history.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

PubMed

Zhao, Jingxin; Zhai, Fei; Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

PubMed Central

Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice.

PubMed

Feng, Yan; Yu, Ying-Hua; Wang, Shu-Ting; Ren, Jing; Camer, Danielle; Hua, Yu-Zhou; Zhang, Qian; Huang, Jie; Xue, Dan-Lu; Zhang, Xiao-Fei; Huang, Xu-Feng; Liu, Yi

2016-01-01

Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. The current study investigates the effects of protective effects of chlorogenic acid (CGA) on D-galactose-induced liver and kidney injury. Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of D-galactose (D-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in D-gal mice (p <0.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in D-gal mice (p <0.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels in the liver and kidney in D-gal mice (p <0.05). These findings suggest that CGA attenuates D-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and anti-inflammatory activities.

Recipient Age and Mortality Risk after Liver Transplantation: A Population-Based Cohort Study.

PubMed

Chen, Hsiu-Pin; Tsai, Yung-Fong; Lin, Jr-Rung; Liu, Fu-Chao; Yu, Huang-Ping

2016-01-01

The aim of the present large population-based cohort study is to explore the risk factors of age-related mortality in liver transplant recipients in Taiwan. Basic information and data on medical comorbidities for 2938 patients who received liver transplants between July 1, 1998, and December 31, 2012, were extracted from the National Health Insurance Research Database on the basis of ICD-9-codes. Mortality risks were analyzed after adjusting for preoperative comorbidities and compared among age cohorts. All patients were followed up until the study endpoint or death. This study finally included 2588 adults and 350 children [2068 (70.4%) male and 870 (29.6%) female patients]. The median age at transplantation was 52 (interquartile range, 43-58) years. Recipients were categorized into the following age cohorts: <20 (n = 350, 11.9%), 20-39 (n = 254, 8.6%), 40-59 (n = 1860, 63.3%), and ≥60 (n = 474, 16.1%) years. In the total population, 428 deaths occurred after liver transplantation, and the median follow-up period was 2.85 years (interquartile range, 1.2-5.5 years). Dialysis patients showed the highest risk of mortality irrespective of age. Further, the risk of death increased with an increase in the age at transplantation. Older liver transplant recipients (≥60 years), especially dialysis patients, have a higher mortality rate, possibly because they have more medical comorbidities. Our findings should make clinicians aware of the need for better risk stratification among elderly liver transplantation candidates.

HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

PubMed

Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

2017-01-01

We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

[Analysis of liver cancer incidence and trend in China].

PubMed

Zuo, Tingting; Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

2015-09-01

The national population-based cancer registration data were used to analyze the liver cancer incidence and trend in China, in order to provide advise for making further strategy on liver cancer prevention and control. Liver cancer data of 2011 were retrieved from the database of the National Cancer Registry. The incident cases of liver cancer were estimated using age-specific rate by urban or rural areas and gender according to the national population in 2011. Liver cancer incidence data from 22 cancer registries were used to analyze the incidence trend during 2000-2011. The estimates of new cases of liver cancer were about 356 thousand in China in 2011. The incidence rate was 26.39/10(5,) and the age-standardized incidence rates by Chinese standard population and by world population were 19.48/10(5) and 19.10/10(5,) respectively.There was an increasing trend of incidence rate of liver cancer in China during 2000-2011 with an average annual percentage change(AAPC) of 1.0% (95%CI: 0.5%-1.4%), 1.2% (95%CI: 0.7%-1.8%)in urban areas and 1.1% (95%CI: 0.5%-1.8%) in rural areas. After age standardization, the incidence rate was significantly decreased, with an AAPC of -1.8% (95%CI: -2.4% to -1.2%), -1.6% (95%CI: -2.2% to -0.9%) in urban and -1.4% (95%CI: -2.5% to -0.3%) in rural areas. Liver cancer is a common cancer in China. As changing in people's dietary habits and implementing neonatal HBV vaccination for years, the exposure to risk factors is reducing, and age-standardized incidence rate is decreasing. While cardinal number of population is big and aging population is growing rapidly in the country, trend of incidence rate is increasing, and the burden of liver cancer is still high in China.

Regulation of mitochondrial trifunctional protein modulates nonalcoholic fatty liver disease in mice

PubMed Central

Nassir, Fatiha; Arndt, Justin J.; Johnson, Sarah A.

2018-01-01

Mitochondrial trifunctional protein (MTP) plays a critical role in the oxidation of long-chain fatty acids. We previously reported that aging mice (>9 months old) heterozygous for an MTP defect (MTP+/−) develop nonalcoholic fatty liver disease (NAFLD). We tested whether a high-fat diet (HFD) accelerates NAFLD in young MTP+/−mice, and whether overexpression of the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 3 (SIRT3) deacetylates MTP and improves mitochondrial function and NAFLD. Three-month-old WT and MTP+/− mice were fed HFD (60% cal fat) for 16 weeks and livers were assessed for fatty acid oxidation (FAO) and NAFLD. Compared with WT, MTP+/− mice displayed reduced hepatic SIRT3 levels and reduced FAO, with increased hepatic steatosis and the inflammatory marker CD68. Hepatic overexpression of SIRT3 in HFD-fed MTP+/− mice increased hepatic MTP protein levels at the posttranscriptional level. Immunoprecipitation of MTP from liver mitochondria followed by Western blot with acetyl-lysine antibody showed higher acetylation of MTP in MTP+/− compared with WT mice. Overexpression of SIRT3 in MTP+/− mice significantly reduced the acetylation of MTP compared with β-galactosidase controls, increased mitochondrial FAO, and reduced hepatic steatosis, CD68, and serum ALT levels. Taken together, our data indicate that deacetylation of MTP by SIRT3 improves mitochondrial function and rescues NAFLD in MTP+/− mice. PMID:29581157

Aging-associated oxidative stress inhibits liver progenitor cell activation in mice

PubMed Central

Wang, Bei; Zhou, Hong; Dang, Shipeng; Shi, Yufang; Hao, Li; Luo, Qingquan; Jin, Min; Zhou, Qianjun; Zhang, Yanyun

2017-01-01

Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging. PMID:28458256

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

PubMed Central

Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

2016-01-01

AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

Projections in donor organs available for liver transplantation in the United States: 2014-2025.

PubMed

Parikh, Neehar D; Hutton, David; Marrero, Wesley; Sanghani, Kunal; Xu, Yongcai; Lavieri, Mariel

2015-06-01

With the aging US population, demographic shifts, and obesity epidemic, there is potential for further exacerbation of the current liver donor shortage. We aimed to project the availability of liver grafts in the United States. We performed a secondary analysis of the Organ Procurement and Transplantation Network database of all adult donors from 2000 to 2012 and calculated the total number of donors available and transplanted donor livers stratified by age, race, and body mass index (BMI) group per year. We used National Health and Nutrition Examination Survey and Centers for Disease Control and Prevention historical data to stratify the general population by age, sex, race, and BMI. We then used US population age and race projections provided by the US Census Bureau and the Weldon Cooper Center for Public Service and made national and regional projections of available donors and donor liver utilization from 2014 to 2025. We performed sensitivity analyses and varied the rate of the rise in obesity, proportion of Hispanics, population growth, liver utilization rate, and donation after cardiac death (DCD) utilization. The projected adult population growth in the United States from 2014 to 2025 will be 7.1%. However, we project that there will be a 6.1% increase in the number of used liver grafts. There is marked regional heterogeneity in liver donor growth. Projections were significantly affected by changes in BMI, DCD utilization, and liver utilization rates but not by changes in the Hispanic proportion of the US population or changes in the overall population growth. Overall population growth will outpace the growth of available donor organs and thus potentially exacerbate the existing liver graft shortage. The projected growth in organs is highly heterogeneous across different United Network for Organ Sharing regions. Focused strategies to increase the liver donor pool are warranted. © 2015 American Association for the Study of Liver Diseases.

Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet.

PubMed

Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L

2014-03-01

Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development and improve liver function. Our data suggest that choline can promote liver health by maintaining cholesterol homeostasis.

Practical difficulties in the diagnosis of transient non-ketotic hyperglycinaemia.

PubMed

Lang, T F; Parr, J R; Matthews, E E; Gray, R G F; Bonham, J R; Kay, J D S

2008-02-01

Making a diagnosis of transient non-ketotic hyperglycinaemia (tNKH) can be difficult. We report an infant who presented in the neonatal period with symptoms of NKH. Metabolic studies performed on day 2 of life showed raised cerebrospinal fluid (CSF) and plasma glycine, and a CSF:plasma glycine ratio consistent with NKH; however, a liver biopsy performed on day 5 revealed normal liver glycine cleavage system activity. Subsequently, the child's clinical condition improved in the absence of any therapeutic medication. Clinical assessment and developmental follow-up at 5 months, 1 year, and 2 years were age-appropriate. Guidance for the investigation and management of future suspected cases of tNKH is discussed.

Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood.

PubMed

Maggiore, G; Riva, S; Sciveres, M

2009-03-01

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.

Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques.

PubMed

Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh

2016-12-01

Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications.

Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques

PubMed Central

Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh

2016-01-01

Background: Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. Methods: In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. Results: With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Conclusion: Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications. PMID:28077898

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

PubMed

Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro

2012-05-01

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of donor age in liver transplantation from donation after circulatory death donors: A decade of experience at Cleveland Clinic.

PubMed

Firl, Daniel J; Hashimoto, Koji; O'Rourke, Colin; Diago-Uso, Teresa; Fujiki, Masato; Aucejo, Federico N; Quintini, Cristiano; Kelly, Dympna M; Miller, Charles M; Fung, John J; Eghtesad, Bijan

2015-12-01

The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation. © 2015 American Association for the Study of Liver Diseases.

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.

PubMed

Whitton, Holly; Singh, Larry N; Patrick, Marissa A; Price, Andrew J; Osorio, Fernando G; López-Otín, Carlos; Bochkis, Irina M

2018-06-01

Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24-deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de-repression of PPAR- and LXR-dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de-repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Alcohol and liver disease in Europe--Simple measures have the potential to prevent tens of thousands of premature deaths.

PubMed

Sheron, Nick

2016-04-01

In the World Health Organisation European Region, more than 2,370,000 years of life are lost from liver disease before the age of 50; more than lung cancer, trachea, bronchus, oesophageal, stomach, colon, rectum and pancreatic cancer combined. Between 60-80% of these deaths are alcohol related, a disease for which no pharmaceutical therapy has yet been shown to improve long-term survival. The toxicity of alcohol is dose related at an individual level, and is dose related at a population level; overall liver mortality is largely determined by population alcohol consumption. Trends in alcohol consumption correlate closely with trends in overall liver mortality, with 3-5-fold decreases or increases in liver mortality in different European countries over the last few decades. The evidence base for alcohol control measures aimed at reducing population alcohol consumption has been subjected to rigorous evaluation; most recently by the Organisation for Economic Co-Operation and Development (OECD). Effective alcohol policy measures reduce alcohol mortality, including mortality from liver disease. The most effective and cost effective measures have been summarised by the OECD and the World Health Organisation: regular incremental above inflation tax increases, a minimum price for alcohol, effective protection of children from alcohol marketing and low level interventions from clinicians. Simple, cheap and effective changes to alcohol policy by European Institutions and member states have the potential to dramatically reduce liver mortality in Europe. Copyright © 2016. Published by Elsevier B.V.

Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

PubMed

Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

2013-01-01

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.

Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in overweight and obese adults: a pilot study.

PubMed

Parker, Helen M; O'Connor, Helen T; Keating, Shelley E; Cohn, Jeffrey S; Garg, Manohar L; Caterson, Ian D; George, Jacob; Johnson, Nathan A

2015-09-14

Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status - the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.

Defining Long-term Outcomes with Living Donor Liver Transplantation in North America

PubMed Central

Olthoff, Kim M.; Smith, Abigail R.; Abecassis, Michael; Baker, Talia; Emond, Jean C.; Berg, Carl L.; Beil, Charlotte A.; Burton, James R.; Fisher, Robert A.; Freise, Christopher E.; Gillespie, Brenda W.; Grant, David R.; Humar, Abhi; Kam, Igal; Merion, Robert M.; Pomfret, Elizabeth A.; Samstein, Benjamin; Shaked, Abraham

2015-01-01

Objective To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers to outcomes of deceased donor liver transplant (DDLT) and identify key variables impacting patient and graft survival. Summary Background Data The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) is a prospective multicenter NIH study comparing outcomes of LDLT and DDLT and associated risks. Methods Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in A2ALL transplanted between 1/1/1998 and 1/31/2014 at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. Results Survival probability at 10 years was 70% for LDLT and 64% for DDLT. Unadjusted survival was higher with LDLT (HR=0.76, p=0.02) but attenuated after adjustment (HR=0.98, p=0.90) as LDLT recipients had lower mean MELD (15.5 vs 20.4) and fewer were transplanted from ICU, inpatient, on dialysis, ventilated, or with ascites. Post-transplant ICU days were less for LDLT. For all recipients female gender and primary sclerosing cholangitis were associated with improved survival, while dialysis and older recipient/donor age were associated with worse survival. Higher MELD score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. Conclusions LDLT provides significant long-term transplant benefit resulting in transplantation at a lower MELD score, decreased death on waitlist, and excellent post-transplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision-making regarding timing of transplant and donor options. Clinical Trials ID NCT00096733. PMID:26258315

Five-Year Follow-Up on Transplanted Organs From Donors After Brain Death After Acute Stroke.

PubMed

Spatenkova, Vera; Pokorna, Eva; Suchomel, Petr

2017-08-01

Efficient intensive care donor management can help alleviate the shortage of organs for transplant. The aim of this study was to investigate the efficiency of management of donors after brain death from our neurointensive care unit. We conducted a prospective observational 5-year follow-up on 29 transplanted organs from 14 brain-dead donors after acute stroke (7 subarachnoid and 4 intracerebral hemorrhages, 3 ischemic strokes). Mean age of donors was 56.2 ± 8.70 years, and mean number of days of artificial ventilation was 5.0 ± 3.84. We transplanted 27 kidneys and 2 livers to 29 patients with mean age of 55.3 ± 9.76 years. No hearts or lungs were transplanted from these donors. Of the 27 patients who underwent kidney transplant, 21 patients (78%) lived 5 years; of those, 17 patients (63%) had functional grafts. One patient (4%) had a primary afunctional graft, and 3 patients (11%) had graft rejection (at 3, 15, and 41 mo). Six patients (22%) died after kidney transplant, with 1 patient in this group having a functional graft, 1 patient having a primary afunctional graft, and 4 patients (15%) having graft rejection (at 1, 12, 44, and 56 mo). The 2 patients with liver transplants lived 5 years with functional grafts. The 5-year follow-up showed that organs from 14 brain-dead donors improved and saved 19 lives, with 17 patients receiving kidney transplants and 2 patients receiving liver transplants. Another 7 patients had only partially improved quality of life.

Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

PubMed

Scott, Jake; Goetz, Matthew Bidwell

2016-08-01

Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities. Published by Elsevier Inc.

Liver Transplantation With Old Grafts: A Ten-Year Experience.

PubMed

Roullet, S; Defaye, M; Quinart, A; Adam, J-P; Chiche, L; Laurent, C; Neau-Cransac, M

2017-11-01

The persistent scarcity of donors has prompted liver transplantation teams to find solutions for increasing graft availability. We report our experience of liver transplantations performed with grafts from older donors, specifically over 70 and 80 years old. We analyzed our prospectively maintained single-center database from January 1, 2005, to December 31, 2014, with 380 liver transplantations performed in 354 patients. Six groups were composed according to donor age: <40 (n = 84), 40 to 49 (n = 67), from 50 to 59 (n = 62), from 60 to 69 (n = 76), from 70 to 79 (n = 64), and ≥80 years (n = 27). Donors <40 years of age had a lower body mass index, died more often from trauma, and more often had cardiac arrest and high transaminase levels. In contrast, older donors (≥70 years of age) died more often from stroke. Recipients of grafts from donors <50 years of age were more frequently infected by hepatitis C virus; recipients of oldest grafts more often had hepatocellular carcinoma. Cold ischemia time was the shortest in donors >80 years of age. Patient survival was not significantly different between the groups. In multivariate analysis, factors predicting graft loss were transaminase peak, retransplantation and cold ischemia time but not donor age. Older donors >70 and >80 years of age could provide excellent liver grafts. Copyright © 2017 Elsevier Inc. All rights reserved.

Drug metabolism and ageing.

PubMed

Wynne, Hilary

2005-06-01

Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome

PubMed Central

Gunewardena, Sumedha S.; Yoo, Byunggil; Peng, Lai; Lu, Hong; Zhong, Xiaobo; Klaassen, Curtis D.; Cui, Julia Yue

2015-01-01

During development, liver undergoes a rapid transition from a hematopoietic organ to a major organ for drug metabolism and nutrient homeostasis. However, little is known on a transcriptome level of the genes and RNA-splicing variants that are differentially regulated with age, and which up-stream regulators orchestrate age-specific biological functions in liver. We used RNA-Seq to interrogate the developmental dynamics of the liver transcriptome in mice at 12 ages from late embryonic stage (2-days before birth) to maturity (60-days after birth). Among 21,889 unique NCBI RefSeq-annotated genes, 9,641 were significantly expressed in at least one age, 7,289 were differently regulated with age, and 859 had multiple (> = 2) RNA splicing-variants. Factor analysis showed that the dynamics of hepatic genes fall into six distinct groups based on their temporal expression. The average expression of cytokines, ion channels, kinases, phosphatases, transcription regulators and translation regulators decreased with age, whereas the average expression of peptidases, enzymes and transmembrane receptors increased with age. The average expression of growth factors peak between Day-3 and Day-10, and decrease thereafter. We identified critical biological functions, upstream regulators, and putative transcription modules that seem to govern age-specific gene expression. We also observed differential ontogenic expression of known splicing variants of certain genes, and 1,455 novel splicing isoform candidates. In conclusion, the hepatic ontogeny of the transcriptome ontogeny has unveiled critical networks and up-stream regulators that orchestrate age-specific biological functions in liver, and suggest that age contributes to the complexity of the alternative splicing landscape of the hepatic transcriptome. PMID:26496202

Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome.

PubMed

Gunewardena, Sumedha S; Yoo, Byunggil; Peng, Lai; Lu, Hong; Zhong, Xiaobo; Klaassen, Curtis D; Cui, Julia Yue

2015-01-01

During development, liver undergoes a rapid transition from a hematopoietic organ to a major organ for drug metabolism and nutrient homeostasis. However, little is known on a transcriptome level of the genes and RNA-splicing variants that are differentially regulated with age, and which up-stream regulators orchestrate age-specific biological functions in liver. We used RNA-Seq to interrogate the developmental dynamics of the liver transcriptome in mice at 12 ages from late embryonic stage (2-days before birth) to maturity (60-days after birth). Among 21,889 unique NCBI RefSeq-annotated genes, 9,641 were significantly expressed in at least one age, 7,289 were differently regulated with age, and 859 had multiple (> = 2) RNA splicing-variants. Factor analysis showed that the dynamics of hepatic genes fall into six distinct groups based on their temporal expression. The average expression of cytokines, ion channels, kinases, phosphatases, transcription regulators and translation regulators decreased with age, whereas the average expression of peptidases, enzymes and transmembrane receptors increased with age. The average expression of growth factors peak between Day-3 and Day-10, and decrease thereafter. We identified critical biological functions, upstream regulators, and putative transcription modules that seem to govern age-specific gene expression. We also observed differential ontogenic expression of known splicing variants of certain genes, and 1,455 novel splicing isoform candidates. In conclusion, the hepatic ontogeny of the transcriptome ontogeny has unveiled critical networks and up-stream regulators that orchestrate age-specific biological functions in liver, and suggest that age contributes to the complexity of the alternative splicing landscape of the hepatic transcriptome.

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults.

PubMed

Xia, Ming-Feng; Bian, Hua; Zhu, Xiao-Peng; Yan, Hong-Mei; Chang, Xin-Xia; Zhang, Lin-Shan; Lin, Huan-Dong; Hu, Xi-Qi; Gao, Xin

2017-06-28

Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults. The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses. Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the 1 H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid levels to the current existing NAFLD prediction scores significantly improved the prediction of NAFLD. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Transplantation With Livers From Deceased Donors Older Than 75 Years.

PubMed

Thorsen, Trygve; Aandahl, Einar Martin; Bennet, William; Olausson, Michael; Ericzon, Bo-Göran; Nowak, Greg; Duraj, Frans; Isoniemi, Helena; Rasmussen, Allan; Karlsen, Tom H; Foss, Aksel

2015-12-01

The availability of donor organs limits the number of patients in need who are offered liver transplantation. Measures to expand the donor pool are crucial to prevent on-list mortality. The aim of this study was to evaluate the use of livers from deceased donors who were older than 75 years. Fifty-four patients who received a first liver transplant (D75 group) from 2001 to 2011 were included. Donor and recipient data were collected from the Nordic Liver Transplant Registry and medical records. The outcome was compared with a control group of 54 patients who received a liver graft from donors aged 20 to 49 years (D20-49 group). Median donor age was 77 years (range, 75-86 years) in the D75 group and 41 years (range, 20-49 years) in the D20-49 group. Median recipient age was 59 years (range, 31-73 years) in the D75 group and 58 years (range, 31-74 years) in the D20-49 group. The 1-, 3-, and 5-year patient/graft survival values were 87/87%, 81/81%, and 71/67% for the D75 group and 88/87%, 75/73%, and 75/73% for the D20-49 group, respectively. Patient (P = 0.89) and graft (P = 0.79) survival did not differ between groups. The frequency of biliary complications was higher in the D75 group (29.6/13%, P = 0.03). Selected livers from donors over age 75 years should not be excluded based on age, which does not compromise patient or graft survival despite a higher frequency of biliary complications.

Recipient-donor age matching in liver transplantation: a single-center experience.

PubMed

Pagano, D; Grosso, G; Vizzini, G; Spada, M; Cintorino, D; Malaguarnera, M; Donati, M; Mistretta, A; Gridelli, B; Gruttadauria, S

2013-09-01

The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-term results of pediatric liver transplantation in a combined pediatric and adult transplant program.

PubMed

Atkison, Paul R; Ross, B Catherine; Williams, Sandy; Howard, John; Sommerauer, John; Quan, Douglas; Wall, William

2002-06-25

Liver transplantation is now routine therapy for a variety of childhood liver diseases; however, there are no detailed reports of long-term results from a Canadian centre. We reviewed data from the first 16 years of a pediatric liver transplantation program to determine survival, complications and long-term outcomes. The outcomes to December 2000 for all children (age less than 18 years) who received a liver transplant at the London Health Sciences Centre between April 1984 and December 1999 were reviewed. The recipients were grouped according to the period in which they received the transplant (period 1, April 1984 to July 1988; period 2, August 1988 to December 1993; or period 3, January 1994 to December 1999). Data were obtained from medical charts; in-person interviews, questionnaires or telephone contact with patients and their families; contact with referring physicians; and school records. Outcome measures included patient survival, retransplantation, complications and long-term outcomes (specifically steroid withdrawal and growth and development). A total of 116 children (29 in period 1, 46 in period 2 and 41 in period 3) (median age 5.6 years at the time of the procedure) received a total of 140 liver grafts (32 in period 1, 57 in period 2 and 51 in period 3). Of the 116 patients, 23 (20%) were less than 1 year old at the time of transplantation. Biliary atresia was the most common indication for liver transplantation (57 [49%] of the 116 patients). The number of patients surviving to 1 year after transplantation was 20 (69%) of the 29 patients from period 1, 40 (87%) of the 46 patients from period 2 and 38 (93%) of the 41 patients from period 3. The percentage of patients receiving reduced size grafts from adult donors, including live donors, increased from 2/32 (6%) in period 1 to 22/51 (43%) in period 3. Retransplantation was required for 9 (31%) of the 29 patients from period 1, 6 (13%) of the 46 patients from period 2 and 7 (17%) of the 41 patients from period 3. Among these patients, 1-year survival was 33% (3/9) for period 1, 83% (5/6) for period 2 and 100% (7/7) for period 3. Eighteen of the 22 deaths occurred within 4 months after surgery. Only 3 (3%) of the 116 patients experienced post-transplant lymphoproliferative disease. Steroids were discontinued (usually within 2 years after surgery) for the following proportions of surviving transplant recipients: 17 (89%) of the 19 patients from period 1, 29 (78%) of the 37 patients from period 2 and 21 (55%) of the 38 patients from period 3. Most of the surviving patients had normal growth (82/94 or 87%) and development (73/94 or 78%), and these outcomes were consistent across the 3 periods of study. Survival and long-term outcomes continue to improve for most children who receive liver transplants. These improvements may be due to improved surgical technique, perioperative care and, to a lesser extent, immunosuppressive therapy.

High incidence of zinc deficiency among Filipino children with compensated and decompensated liver disease.

PubMed

Umusig-Quitain, Perlina; Gregorio, Germana V

2010-02-01

The role of zinc in the nutrition and growth of children with chronic liver disease is poorly defined. The present study determined the serum zinc levels of children with compensated liver disease (CLD) and decompensated liver disease (DLD) and compared this with healthy children. Zinc levels were also correlated with the severity of liver disease as measured by Child-Pugh scores. The study comprised of 60 children 0-10 years of age with chronic liver disease, defined as CLD (n = 30) if the Child-Pugh score was < 6, and DLD (n = 30) if the Child-Pugh score was > or = 6. Thirty healthy children 0-10 years served as controls. Serum zinc levels were measured by atomic absorption spectrometry. The 90 patients included 30 with CLD (mean age: 4.54 years: 21 boys; mean Child-Pugh score: 5.83), 30 with DLD (mean age: 1.39 years; 17 boys; mean Child-Pugh score: 9.53) and 30 healthy children (mean age: 4.6; 16 boys). Zinc levels of patients with CLD were significantly lower compared with the healthy controls (Mean [standard deviation]: 68.07 [31.55]vs 89.9 [25.9]microg/dL, P = 0.000), but significantly higher compared to the patients with DLD (48.8 [26.8]microg/dL). Correlation studies showed that the higher the Child-Pugh score, the lower the zinc levels (r = -0.460) Children with chronic liver disease, whether in a compensated or decompensated state, had lower serum zinc levels compared with the healthy controls. As the severity of liver disease worsened, the zinc levels decreased. The study suggests that zinc supplementation should constitute part of the micronutrient intake of children with chronic liver disease.

[Prevalence of no alcohol fatty liver disease (NAFLD) in a population of obese children in Valencia, Venezuela].

PubMed

Pontiles de Sánchez, Milagros; Morón de Salim, Alba; Rodríguez de Perdomo, Henny; Perdomo Oramas, Germán

2014-06-01

No Alcoholic Fatty Liver Disease (NAFLD) is characterized by an abnormal accumulation of fat in hepatocytes, without alcohol, where overweight and obesity are determinants. Ecosonografia evaluated the prevalence of fatty liver in obese pediatric patients and its relation to nutritional assessment. The sample consisted of 85 children (51 females, 34 males), age 3-17. The abdominal ecosonography, BMI, waist circumference were performed; Godard Test for physical activity, history of diabetes, dyslipidemia, obesity and cardiovascular disease were questioned. Lipid profile, glucose and insulin resistance were determined. Data analyzed from descriptive and comparative tables. We obtained: mean age 9.8 ± 2.7 females and males 9.6 ± 2.7 years. The ecosonography indicated 50% and 50% fatty liver-pancreas fatty liver in children aged 3-6 years; 7-11 years 39.7% fatty liver-pancreas; 12-17yrs 31.6% fatty liver-pancreas (p > 0.05); BMI > 26 kg/m2 42.9% fatty liver-pancreas; 21 to 25 kg/m2 44.7% fatty liver; 15 to 20 kg/m2 60%fatty liver-pancreas (p> 0.05). 97.6% with high CC; 68.2% with inadequate physical activity; high frequency of history of chronic non-communicable diseases. We concluded that this population had predominantly fatty liver fatty replacement of the pancreas (HG-RGP) in the groups with higher BMI, CC and high male unrelated insulin resistance, altered lipid profile and diagnosis HG. We inferred that the anthropometric assessment of waist circumference and abdominal ecosonography indicate the presence of visceral obesity, a condition that predisposes to hepatic steatosis, pancreas and/or liver-pancreas.

Levels and interactions of plasma xanthine oxidase, catalase and liver function parameters in Nigerian children with Plasmodium falciparum infection.

PubMed

Iwalokun, B A; Bamiro, S B; Ogunledun, A

2006-12-01

Elevated plasma levels of xanthine oxidase and liver function parameters have been associated with inflammatory events in several human diseases. While xanthine oxidase provides in vitro protection against malaria, its pathophysiological functions in vivo and interactions with liver function parameters remain unclear. This study examined the interactions and plasma levels of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32), and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age-matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100-550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850-87100 parasites/microL) was observed in the malarial children. Further comparison with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05) lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4 U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the asymptomatic and symptomatic malaria children studied. 75% of control, 45% of asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05) correlations between liver function parameters and xanthine oxidase (r=0.57-0.64) only in the severe malaria group. We conclude that elevated levels of XO and liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in Nigerian children, with both parameters interacting differently to modulate the catalase response in asymptomatic and symptomatic falciparum malaria.

Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2018-04-01

Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

Leptospira Exposure and Patients with Liver Diseases: A Case-Control Seroprevalence Study

PubMed Central

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Ramos-Nevárez, Agar; Margarita Cerrillo-Soto, Sandra; Alberto Guido-Arreola, Carlos

2016-01-01

The seroepidemiology of Leptospira infection in patients suffering from liver disease has been poorly studied. Information about risk factors associated with infection in liver disease patients may help in the optimal planning of preventive measures. We sought to determine the association of Leptospira IgG seroprevalence and patients with liver diseases, and to determine the characteristics of the patients with Leptospira exposure. We performed a case-control study of 75 patients suffering from liver diseases and 150 age- and gender-matched control subjects. Diagnoses of liver disease included liver cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver abscess. Sera of participants were analyzed for the presence of anti- Leptospira IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150 control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age- and gender-matched case control study about Leptospira seroprevalence in patients with liver diseases. Results indicate that Leptospira infection is associated with chronic and acute liver diseases. Results warrants for additional studies on the role of Leptospira exposure in chronic liver disease. PMID:27493589

Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers.

PubMed

Chun, Sung Kook; Lee, Sooyeon; Flores-Toro, Joseph; U, Rebecca Y; Yang, Ming-Jim; Go, Kristina L; Biel, Thomas G; Miney, Catherine E; Pierre Louis, Schiley; Law, Brian K; Law, Mary E; Thomas, Elizabeth M; Behrns, Kevin E; Leeuwenburgh, Christiaan; Kim, Jae-Sung

2018-05-17

Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo. Primary hepatocytes isolated from each age group were also exposed to simulated in vitro I/R. Biochemical, genetic, and imaging analyses were performed to assess cell death, autophagy flux, mitophagy, and mitochondrial function. Compared to young mice, old livers showed accelerated liver injury following mild I/R. Reperfusion of old hepatocytes also showed necrosis, accompanied with defective autophagy, onset of the mitochondrial permeability transition, and mitochondrial dysfunction. Biochemical analysis indicated a near-complete loss of both SIRT1 and MFN2 after I/R in old hepatocytes, which did not occur in young cells. Overexpression of either SIRT1 or MFN2 alone in old hepatocytes failed to mitigate I/R injury, while co-overexpression of both proteins promoted autophagy and prevented mitochondrial dysfunction and cell death after reperfusion. Genetic approaches with deletion and point mutants revealed that SIRT1 deacetylated K655 and K662 residues in the C-terminus of MFN2, leading to autophagy activation. The SIRT1-MFN2 axis is pivotal during I/R recovery and may be a novel therapeutic target to reduce I/R injury in aged livers. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Heavy metal and mineral concentrations and their relationship to histopathological findings in the bowhead whale (Balaena mysticetus).

PubMed

Rosa, Cheryl; Blake, John E; Bratton, Gerald R; Dehn, Larissa-A; Gray, Matthew J; O'Hara, Todd M

2008-07-25

The bowhead whale (Balaena mysticetus) is a species endangered over much of its range that is of great cultural significance and subsistence value to the Inuit of Northern Alaska. This species occupies subarctic and arctic regions presently undergoing significant ecological change and hydrocarbon development. Thus, understanding the health status of the Bering-Chukchi-Beaufort Sea (BCBS) stock of bowhead whales is of importance. In this study, we evaluated the concentrations of six essential and non-essential elements (Zn, tHg, Ag, Se, Cu and Cd) in liver and kidney of bowhead whales (n=64). These tissues were collected from the Inuit subsistence hunt in Barrow, Wainwright and Kaktovik, Alaska between 1983 and 2001. Reference ranges of these elements (including previously reported data from 1983-1997) were developed for this species as part of a health assessment effort, and interpreted using improved aging techniques (aspartic acid racemization and baleen isotopic (13)C methods) to evaluate trends over time with increased statistical power. Interactions between element concentrations and age, sex and harvest season were assessed. Age was found to be of highest significance. Sex and harvest season did not effect the concentrations of these elements, with the exception of renal Se levels, which were significantly higher in fall seasons. In addition, histological evaluation of tissues from whales collected between 1998-2001 was performed. Associations between concentrations of Cd in kidney and liver and scored histopathological changes were evaluated. Liver Cd concentration was strongly associated with the degree of lung fibromuscular hyperplasia (P=0.001) and moderately associated with the degree of renal fibrosis (P=0.03). Renal Cd concentration influenced the degree of lung fibromuscular hyperplasia and renal fibrosis (P=0.01). A significant age effect was found for both pulmonary fibromuscular hyperplasia and renal fibrosis, indicating age may be a causative factor. Improvements in aging techniques and the addition of histological indices help clarify the relationships between elements and the influence of life history parameters on concentrations of these elements and potential impacts on health. These data provide essential baseline input useful for monitoring the effects of arctic ecosystem change as it relates to global climate change and industrial development, as well as help inform epidemiological studies examining the public health implications of heavy metals in subsistence foods.

Recurrent Primary Biliary Cirrhosis: Peritransplant Factors and Ursodeoxycholic Acid Treatment Post-Liver Transplant

PubMed Central

Guy, Jennifer E.; Qian, Peiqing; Lowell, Jeffrey A.; Peters, Marion G.

2014-01-01

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known. PMID:16184542

Neonatal hemochromatosis. Case series from Bahrain.

PubMed

Isa, Hasan M; Mohamed, Afaf M

2013-12-01

To review clinical presentations, diagnosis, response to treatment, and outcome of infants with neonatal hemochromatosis (NH). This is a retrospective review of all cases admitted to the Pediatric Department at Salmaniya Medical Center, Manama, Bahrain between March 2008 and May 2011. The diagnosis was based on serum iron and ferritin, alpha-fetoprotein levels (AFP), liver and buccal biopsies, and abdominal MRI scan. Ten patients (8 males and 2 females) were diagnosed with NH. Two patients were intrauterine growth restriction (IUGR) and 6 were preterm. The median birth weight was 1.700 grams. The median age at presentation was 16 days, and at diagnosis was 23 days. Two patients had positive consanguinity. Clinical presentations of the infants were hepatosplenomegaly (n=5), ascites (n=3), and hypoglycemia (n=6). All patients had raised ferritin levels, prolonged prothrombin time, and 9 patients had high serum iron and serum AFP. Abdominal MRI showed iron overload in the liver (n=8). Liver biopsies showed evidence of hemochromatosis (n=3). Buccal biopsies stained positive for iron (n=1). Eight patients received antioxidant therapy and survived. Two patients passed away. Neonatal hemochromatosis is a rare liver disease of newborns with a spectrum of clinical severity. Elevated serum ferritin and AFP support the diagnosis after excluding other causes of neonatal liver failure. The use of antioxidant therapy helps to improve the outcome.

[Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty years].

PubMed

Chen, Jian-guo; Zhu, Jian; Zhang, Yong-hui; Chen, Yong-sheng; Ding, Lu-lu; Lu, Jian-hua; Zhu, Yuan-rong

2012-07-01

To describe and analyze the charecteristics and trends of liver cancer mortality during the past fifty years in Qidong, China. Retrospective mortality survey was conducted to get the data on liver cancer death in the period of 1958-1971, and the data from 1972 to 2007 were obtained from the records of cancer registration in Qidong. The crude mortality rate (CR) of liver cancer, and age-standardized rate by Chinese population (CASR) and by world population (WASR) were calculated and analyzed. The total percent changes (PC) and annual percent changes (APC) were used for evaluating the increasing trends of the mortality. The sex-specific rate, age-specific rate, truncated rate of the age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period-rate, and the rate for age-birth cohort were compared. The natural death rate in Qidong residents for the past five-decade period experienced a wave interval of 8.62‰ in 1958 down to 5.37‰ in 1979, and up to 7.75‰ in 2007. The mortality rate for all-site cancers was increased from 56.69 per 100, 000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per 100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per 100, 000 in 2007. According to the registration data of 1972 - 2007, the death from liver cancer was accounted for 34.88% of all deaths due to cancers, with a CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100, 000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100, 000, and the cumulative rate for the age group 0-74 and the cumulative risk were 5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of 1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing variation tendency. The APCs for CASR and WASR, however, were decreasing, with a percentage of -1.11%, and -0.84%, respectively. The age-specific mortality rates by period showed a decreasing trend for those under age of 44. Moreover, age-birth cohort analysis showed a more rapid lowering mortality in the age groups 35-, 30-, 25-, and 15-, that is, those born after 1950's. Liver cancer remains the leading death cause due to cancers in Qidong, with a continuing higher crude mortality rate. Yet the age-standardized mortality rate has presented a declining posture. The liver cancer mortality in young people in Qidong demonstrates a continuously falling trend. The campaign for the control of liver cancer in Qidong has achieved initial success.

Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats.

PubMed

Chang, Eugene; Kim, Lisa; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Park, Cheol-Young

2015-07-07

To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe (10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides (TG), free fatty acids (FFA), and total cholesterol (TC) in blood and TG, FFA, and TG in liver tissue were measured. mRNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe (10 μmol/L) together with or without palmitic acid (PA, 0.5 mmol/L, 24 h). Transmission electron microscopy (TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression. In the OLETF rats that received ezetimibe (10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight (P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls (P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe (P < 0.05). In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe (P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced mRNA and protein expression involved in autophagy (P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.

Acute-On-Chronic Liver Failure: Causes, Clinical Characteristics and Predictors of Mortality.

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan

2017-01-01

To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Cross-sectional study. Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included. Patients with ACLF, as defined by the Asian Pacific Association for the Study of Liver (APASL, 2014) were identified. Predictors of mortality were identified using chi-square or Fisher's exact test. Included in the study were 72 patients with mean age of 36.71 years, 46 (63.9%) being males. Among them, 61 developed ACLF. Commonest causes of chronic liver disease (CLD) were chronic viral hepatitis (37, 51.4%) and autoimmune hepatitis (14, 19.4%). Commonest causes of acute liver injury (ALI) were acute viral hepatitis (24, 33.3%) and drug induced liver injury (DILI) (17, 23.6%). Among those with ACLF, 24 (39.3%) patients died with median survival of 17.1 ±13.5 days. Mortality was significantly associated with Child Turcotte Pugh (CTP) score ≥13 (p=0.010), model for end-stage liver disease (MELD) score ≥30 (p=0.001), age >40 years (p=0.036), organ failures (OF) ≥3 (p <0.0001), portosystemic encephalopathy (PSE) (p <0.0001), renal failure (p <0.0001) and urosepsis (p <0.0001). Acute viral hepatitis and DILI are commonest causes of ACLF. Mortality is high in ACLF patients having OF ≥3, CTP ≥13, MELD ≥30, age >40 years, PSE, renal failure and urosepsis.

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients.

PubMed

Lee, Jinho; Shin, Joon-Shik; Kim, Me-Riong; Byun, Jang-Hoon; Lee, Seung-Yeol; Shin, Ye-Sle; Kim, Hyejin; Byung Park, Ki; Shin, Byung-Cheul; Lee, Myeong Soo; Ha, In-Hyuk

2015-07-01

The objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. Of 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. A total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. The prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.

PubMed

Calvo, Pier Luigi; Serpe, Loredana; Brunati, Andrea; Nonnato, Antonello; Bongioanni, Daniela; Olio, Dominic Dell'; Pinon, Michele; Ferretti, Carlo; Tandoi, Francesco; Carbonaro, Giulia; Salizzoni, Mauro; Amoroso, Antonio; Romagnoli, Renato; Canaparo, Roberto

2017-06-01

The aim of the present study was to investigate the influence of the cytochrome P450 (CYP) 3A4/5 genotype in paediatric liver transplant recipients and donors, and the contribution of age and gender to tacrolimus disposition on the first day after transplantation. The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C 0 ) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years. Donor CYP3A5 genotype appears to be significantly associated with tacrolimus disposition on the first day after liver transplantation (P < 0.0002). Other physiological factors, such as recipient age and donor gender may also play a role and lead to significant differences in tacrolimus C 0 and tacrolimus concentration/weight-adjusted dose ratio on day 1. However, according to the general linear model, only recipient age appears to be independently associated with tacrolimus disposition on the first day after liver transplantation (P < 0.03). Indeed, there was a faster tacrolimus metabolism in children under 6 years of age (P < 0.02). Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant. This suggests that increasing the starting tacrolimus doses in paediatric patients under 6 years of age who receive a graft from a male extensive metabolizer may enhance the possibility of their tacrolimus levels reaching the therapeutic range sooner. © 2017 The British Pharmacological Society.

Randomized clinical trial: benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease.

PubMed

Rezende, Rosamar E F; Duarte, Sebastião M B; Stefano, Jose T; Roschel, Hamilton; Gualano, Bruno; de Sá Pinto, Ana L; Vezozzo, Denise C P; Carrilho, Flair J; Oliveira, Claudia P

2016-08-01

The aim of the study was to evaluate the effectiveness of aerobic physical activity in reducing the frequency of hepatic steatosis and metabolic and cardiovascular risk in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). Forty sedentary postmenopausal women (mean age 55.3 ± 8.0 y) with biopsy-proven NAFLD were randomly divided into two groups: an exercising group (19 participants) and a control group (nonexercising, 21 participants). The exercise group underwent a supervised aerobic physical activity program of 120 min/wk for 24 weeks. The anthropometric parameters; body composition; hepatic, lipid, and glycemic profiles; homeostasis model assessment of insulin resistance index; cytokines; transient elastography (FibroScan; liver stiffness/controlled attenuation parameter); and cardiopulmonary exercise test were evaluated at baseline and after 24 weeks of protocol. At baseline there were no significant differences in anthropometric, metabolic, and inflammatory parameters-stiffness and liver fat content by FibroScan between the groups. After 24 weeks, we observed a decrease of waist circumference, an increase of high-density lipoprotein cholesterol levels (P < 0.05), and improved cardiopulmonary functional capacity in the exercise group. In addition, the controlled attenuation parameter analysis showed no significant decrease of hepatic steatosis in the exercise group. With regard to the systemic inflammation, there were, however, no significant differences in the cytokines between the groups. An aerobic physical activity program of 24 weeks in NAFLD postmenopausal women showed improvement in some variables such as waist circumference, high-density lipoprotein cholesterol, and cardiopulmonary performance that may be beneficial in improving cardiovascular risk factors in this population.

Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.

PubMed

Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo

2017-01-28

The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 5 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.

Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

PubMed Central

Huizer-Pajkos, Aniko; Cogger, Victoria C.; McLachlan, Andrew J.; Le Couteur, David G.; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

2011-01-01

We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p < .05). In old age, there was significant reduction of the intercompartmental rate constant k1 (0.34 ± 0.10s-1, old; 0.61 ± 0.38s-1, young; p < .05) and the permeability-surface area product for the transfer of acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p < .005). There was no difference in k3, the measure of sequestration of acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. PMID:21300741

Tolerance of aged Fischer 344 rats against chlordecone-amplified carbon tetrachloride toxicity.

PubMed

Murali, B; Korrapati, M C; Warbritton, Alan; Latendresse, John R; Mehendale, Harihara M

2004-06-01

We have investigated the effects of chlordecone 1(CD)+CCl4 combination in adult (3 months), middle aged (14 months), and old aged (24 months) male Fischer 344 (F344) rats. After a non-toxic dietary regimen of CD (10 ppm) or normal powdered diet for 15 days, rats received a single non-toxic dose of CCl4 (100 microl/kg, i.p., 1:4 in corn oil) or corn oil (500 microl/kg, i.p.) alone on day 16. Liver injury was assessed by plasma ALT, AST, and histopathology during a time course of 0-96 h. Liver tissue repair was measured by [3H-CH3]-thymidine (3H-T) incorporation into hepatic nuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Hepatomicrosomal CYP2E1 protein, enzyme activity, and covalent binding of 14CCl4-derived radiolabel were measured in normal and CD fed rats. Exposure to CCl4 alone caused modest liver injury only in 14- and 24-month-old rats but neither progression of injury nor mortality. The CD+CCl4 combination led to 100% mortality in 3-month-old rats by 72 h, whereas none of the 14- and 24-month-old rats died. Both 3- and 14-month-old rats exposed to CD+Cl4 had identical liver injury up to 36 h indicating that bioactivation-mediated CCl4 injury was the same in the two age groups. Thereafter, liver injury escalated only in 3-month-old while it declined in 14-month-old rats. In 24-month-old rats initial liver injury at 6 h was similar to the 3- and 14-month-old rats and thereafter did not develop to the level of the other two age groups, recovering from injury by 96 h as in the 14-month-old rats. Neither hepatomicrosomal CYP2E1 protein nor the associated p-nitrophenol hydroxylase activity or covalent binding of 14CCl4-derived radiolabel to liver tissue differed between the age groups or diet regimens 2 h after the administration of 14CCl4. Compensatory liver tissue repair (3H-T, PCNA) was prompt and robust soon after CCl4 liver injury in the 14- and 24-month-old rats. In stark contrast, in the 3-month-old rats it failed allowing unabated progression of liver injury. These findings suggest that stimulation of early onset and robust liver tissue repair rescue the 14- and 24-month-old F344 rats from the lethal effect of the CD+CCl4 combination.

The effect of Saccharomyces boulardii in patients eligible for liver transplantation.

PubMed

Liboredo, Juliana Costa; Ferrari, Maria de Lourdes Abreu; Vilela, Eduardo Garcia; Lima, Agnaldo Soares; Correia, Maria Isabel Toulson Davisson

2014-09-12

The aim of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability, laboratory parameters and MELD and Child-Pugh severity scores in cirrhotic patients eligible for liver transplantation. Eighteen patients followed in a Transplant Outpatient Clinic were evaluated immediately before the beginning of treatment, after a 30-day period of treatment period with probiotics and at the end of the second study month (after a thirty-day period without probiotics). Fifteen healthy controls also underwent the intestinal permeability test (lactulose/mannitol). Before the probiotic, the median lactulose/ mannitol ratio was greater in the cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls (0.0030, range 0.0020-0.0013) (p < 0.05). Eight of fifteen patients, half of whom had ascites, showed increased intestinal permeability above the higher value observed in the controls. No significant association was found between the severity scores for liver disease, age, presence of ascites and intestinal permeability immediately before the beginning of study. After treatment with S. boulardii, there was no improvement in intestinal permeability or significant differences in the laboratory parameters for the three evaluations. Patients eligible for liver transplants presented with increased intestinal permeability compared to healthy controls. A thirty-day treatment with S. boulardii did not improve this intestinal permeability or the severity scores, nor did it impact the laboratory parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: β-cyclodextrin complex

PubMed Central

Abosehmah-Albidy, A. Z. M.; York, P.; Wong, V.; Losowsky, M. S.; Chrystyn, H.

1997-01-01

Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease. Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study. Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD. Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease. PMID:9241094

Decision Making in Liver Transplant Selection Committees

PubMed Central

Volk, Michael L; Biggins, Scott W; Huang, Mary Ann; Argo, Curtis K; Fontana, Robert J; Anspach, Renee R

2011-01-01

Background In order to receive a liver transplant, patients must first be placed on the waiting list – a decision made in most transplant centers by a multidisciplinary committee. The function of these committees has never been studied. Objectives To describe decision making in liver transplant committees and identify opportunities for process improvement. Design Observational multi-center Setting We observed 63 meetings and interviewed 50 committee members at 4 liver transplant centers. Study Subjects Transplant committee members. Measurements Recorded transcripts and field notes were analyzed using standard qualitative sociological methods. Results While the structure of meetings varied by center, the process was uniform and involved reviewing possible reasons for patient exclusion using primarily inductive reasoning. Stated justifications for excluding patients were a) too well, b) non-hepatic comorbidities or advanced age, c) too sick in the setting of advanced liver disease, d) substance abuse, or e) other psychosocial barriers. Dominant themes identified included members’ angst over deciding who lives and dies, a high correlation between psychosocial barriers to transplant and patients’ socioeconomic status, and the influence of external forces on decision making. Consistently identified barriers to effective group decision making were: 1) unwritten center policies, and 2) confusion regarding advocacy versus stewardship roles. Limitations The use of qualitative methods provides broad understanding but limits specific inferences. These four centers may not be reflective of every transplant center nationwide. Conclusion The difficult decisions made by these committees are reasonably consistent and always well-intentioned, but might be improved by more explicit written policies and clarifying roles. This process may help inform resource allocation in other areas of medicine. Primary funding source The Greenwall Foundation. PMID:22007044

Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study.

PubMed

Axley, Page; Kodali, Sudha; Kuo, Yong-Fang; Ravi, Sujan; Seay, Toni; Parikh, Nina M; Singal, Ashwani K

2018-05-01

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%-10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD. Thirty well-defined NAFLD patients (mean age 52 years, 67% females, mean BMI 38) were randomized 1:1 to control group: counselling on healthy diet and exercise, or intervention group: text messages in addition to healthy life style counselling. NAFLD text messaging program sent weekly messages for 22 weeks on healthy life style education. Primary outcome was change in weight. Secondary outcomes were changes in liver enzymes and lipid profile. Intervention group lost an average of 6.9 lbs. (P = .03) compared to gain of 1.8 lbs. in the control group (P = .45). Intervention group also showed a decrease in ALT level (-12.5 IU/L, P = .035) and improvement in serum triglycerides (-28 mg/dL, P = .048). There were no changes in the control group on serum ALT level (-6.1 IU/L, P = .46) and on serum triglycerides (-20.3 mg/dL P = .27). Using one-way analysis of variance, change in outcomes in intervention group compared to control group was significant for weight (P = .02) and BMI (P = .02). Text messaging on healthy life style is associated with reduction in weight in NAFLD patients. Larger studies are suggested to examine benefits on liver histology, and assess long-term impact of this approach in patients with NAFLD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter

PubMed Central

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-01-01

OBJECTIVES: Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. METHODS: In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical–chemical assays. RESULTS: The median age was 56 years (25–78 years); 51.7% were women and median body mass index was 31.9 kg/m2 (22.4–44.8 kg/m2). After 14 days, a significant CAP reduction (14.0% P<0.001) was observed from 295 dB/m (216–400 dB/m) to 266 dB/m (100–353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). CONCLUSIONS: This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover. PMID:27311064

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter.

PubMed

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-06-16

Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical-chemical assays. The median age was 56 years (25-78 years); 51.7% were women and median body mass index was 31.9 kg/m(2) (22.4-44.8 kg/m(2)). After 14 days, a significant CAP reduction (14.0%; P<0.001) was observed from 295 dB/m (216-400 dB/m) to 266 dB/m (100-353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover.

Effect of compound glycyrrhizin injection on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment.

PubMed

Cao, Zong-xin; Zhao, Zhong-fang; Zhao, Xiu-fen

2006-12-01

To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 + /CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolysaccharide-induced sickness behavior.

PubMed

Townsend, Brigitte E; Chen, Yung-Ju; Jeffery, Elizabeth H; Johnson, Rodney W

2014-11-01

Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. Sulforaphane increases antioxidant enzymes including NAD(P)H quinone oxidoreductase and heme oxygenase I and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide (LPS)-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days before an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 hours after LPS, and mRNA was quantified in liver and brain at 24 hours. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin-1β (IL-1β) expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. In addition, IL-1β was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 β, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolysaccharide-induced sickness behavior

PubMed Central

Townsend, Brigitte E.; Chen, Yung-Ju; Jeffery, Elizabeth H.; Johnson, Rodney W.

2015-01-01

Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. SFN increases antioxidant enzymes including NAD(P)H quinone oxidoreductase (NQO1) and heme oxygenase I (HMOX1) and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days prior to an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 h following LPS, and mRNA quantified in liver and brain at 24 h. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin (IL)-1β expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. Additionally, IL-1β was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 β, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS. PMID:25439028

Threonine supplementation reduces dietary protein and improves lipid metabolism in Pekin ducks.

PubMed

Jiang, Y; Tang, J; Xie, M; Wen, Z G; Qiao, S Y; Hou, S S

2017-12-01

1. This study was conducted to investigate the efficiency of threonine (Thr) supplementation on reducing dietary crude protein (CP) content and the effects of Thr on lipid metabolism in Pekin ducks. The effects of dietary CP concentration (160, 190 and 220 g/kg) and Thr supplemental concentration (0, 0.7, 1.4, 2.1 and 2.8 g/kg) on growth performance, carcass, liver lipid and plasma profiles were determined in Pekin ducks from 1-21 d of age. 2. A total of 720-d-old male Pekin ducks were randomly allotted to 1 of 15 dietary treatments with 6 replicate cages of 8 birds per cage for each treatment according to average body weight. 3. Dietary Thr supplementation improved growth performance and breast muscle percentage at all CP diets, and ducks fed Thr-supplemented diets had higher plasma concentrations of some plasma amino acids. Thr supplementation reduced the concentrations of total lipid, triglyceride, cholesterol in liver, and plasma low density lipoprotein cholesterin concentration at 160 and 190 g/kg CP, whereas it increased triglyceride concentration at 160 g/kg CP. 4. Thr requirements based on quadratic broken-line model estimation were 6.6 and 7.0 g/kg for optimal average daily gain (ADG), and 6.7 and 7.3 g/kg for breast muscle percentage of Pekin ducks from 1-21 d of age at 190 and 220 g/kg CP, respectively. The dietary Thr requirements and estimated ADG (55.18 vs. 55.86 g/d/bird) and breast muscle percentage (2.79% vs. 2.75%) of Pekin ducks did not differ between 190 and 220 g/kg CP according to the t-test results. 5. Dietary CP level could be reduced to 190 g/kg in Pekin ducks from 1-21 d of age with Thr supplementation to balance dietary amino acids, and Thr supplementation prevented excess liver lipid deposition in this instance.

Heavy metals in laughing gulls: Gender, age and tissue differences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gochfeld, M.; Belant, J.L.; Shukla, T.

1996-12-01

The authors examined concentrations of lead, cadmium, mercury, manganese, selenium, and chromium in feathers, liver, kidney, heart, and muscle of known-aged laughing gulls (Larus atricilla) that hatched in Barnegat Bay, New Jersey and were collected at John F. Kennedy International Airport, New York 1 to 7 years later. Concentrations differed significantly among tissues, and tissue entered all the regression models explaining the greatest variation in metal levels. Age of bird contributed significantly to the models for lead, cadmium, selenium, and chromium. Although there were significant gender differences in all body measurements except wing length, there were few differences in metalmore » levels. Males had significantly higher lead levels in feathers, and females had significantly higher selenium levels in heart and muscle tissue. For lead, 3-year olds had the highest levels in the heart, liver, and kidney, and levels were lower thereafter. Mercury levels in feathers and heart decreased significantly with age. Cadmium levels increased significantly with age for feathers, heart, liver, and muscle, although there was a slight decrease in the 7-year olds. Selenium levels decreased significantly with age for all tissues. Chromium levels increased with age for liver and heart.« less

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet.

PubMed

Mitchell, Sarah J; Martin-Montalvo, Alejandro; Mercken, Evi M; Palacios, Hector H; Ward, Theresa M; Abulwerdi, Gelareh; Minor, Robin K; Vlasuk, George P; Ellis, James L; Sinclair, David A; Dawson, John; Allison, David B; Zhang, Yongqing; Becker, Kevin G; Bernier, Michel; de Cabo, Rafael

2014-03-13

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Beneficial effect of a weight-stable, low-fat/low-saturated fat/low-glycaemic index diet to reduce liver fat in older subjects

PubMed Central

Utzschneider, Kristina M.; Bayer-Carter, Jennifer L.; Arbuckle, Matthew D.; Tidwell, Jaime M.; Richards, Todd L.; Craft, Suzanne

2014-01-01

Non-alcoholic fatty liver disease is associated with insulin resistance and dyslipidaemia and can progress to steatohepatitis and cirrhosis. We sought to determine whether dietary fat and saturated fat content alter liver fat in the absence of weight change in an older population. Liver fat was quantified by magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low-fat/low-saturated fat/low-glycaemic index (LGI) (LSAT: 23% fat/7% saturated fat/GI < 55) or a high-fat/high-saturated fat/high-GI (HSAT: 43% fat/24% saturated fat/GI > 70) diet in older subjects. In the present study, twenty subjects (seven males/thirteen females; age 69·3 (sem 1·6) years, BMI 26·9 (sem 0·8) kg/m2) were randomised to the LSAT diet and fifteen subjects (six males/nine females; age 68·6 (sem 1·8) years, BMI 28·1 (sem 0·9) kg/m2) to the HSAT diet. Weight remained stable. Liver fat decreased significantly on the LSAT diet (median 2·2 (interquartile range (IQR) 3·1) to 1·7 (IQR 1·8) %, P=0·002) but did not change on the HSAT diet (median 1·2 (IQR 4·1) to 1·6 (IQR 3·9) %). The LSAT diet lowered fasting glucose and total cholesterol, HDL-cholesterol and LDL-cholesterol and raised TAG (P<0·05), while the HSAT diet had no effect on glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol (P<0·05). Fasting insulin and homeostasis model of insulin resistance did not change significantly on either diet, but the Matsuda index of insulin sensitivity improved on the LSAT diet (P<0·05). Assignment to the LSAT ν. HSAT diet was a predictor of changes in lipid parameters but not liver fat. We conclude that diet composition may be an important factor in the accumulation of liver fat, with a low-fat/low-saturated fat/LGI diet being beneficial. PMID:22849970

Clinical Predictors of Liver Fibrosis in Patients With Chronic Hepatitis B Virus Infection From Children to Adults.

PubMed

Wu, Jia-Feng; Song, Shih-Hsi; Lee, Chee-Seng; Chen, Huey-Ling; Ni, Yen-Hsuan; Hsu, Hong-Yuan; Wu, Tzee-Chung; Chang, Mei-Hwei

2018-04-11

This study aimed to elucidate predictors of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection. Transient elastography was performed to define liver stiffness in 533 patients with chronic HBV infection (mean age ± standard deviation, 30.72 ± 0.57 years). Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by enzyme-linked immunosorbent assay. Single-nucleotide polymorphisms in the gene encoding interleukin 1β (IL-1β) were examined in patients with chronic HBV infection with and without liver fibrosis. Male sex, age ≥18 years, and serum α-fetoprotein level >3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥7 kPa (P = .005, .019, and <.001, respectively). HBV e antigen (HBeAg)-negative hepatitis is associated with increased liver stiffness (P < .001). Elevation of the serum IL-1β level was demonstrated in subjects with liver fibrosis. IL-1β was upregulated in Huh7 cells transfected with HBV mutants associated with HBeAg-negative hepatitis. The AA genotype at rs16944 and the CC genotype at rs1143627 in the gene encoding IL-1β were associated with higher serum IL-1β levels and liver fibrosis. Male sex, age ≥18 years, elevated α-fetoprotein level, and HBeAg-negative hepatitis are risk factors for liver fibrosis. IL-1β is involved in the progression of liver fibrosis in subjects with HBeAg-negative hepatitis.

The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study.

PubMed

Sultanik, P; Kramer, L; Soudan, D; Bouam, S; Meritet, J-F; Vallet-Pichard, A; Fontaine, H; Bousquet, L; Boueyre, E; Corouge, M; Sogni, P; Pol, S; Mallet, V

2016-09-01

There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement. © 2016 John Wiley & Sons Ltd.

Liver Cancer Mortality and Food Consumption in Serbia, 1991-2010: An Ecological Study.

PubMed

Ilić, Milena; Radoman, Kristina; Konević, Slavica; Ilić, Irena

2016-06-01

This paper investigates the correlation between liver cancer mortality and consumption of food-groups in Serbia. We conducted an ecological study. The study comprised the population of the Republic of Serbia (about 7.5 million inhabitants) during the period 1991-2010. This ecological study included the data on food consumption per capita which were obtained by the Household Budget Survey and mortality data for liver cancer made available by the National Statistical Office. Linear trend model was used to assess a trend of age-adjusted liver cancer mortality rates (per 100,000 persons) that were calculated by the method of direct standardization using the World Standard Population. Pearson correlation was performed to examine the association between liver cancer mortality and per capita food consumption quantified with a correlation coefficient (r value). In Serbia, over the past two decades a significantly decreasing trend of liver cancer mortality rates has been observed (p<0.001). Liver cancer mortality was significantly (p<0.01) positively correlated with animal fat, beef, wine and spirits intake (r=0.713, 0.631, 0.632 and 0.745, respectively). A weakly positive correlation between milk consumption and mortality from liver cancer (r=0.559, p<0.05) was found only among women. The strongest correlation was found between spirits consumption and liver cancer mortality rates in women (r=0.851, p<0.01). A negative correlation between coffee consumption and age-adjusted liver cancer mortality rates was found (r=0.516, p<0.05) only for the eldest men (aged 65 years or older). Correlations between liver cancer and dietary habits were observed and further effort is needed in order to investigate a possible causative association, using epidemiological analytical studies. Copyright© by the National Institute of Public Health, Prague 2015.

Donor age does not influence 12-month outcome after orthotopic liver transplantation.

PubMed

Faber, W; Seehofer, D; Puhl, G; Guckelberger, O; Bertram, C; Neuhaus, P; Bahra, M

2011-12-01

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease to date. The discrepancy between the numbers of donor livers and recipients has become a significant problem, resulting in a high patient mortality on the waiting list. Due to this, an expansion of the donor pool is necessary, for example, by accepting donor grafts from elderly donors. The aim of this study was to investigate the outcome after OLT depending on donor age. We retrospectively evaluated the outcome of 272 full-size cadaveric initial single OLTs within 12 months after OLT. The outcome was analyzed by dividing the collective into four donor age categories: donor age under 50, between 50 and 59, between 60 and 69, and 70 years or above. The outcome after OLT in these patients was retrospectively reviewed by using a prospective database. Patients positive for hepatitis C were excluded from the analysis. No increase of initial nonfunction was observed. Furthermore, no significant differences with regard to surgical complications and serum liver parameter were observed between the groups. Neither patient mortality rates nor rejection rates were different between the groups. However, ischemic-type biliary lesion rates increased significantly with donor age over 70 years (P<.05). The acceptance of liver grafts from older donors is a possible alternative to narrow the gap between donated and required organs. Safe use under optimal protocols is necessary to avoid a deterioration of post-OLT results. Copyright © 2011 Elsevier Inc. All rights reserved.

Simulation and experimental research on micro-channel for detecting cell status in bio-artificial liver.

PubMed

Wu, Changzhe; Cao, Yue; Huo, Xiaolin; Li, Ming

2015-01-01

Bioartificial liver support system (BALSS) based on culturing hepatocytes is an important research field for the treatment of acute liver failure. It is necessary to monitor the state of liver cell functions during the treatment of BALSS in order to guide clinical treatment. To design a micro-channel chip to achieve flash mixing for timely detection of liver cell status in bioreactors and improving liver cells growth environment to ensure the efficacy of the bio-artificial liver support system. Alanine aminotransferase (ALT) and Urea are chosen as detection indicators to reflect the degree of liver cell injury and the detoxification function. A diamond tandem structure micro-channel is designed and optimized to achieve the efficient mixing of serum and ALT or Urea reagent. The simulation and experimental results show that the diamond tandem structure micro-channel can significantly improve the mixing efficiency and meet the online detecting requirements. The easily controllable diamond tandem structure micro-channel combines the advantages of active and passive mixer and can effectively mix the serum and ALT or Urea reagent. It lays the foundation for online monitoring of liver cells and will help to improve the viability of liver cell in the bioreactor.

Results of liver transplantation from old donors.

PubMed

Dudek, K; Kornasiewicz, O; Remiszewski, P; Zieniewicz, K; Wróblewski, T; Krawczyk, M

2014-10-01

Faced with a shortage of organs for liver transplantation, the use of grafts from older donors is justified. However, there remains little consensus on how this use impacts the graft and patient outcomes after transplantation from these older donors. The aim of the present analysis was to assess the graft and patient outcomes after liver transplantation from deceased donors >60 years of age. From January 2007 to January 2011, 505 subjects were identified as liver graft donors after brain death, of which 7.35% were ≥60. To determine the effect of donor age on graft and patient outcomes, we analyzed donor age, recipient age, the Model for End-State Liver Disease (MELD) score of recipients at the time of transplantation, early posttransplant complications, and mortality. The posttransplant follow-up was 29 ± 25.5 months, and 3-year patient mortality from donors, grouped according to age, was 7.92% with donors <30; 15.78% with donors 30-50, 10.68% with donors 50-60, and 12.50% with donors >60. After analysis of patient and graft survival based on donor graft age, 3-year patient survival according donor age was 89.29% with donors <30, 83.85% with donors 30-50, 89.89% with donors 50-60, and 87.50% with donors >60. Analysis showed overall patient and graft survival rates from older donors were not worse than those from younger donors (P > .1). Among the cases, 3-year patient survival according to MELD score was 91.19% with a MELD of I, 85.37% with a MELD of II, and 67.67% with a MELD of III; differences in graft and patient survival when comparing low MELD I and high MELD III were significantly different (P < .01). A more advanced age of a donor should not be a contraindication for liver transplantation. The present analysis shows that liver grafts from donors >60 can be used safely in older recipients who presented with relatively low MELD scores. Analyses also indicate that high MELD obtained before transplantation may be an important prognostic factor for graft and patient survival.

Insulin Therapy Improves Adeno-Associated Virus Transduction of Liver and Skeletal Muscle in Mice and Cultured Cells.

PubMed

Carrig, Sean; Bijjiga, Enoch; Wopat, Mitchell J; Martino, Ashley T

2016-11-01

Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α 1 -antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV-schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates that AAV transduction of liver or skeletal muscle can be improved by insulin therapy.

The genetic architecture of liver enzyme levels: GGT, ALT and AST.

PubMed

van Beek, Jenny H D A; de Moor, Marleen H M; de Geus, Eco J C; Lubke, Gitta H; Vink, Jacqueline M; Willemsen, Gonneke; Boomsma, Dorret I

2013-07-01

High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

Levels of persistent organic pollutants (POPs) in a coastal northern Norwegian population with high fish-liver intake.

PubMed

Sandanger, T M; Brustad, M; Sandau, C D; Lund, E

2006-05-01

Recent research has again raised the issue regarding the potential health effects of long term exposure to persistent organic pollutants (POPs) in the context of a risk-benefit analysis. There remains clear evidence of the beneficial effects of fish consumption on public health and in particular fatty fish with its essential fatty acids. In addition to providing fatty acids, fish fat constitutes an essential source to vitamin D for the northern Norwegian population. Norwegian Food Control Authorities have recommended that children and women of childbearing age should not consume fish liver due to the risk associated with high intake of POPs. The aim of this study was to assess the influence of fish liver intake on the levels of PCBs and chlorinated pesticides in a rural coastal community (n = 31) in northern Norway, applying a cross-sectional design. The geometric mean plasma levels of sum of PCBs (14 congeners) and p,p'-DDE was found to be 558 microg kg(-1) lipids and 179 microg kg(-1) lipids, respectively. These levels were not significantly affected by the reported intake of fish liver, when age and gender were considered. Age in particular, but also gender were significant predictors for most compounds. When merging the dataset with an urban population with considerable lower intake of fish liver, the intake of cod liver still did not significantly affect the levels of PCBs and p,p'-DDE when adjusted for age and gender. Age and gender remain the strongest predictors of plasma levels of POPs in this study whereas fish liver intake was not significantly associated with the POPs.

Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

PubMed

Yang, Ye; Li, Yun; Yin, Dengke; Chen, Song; Gao, Xiangdong

2016-06-01

Coptis chinensis Franch (Huanglian) is commonly used to treat diabetes in China. In this study, the effects of the C. chinensis Franch polysaccharides (CCP) on advanced glycation end product (AGE) formation in vitro and in streptozotocin-induced diabetic mice were investigated. CCP significantly inhibited all the three periods of nonenzymatic protein glycation in vitro, including Amadori product, dicarbonyl compound, and AGE formation (P < .01). In diabetic mice, the administration of CCP not only improved both bodyweight and serum insulin and decreased fasting blood glucose and glycated serum protein concentrations but also decreased the AGE accumulations and morphological abnormalities in pancreas and liver. The inhibitory effects of CCP on AGE formation afford a potential therapeutic use in the prevention and treatment of diabetes.

[Mortality and survival analysis of liver cancer in China].

PubMed

Zheng, Rongshou; Zuo, Tingting; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

2015-09-01

Based on the cancer registry data to analyze the mortality and survival of liver cancer in China. Liver cancer data of 2011 were retrieved from the National Cancer Registry Database.Liver cancer deaths were estimated using age-specific rate by areas and gender according to the national population in 2011. Mortality data from 22 cancer registries during 2000-2011 were used to analyze the mortality trend, and data from 17 cancer registries during 2003-2005 were used for survival analysis. The estimates of liver cancer deaths were about 322 thousand in 2011 with a crude mortality rate of 23.93/10(5).There was an increasing trend of crude mortality rate of liver cancer during 2000-2011 in 22 Chinese cancer registries with an average annual percentage change of 0.7% (95%CI: 0.2%-1.2%), 1.1% in urban and 0.4% in rural areas. After age standardization with Segi's population, the mortality rate was significantly decreased, with an APC of -2.3%, -1.9% in urban and -2.2% in rural populations. The 5-year age standardized relative survival was 10.1% (95%CI: 9.5% to 10.7%), and the 1-, 3- and the 5-year observed survival rates were 27.2%, 12.7%, and 8.9%, respectively. Liver cancer is a major cancer threatening people's lives and health in China, and the liver cancer burden is still high.

Adverse Events in Treating Smear-Positive Tuberculosis Patients in China

PubMed Central

Zhang, Tao; Du, Jian; Yin, Xiaoyan; Xue, Fuzhong; Liu, Yanxun; Li, Runzi; Luo, Cheng; Li, Liang; Li, Xiujun

2015-01-01

This study aimed to estimate the adverse events (AE) rate during anti-tuberculosis treatment and to explore AE-related risk factors. New and previously treated smear-positive tuberculosis (TB) cases were enrolled from eight regions in China between April 2009 and October 2010. The AE rate was estimated, and AE risk factors during anti-TB treatment were assessed using Cox proportional models. Among 2091 Chinese subjects with anti-TB treatment, 462 (22.1%, 95% confidence interval (CI), 20.3–23.9) patients developed AE, with liver injury and gastrointestinal reactions constituting the most common AE. Specifically, 9.8% (95% CI, 8.5–11.1) and 6.3% (95% CI, 5.3–7.4) developed liver injuries and gastrointestinal reactions, respectively. We found that AE rate differed by regions, TB knowledge score, symptoms score and smoking status. Liver injuries were associated with age, sex and smoking status; gastrointestinal reactions were associated with education level and symptom score. Improving patients’ knowledge on TB could reduce AE rate. PMID:26729141

Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

PubMed

Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

2014-01-01

Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and control subjects.

Effects of chronic copper exposure during early life in rhesus monkeys.

PubMed

Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

2005-05-01

Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

Liver transplantation in infants younger than 1 year of age.

PubMed Central

Colombani, P M; Cigarroa, F G; Schwarz, K; Wise, B; Maley, W E; Klein, A S

1996-01-01

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults. PMID:8645039

Acetaminophen (Paracetamol) induced acute liver failure - A social problem in an era of increasing tendency to self-treatment.

PubMed

Wróblewski, Tadeusz; Kobryń, Konrad; Kozieł, Sławomir; Ołdakowska-Jedynak, Urszula; Pinkas, Jarosław; Danielewicz, Roman; Ziarkiewicz-Wróblewska, Bogna; Krawczyk, Marek

2015-01-01

The widespread availability of medication without prescription, so-called over the counter (OTC), and the rapid development of health consciousness of Poles is associated with broad access to medical information in the mass media. This causes patients to recognize their own disease, cancel doctor's appointments, and begin self-treatment. This time and money-saving behavior, often signaled by pain, usually leads to the treatment of symptoms alone, without seeking the cause of the disease.The aim of the study was to present life-threatening paracetamol poisoning, and the treatment of acute liver failure. In 2002-2014, 35 patients were hospitalized due to acute paracetamol poisoning: 17 female and 18 male patients aged between 17-59 (mean 32.3 years). Patients were treated in the surgical intensive care unit, where their parameters of liver and renal function were continuously monitored. If there was no improvement in the liver function, patients underwent albumin dialysis with the Prometheus system and were qualified for liver transplantation (LTx). 26 patients were treated pharmacologically and 7 out of 9 patients who underwent LTx were dialyzed. Overall, 11 patients had 26 albumin dialysis in total; 4 patients died - 1 post-transplant and 3 pre-transplant. Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

Global lessons in graft type and pediatric liver allocation: A path toward improving outcomes and eliminating wait-list mortality.

PubMed

Hsu, Evelyn K; Mazariegos, George V

2017-01-01

Current literature and policy in pediatric liver allocation and organ procurement are reviewed here in narrative fashion, highlighting historical context, ethical framework, technical/procurement considerations, and support for a logical way forward to an equitable pediatric liver allocation system that will improve pediatric wait-list and posttransplant outcomes without adversely affecting adults. Where available, varying examples of successful international pediatric liver allocation and split-liver policy will be compared to current US policy to highlight potential strategies that can be considered globally. Liver Transplantation 23:86-95 2017 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Liver transplantation using elderly donors: a risk factor analysis.

PubMed

Kim, Dae Y; Moon, Jang; Island, Eddie R; Tekin, Akin; Ganz, Susan; Levi, David; Selvaggi, Gennaro; Nishida, Seigo; Tzakis, Andreas G

2011-01-01

Survival after liver transplantation is negatively impacted by use of elderly deceased donors, but excluding them would increase waiting times and waiting list mortality. We reviewed our experience with liver transplantation (LT) utilizing livers from deceased donors 65 yr of age and older to identify those factors that impact graft survival. All adult patients (≥ 18 yr old) who underwent primary LT using deceased donor livers from donors aged ≥ 65 yr between February 1995 and November 2003 were included. With multivariate analysis we found four unfavorable characteristics significantly associated with higher post-transplant graft failure rate. These characteristics are hepatitis C as an etiology of liver disease, Model for End-Stage Liver Disease score >20, serum glucose level of donor > 200 mg/dL at the time of liver recovery, and skin incision to aortic cross-clamp time > 40 minutes in the donor surgery. The five-yr estimated graft survival rates having 0, 1, 2, 3, and 4 unfavorable characteristics were 100%, 82.0%, 81.7%, 39.3%, and 25.0%, respectively (p < 0.05). Our data demonstrated good graft survival can be achieved in LT using elderly donor liver allografts with appropriate patient selection, donor blood glucose management and efficient liver recovery with minimal manipulation of the liver during donor surgery. © 2010 John Wiley & Sons A/S.

Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

PubMed

Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

2017-11-01

Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

Results of Liver Transplantation With Donors Older than 75 Years: A Case-Control Study.

PubMed

León Díaz, F J; Fernández Aguilar, J L; Sánchez Pérez, B; Montiel Casado, C; Aranda Narváez, J M; Pérez Daga, J A; Suárez Muñoz, M Á; Santoyo Santoyo, J

2016-09-01

The inclusion of elderly donors can increase the pool of organs available for transplantation. The objective of this study was to compare clinical outcomes and survival rates of patients who received livers from donors aged ≥75 years versus younger donors. We considered all liver transplantations performed in our unit from January 2006 to January 2015. Thirty-two patients received a liver from a cadaveric donor aged ≥75 years (study group), and their outcomes were compared with those of patients who received a liver from a younger donor (control group) immediately before and after each transplantation in the study group. This is a descriptive, retrospective, case-control study carried out to analyze the characteristics of donors and recipients as well as the clinical course and survival of recipients of older and younger donors. Statistically significant differences were observed according to donors' age (53.3 ± 13.6 vs 79 ± 3.4 years; P < .001). In total, 6.2% of the recipients of a liver from a donor aged <75 years required retransplantation versus 15.6% of recipients of donors ≥75 years. Patient survivals at 1, 3, and 5 years, respectively, were 89%, 78.6%, and 74.5% for recipients of donors <75 years versus 83.4%, 79.4%, and 59.6% for the study group. Livers from older donors can be safely used for transplantation with acceptable survival rates. However, survival rates are lower for recipients of livers from older donors compared with younger donors, and survival only increased with retransplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk analysis of ischemic-type biliary lesions after liver transplant using octogenarian donors.

PubMed

Ghinolfi, Davide; De Simone, Paolo; Lai, Quirino; Pezzati, Daniele; Coletti, Laura; Balzano, Emanuele; Arenga, Giuseppe; Carrai, Paola; Grande, Gennaro; Pollina, Luca; Campani, Daniela; Biancofiore, Gianni; Filipponi, Franco

2016-05-01

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic-type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre-LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow-up after LT was 2.1 years (range, 0.7-5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age-Model for End-Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End-Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588-598 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

Human brain mass: similar body composition associations as observed across mammals.

PubMed

Heymsfield, Steven B; Müller, Manfred J; Bosy-Westphal, Anja; Thomas, Diana; Shen, Wei

2012-01-01

A classic association is the link between brain mass and body mass across mammals that has now been shown to derive from fat-free mass (FFM) and not fat mass (FM). This study aimed to establish for the first time the associations between human brain mass and body composition and to compare these relations with those established for liver as a reference organ. Subjects were 112 men and 148 women who had brain and liver mass measured by magnetic resonance imaging with FM and FFM measured by dual-energy X-ray absorptiometry. Brain mass scaled to height (H) with powers of ≤0.6 in men and women; liver mass and FFM both scaled similarly as H(~2) . The fraction of FFM as brain thus scaled inversely to height (P < 0.001) while liver mass/FFM was independent of height. After controlling for age, brain, and liver mass were associated with FFM while liver was additionally associated with FM (all models P ≤ 0.01). After controlling for age and sex, FFM accounted for ~5% of the variance in brain mass while levels were substantially higher for liver mass (~60%). Brain mass was significantly larger (P < 0.001) in men than in women, even after controlling for age and FFM. As across mammals, human brain mass associates significantly, although weakly, with FFM and not FM; the fraction of FFM as brain relates inversely to height; brain differs in these relations from liver, another small high metabolic rate organ; and the sexual dimorphism in brain mass persists even after adjusting for age and FFM. Copyright © 2012 Wiley Periodicals, Inc.

Patterns and Trends of Liver Cancer Incidence Rates in Eastern and Southeastern Asian Countries (1983-2007) and Predictions to 2030.

PubMed

Wu, Jie; Yang, Shigui; Xu, Kaijin; Ding, Cheng; Zhou, Yuqing; Fu, Xiaofang; Li, Yiping; Deng, Min; Wang, Chencheng; Liu, Xiaoxiao; Li, Lanjuan

2018-05-01

We examined temporal trends in liver cancer incidence rates overall and by histological type from 1983 through 2007. We predict trends in liver cancer incidence rates through 2030 for selected Eastern and Southeastern Asian countries. Data on yearly liver cancer incident cases by age group and sex were drawn from 6 major selected Eastern and Southeastern Asian countries or regions with cancer registries available in the CI5plus database, including China, Japan, Hong Kong Special Administrative Region (SAR), the Philippines, Singapore, and Thailand. We also analyzed data for the United States and Australia for comparative purposes. Age-standardized incidence rates were calculated and plotted from 1983 through 2007. Numbers of new cases and incidence rates were predicted through 2030 by fitting and extrapolating age-period-cohort models. The incidence rates of liver cancer have been decreasing, and decreases will continue in all selected Eastern and Southeastern Asian countries, except for Thailand, whose liver cancer incidence rate will increase due to the increasing incidence rate of intrahepatic cholangiocarcinomas. Even though the incidence rates of liver cancer are predicted to decrease in most Eastern and Southeastern Asian countries, the burden, in terms of new cases, will continue to increase because of population growth and aging. Based on an analysis of data from cancer registries from Asian countries, incidence rates of liver cancer are expected to decrease through 2030 in most Eastern and Southeastern Asian countries. However, in Thailand, the incidence rate of intrahepatic cholangiocarcinomas is predicted to increase, so health education programs are necessary. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Employment after liver transplantation: a review.

PubMed

Huda, A; Newcomer, R; Harrington, C; Keeffe, E B; Esquivel, C O

2015-03-01

Return to productive employment is often an important milestone in the recovery and rehabilitation process after liver transplantation (OLT). This literature review identifies factors associated with employment in patients who underwent OLT. We searched PubMed for articles that addressed the various factors affecting employment after OLT. The studies demonstrated improvement in the quality of life and examined factors that predicted whether patients would return to work after OLT. Demographic variable associated with posttransplant employment included young age, male sex, college degree, Caucasian race, and pretransplant employment. Patients with alcohol-related liver disease had a significantly lower rate of employment than did those with other etiologies of liver disease. Recipients who were employed after transplantation had a significantly better posttransplant functional status than did those who were not employed. Economic pressures are increasing the expectation that patients who undergo successful OLT will return to work. Thus, transplant teams need to have a better understanding of posttransplant work outcomes for this vulnerable population, and greater attention must be paid to the full social rehabilitation of transplant recipients. Specific interventions for OLT recipients should be designed to evaluate and change their health perceptions and encourage their return to work. Published by Elsevier Inc.

Improvement in liver pathology of patients with β-thalassemia treated with deferasirox for at least 3 years.

PubMed

Deugnier, Yves; Turlin, Bruno; Ropert, Martine; Cappellini, M Domenica; Porter, John B; Giannone, Vanessa; Zhang, Yiyun; Griffel, Louis; Brissot, Pierre

2011-10-01

Most data on the effects of iron chelation therapy for patients with liver fibrosis come from small studies. We studied the effects of the oral iron chelator deferasirox on liver fibrosis and necroinflammation in a large population of patients with iron overload β-thalassemia. We studied data from 219 patients with β-thalassemia, collected from histologic analyses of biopsy samples taken at baseline and after at least 3 years of treatment with deferasirox. Treatment response was assessed from liver iron concentrations at baseline and the end of the study. Liver fibrosis, necroinflammation, and markers of iron overload and liver enzymes were recorded. Patients were also assessed, by serologic analysis at baseline, for hepatitis C virus infection. By the end of the study, stability of Ishak fibrosis staging scores (change of -1, 0, or +1) or improvements (change of ≤-2) were observed in 82.6% of patients; Ishak necroinflammatory scores improved by a mean value of -1.3 (P<.001). Improvements in fibrosis stage and necroinflammation were independent of hepatitis C virus exposure or reduction in liver iron concentration defined by the response criteria. Absolute changes in concentrations of liver iron by the end of the study did not correlate with improved Ishak fibrosis or necroinflammatory scores. Deferasirox treatment for 3 or more years reversed or stabilized liver fibrosis in 83% of patients with iron-overloaded β-thalassemia. This therapeutic effect was independent of reduced concentration of liver iron (defined by the response criteria) or previous exposure to hepatitis C virus. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Surgically-Induced Weight Loss Significantly Improves Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome

PubMed Central

Mattar, Samer G.; Velcu, Laura M.; Rabinovitz, Mordechai; Demetris, A J.; Krasinskas, A M.; Barinas-Mitchell, Emma; Eid, George M.; Ramanathan, Ramesh; Taylor, Debra S.; Schauer, Philip R.

2005-01-01

Objective: To evaluate the effects of surgical weight loss on fatty liver disease in severely obese patients. Summary Background Data: Nonalcoholic fatty liver disease (NAFLD), a spectrum that extends to liver fibrosis and cirrhosis, is rising at an alarming rate. This increase is occurring in conjunction with the rise of severe obesity and is probably mediated in part by metabolic syndrome (MS). Surgical weight loss operations, probably by reversing MS, have been shown to result in improvement in liver histology. Methods: Patients who underwent laparoscopic surgical weight loss operations from March 1999 through August 2004, and who agreed to have an intraoperative liver biopsy followed by at least one postoperative liver biopsy, were included. Results: There were 70 patients who were eligible. All patients underwent laparoscopic operations, the majority being laparoscopic Roux-en-Y gastric bypass. The mean excess body weight loss at time of second biopsy was 59% ± 22% and the time interval between biopsies was 15 ± 9 months. There was a reduction in prevalence of metabolic syndrome, from 70% to 14% (P < 0.001), and a marked improvement in liver steatosis (from 88% to 8%), inflammation (from 23% to 2%), and fibrosis (from 31% to 13%; all P < 0.001). Inflammation and fibrosis resolved in 37% and 20% of patients, respectively, corresponding to improvement of 82% (P < 0.001) in grade and 39% (P < 0.001) in stage of liver disease. Conclusion: Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome. PMID:16192822

Optimizing repeat liver transplant graft utility through strategic matching of donor and recipient characteristics.

PubMed

Hung, Kenneth; Gralla, Jane; Dodge, Jennifer L; Bambha, Kiran M; Dirchwolf, Melisa; Rosen, Hugo R; Biggins, Scott W

2015-11-01

Repeat liver transplantation (LT) is controversial because of inferior outcomes versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been proposed. We aimed to identify combinations of Model for End-Stage Liver Disease (MELD), donor risk index (DRI), and recipient characteristics achieving this graft survival threshold. We identified re-LT recipients listed in the United States from March 2002 to January 2010 with > 90 days between primary LT and listing for re-LT. Using Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI, and recipient characteristics attaining >50% expected 1-year graft survival. Re-LT recipients (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African American recipients, lower-DRI livers were required to achieve the graft survival threshold. Use of high-DRI livers (>1.44) in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the graft survival threshold with recipient age ≥ 60 years (any race), as well as at age ≥ 50 years for Caucasians and at age < 50 years for African Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk re-LT recipients (HCV infected, older age, African American race, high MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected) can achieve the survival threshold with varying DRI and MELD scores. © 2015 American Association for the Study of Liver Diseases.

Donor Age-Based Analysis of Liver Transplantation Outcomes: Short- and Long-Term Outcomes Are Similar Regardless of Donor Age.

PubMed

Chapman, William C; Vachharajani, Neeta; Collins, Kelly M; Garonzik-Wang, Jackie; Park, Yikyung; Wellen, Jason R; Lin, Yiing; Shenoy, Surendra; Lowell, Jeffrey A; Doyle, M B Majella

2015-07-01

The shortage of donor organs has led to increasing use of extended criteria donors, including older donors. The upper limit of donor age that produces acceptable outcomes continues to be explored. In liver transplantation, with appropriate selection, graft survival and patient outcomes would be comparable regardless of age. We performed a retrospective analysis of 1,036 adult orthotopic liver transplantations (OLT) from a prospectively maintained database performed between January 1, 2000 and December 31, 2013. The study focus group was liver transplantations performed using grafts from older (older than 60 years) deceased donors. Deceased donor liver transplantations done during the same time period using grafts from younger donors (younger than 60 years) were analyzed for comparison. Both groups were further divided based on recipient age (less than 60 years and 60 years or older). Donor age was the primary variable. Recipient variables included were demographics, indication for transplantation, Model for End-Stage Liver Disease (MELD), graft survival, and patient survival. Operative details and postoperative complications were analyzed. Patient demographics and perioperative details were similar between groups. Patient and graft survival rates were similar in the 4 groups. Rates of rejection (p = 0.07), bile leak (p = 0.17), and hepatic artery thrombosis were comparable across all groups (p = 0.84). Hepatitis C virus recurrence was similar across all groups (p = 0.10). Thirty-one young recipients (less than 60 years) received grafts from donors aged 70 or older. Their survival and other complication rates were comparable to those in the young donor to young recipient group. Comparable outcomes in graft and patient survivals were achieved using older donors (60 years or more), regardless of recipient age, without increased rate of complications. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Serum aminotransferase changes with significant weight loss: sex and age effects.

PubMed

Suzuki, Ayako; Binks, Martin; Sha, Ronald; Wachholtz, Amy; Eisenson, Howard; Diehl, Anna Mae

2010-02-01

In obese subjects, the liver may be differentially affected by significant weight loss depending on as yet unknown factors. We explored clinical factors associated with serum alanine aminotransferase (ALT) changes during significant weight loss in a residential weight loss program. Clinical data from 362 adults who received a comprehensive weight loss intervention (ie, diets, physical fitness, and behavioral modification) in the program were analyzed. Serum ALT was used as a surrogate marker of liver injury. The ALT changes during the program were calculated to create study outcome categories (improvement, no change, or deterioration of ALT during significant weight loss). Variables of demography, lifestyle, and comorbidities at baseline, and total/rate of weight change during the program were explored for associations with the ALT change categories using multiple logistic regression models. Variation by sex was apparent among predictors of ALT deterioration; men with rapid weight loss and women with higher initial body mass index were more likely to experience ALT deterioration, whereas men with prior alcohol consumption were less likely to experience ALT deterioration even after adjusting for baseline ALT (Ps < .03). Variation by age was apparent among predictors of ALT improvement; younger patients with current smoking and older patients with rapid weight loss, diabetes or impaired fasting glucose, or sleep apnea or who followed a reduced-carbohydrate diet were less likely to experience ALT improvement (Ps < .05). A number of clinical factors influence ALT changes during weight loss in sex- and age-specific manners. The patterns that we detected may have pathophysiologic significance beyond the practical implications of our findings in clinical practice related to underlying changes in fat metabolism. Copyright 2010 Elsevier Inc. All rights reserved.

Toxic Hepatitis

MedlinePlus

... susceptible to the effects of toxins. Having hepatitis. Chronic infection with a hepatitis virus (hepatitis B, hepatitis C, or one of the other — extremely rare — hepatitis viruses that may persist in the body) makes your liver more vulnerable. Aging. As you age, your liver breaks down harmful ...

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.

2014-07-15

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local diseasemore » control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.« less

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.

PubMed

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; Dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-08-07

To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.

A kinetic study of the natural induction of liver steatosis in Greylag Landaise geese: the role of hyperphagia.

PubMed

Fernandez, X; Guy, G; Laverze, J B; Bonnefont, C; Knudsen, C; Fortun-Lamothe, L

2016-08-01

We have previously demonstrated that a sharp rise in feed intake (hyperphagia) and spontaneous liver steatosis could be experimentally induced in domestic Greylag geese by combining a short photoperiod and a sequence of feed restriction followed by ad libitum corn feeding during the fall and the winter. In this previous work, however, individual feed intake could not be recorded. The present study aimed at evaluating the relationship between level and pattern of hyperphagia and liver weight with an individual control of feed intake in individually housed (IH) geese, while comparing the performances with group housed (GH) geese. A total of 300 male geese of 19 weeks of age, were provided with corn ad libitum after an initial feed restriction period. From 21 to 23 weeks of age, the daylight duration was progressively reduced from 10 to 7 h and kept as such until the end of the experiment (week 36). In all, 30 GH and 30 IH geese were slaughtered at 19, 27, 30, 32 and 36 weeks of age. Feed intake was measured per group in GH geese and individually in IH geese. During the 1st week of corn feeding, the average feed intake rose up to 600 g/goose per day in GH geese but not in IH geese where the feed intake rose gradually from 300 to 400 g/day. The liver weight increased from 93 g (week 19) to 497 g (week 32; P<0.05) in GH birds. In IH birds, liver weights were, on average, much lower (ranging from 220 to 268 g) than in GH birds (P<0.05). In GH and IH bird, the variability in the individual response to corn feeding was very high (liver weight cv ranging from 63% to 83% depending on slaughter age). A close correlation between corn consumption and liver weight was evidenced in IH birds at each slaughter age (R 2 ranging from 0.62 to 0.79), except at 36 weeks of age where this correlation was weak (R 2=0.14). The variability in the extent of liver steatosis is very high and our results in IH birds clearly point out the major role of hyperphagia, mainly at the beginning of the ad libitum corn feeding period, on the development of spontaneous liver steatosis.

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

PubMed Central

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-01-01

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median (25th-75th centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients. PMID:26269683

A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

PubMed

Wang, He; Lu, Shi-Chun; He, Lei; Dong, Jia-Hong

2018-02-01

Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

PubMed

Anadol, Evrim; Lust, Kristina; Boesecke, Christoph; Schwarze-Zander, Carolynne; Mohr, Raphael; Wasmuth, Jan-Christian; Rockstroh, Jürgen Kurt; Trebicka, Jonel

2018-01-01

Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE). 83% were male with a median age of 45, while 131 were co-infected with viral hepatitis. Overall, 18% had significant fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were independently associated with significant fibrosis, while HCV (OR:5.8), exposure to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below 40copies/mL (OR:0.4) was independently associated with significant fibrosis, and didanosine (OR:20.8) with cirrhosis. In conclusion, history of exposure to didanosine and azidothymidine continues to have an impact on the presence of liver cirrhosis in HIV patients. However, HCV co-infection and ongoing HIV-replication have the strongest effect on development of significant fibrosis in these patients.

Outcome of acute liver failure in the elderly.

PubMed

Schiødt, Frank V; Chung, Raymond T; Schilsky, Michael L; Hay, J Eileen; Christensen, Erik; Lee, William M

2009-11-01

Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15-81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF; this rate of acetaminophen-induced ALF was significantly higher than that in patients > or = 60 years (group 2; n = 110; 23.6% with acetaminophen-induced ALF, P < 0.001). The overall survival rate was 72.7% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 67.9% in group 1 and 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in contrast to previous studies, we have demonstrated a relatively good spontaneous survival rate for older patients with ALF when it is corrected for etiology. However, overall survival was better for younger non-acetaminophen patients. Fewer older patients were listed for transplantation.

Outcome of Acute Liver Failure in the Elderly

PubMed Central

Schiødt, Frank V.; Chung, Raymond T.; Schilsky, Michael L.; Hay, J. Eileen; Christensen, Erik; Lee, William M.

2011-01-01

Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age ≥ 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15–81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF; this rate of acetaminophen-induced ALF was significantly higher than that in patients ≥ 60 years (group 2; n = 110; 23.6% with acetaminophen-induced ALF, P < 0.001). The overall survival rate was 72.7% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 67.9% in group 1 and 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in contrast to previous studies, we have demonstrated a relatively good spontaneous survival rate for older patients with ALF when it is corrected for etiology. However, overall survival was better for younger non-acetaminophen patients. Fewer older patients were listed for transplantation. PMID:19877205

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".

In vitro differentiated hepatic oval-like cells enhance hepatic regeneration in CCl4 -induced hepatic injury.

PubMed

Awan, Sana Javaid; Baig, Maria Tayyab; Yaqub, Faiza; Tayyeb, Asima; Ali, Gibran

2017-01-01

Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl 4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP + mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes. Efficiency of oval cells to reduce hepatocyte injury was studied by determining cell viability, release of LDH, and biochemical tests in a co-culture system. Further, in vivo repair potential of differentiated oval cells was determined in CCl 4 -induced fibrotic model by gene expression analysis, biochemical tests, mason trichrome, and Sirius red staining. Differentiated oval cells expressed hepatic oval cells-specific markers AFP, ALB, CK8, CK18, CK19. These differentiated cells when co-cultured with injured hepatocytes showed significant hepato-protection as measured by reduction in apoptosis, LDH release, and improvement in liver functions. Transplantation of differentiated oval cells like cells in fibrotic livers exhibited enhanced homing, reduced liver fibrosis, and improved liver functions by augmenting hepatic microenvironment by improved liver functions. This preconditioning strategy to differentiate BMSCs into oval cell leads to improved survival and homing of transplanted cells. In addition, reduction in fibrosis and functional improvement in mice with CCl 4 -induced liver fibrosis was achieved. © 2016 International Federation for Cell Biology.

The cadmium status of horses from central Europe depending on breed, sex, age and living area.

PubMed

Anke, M; Kośla, T; Groppel, B

1989-07-01

The Cd status of animals is best reflected by kidneys and much worse by liver and hair. Breed (heavy- and warm-blooded horses) only took an insignificant effect on the Cd content of kidneys and liver. On the average, however, warm-blooded horses stored more Cd than heavy ones. Geldings from Cd-exposed living areas accumulated insignificantly more Cd in liver, kidneys and hair than mares. The influence of age on the Cd content of kidneys and liver of Cd-exposed horses was significant. The Cd exposure of a living area was very well reflected by kidneys and liver. On the average, horses from two areas with nonferrous metal smelting stored 1000 mg Cd/kg kidney dry matter and 100 to 200 mg Cd/kg liver dry matter. The highest Cd concentration of the kidneys of horses amounted to 2.6 and 2.3 g/kg dry matter, resp.

Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination with ω-6/9 lipid emulsions.

PubMed

Angsten, Gertrud; Finkel, Yigael; Lucas, Steven; Kassa, Ann-Marie; Paulsson, Mattias; Lilja, Helene Engstrand

2012-09-01

Newborn infants with short bowel syndrome (SBS) represent a high-risk group of developing intestinal failure-associated liver disease (IFALD), which may be fatal. However, infants have a great capacity for intestinal growth and adaptation if IFALD can be prevented or reversed. A major contributing factor to IFALD may be the soybean oil-based intravenous lipid emulsions used since the introduction of parenteral nutrition (PN) 40 years ago. This retrospective study compares the outcome in 20 neonates with SBS treated with parenteral fish oil (Omegaven) in combination with ω-6/9 lipid emulsions (ClinOleic) with the outcome in a historical cohort of 18 patients with SBS who received a soybean oil-based intravenous lipid emulsion (Intralipid). Median gestational age was 26 weeks in the treatment group and 35.5 weeks in the historical group. All patients were started on PN containing Intralipid that was switched to ClinOleic/Omegaven in the treatment group at a median age of 39 gestational weeks. In the treatment group, direct bilirubin levels were reversed in all 14 survivors with cholestasis (direct bilirubin >50 umol/L). Median time to reversal was 2.9 months. Only 2 patients died of liver failure (10%). In the historical cohort, 6 patients (33%) died of liver failure, and only 2 patients showed normalization of bilirubin levels. Parenteral fish oil in combination with ω-6/9 lipid emulsions was associated with improved outcome in premature neonates with SBS. When used instead of traditional soybean-based emulsions, this mixed lipid emulsion may facilitate intestinal adaptation by increasing the IFALD-free period.

Determination of Selected Amino Acids in Serum of Patients with Liver Disease.

PubMed

Kanďár, Roman; Drábková, Petra; Toiflová, Tereza; Čegan, Alexander

2016-01-01

The determination of amino acids can be a reliable approach for extended diagnosis of liver diseases. This is because liver disease can be a cause of impaired amino acid metabolism. Therefore, a method for the determination of serum amino acids, applicable for clinical purposes, is necessary. The aim of this study was to find differences in the levels of selected amino acids between patients with liver disease and a control group. Samples of peripheral venous blood were obtained from a group of patients with liver disease (n = 131, 59 women at an average age of 60 years and 72 men at an average age of 52 years) and a control group (n = 105, 47 women at an average age of 62 years and 58 men at an average age of 58 years). Before the separation, the amino acids were derivatized with naphthalene-2,3-dicarboxaldehyde. For the separation, reverse phase column was used. The effluent was monitored with a fluorescence detector. There were significant differences in the concentrations of some amino acids between the patients and the control group, but also between women and men. Correlations between some amino acids and markers of liver blood tests and lipid metabolism were observed. A simple, relatively rapid and selective HPLC method with fluorescence detection for the determination of selected amino acids in serum has been developed.

Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial.

PubMed

Hallsworth, Kate; Thoma, Christian; Hollingsworth, Kieren G; Cassidy, Sophie; Anstee, Quentin M; Day, Christopher P; Trenell, Michael I

2015-12-01

Although lifestyle changes encompassing weight loss and exercise remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management, the effect of different types of exercise on NAFLD is unknown. This study defines the effect of modified high-intensity interval training (HIIT) on liver fat, cardiac function and metabolic control in adults with NAFLD. Twenty-three patients with NAFLD [age 54±10 years, body mass index (BMI) 31±4 kg/m(2), intra-hepatic lipid >5%) were assigned to either 12 weeks HIIT or standard care (controls). HIIT involved thrice weekly cycle ergometry for 30-40 min. MRI and spectroscopy were used to assess liver fat, abdominal fat and cardiac structure/function/energetics. Glucose control was assessed by oral glucose tolerance test and body composition by air displacement plethysmography. Relative to control, HIIT decreased liver fat (11±5% to 8±2% compared with 10±4% to 10±4% P=0.019), whole-body fat mass (35±7 kg to 33±8 kg compared with 31±9 kg to 32±9 kg, P=0.013), alanine (52±29 units/l to 42±20 units/l compared with 47±22 units/l to 51±24 units/l, P=0.016) and aspartate aminotransferase (AST; 36±18 units/l to 33±15 units/l compared with 31±8 units/l to 35±8 units/l, P=0.017) and increased early diastolic filling rate (244±84 ml/s to 302±107 ml/s compared with 255±82 ml/s to 251±82 ml/s, P=0.018). There were no between groups differences in glucose control. Modified HIIT reduces liver fat and improves body composition alongside benefits to cardiac function in patients with NAFLD and should be considered as part of the broader treatment regimen by clinical care teams. ISRCTN trial ID: ISRCTN78698481. © 2015 Authors; published by Portland Press Limited.

The utility of liver function tests for mortality prediction within one year in primary care using the algorithm for liver function investigations (ALFI).

PubMed

McLernon, David J; Dillon, John F; Sullivan, Frank M; Roderick, Paul; Rosenberg, William M; Ryder, Stephen D; Donnan, Peter T

2012-01-01

Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.

Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

PubMed

Mahmoud, Y I; Hegazy, H G

2016-01-01

Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.

Transport Advances in Disposable Bioreactors for Liver Tissue Engineering

NASA Astrophysics Data System (ADS)

Catapano, Gerardo; Patzer, John F.; Gerlach, Jörg Christian

Acute liver failure (ALF) is a devastating diagnosis with an overall survival of approximately 60%. Liver transplantation is the therapy of choice for ALF patients but is limited by the scarce availability of donor organs. The prognosis of ALF patients may improve if essential liver functions are restored during liver failure by means of auxiliary methods because liver tissue has the capability to regenerate and heal. Bioartificial liver (BAL) approaches use liver tissue or cells to provide ALF patients with liver-specific metabolism and synthesis products necessary to relieve some of the symptoms and to promote liver tissue regeneration. The most promising BAL treatments are based on the culture of tissue engineered (TE) liver constructs, with mature liver cells or cells that may differentiate into hepatocytes to perform liver-specific functions, in disposable continuous-flow bioreactors. In fact, adult hepatocytes perform all essential liver functions. Clinical evaluations of the proposed BALs show that they are safe but have not clearly proven the efficacy of treatment as compared to standard supportive treatments. Ambiguous clinical results, the time loss of cellular activity during treatment, and the presence of a necrotic core in the cell compartment of many bioreactors suggest that improvement of transport of nutrients, and metabolic wastes and products to or from the cells in the bioreactor is critical for the development of therapeutically effective BALs. In this chapter, advanced strategies that have been proposed over to improve mass transport in the bioreactors at the core of a BAL for the treatment of ALF patients are reviewed.

Temporal trends in population-based death rates associated with chronic liver disease and liver cancer in the United States over the last 30 years.

PubMed

Kim, Yuhree; Ejaz, Aslam; Tayal, Amit; Spolverato, Gaya; Bridges, John F P; Anders, Robert A; Pawlik, Timothy M

2014-10-01

The health and economic burden from liver disease in the United States is substantial and rising. The objective of this study was to characterize temporal trends in mortality from chronic liver disease and liver cancer and the incidence of associated risk factors using population-based data over the past 30 years. Population-based mortality data were obtained from the National Vital Statistics System, and population estimates were derived from the national census for US adults (aged >45 years). Crude death rates (CDRs), age-adjusted death rates (ADRs), and average annual percentage change (AAPC) statistics were calculated. In total, 690,414 deaths (1.1%) were attributable to chronic liver disease, whereas 331,393 deaths (0.5%) were attributable to liver cancer between 1981 and 2010. The incidence of liver cancer was estimated at 7.1 cases per 100,000 population. Mortality rates from chronic liver disease and liver cancer increased substantially over the past 3 decades, with ADRs of 23.7 and 16.6 per 100,000 population in 2010, respectively. The AAPC from 2006 to 2010 demonstrated an increased ADR for chronic liver disease (AAPC, 1.5%; 95% confidence interval, 0.3%-2.8%) and liver cancer (AAPC, 2.6%; 95% confidence interval, 2.4%-2.7%). A comprehensive approach that involves primary and secondary prevention, increased access to treatment, and more funding for liver-related research is needed to address the high death rates associated with chronic liver disease and liver cancer in the United States. © 2014 American Cancer Society.

Quality measurement and improvement in liver transplantation.

PubMed

Mathur, Amit K; Talwalkar, Jayant

2018-06-01

There is growing interest in the quality of health care delivery in liver transplantation. Multiple stakeholders, including patients, transplant providers and their hospitals, payers, and regulatory bodies have an interest in measuring and monitoring quality in the liver transplant process, and understanding differences in quality across centres. This article aims to provide an overview of quality measurement and regulatory issues in liver transplantation performed within the United States. We review how broader definitions of health care quality should be applied to liver transplant care models. We outline the status quo including the current regulatory agencies, public reporting mechanisms, and requirements around quality assurance and performance improvement (QAPI) activities. Additionally, we further discuss unintended consequences and opportunities for growth in quality measurement. Quality measurement and the integration of quality improvement strategies into liver transplant programmes hold significant promise, but multiple challenges to successful implementation must be addressed to optimise value. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Prognostic marker for liver disease due to alpha1-antitrypsin deficiency.

PubMed

Pferdmenges, D C; Baumann, U; Müller-Heine, A; Framke, T; Pfister, E-D

2013-09-01

Only some Alpha1-antitrypsin deficiency (A1ATD) PiZZ patients develop liver cirrhosis and portal hypertension. Aim of the study was to investigate the course of liver disease associated with PiZZ A1ATD and to determine prognostic factors. We retrospectively reviewed the clinical and laboratory data of all PiZZ children up to 18 years of age admitted to our centre since 1978. 53 patients (age at first visit 2 days to 12 years) met our criteria. The children were divided into 2 groups: group 1 'bad prognosis', meaning the patients which were on the waiting list for liver transplantation (LTx), had a liver transplantation or had died, and group 2 'good prognosis', containing the patients they were living with their own liver. We analysed family history including smoking, gestational age, maternal age at delivery, date of birth, sex, neonatal history, breast-feeding, symptoms at presentation, clinical and laboratory data and date of LTx and/or death. Various anamnesis parameters such as manifestation of neonatal cholestasis showed no prognostic significance. In contrast the laboratory parameters thrombocytes (p=0.008), bilirubin (p<0.001), prothrombin time (p<0.001), choline-sterase (p<0.001), gamma-GT (p=0.001) and GOT (p=0.002) showed a correlation with a liver transplantation and/or death. Prognosis is difficult to determine at an early stage of this disease, but various laboratory parameters can help to predict an outcome. Therefore a regular follow-up is necessary for the children. © Georg Thieme Verlag KG Stuttgart · New York.

Radiation Exposure Enhances Hepatocyte Proliferation in Neonatal Mice but not in Adult Mice.

PubMed

Shang, Yi; Sawa, Yurika; Blyth, Benjamin J; Tsuruoka, Chizuru; Nogawa, Hiroyuki; Shimada, Yoshiya; Kakinuma, Shizuko

2017-08-01

There is a natural tendency to expect that irradiation of an infant organ prior to development-related expansion will result in a higher risk of developing cancer than that of fully-developed adult tissue, and this has generally been observed. However, if tissues also vary in their initial responses to radiation depending on age, the interplay between tissue- and age-dependent risk would potentially be quite complex. We have previously shown opposing age-dependent induction of apoptosis for the intestinal epithelium and hematopoietic cells in mice, but such data are not yet available for the liver. Here, we have examined markers of DNA damage, initiation of DNA damage responses, cell cycle arrest, apoptosis and proliferation, as well as gene expression, in the B6C3F1 mouse liver over the hours and days after irradiation of mice at 1 or 7 weeks of age. We found that induction and resolution of radiation-induced DNA damage is not accompanied by significant changes in these cellular end points in the adult liver, while in infant hepatocytes modest induction of p53 accumulation and p21-mediated cell cycle arrest in a small fraction of damaged cells was overshadowed by a further stimulation of proliferation over the relatively high levels already found in the neonatal liver. We observed distinct expression of genes that regulate cell division between the ages, which may contribute to the differential responses. These data suggest that the growth factor signaling environment of the infant liver may mediate radiation-induced proliferation and increased liver cancer risk after irradiation during early life.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients with Acute Liver Injury or Failure

PubMed Central

Roberts, Dean W.; Lee, William M.; Hinson, Jack A.; Bai, Shasha; Swearingen, Christopher J.; Stravitz, R. Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M.; Rule, Jody; Fontana, Robert J.; Ganger, Daniel; Reddy, K. Rajender; Liou, Iris; Fix, Oren; James, Laura P.

2017-01-01

Background & Aims A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts. Methods We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using Fisher’s Exact for categorical variables and Kruskal-Wallis Test or Rank-Sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median (and range) AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P<.001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive-predictive value of 89.2%, and a negative-predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen–associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusion The competitive immunoassay AcetaSTAT demonstrates a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. PMID:27641661

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

PubMed Central

ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: assessment with plasma citrulline in a rodent model.

PubMed

Beaufrère, A M; Neveux, N; Patureau Mirand, P; Buffière, C; Marceau, G; Sapin, V; Cynober, L; Meydinal-Denis, D

2014-11-01

Glutamine is the preferred fuel for the rat small intestine and promotes the growth of intestinal mucosa, especially in the event of gut injury. Quantitatively, glutamine is one important precursor for intestinal citrulline release. The aim of this study was to determine whether the effect of glutamine on the increase in intestinal villus height is correlated with an increase in both gut mass and citrulline plasma level in very old rats. We intermittently supplemented very old (27-mo) female rats with oral glutamine (20% of diet protein). Intestinal histomorphometric analysis of the small bowel was performed. Amino acids, in particular citrulline, were measured in the plasma, liver and jejunum. Markers of renal (creatinine, urea) and liver (alanine aminotransferase [ALT]) and aspartate aminotransferase (AST) functions were measured to evaluate renal and liver functions in relation to aging and to glutamine supplementation. Liver glutathione was also determined to evaluate cellular redox state. Glutamine supplementation maintains the body weight of very old rats, not by limiting sarcopenia but rather by increasing the organ mass of the splanchnic area. Total intestine mass was significantly higher in glutamine-supplemented rats than in controls (15%). Measurement of villus height and crypt depth demonstrated that the difference between villus and crypt was significantly improved in glutamine pre-treated rats compared to controls (~ 11%). Plasma citrulline also increased by 15% in glutamine-supplemented rats compared to controls. Citrulline appears as a biomarker of enterocyte mass in villous atrophy associated with advanced age. Non-invasive measurement of this metabolite may be useful in following the state of the gastrointestinal tract in very old people, whose numbers are increasing worldwide and the care of whom is a major public health issue. The gut may contribute to the malnutrition caused by malabsorption frequently observed in the elderly.

Kidney and liver transplantation in the elderly.

PubMed

Sutherland, A I; IJzermans, J N M; Forsythe, J L R; Dor, F J M F

2016-01-01

Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation. The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike. Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients. Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

PubMed

Lemon, Stanley M; Walker, Christopher M

2018-05-07

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Wong, Weng-Yew; Poudyal, Hemant; Ward, Leigh C.; Brown, Lindsay

2012-01-01

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome. PMID:23201770

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C.

PubMed

Boursier, J; Brochard, C; Bertrais, S; Michalak, S; Gallois, Y; Fouchard-Hubert, I; Oberti, F; Rousselet, M-C; Calès, P

2014-07-01

Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis. © 2014 John Wiley & Sons Ltd.

Tricho-hepato-enteric syndrome with novel SKIV2L gene mutations

PubMed Central

Hiejima, Eitaro; Yasumi, Takahiro; Nakase, Hiroshi; Matsuura, Minoru; Honzawa, Yusuke; Higuchi, Hirokazu; Okafuji, Ikuo; Yorifuji, Tohru; Tanaka, Takayuki; Izawa, Kazushi; Kawai, Tomoki; Nishikomori, Ryuta; Heike, Toshio

2017-01-01

Abstract Rationale: Tricho-hepato-enteric syndrome (THES) is a rare disorder caused by mutations in the TTC37 or SKIV2L genes and characterized by chronic diarrhea, liver disease, hair abnormalities, and high mortality in early childhood due to severe infection or liver cirrhosis. Patient concerns: The patient is the second child of three siblings born to non-consanguineous healthy Japanese parents. She had intrauterine growth retardation and was delivered at 33 weeks of gestation due to placental abruption. She presented with watery diarrhea, elevated levels of liver enzymes, multiple episodes of recurrent bacterial infection, and mild mental retardation. She had facial dysmorphism, including prominent forehead and hypertelorism, and had woolly hair without trichorrhexis nodosa. Diagnosis: Clinical features led to consideration of THES. Novel compound heterozygous nonsense mutations, c.1420G>T (p.Q474∗) and c.3262G>T (p.E1088∗), in the SKIV2L gene were identified in the patient, and decreased levels of SKIV2L protein expression were revealed by flow cytometry and confirmed by western blot analysis using patient peripheral blood mononuclear cells (PBMCs). Interventions: Total parenteral nutrition was required from day 30 to day 100. Trimethoprim-sulfamethoxazole prophylaxis was started at the age of 7 years after multiple episodes of bacterial pneumonia and otitis media. Outcomes: Chronic diarrhea persisted for more than 10 years, but the symptoms gradually improved with age. At the age of 13 years, she started a normal diet in combination with oral nutritional supplementation and her height and weight were just below the 3rd percentile for healthy individuals. She developed secondary sex characteristics, and menarche occurred at the age of 12 years. Facial dysmorphism, including prominent forehead and hypertelorism, and woolly hair without trichorrhexis nodosa became noticeable as she matured. Lessons: Physicians must be aware of THES when they encounter a patient with infantile diarrhea, hair abnormalities, immune deficiency, mental retardation, and liver disease. Moreover, flow cytometric detection of SKIV2L protein in PBMCs may facilitate early diagnosis. PMID:29145277

Hepatoerythropoietic porphyria precipitated by viral hepatitis.

PubMed Central

Hift, R J; Meissner, P N; Todd, G

1993-01-01

Porphyria cutanea tarda (PCT), the condition resulting from a deficiency of hepatic uroporphyrinogen decarboxylase activity, is the commonest form of porphyria. Both acquired and familial form exist and are commonly associated in adults with liver disease and hepatic iron overload. The condition is extremely rare in children; most cases of childhood PCT are familial and some particularly severe cases have been shown to have a hepatoerythropoietic porphyria or homozygous uroporphyrinogen decarboxylase deficiency. A case is described of hepatoerythropoietic porphyria in which the disease was first precipitated at the age of two by a coincidental hepatitis A infection and improved as the hepatitis cleared. This paper reviews the evidence that viral hepatitis may precipitate overt PCT in children in a manner analogous to the precipitation of PCT in adults by alcohol associated liver disease. PMID:7902313

Gutuo Jiejiu decoction improves survival of patients with severe alcoholic hepatitis: A retrospective cohort study.

PubMed

Mou, Hong-Yuan; Nie, Hong-Ming; Hu, Xiao-Yu

2017-04-28

To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH). We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed. One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients' baseline characteristics ( P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group ( P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant ( P < 0.05). No significant differences in complications and adverse effects were found between the two groups. Gutuo Jiejiu decoction could improve the survival rates and clinical parameters of liver injury in patients with SAH, and may represent a new option for treating SAH.

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

PubMed Central

Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

2006-01-01

Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly methylated, that this condition takes place as an age-related phenomenon and that the early setting and spreading over time of an epigenetically methylated hepatocyte subpopulation, might be related to liver tumorigenesis. PMID:16606445

Experimental and clinical evidence for modification of hepatic ischaemia–reperfusion injury by N-acetylcysteine during major liver surgery

PubMed Central

Jegatheeswaran, Santhalingam; Siriwardena, Ajith K

2011-01-01

Background Hepatic ischaemia–reperfusion (I/R) injury occurs in both liver resectional surgery and in transplantation. The biochemistry of I/R injury involves short-lived oxygen free radicals. N-acetylcysteine (NAC) is a thiol-containing synthetic compound used in the treatment of acetaminophen toxicity. The present study is a detailed overview of the experimental and clinical evidence for the use of NAC as a pharmaco-protection agent in patients undergoing major liver surgery or transplantation. Methods A computerized search of the Medline, Embase and SCI databases for the period from 1st January 1988 to 31st December 2008 produced 40 reports. For clinical studies, the quality of reports was assessed according to the criteria reported by the Cochrane communication review group. Results Nineteen studies evaluated NAC in experimental liver I/R injury. NAC was administered before induction of ischaemia in 13. The most widely used concentration was 150 mg/kg by intravenous bolus. Fifteen studies report an improvement in outcome, predominantly a reduction in transaminase. Seven studies used an isolated perfused liver model with all showing improvement (predominantly an improvement in bile production after N-acetylcysteine). Two out of four transplantation models showed an improvement in hepatic function. Clinical studies in transplantation show a modest improvement in transaminase levels with no beneficial effect on either patient or graft survival. Conclusion N-acetylcysteine, given before induction of a liver I/R injury in an experimental model can ameliorate liver injury. Clinical outcome data are limited and there is currently little evidence to justify use either in liver transplantation or in liver resectional surgery. PMID:21241423

Comparison of Cox's Regression Model and Parametric Models in Evaluating the Prognostic Factors for Survival after Liver Transplantation in Shiraz during 2000-2012.

PubMed

Adelian, R; Jamali, J; Zare, N; Ayatollahi, S M T; Pooladfar, G R; Roustaei, N

2015-01-01

Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. To compare Cox's regression model with parametric models for determining the independent factors for predicting adults' and pediatrics' survival after liver transplantation. This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Parametric regression model is a good alternative for the Cox's regression model.

Pediatric Liver Transplantation: Our Experiences.

PubMed

Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

2016-10-01

The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months-17 years). The 4 most common reasons for liver transplantation were: Wilson's disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature.

The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome.

PubMed

Aguilar-Olivos, Nancy E; Almeda-Valdes, Paloma; Aguilar-Salinas, Carlos A; Uribe, Misael; Méndez-Sánchez, Nahum

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

In vivo antioxidant activity of total flavonoids from indocalamus leaves in aging mice caused by D-galactose.

PubMed

Jin, Sheng-lang; Yin, Yong-guang

2012-10-01

The aim of this thesis is to explore antioxidant activity of total flavonoids extracted from indocalamus leaves. Aging mice model was established by D-galactose induction. Three groups of mice were treated with total flavonoids extracted from indocalamus leaves at doses of 20, 40 and 80 mg/kg d bw respectively. The antioxidant status in the aging mice was measured by determining the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and total anti-oxidant capability (T-AOC) in the serum and liver and malondialdehyde (MDA) content in the serum, liver and brain. Compared with control group, extracts of indocalamus leaves significantly enhanced activities of SOD, GSH-Px, CAT in the serum and liver, and decreased MDA content in the serum, liver and brain at the tested doses. Total flavonoids extracted from indocalamus leaves demonstrated the potent antioxidant activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Role of FibroScan in liver fibrosis evaluation in patients with chronic hepatitis B virus infection and related influencing factors].

PubMed

Xie, Q X; Xu, N; Jiang, X P; Zhang, Y F; Zhang, Z H; Li, J B; Hu, X Y; Li, X

2016-09-20

Objective: To investigate the role of FibroScan(FS)in liver fibrosis evaluation in patients with chronic hepatitis B virus(HBV)infection and related influencing factors. Methods: A total of 313 patients with chronic HBV infection were enrolled, and liver tissue was obtained through ultrasound-guided"1-second fast tissue cutting". The liver stiffness measurement(LSM)was determined by FS, serum HBeAg and liver function were measured, and the patients' demographic data were recorded. The t -test was used for comparison of normally distributed data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed data between groups; the Spearman or Pearson correlation coefficient was used for correlation analysis; the ROC curve and AUC were used to evaluate the efficiency of FS in the diagnosis of liver fibrosis ≥S2. Results: LSM was positively correlated with liver inflammation grade and fibrosis stage( r = 0.428 and 0.402 in HBeAg-positive group and r = 0.296 and 0.283 in HBeAg-negative group, all P < 0.001). The correlation of LSM with sex, age, alanine aminotransferase(ALT)level, and total bilirubin(TBil)was affected by HBeAg status and ALT level, and LSM was only positively correlated with TBil in HBeAg-negative group( r = 0.298, P < 0.001). In patients with ALT ≥2×upper limit of normal(ULN), FS had a low efficiency in the diagnosis of liver fibrosis ≥S2(AUC < 0.75, P > 0.05), regardless of their HBeAg status. The cut-off values of FS in the diagnosis of liver fibrosis ≥S2 varied with ALT level and HBeAg status, and in the ALT <1×ULN and 1-2×ULN groups, the cut-off values of FS in the diagnosis of liver fibrosis ≥S2 in patients with positive and negative HBeAg were 5.85 kPa/7.3 kPa and 6.35 kPa/8.5 kPa, respectively. In the patients with positive HBeAg in ALT < 2×ULN group, LSM was positively correlated with age( r = 0.278, P = 0.014). FS had relatively high diagnostic efficiency in patients aged > 30 years(AUC = 0.867, P < 0.001)and low diagnostic efficiency in patients aged≤30 years(AUC = 0.632, P > 0.05). Conclusion: LSM is positively correlated with liver inflammation grade and fibrosis stage. The cut-off value of FS in the diagnosis of marked liver fibrosis is affected by age, ALT level, and HBeAg status. FS has low diagnostic efficiency in patients aged ≤30 years.

Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.

PubMed

Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang

2018-02-07

Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Unilobar Versus Bilobar Biliary Drainage: Effect on Quality of Life and Bilirubin Level Reduction

PubMed Central

Gamanagatti, Shivanand; Singh, Tejbir; Sharma, Raju; Srivastava, Deep N; Dash, Nihar Ranjan; Garg, Pramod Kumar

2016-01-01

Background: Percutaneous biliary drainage is an accepted palliative treatment for malignant biliary obstruction. Purpose: To assess the effect on quality of life (QOL) and bilirubin level reduction in patients with inoperable malignant biliary obstruction treated by unilobar or bilobar percutaneous transhepatic biliary drainage (PTBD). Materials and Methods: Over a period of 2 years, 49 patients (age range, 22–75 years) of inoperable malignant biliary obstruction were treated by PTBD. Technical and clinical success rates, QOL, patency rates, survival rates, and complications were recorded. Clinical success rates, QOL, and bilirubin reduction were compared in patients treated with complete (n = 21) versus partial (n = 28) liver parenchyma drainage. QOL before and 1 month after biliary drainage were analyzed retrospectively between these two groups. Results: Biliary drainage was successful in all 49 patients, with an overall significant reduction of the postintervention bilirubin levels (P < 0.001) resulting in overall clinical success rate of 89.97%. Clinical success rates were similar in patients treated with whole-liver drainage versus partial-liver drainage. Mean serum bilirubin level before PTBD was 19.85 mg/dl and after the procedure at 1 month was 6.02 mg/dl. The mean baseline functional score was 39.35, symptom scale score was 59.55, and global health score was 27.45. At 1 month, mean functional score was 61.25, symptom scale score was 36.0 4, and global health score was 56.33, with overall significant improvement in QOL (<0.001). There was a statistically significant difference in the improvement of the QOL scores (P = 0.002), among patients who achieved clinical success, compared with those patients who did not achieve clinical success at 1 month. We did not find any significant difference in the QOL scores in patients according to the amount of liver drained (unilateral or bilateral drainage), the type of internalization used (ring biliary or stent). Overall, minor and major complications rates were 14.3% and 8.1%, respectively. Conclusion: Percutaneous biliary drainage provides good palliation of malignant obstructive jaundice. Partial-liver drainage achieved results as good as those after complete liver drainage with significant improvements in QOL and reduction of the bilirubin level. PMID:26962281

Heavy metals in Franklin`s gull tissues: Age and tissue differences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, J.; Gochfeld, M.

1999-04-01

The authors examined the concentrations of lead, cadmium, chromium, mercury, manganese, and selenium in feathers, liver, kidney, heart, brain, and breast muscle of Franklin`s gulls (Larus pipixcan) nesting in northwestern Minnesota, USA, in 1994. Between 16% (chromium) and 71% (selenium, manganese) of the variation in metal concentrations was explained by tissue and age, except for selenium and arsenic, which were only explained by tissue. Of 35 possible differences (seven metals in five tissues), 24 significant age-related differences were found in Franklin`s gulls, with young generally having lower concentrations of metals in all of their tissues than adults. A notable exceptionmore » was the liver; young had significantly higher concentrations of selenium, chromium, manganese, and arsenic than did adults. Three notable findings were the following: young had significantly higher concentrations of selenium, chromium, manganese, and arsenic in their liver than did adults; young had 30 times as much chromium in the liver than adults; and adults had greatly elevated concentrations of cadmium in feathers, kidney, and liver.« less

[Clinical and experimental study of treating aplastic anemia with fetal liver cell suspension and fetal liver cell-free suspension].

PubMed

Han, J R; Yuan, S W; Ren, Q F

1990-06-01

Fresh fetal liver obtained from 3- to 6-month fetus was prepared. Fetal liver cell suspension (FLC) or fetal liver cell-free suspension (FLCF) were then transfused into two groups of patient of aplastic anemia. 15 of 21 patients of aplastic anemia treated with FLC showed reconstitution of haemopoietic function or improvement of peripheral blood pictures, while 27 of 30 patients treated with FLCF showed reconstitution or improvement. It is verified that there is a stimulating factor for CFU-CM, BFU-E, and CFU-E and also a immunologic stimulant for improving the nonspecific immunologic function of the organism as shown by clinical analysis and experimental study. It is obvious that the therapeutic effect of FLCF is much better than that of the FLC.

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

PubMed

Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

2018-01-11

There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute-on-chronic liver failure suggests poor outcome and need for early intervention. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats

PubMed Central

Chang, Eugene; Kim, Lisa; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Park, Cheol-Young

2015-01-01

AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe (10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides (TG), free fatty acids (FFA), and total cholesterol (TC) in blood and TG, FFA, and TG in liver tissue were measured. mRNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe (10 μmol/L) together with or without palmitic acid (PA, 0.5 mmol/L, 24 h). Transmission electron microscopy (TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression. RESULTS: In the OLETF rats that received ezetimibe (10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight (P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls (P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe (P < 0.05). In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe (P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced mRNA and protein expression involved in autophagy (P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy. PMID:26167075

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

PubMed

Damm, Robert; Seidensticker, Ricarda; Ulrich, Gerhard; Breier, Leonie; Steffen, Ingo G; Seidensticker, Max; Garlipp, Benjamin; Mohnike, Konrad; Pech, Maciej; Amthauer, Holger; Ricke, Jens

2016-07-20

In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001). Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

A quarter century experience in liver trauma: a plea for early computed tomography and conservative management for all hemodynamically stable patients.

PubMed

Petrowsky, Henrik; Raeder, Susanne; Zuercher, Lucia; Platz, Andreas; Simmen, Hans Peter; Puhan, Milo A; Keel, Marius J; Clavien, Pierre-Alain

2012-02-01

Advances in diagnostic imaging and the introduction of damage control strategy in trauma have influenced our approach to treating liver trauma patients. The objective of the present study was to investigate the impact of change in liver trauma management on outcome. A total of 468 consecutive patients with liver trauma treated between 1986 and 2010 at a single level 1 trauma center were reviewed. Mechanisms of injury, diagnostic imaging, hepatic and associated injuries, management (operative [OM] vs. nonoperative [NOM]), and outcome were evaluated. The main outcome analysis compared mortality for the early study period (1986-1996) versus the later study period (1997-2010). 395 patients (84%) presented with blunt liver trauma and 73 (16%) with penetrating liver trauma. Of these, 233 patients were treated with OM (50%) versus 235 with NOM (50%). The mortality rate was 33% for the early period and 20% for the later period (odds ratio 0.19; 95% CI 0.07-0.50, P = 0.001). A significantly increased use of computed tomography (CT) as the initial diagnostic modality was observed in the late period, which almost completely replaced peritoneal lavage and ultrasound. There was a significant shift to NOM in the later period (early 15%, late 63%) with a low conversion rate to OM of 4.2%. Age, degree of hepatic and head injury, injury severity, intubation at admission, and early period were independent predictors of mortality in the multivariate analysis. Integration of CT in early trauma-room management and shift to NOM in hemodynamically stable patients resulted in improved survival and should be the gold standard management for liver trauma.

Aging enhances liver fibrotic response in mice through hampering extracellular matrix remodeling.

PubMed

Delire, Bénédicte; Lebrun, Valérie; Selvais, Charlotte; Henriet, Patrick; Bertrand, Amélie; Horsmans, Yves; Leclercq, Isabelle A

2016-12-09

Clinical data identify age as a factor for severe liver fibrosis. We evaluate whether and how aging modulates the fibrotic response in a mouse model. Liver fibrosis was induced by CCl 4 injections (thrice weekly for 2 weeks) in 7 weeks- and 15 months-old mice (young and old, respectively). Livers were analyzed for fibrosis, inflammation and remodeling 48 and 96 hours after the last injection. Old mice developed more severe fibrosis compared to young ones as evaluated by sirius red morphometry. Expression of pro-fibrogenic genes was equally induced in the two age-groups but enhanced fibrolysis in young mice was demonstrated by a significantly higher Mmp13 induction and collagenase activity. While fibrosis resolution occurred in young mice within 96 hours, no significant fibrosis attenuation was observed in old mice. Although recruitment of monocytes-derived macrophages was similar in young and old livers, young macrophages had globally a remodeling phenotype while old ones, a pro-fibrogenic phenotype. Moreover, we observed a higher proportion of thick fibers and enhanced expression of enzymes involved in collagen maturation in old mice. Impaired fibrolysis of a matrix less prone to remodeling associated with a pro-inflammatory phenotype of infiltrated macrophages contribute to a more severe fibrosis in old mice.

An mtDNA mutation accelerates liver aging by interfering with the ROS response and mitochondrial life cycle.

PubMed

Niemann, Jan; Johne, Cindy; Schröder, Susanne; Koch, Franziska; Ibrahim, Saleh M; Schultz, Julia; Tiedge, Markus; Baltrusch, Simone

2017-01-01

Mitochondrial dysfunction affects liver metabolism, but it remains unclear whether this interferes with normal liver aging. We investigated several mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse strain compared with the control C57BL/6NTac strain over 18 months of life. The C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac-mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen species (ROS) production to C57BL/6NTac mice. Whereas ROS increased almost equally up to 9 months in both strains, different mitochondrial adaptation strategies resulted in decreasing ROS in advanced age in C57BL/6NTac mice, but persistent ROS production in C57BL/6NTac-mtNODLtJ mice. Only the conplastic strain developed elongated mitochondrial networks with artificial loop structures, depressed autophagy, high mitochondrial respiration and up-regulated antioxidative response. Our results indicate that mtDNA mutations accelerate liver ballooning degeneration and carry a serious risk of premature organ aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Fatty liver in children

PubMed Central

Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

2009-01-01

Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 ± 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 ± 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). Conclusion: The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children. PMID:19536316

The significance of cutaneous spider naevi in children

PubMed Central

Finn, S M; Rowland, M; Lawlor, F; Kinsella, W; Chan, L; Byrne, O; O'Mahony, O; Bourke, B

2006-01-01

Background Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. Aim To evaluate the occurrence of spider naevi in children with and without liver disease. Methods The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. Results Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. Conclusions Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions. PMID:16595646

The use of old donors in liver transplantation.

PubMed

Dasari, Bobby V M; Schlegel, Andrea; Mergental, Hynek; Perera, M Thamara P R

2017-04-01

The process of ageing has an impact on the entire human body including the organ systems. In transplantation, professionals are daily faced with risk assessment of suitable donor offers , whether to accept a liver graft for a specific recipient. In this context, livers from elderly donors are more frequently accepted for transplantation, to increase the donor pool and compensate the high waiting list mortality. In the current practice it is not unusual to accept 60-year old donor livers for transplantation, as the donor demographics have significantly changed over the years. However, controversy exists regarding the use of livers from donors above 70 or 80 years, particular in combination with other risk factors, e.g. liver steatosis, warm ischaemia or long cold storage. This review focuses first on the impact of ageing on liver morphology and function. Second, we will highlight outcome after transplantation from elderly donors. Finally, we describe further risk factors and donor-recipient selection under the scope of old donor organs and include our institutional experience and policy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

PubMed

Özçay, Figen; Barış, Zeren; Moray, Gökhan; Haberal, Nihan; Torgay, Adnan; Haberal, Mehmet

2015-11-01

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation. In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.

Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers.

PubMed

Rodríguez de Lope, Carlos; Reig, María; Matilla, Ana; Ferrer, María Teresa; Dueñas, Eva; Mínguez, Beatriz; F Castroagudín, Javier; Ortiz, Inmaculada; Pascual, Sonia; Lledó, José Luis; Gallego, Adolfo; Arenas, Juan I; Aracil, Carles; Forne, Montserrat; Muñoz, Carolina; Pons, Fernando; Sala, Margarita; Iñarrairaegui, Mercedes; Martin-Llahi, Marta; Andreu, Victoria; Garre, Carmen; Rendón, Paloma; Fuentes, Javier; Crespo, Javier; Rodríguez, Manuel; Bruix, Jordi; Varela, María

2017-07-21

In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Liver transplantation for the treatment of hyperammonemia due to urea cycle disorder: report of four cases].

PubMed

Zhu, Zhijun; Sun, Liying; Wei, Lin; Qu, Wei; Zeng, Zhigui; Liu, Ying; Zhang, Liang; He, Enhui; Wang, Dong

2015-02-01

To analyze clinical efficacy and prognosis of liver transplantation in children with hyperammonemia caused by urea cycle disorders. A retrospective analysis was performed on the occurrence of disease, operation and the follow-up post liver transplantation in 4 patients with urea cycle disorders who underwent liver transplantation during June 2001 to May 2014. Four girls were diagnosed with ornithine carbamoyl transferase deficiency by genetic test. They had the clinical onset at the age of 1.5 to 3.0 years. Liver transplantation had been performed at their age of 53.9 months, 40.6 months, 40.3 months and 22.8 months, respectively. The grafts of case 1 and case 2 were from left lateral lobe of liver of cadaveric donor, the graft of case 3 was from left lateral lobe of liver of a living donor, the graft of case 4 was a whole liver of a dead child. The liver function of 4 patients gradually returned to normal, blood ammonia levels were normal and restored the normal diet, 4 children were discharged on postoperative 25-30 days. Regular follow-up was done, the liver function, biochemical features and growth status have been followed up for 162.2 months, 124.2 months, 12.0 months and 4.8 months after liver transplantation, respectively. Now, all the four cases are healthy and growth is normal. Liver transplantation is an important way to the patients with severe hyperammonemia caused by urea cycle disorders. In this study, the patients with ornithine carbamoyl transferase defect got satisfactory long-term outcome after liver transplantation.

Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice.

PubMed

Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Schnellmann, Rick G; Lemasters, John J; Zhong, Zhi

2015-07-01

Inclusion of liver grafts from cardiac death donors (CDD) would increase the availability of donor livers but is hampered by a higher risk of primary non-function. Here, we seek to determine mechanisms that contribute to primary non-function of liver grafts from CDD with the goal to develop strategies for improved function and outcome, focusing on c-Jun-N-terminal kinase (JNK) activation and mitochondrial depolarization, two known mediators of graft failure. Livers explanted from wild-type, inducible nitric oxide synthase knockout (iNOS(-/-)), JNK1(-/-) or JNK2(-/-) mice after 45-min aorta clamping were implanted into wild-type recipients. Mitochondrial depolarization was detected by intravital confocal microscopy in living recipients. After transplantation of wild-type CDD livers, graft iNOS expression and 3-nitrotyrosine adducts increased, but hepatic endothelial NOS expression was unchanged. Graft injury and dysfunction were substantially higher in CDD grafts than in non-CDD grafts. iNOS deficiency and inhibition attenuated injury and improved function and survival of CDD grafts. JNK1/2 and apoptosis signal-regulating kinase-1 activation increased markedly in wild-type CDD grafts, which was blunted by iNOS deficiency. JNK inhibition and JNK2 deficiency, but not JNK1 deficiency, decreased injury and improved function and survival of CDD grafts. Mitochondrial depolarization and binding of phospho-JNK2 to Sab, a mitochondrial protein linked to the mitochondrial permeability transition, were higher in CDD than in non-CDD grafts. iNOS deficiency, JNK inhibition and JNK2 deficiency all decreased mitochondrial depolarization and blunted ATP depletion in CDD grafts. JNK inhibition and deficiency did not decrease 3-nitrotyrosine adducts in CDD grafts. The iNOS-JNK2-Sab pathway promotes CDD graft failure via increased mitochondrial depolarization, and is an attractive target to improve liver function and survival in CDD liver transplantation recipients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Long-term results using old liver grafts for transplantation: sexagenerian versus liver donors older than 70 years.

PubMed

Jiménez-Romero, Carlos; Clemares-Lama, Marta; Manrique-Municio, Alejandro; García-Sesma, Alvaro; Calvo-Pulido, Jorge; Moreno-González, Enrique

2013-09-01

The most practical measure to augment the available number of liver grafts and thus reduce waiting list mortality is to increase the donor age limit. We hypothesized that with careful selection of old liver donors without age limit it should be possible to obtain good patient and graft survival. The present study comprises 351 adults who underwent liver transplantation. They were divided into three groups according to the age of the liver donors: group 1: 226 recipients of donors <60 years; group 2: 75 recipients of donors between 60 and 70 years; and group 3: 50 recipients of donors >70 years. A comparative study among the groups was performed. Patient survival rates at 1, 3, and 5 years were, respectively, 81.0, 76.1, and 71.1 % in group 1; 83.8, 74, and 72.2 % in group 2; and 76, 70.0, and 62.9 % in group 3 (P = NS). Graft survival at 1, 3, and 5 years was, respectively, 74.8, 69.0, and 64.1 % in group 1; 82.7, 71.4, and 69.6 % in group 2; and 71.4, 64.8, and 58.3 % in group 3 (P = NS). We analyzed the use of older grafts in recipients with HCV cirrhosis and did not find significant differences in patient and graft survival at 1, 3, and 5 years. In multivariate analysis increased donor body mass index and decreased recipient albumin were associated with lower patient and graft survival. Because patient and graft survival rates are not affected by donor age, well-selected older donor livers can be safely used if they show good function and preharvesting conditions.

Donor-transmitted, donor-derived, and de novo cancer after liver transplant.

PubMed

Chapman, Jeremy R; Lynch, Stephen V

2014-03-01

Cancer is the third most common cause of death (after cardiovascular disease and infection) for patients who have a functioning kidney allograft. Kidney and liver transplant recipients have similar cancer risks because of immunosuppression but different risks because of differences in primary diseases that cause renal and hepatic failure and the inherent behavior of cancers in the liver. There are 4 types of cancer that may develop in liver allograft recipients: (1) recurrent cancer, (2) donor-transmitted cancer, (3) donor-derived cancer, and (4) de novo cancer. Identification of potential donor cancer transmission may occur at postmortem examination of a deceased donor or when a probable donor-transmitted cancer is identified in another recipient. Donor-transmitted cancer after liver transplant is rare in Australia, the United Kingdom, and the United States. Aging of the donor pool may increase the risk of subclinical cancer in donors. Liver transplant recipients have a greater risk of de novo cancer than the general population, and risk factors for de novo cancer in liver transplant recipients include primary sclerosing cholangitis, alcoholic liver disease, smoking, and increased age. Liver transplant recipients may benefit from cancer screening because they have a high risk, are clearly identifiable, and are under continuous medical supervision.

Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure.

PubMed

Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

2018-03-24

Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate to the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-antibody, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by gene ontology enrichment analysis. Cell viability was evaluated in cell lines knocked-down for PDHA1 or LDH-A and in cells incubated with the LDH inhibitor galloflavin after treatment with CD95-antibody. We evaluated whether the histone acetyltransferase inhibitor garcinol or galloflavin could reduce liver damage in mice with acute liver failure. Levels and activities of PDHC and LDH were increased in nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-CoA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to damage response. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus, leading to increased nuclear concentrations of acetyl-CoA and lactate. This results in histone H3 hyper-acetylation and expression of damage response genes. Inhibition of PDHC and LDH reduces liver damage and improves survival in mice with acute liver failure. Thus, PDHC and LDH are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive deterioration of liver function resulting in high mortality. In experimental mouse models of acute liver failure, we found that two metabolic enzymes, namely pyruvate dehydrogenase complex and lactic dehydrogenase, translocate to the nucleus resulting in detrimental gene expression. Treatment with an inhibitor of these two enzymes was found to reduce liver damage and to improve survival. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Aging promotes neoplastic disease through effects on the tissue microenvironment.

PubMed

Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

2016-12-06

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

Age-related Changes in the Hepatic Microcirculation in Mice

PubMed Central

Ito, Yoshiya; Sørensen, Karen K.; Bethea, Nancy W.; Svistounov, Dmitri; McCuskey, Margaret K.; Smedsrød, Bård H.; McCuskey, Robert S.

2007-01-01

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers. PMID:17582718

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

PubMed Central

2017-01-01

Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC). AGEs and RAGE are upregulated in liver fibrosis, and the silencing of RAGE reduced collagen deposition and the tumor growth of HCC. Nevertheless, data relating to Glo-I in fibrosis and cirrhosis are preliminary. Glo-I expression was found to be reduced in early and advanced cirrhosis with a subsequent increase of MGO-levels. On the other hand, pharmacological modulation of Glo-I resulted in the reduced activation of hepatic stellate cells and therefore reduced fibrosis in the CCl4-model of cirrhosis. Thus, current research highlighted the Glo-I/AGE/RAGE system as an interesting therapeutic target in chronic liver diseases. These findings need further elucidation in preclinical and clinical studies. PMID:29156655

[Disease burden of liver cancer in the Chinese population, in 1990 and 2013].

PubMed

Wang, L J; Yin, P; Liu, Y N; Liu, J M; Qi, J L; Zhou, M G

2016-06-01

To analyze the disease burden of liver cancer in the Chinese population in 1990 and 2013. Data from Global Burden of Diseases 2013 (GBD2013) was used to analyze the disease burden of liver cancer in China. The main outcome measurements would include mortality and disability-adjusted life years (DALY). Again, GBD global standard population in 2013 was used as the reference population to calculate the age-standardized rate. Related changes on percentage from 1990 to 2013 were calculated to analyze the changing patterns of disease burden for liver cancer in China. In 2013, a total of 358 100 people died of liver cancer, with the crude death rate as 25.85/100 000, in China. Number of deaths due to liver cancer secondary to hepatitis B was 163 600 (accounting for 45.69%). Number of deaths due to liver cancer secondary to hepatitis C was 134 200 (accounting for 37.48%) with DALY due to liver cancer appeared as 40.80 million person years. In 2013, the leading causes of DALY related to liver cancer was liver cancer secondary to hepatitis B, followed by liver cancer secondary to hepatitis C, liver cancer secondary to alcohol use, other liver cancers, with related DALYs as 4 652.0, 3 394.3, 964.3 and 592.1 thousands person years, respectively. The disease burdens of liver cancer secondary to various kinds of liver cancer were significantly higher in males than in females. Compared with 1990, the standardized mortality of liver cancer reduced by 25.00%, the DALY attributable to liver cancer increased by 16.95% and the standardized DALY rate attributable to liver cancer reduced by 33.47%. The burden of liver cancer secondary to hepatitis C became more serious and the standardized death rate increased by 106.18%, together with the standardized DALY rate increased by 91.68% in the past 23 years. Disease burden of liver cancer among young adults and the elderly were most serious. When comparing with the data in 1990, the standardized DALY rate showed declining trend in all the age groups, with the most seen in the 5-14 year group. The standardized DALY rate, secondary to hepatitis B had a 46.37% decrease in the 5-14 year olds. The standardized DALY rate secondary to hepatitis C showed an increasing trend in all the age groups. Liver cancer had been one of the serious diseases that causing heavy disease burden in China. In recent years, the disease burden of liver cancer secondary to hepatitis B decreased but the disease burden of liver cancer secondary to hepatitis C significantly increased. Disease burden on liver cancer in male population was significantly higher than that in females, showing that related targeted prevention and control measures should be imminently carried out.

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

PubMed

Press, Craig A; Morgan, Lindsey; Mills, Michele; Stack, Cynthia V; Goldstein, Joshua L; Alonso, Estella M; Wainwright, Mark S

2017-01-01

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. Retrospective cohort study. Tertiary care pediatric hospital. Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. None. Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p < 0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p < 0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p < 0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p < 0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p > 0.05). Spectral electroencephalogram classification correlated with outcome (p < 0.05). Spectral electroencephalogram analysis can be used to evaluate even young patients for hepatic encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute liver failure.

Platelets in liver disease, cancer and regeneration.

PubMed

Kurokawa, Tomohiro; Ohkohchi, Nobuhiro

2017-05-14

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

"Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology.

PubMed

Graham, Jay A; Guarrera, James V

2014-08-01

As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex vivo techniques such as hypothermic, normothermic, and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury. Moreover, other preservation techniques such as oxygen persufflation are explored as they may also have a role in improving function of "marginal" liver allografts. Currently, marginal livers are frequently discarded or can relegate the patient to early allograft dysfunction and primary non-function. Bench to bedside advances are rapidly emerging and hold promise for expanding liver transplantation access and improving outcomes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Early graft dysfunction and mortality rate in marginal donor liver transplantation.

PubMed

Sarkut, Pmar; Gülcü, Bariş; Işçimen, Remzi; Kiyici, Murat; Türker, Gürkan; Topal, Naile Bolca; Ozen, Yilmaz; Kaya, Ekrem

2014-01-01

To determine the effect of marginal donor livers on mortality and graft survival in liver transplantation (LT) recipients. Donors with any 1 of following were considered marginal donors: age ≥65 years, sodium level ≥ 165 mmol/L and cold ischemia time ≥ 12 h. Donors were classified according to the donor risk index (DRI) < 1.7 and ≥ 1.7. The transplant recipients' model for end-stage liver disease (MELD) scores were considered low if < 20 and high if ≥ 20. Early graft dysfunction (EGD) and mortality rate were evaluated. During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI > 1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥ 1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥ 1.7 and patients that received standard donor livers. Marginal and DRI ≥ 1.7 donors negatively affected LT outcomes, but not significantly.

Non-invasive fibrosis tests are correlated with necroinflammatory actvity of liver in patients with chronic hepatitis B.

PubMed

Ozyalvacli, G; Kucukbayrak, A; Kurt, M; Gurel, K; Gunes, O; Ustun, C; Akdeniz, H

2014-01-01

The gold standarda method used for assessing necroinflammatory activity and fibrosis in the liver is a liver biopsy which has many disadvantages. Therefore, many investigators have been trying to develop non-invasive tests for predicting liver fibrosis score (LFS) of these patients. The aim of this study is to describe the relationship between certain non-invasive fibrosis markers with LFS and histological activity index (HAI) detected histopathologically by liver biopsy in chronic hepatitis B patients. A total of 54 patients who had undergone a liver biopsy with the diagnosis of chronic HBV infection were included in the study. Ishak scoring was used for the evaluation of liver fibrosis, and a modified Knodell HAI was used for demonstration of necroinflammation. In this study, non-invasive fibrosis tests were calculated as described in previous studies. Histological acitivity index was positively correlated with age, age/platelet index, cirrhosis discriminant score (CDS), AST/platelet ratio index (APRI), AST/platelet/GGT/AFP index (APGA), fibro-quotient (Fibro-Q), Goteburg University Cirrhosis Index (Guci), and Platelet/Age/Phosphatase/AFP/AST index (PAPAS). When divided into two groups according to HAI, Guci and APGA were found significantly different both in >4 and >4 HAI groups than the other group. In ROC analysis performed for LFS; PAPAS, APGA, FFI and APRI were the markers having the highest AUC levels, and in ROC analysis performed for HAI; Guci, APRI and APGA were the markers with the highest AUC levels. APRI, APGA and GUCI tests may be helpful in prediction of necroinflammatory scores in the liver.

Herpes zoster correlates with pyogenic liver abscesses in Taiwan.

PubMed

Mei-Ling, Shen; Kuan-Fu, Liao; Sung-Mao, Tsai; Cheng-Li, Lin Ms; Shih-Wei, Lai

2016-12-01

The purpose of the paper was to explore the relationship between herpes zoster and pyogenic liver abscesses in Taiwan. This was a nationwide cohort study. Using the database of the Taiwan National Health Insurance Program, there were 33049 subjects aged 20-84 years who were newly diagnosed with herpes zoster from 1998 to 2010 that were selected for our study, and they were our herpes zoster group. 131707 randomly selected subjects without herpes zoster were our non-herpes zoster group. Both groups were matched by sex, age, other comorbidities, and the index year of their herpes zoster diagnosis. The incidence of pyogenic liver abscesses at the end of 2011 was then estimated. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratio and 95% confidence interval for pyogenic liver abscesses associated with herpes zoster and other comorbidities. The overall incidence rate was 1.38-fold higher in the herpes zoster group than in the non-herpes zoster group (4.47 vs. 3.25 per 10000 person-years, 95% confidence interval 1.32, 1.44). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscesses was 1.34 in the herpes zoster group (95% confidence interval 1.05, 1.72) when compared with the non-herpes zoster group. Sex (in this case male), age, presence of biliary stones, chronic kidney diseases, chronic liver diseases, cancers, and diabetes mellitus were also significantly associated with pyogenic liver abscesses. Patients with herpes zoster are associated with an increased hazard of developing pyogenic liver abscesses.

Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.

PubMed

Alkerwi, Ala'a; Sauvageot, Nicolas; Crichton, Georgina E; Elias, Merrill F; Stranges, Saverio

2016-05-01

This study examined the association of chocolate consumption with insulin resistance and serum liver enzymes in a national sample of adults in Luxembourg. A random sample of 1153 individuals, aged 18-69 years, was recruited to participate in the cross-sectional Observation of Cardiovascular Risk Factors in Luxembourg study. Chocolate consumption (g/d) was obtained from a semi-quantitative FFQ. Blood glucose and insulin levels were used for the homoeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers such as serum γ-glutamyl-transpeptidase (γ-GT), serum aspartate transaminase and serum alanine transaminase (ALT) (mg/l) were assessed using standard laboratory assays. Chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities. After excluding subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (β=-0·16, P=0·004), serum insulin levels (β=-0·16, P=0·003) and γ-GT (β=-0·12, P=0·009) and ALT (β=-0·09, P=0·004), after adjustment for age, sex, education, lifestyle and dietary confounding factors, including intakes of fruits and vegetables, alcohol, polyphenol-rich coffee and tea. This study reports an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders. Further observational prospective research and well-designed randomised-controlled studies are needed to confirm this cross-sectional relationship and to comprehend the role and mechanisms that different types of chocolate may play in insulin resistance and cardiometabolic disorders.

A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

PubMed

VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

2017-12-01

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver Diseases.

Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease.

PubMed

Centis, Elena; Moscatiello, Simona; Bugianesi, Elisabetta; Bellentani, Stefano; Fracanzani, Anna Ludovica; Calugi, Simona; Petta, Salvatore; Dalle Grave, Riccardo; Marchesini, Giulio

2013-04-01

Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Vitamin D deficiency and its relation to bone mineral density and liver fibrosis in HIV-HCV coinfection.

PubMed

El-Maouche, Diala; Mehta, Shruti H; Sutcliffe, Catherine G; Higgins, Yvonne; Torbenson, Michael S; Moore, Richard D; Thomas, David L; Sulkowski, Mark S; Brown, Todd T

2013-01-01

Fractures and cirrhosis are major causes of morbidity and mortality among HIV-HCV-coinfected individuals. It is not known whether vitamin D deficiency is associated with these outcomes. Between 2005 and 2007, 116 HIV-HCV-coinfected individuals underwent dual-energy X-ray absorptiometry within 1 year of a liver biopsy. 25-Hydroxyvitamin D (25OHD) and parathyroid hormone were measured from archived samples. Low bone mineral density (BMD) was defined as BMD≥2 standard deviations lower than age-, sex- and race-matched controls (Z-score ≤-2.0) at the total hip, femoral neck or lumbar spine. Histological fibrosis staging was assessed according to the METAVIR system (0 [no fibrosis] to 4 [cirrhosis]). The cohort was 87% African-American and 63% male. The median age (IQR) was 49.9 years (46.5-53.3). A total of 89% had a CD4(+) T-cell count >200 cells/mm(3) and 64% were receiving HAART. The median 25OHD was 19 ng/ml (IQR 11.0-26.0). Hypovitaminosis D (25OHD≤15 ng/ml) was present in 41% and secondary hyperparathyroidism, defined by parathyroid hormone >65 pg/ml, was present in 24%. In total, 27% had low BMD (Z-score ≤-2) at the spine, femoral neck or total hip, and 39% had significant hepatic fibrosis (METAVIR≥2). In multivariate analysis, vitamin D deficiency was not associated with significant fibrosis or with BMD at any site. Vitamin D deficiency was highly prevalent in this mostly African-American HIV-HCV-coinfected population, but was not related to BMD or liver disease severity. These data suggest that efforts to increase vitamin D levels in this population may not improve bone or liver outcomes.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

PubMed

Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

2013-09-03

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

PubMed Central

Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma

PubMed Central

Yanik, Elizabeth L.; Chinnakotla, Srinath; Gustafson, Sally K.; Snyder, Jon J.; Israni, Ajay K.; Segev, Dorry L.; Engels, Eric A.

2016-01-01

Background For recipients of liver transplants for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus, an immunosuppressant with anti-carcinogenic properties, may reduce HCC recurrence and improve survival. Methods The U.S. Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early sirolimus use with recurrence, cancer-specific mortality, and all-cause mortality adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of IL-2 induction therapy, and allocated and calculated model for end-stage liver disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Results Among the 3,936 included HCC liver transplants, 234 (6%) were sirolimus users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in sirolimus users and non-users (adjusted hazard ratio [HR] =1.01, 95%CI=0.73–1.39). HCC recurrence and cancer-specific mortality rates appeared lower in sirolimus users, but associations were not statistically significant (recurrence HR=0.86, 95%CI=0.45–1.65; cancer-specific mortality HR=0.80, 95%CI=0.43–1.50). Among recipients >55 years old, associations were suggestive of better outcomes for sirolimus users (all-cause mortality HR=0.62, 95%CI=0.38–1.01; recurrence HR=0.52, 95%CI=0.19–1.44; cancer-specific mortality HR=0.34, 95%CI=0.11–1.09), while among recipients ≤55 years old, sirolimus users had worse outcomes (all-cause mortality HR=1.76, 95%CI=1.12–2.75; recurrence HR=1.49, 95%CI=0.62–3.61; cancer-specific mortality HR=1.54, 95%CI=0.71–3.32). Conclusions Among HCC liver recipients overall, sirolimus did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation. PMID:26784951

Impact of elderly donors for liver transplantation: A single-center experience.

PubMed

Kamo, Naoko; Kaido, Toshimi; Hammad, Ahmed; Ogawa, Kohei; Fujimoto, Yasuhiro; Uemura, Tadahiro; Mori, Akira; Hatano, Etsuro; Okajima, Hideaki; Uemoto, Shinji

2015-05-01

Elderly donor grafts for liver transplantation (LT) are recognized to be marginal grafts. The present study investigated the impact of using elderly donors for LT. Between June 1990 and August 2012, 1631 patients received LT at Kyoto University Hospital. Out of 1631 patients, 1597 patients received living donor liver transplantation (LDLT), whereas the other 34 patients underwent deceased donor liver transplantation (DDLT). Seventy-five grafts that were used came from individuals who were ≥60 years old. We retrospectively analyzed the recipients' survival rates according to donor age. The overall survival rates of the recipients of all LDLT (P < 0.001), adult-to-adult LDLT (P = 0.007), all DDLT (P = 0.026), and adult-to-adult DDLT (P = 0.011) were significantly lower for the elderly donor group versus the younger group and especially for those who were hepatitis C-positive. A multivariate analysis revealed that donor age, ABO incompatibility, and preoperative intensive care unit stay were independent risk factors for poor patient survival in adult-to-adult LDLT. However, no significant differences existed between the 2 groups among those who received adult-to-adult LDLT in and after April 2006. No significant association was found between donor age and incidence of acute cellular rejection. In conclusion, donor age was closely related to the survival rate for LDLT and DDLT, although the impact of donor age was not shown in the recent cases. © 2015 American Association for the Study of Liver Diseases.

Reversal of hepatocyte senescence after continuous in vivo cell proliferation.

PubMed

Wang, Min-Jun; Chen, Fei; Li, Jian-Xiu; Liu, Chang-Cheng; Zhang, Hai-Bin; Xia, Yong; Yu, Bing; You, Pu; Xiang, Dao; Lu, Lian; Yao, Hao; Borjigin, Uyunbilig; Yang, Guang-Shun; Wangensteen, Kirk J; He, Zhi-Ying; Wang, Xin; Hu, Yi-Ping

2014-07-01

A better understanding of hepatocyte senescence could be used to treat age-dependent disease processes of the liver. Whether continuously proliferating hepatocytes could avoid or reverse senescence has not yet been fully elucidated. We confirmed that the livers of aged mice accumulated senescent and polyploid hepatocytes, which is associated with accumulation of DNA damage and activation of p53-p21 and p16(ink4a)-pRB pathways. Induction of multiple rounds continuous cell division is hard to apply in any animal model. Taking advantage of serial hepatocyte transplantation assays in the fumarylacetoacetate hydrolase-deficient (Fah(-/-)) mouse, we studied the senescence of hepatocytes that had undergone continuous cell proliferation over a long time period, up to 12 rounds of serial transplantations. We demonstrated that the continuously proliferating hepatocytes avoided senescence and always maintained a youthful state. The reactivation of telomerase in hepatocytes after serial transplantation correlated with reversal of senescence. Moreover, senescent hepatocytes harvested from aged mice became rejuvenated upon serial transplantation, with full restoration of proliferative capacity. The same findings were also true for human hepatocytes. After serial transplantation, the high initial proportion of octoploid hepatocytes decreased to match the low level of youthful liver. These findings suggest that the hepatocyte "ploidy conveyer" is regulated differently during aging and regeneration. The findings of reversal of hepatocyte senescence could enable future studies on liver aging and cell therapy. © 2014 by the American Association for the Study of Liver Diseases.

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

PubMed

Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

2016-10-01

Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Major Challenges Limiting Liver Transplantation in the United States

PubMed Central

Wertheim, Jason A.; Petrowsky, Henrik; Saab, Sammy; Kupiec-Weglinski, Jerzy W.; Busuttil, Ronald W.

2011-01-01

Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma. PMID:21672146

Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series

PubMed Central

Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.

2011-01-01

MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191

Mortality Caused by Chronic Liver Disease Among American Indians and Alaska Natives in the United States, 1999–2009

PubMed Central

Suryaprasad, Anil; Byrd, Kathy K.; Redd, John T.; Perdue, David G.; Manos, M. Michele; McMahon, Brian J.

2014-01-01

Objectives. We compared chronic liver disease (CLD) mortality from 1999 to 2009 between American Indians and Alaska Natives (AI/ANs) and Whites in the United States after improving CLD case ascertainment and AI/AN race classification. Methods. We defined CLD deaths and causes by comprehensive death certificate-based diagnostic codes. To improve race classification, we linked US mortality data to Indian Health Service enrollment records, and we restricted analyses to Contract Health Service Delivery Areas and to non-Hispanic populations. We calculated CLD death rates (per 100 000) in 6 geographic regions. We then described trends using linear modeling. Results. CLD mortality increased from 1999 to 2009 in AI/AN persons and Whites. Overall, the CLD death rate ratio (RR) of AI/AN individuals to Whites was 3.7 and varied by region. The RR was higher in women (4.7), those aged 25 to 44 years (7.4), persons residing in the Northern Plains (6.4), and persons dying of cirrhosis (4.0) versus hepatocellular carcinoma (2.5), particularly those aged 25 to 44 years (7.7). Conclusions. AI/AN persons had greater CLD mortality, particularly from premature cirrhosis, than Whites, with variable mortality by region. Comprehensive prevention and care strategies are urgently needed to stem the CLD epidemic among AI/AN individuals. PMID:24754616

Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population.

PubMed

Choi, Jonggi; Han, Seungbong; Kim, Namkug; Lim, Young-Suk

2017-11-01

Most mortalities from liver disease and liver cancer worldwide are attributable to hepatitis B virus (HBV) and hepatitis C virus. Despite remarkable advances in the treatment of HBV over past decades, limited population-level data are available regarding its impact on burden of liver disease and liver cancer. Mortality data from liver disease and liver cancer were obtained from the national death certificate database of Korea, an HBV-endemic country, between 1999 and 2013, and were analyzed by Joinpoint analysis. For liver disease, number of annual deaths decreased by 62.3% (95% confidence interval [CI], 62.0-62.6), crude death rate (CDR) decreased by 64.6% (95% CI, 64.3-64.9) from 21.2 to 7.5 per 100,000 population, and age-standardized death rate (ADR) declined by 75.0% (95% CI, 74.7-75.3), between 1999 and 2013. In contrast, for liver cancer, number of annual deaths increased by 17.8% (95% CI, 17.6-18.0) and CDR increased by 10.2% (95% CI, 10.0-10.4) from 20.5 to 22.6, although ADR decreased by 26.9% (95% CI, 26.6-27.2). The annual number of patients receiving oral antiviral agents against HBV increased from 1,716 to 187,226 during the study period. The increase in mean age at death from liver disease was significantly greater than that from liver cancer (8.8 vs. 6.1 years: P = 0.02). Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in an HBV-endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy. (Hepatology 2017;66:1454-1463). © 2017 by the American Association for the Study of Liver Diseases.

A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991

PubMed Central

Sharma, Akshay; Messina, Lauren C.; Zlotorzynska, Maria; Miller, Lesley; Binswanger, Ingrid A.

2015-01-01

Objectives. We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies. Methods. We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose. Results. Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort. Conclusions. Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast. PMID:25790417

Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver Hypertrophy.

PubMed

Huang, Steven Y; Aloia, Thomas A

2017-12-01

Portal vein embolization (PVE) is associated with a high technical and clinical success rate for induction of future liver remnant hypertrophy prior to surgical resection. The degree of hypertrophy is variable and depends on multiple factors, including technical aspects of the procedure and underlying chronic liver disease. For patients with insufficient liver volume following PVE, adjunctive techniques, such as intra-portal administration of stem cells, dietary supplementation, transarterial embolization, and hepatic vein embolization, are available. Our purpose is to review the state-of-the-art technique associated with high-quality PVE and to discuss options to improve hypertrophy of the future liver remnant.

Age dependency of base modification in rabbit liver DNA

NASA Technical Reports Server (NTRS)

Yamamoto, O.; Fuji, I.; Yoshida, T.; Cox, A. B.; Lett, J. T.

1988-01-01

Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats.

PubMed

Ziamajidi, Nasrin; Behrouj, Hamid; Abbasalipourkabir, Roghayeh; Lotfi, Fatemeh

2018-04-01

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.

Comparison of Cox’s Regression Model and Parametric Models in Evaluating the Prognostic Factors for Survival after Liver Transplantation in Shiraz during 2000–2012

PubMed Central

Adelian, R.; Jamali, J.; Zare, N.; Ayatollahi, S. M. T.; Pooladfar, G. R.; Roustaei, N.

2015-01-01

Background: Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. Objective: To compare Cox’s regression model with parametric models for determining the independent factors for predicting adults’ and pediatrics’ survival after liver transplantation. Method: This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Result: Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Conclusion: Parametric regression model is a good alternative for the Cox’s regression model. PMID:26306158

Pediatric Liver Transplantation: Our Experiences

PubMed Central

Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

2016-01-01

Objective: The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Materials and Methods: Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. Results: In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months–17 years). The 4 most common reasons for liver transplantation were: Wilson’s disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. Conclusion: The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature. PMID:28149148

[Cholestatic icterus due to oral contraceptives].

PubMed

Pestel, M; Lambert, C; Jeanmougin, M

1973-03-01

A case report of cholestatic jaundice in a 25 year old woman, who had had jaundice at age 4 years, and had taken Stediril (a combined oral contraceptive) for 1 month, implicates either the pill or a possibly hereditary hyperlipidemia. The jaundice developed in 2 weeks with vomiting, epigastric pain, anorexia, then discolored urine and feces, and intense pruritus. On hospitalization the patient had moderate bilirubinemia (56 mg/1), low alkaline phosphatase (13 U.K.) and slightly high serum glutamate pyruvate transaminase (270 U.W.). There were elevated serum cholesterol (3 gm/1), triglycerides (2.05 gm/1), total lipids (10.6 gm/1), and a definitely increased pre-beta lipoprotein, suggesting hyperlipidemia type IV (Frederickson classification). Liver biopsy showed fibrosis of the portal spaces lymphocytic infiltration, canalicular and intrahepatocytic thrombi. On laparoscopy the liver had a regular lower border, normal volume color and surface. Albumin, prothrombin and flocculation tests were normal. The patient's jaundice lasted about 1 month, then liver function slowly improved, although pruritus remained intense. Probably this jaundice was due to oral contraceptives, in a patient predisposed either by jaundice in childhood or endogenous hyperlipidemia.

Systemic effects of inflammation on health during chronic HIV infection.

PubMed

Deeks, Steven G; Tracy, Russell; Douek, Daniel C

2013-10-17

Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging. Copyright © 2013 Elsevier Inc. All rights reserved.

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

PubMed

Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

2016-07-01

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. © 2016 Royal Australasian College of Physicians.

Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: Results from a case-control study.

PubMed

Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Wilms, Christian; Hüsing-Kabar, Anna; Görlich, Dennis; Kabar, Iyad; Schmidt, Hartmut H J

2017-01-01

The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3-5 sessions). Independent of the underlying etiology, MARS improved the patients' bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0-15.3); SMT 3.3% (95% CI: 0-9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0-44.7), SMT 11.1% (95% CI: 0-31.7), p = 0.478). Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.

Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: Results from a case-control study

PubMed Central

Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Wilms, Christian; Hüsing-Kabar, Anna; Görlich, Dennis; Kabar, Iyad; Schmidt, Hartmut H. J.

2017-01-01

Background The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. Aim We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). Methods We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). Results The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3–5 sessions). Independent of the underlying etiology, MARS improved the patients’ bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0–15.3); SMT 3.3% (95% CI: 0–9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0–44.7), SMT 11.1% (95% CI: 0–31.7), p = 0.478). Conclusions Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease. PMID:28403210

Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

PubMed Central

Song, Fang; Xie, Mei-Lin; Zhu, Lu-Jia; Zhang, Ke-Ping; Xue, Jie; Gu, Zhen-Lun

2006-01-01

AIM: To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism. METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured. RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved. In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation. CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fat-induced fatty liver. The mechanism might be associated with its antioxidation. PMID:16865778

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Wenxuan; Lu, Chunfeng; Yao, Lu

Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartatemore » aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.« less

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

PubMed

Guichelaar, Maureen M J; Kendall, Rebecca; Malinchoc, Michael; Hay, J Eileen

2006-09-01

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

PubMed

Malekzadeh, Fatemeh; Sepanlou, Sadaf Ghajarieh; Poustchi, Hossein; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza

2015-07-01

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries is necessary for improving the accuracy of future updates of GBD in these countries.

Acute Viral Hepatitis in Pediatric Age Groups.

PubMed

Kc, Sudhamshu; Sharma, Dilip; Poudyal, Nandu; Basnet, Bhupendra Kumar

2014-01-01

Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December 2010 were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0-5, 5-10 and 5-15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%), Hepatitis E virus in 24 (8%), Hepatitis B virus in 15 (5%). In 7(2%) patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery.

Liver imaging at 3.0 T: diffusion-induced black-blood echo-planar imaging with large anatomic volumetric coverage as an alternative for specific absorption rate-intensive echo-train spin-echo sequences: feasibility study.

PubMed

van den Bos, Indra C; Hussain, Shahid M; Krestin, Gabriel P; Wielopolski, Piotr A

2008-07-01

Institutional Review Board approval and signed informed consent were obtained by all participants for an ongoing sequence optimization project at 3.0 T. The purpose of this study was to evaluate breath-hold diffusion-induced black-blood echo-planar imaging (BBEPI) as a potential alternative for specific absorption rate (SAR)-intensive spin-echo sequences, in particular, the fast spin-echo (FSE) sequences, at 3.0 T. Fourteen healthy volunteers (seven men, seven women; mean age +/- standard deviation, 32.7 years +/- 6.8) were imaged for this purpose. Liver coverage (20 cm, z-axis) was always performed in one 25-second breath hold. Imaging parameters were varied interactively with regard to echo time, diffusion b value, and voxel size. Images were evaluated and compared with fat-suppressed T2-weighted FSE images for image quality, liver delineation, geometric distortions, fat suppression, suppression of the blood signal, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). An optimized short- (25 msec) and long-echo (80 msec) BBEPI provided full anatomic, single breath-hold liver coverage (100 and 50 sections, respectively), with resulting voxel sizes of 3.3 x 2.7 x 2.0 mm and 3.3 x 2.7 x 4.0 mm, respectively. Repetition time was 6300 msec, matrix size was 160 x 192, and an acceleration factor of 2.00 was used. b Values of more than 20 sec/mm(2) showed better suppression of the blood signal but b values of 10 sec/mm(2) provided improved volume coverage and signal consistency. Compared with fat-suppressed T2-weighted FSE, the optimized BBEPI sequence provided (a) comparable image quality and liver delineation, (b) acceptable geometric distortions, (c) improved suppression of fat and blood signals, and (d) high CNR and SNR. BBEPI is feasible for fast, low-SAR, thin-section morphologic imaging of the entire liver in a single breath hold at 3.0 T. (c) RSNA, 2008.

Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

PubMed

Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

2016-10-01

Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. © 2016 UICC.

Intermittent fasting favored the resolution of Salmonella typhimurium infection in middle-aged BALB/c mice.

PubMed

Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Reyna-Garfias, Humberto; Arciniega-Martínez, Ivonne Maciel; Reséndiz-Albor, Aldo Arturo; Abarca-Rojano, Edgar; Cruz-Hernández, Teresita Rocío; Drago-Serrano, Maria Elisa

2016-02-01

Intermittent fasting (IF) reportedly increases resistance and intestinal IgA response to Salmonella typhimurium infection in mature mice. The aim of this study was to explore the effect of aging on the aforementioned improved immune response found with IF. Middle-aged male BALB/c mice were submitted to IF or ad libitum (AL) feeding for 40 weeks and then orally infected with S. typhimurium. Thereafter, infected animals were all fed AL (to maximize their viability) until sacrifice on day 7 or 14 post-infection. We evaluated body weight, bacterial load (in feces, Peyer's patches, spleen and liver), total and specific intestinal IgA, lamina propria IgA+ plasma cells, plasma corticosterone, and messenger RNA (mRNA) expression of α-chain, J-chain, and the polymeric immunoglobulin receptor (pIgR) in liver and intestinal mucosa. In comparison with the infected AL counterpart, the infected IF group (long-term IF followed by post-infection AL feeding) generally had lower intestinal and systemic bacterial loads as well as higher total IgA on both post-infection days. Both infected groups showed no differences in corticosterone levels, body weight, or food and caloric intake. The increase in intestinal IgA was associated with enhanced pIgR mRNA expression in the intestine (day 7) and liver. Thus, to maintain body weight and caloric intake, IF elicited metabolic signals that possibly induced the increased hepatic and intestinal pIgR mRNA expression found. The increase in IgA probably resulted from intestinal IgA transcytosis via pIgR. This IgA response along with phagocyte-induced killing of bacteria in systemic organs (not measured) may explain the resolution of the S. typhimurium infection.

Dietary Components Affect the Plasma and Tissue Levels of Lutein in Aged Rats with Lutein Deficiency--A Repeated Gavage and Dietary Study.

PubMed

Sheshappa, Mamatha Bangera; Ranganathan, Arunkumar; Bhatiwada, Nidhi; Talahalli, Ramprasad Ravichandra; Vallikannan, Baskaran

2015-10-01

The aim of this study was to find out the influence of selected dietary components on plasma and tissue response of repeated micellar and dietary lutein in aged rats with lutein deficiency. In repeated (16 d) gavage study, micellar lutein was co-ingested with either phosphatidylcholine (PC), lyso-phosphatidylcholine (lysoPC), β-carotene, dietary fiber or vegetable fat (3% soybean oil). In dietary study, rats were fed (4 wk) semi-synthetic diet either with lutein + PC, lutein + dietary fiber or B. alba (lutein source) + PC. The post-prandial plasma and tissue response of lutein was measured by HPLC. Results showed that micellar fat, PC and lysoPC significantly (P ≤ 0.05) increased the lutein levels in plasma (31.1%, 26.8%, and 34.9%), liver (27.4%, 29.5%, and 8.6%), and eyes (63.5%, 90.2%, and 86%) compared to the control group (group gavaged micelles with no dietary components studied). Similarly, dietary study showed an enhanced plasma, liver, and eye lutein levels by 44.8%, 24.1%, and 42.0% (lutein + PC group) and 51.7%, 39.8%, and 31.7% (B.alba + PC group), respectively compared to control. The activity of antioxidant enzymes in plasma and liver of both the studies were also affected compared to control. Result reveals, that PC enhance the intestinal absorption of both micellar and dietary lutein which is either in free or bound form with food matrices in aged rats with lutein deficiency. Hence, PC at a concentration used in this study can be considered to improve the lutein bioavailability in lutein deficiency. Lutein and zeaxanthin are macular pigments acquired mostly from greens, that play an significant role in protecting vision from Age related macular degeneration (AMD). However, their biological availability is poor and affected by dietary components. This study demonstrates the positive influence of dietary PC and lyso PC in improving intestinal uptake of lutein. Our previous and present finding shows there is a possibility of developing functional/supplemental foods with PC and lyso PC targeted to elderly populace thus minimizing or delaying the vision complication associated like AMD. © 2015 Institute of Food Technologists®

Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group.

PubMed

Ng, Vicky L; Li, Ruosha; Loomes, Kathleen M; Leonis, Mike A; Rudnick, David A; Belle, Steven H; Squires, Robert H

2016-09-01

Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P < 0.001). Mortality 21 days after enrollment was highest in participants enrolled with severe HE (grades III or IV) or demonstrating HE progression. Four percent of participants without recorded clinical HE in the 7 days after enrollment, however, died within 21 days. Improved assessment of neurological injury and pediatric acute liver failure prognostication schema are needed.

Preoperative Recipient Parameters Allow Early Estimation of Postoperative Outcome and Intraoperative Transfusion Requirements in Liver Transplantation.

PubMed

Schumacher, Carsten; Eismann, Hendrik; Sieg, Lion; Friedrich, Lars; Scheinichen, Dirk; Vondran, Florian W R; Johanning, Kai

2018-01-01

Liver transplantation is a complex intervention, and early anticipation of personnel and logistic requirements is of great importance. Early identification of high-risk patients could prove useful. We therefore evaluated prognostic values of recipient parameters commonly available in the early preoperative stage regarding postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. All adult patients undergoing first liver transplantation at Hannover Medical School between January 2005 and December 2010 were included in this retrospective study. Demographic, clinical, and laboratory data as well as clinical courses were recorded. Prognostic values regarding 30- and 90-day outcomes were evaluated by uni- and multivariate statistical tests. Identified risk parameters were used to calculate risk scores. There were 426 patients (40.4% female) included with a mean age of 48.6 (11.9) years. Absolute 30-day mortality rate was 9.9%, and absolute 90-day mortality rate was 13.4%. Preoperative leukocyte count >5200/μL, platelet count <91 000/μL, and creatinine values ≥77 μmol/L were relevant risk factors for both observation periods ( P < .05, respectively). A score based on these factors significantly differentiated between groups of varying postoperative outcomes and intraoperative transfusion requirements ( P < .05, respectively). A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

Effects of Pomegranate and Orange Juice on Antioxidant Status in Non-Alcoholic Fatty Liver Disease Patients: A Randomized Clinical Trial.

PubMed

Ekhlasi, Golnaz; Shidfar, Farzad; Agah, Shahram; Merat, Shahin; Hosseini, Agha Fatemeh

2015-12-01

The fruit of the pomegranate (Punica granatum) has a high content of polyphenols and is renowned for its antioxidant capabilities. In particular, it is recognized as reducing oxidative stress and, therefore, playing a productive role in obstructing the pathogenesis of fatty liver disease. The aim of the present study was to evaluate the effects of consumingpomegranate juice (high in antioxidant content) and orange juice (low in antioxidant content) when combined with a hypocaloric diet on liver enzymes and the antioxidant status of patients. In a randomized clinical trial, 65 patients who exhibited non-alcoholic fatty liver disease (NAFLD) at a mean age of 39+/-8 years received 250 mL pomegranate juice or orange juice per day as a substitute for two servings of fruit in a hypocaloric diet over a period of 12 weeks. The subjects' levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidant capacity (TAC), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) were measured at the beginning and end of the study. At the end of the study, the levels of liver enzymes and body mass index (BMI) had significantly decreased in both groups. A significant increase in TAC was also observed in the subjects in the pomegranate group (p <0.01). Consumption of fruits that are high in antioxidants could represent a useful means to improve the antioxidant status of NAFLD patients who follow a hypocaloric diet.

Evaluation of Encapsulated Liver Cell Spheroids in a Fluidised-Bed Bioartificial Liver for Treatment of Ischaemic Acute Liver Failure in Pigs in a Translational Setting

PubMed Central

Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey

2013-01-01

Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale. PMID:24367515

Undifferentiated (embryonal) liver sarcoma: synchronous and metachronous occurrence with neoplasms other than mesenchymal liver hamartoma.

PubMed

Gasljevic, Gorana; Lamovec, Janez; Jancar, Janez

2011-08-01

Undifferentiated (embryonal) liver sarcoma (UELS) is a rare tumor that typically occurs in children. The association of UELS with neoplasm other than mesenchymal liver hamartoma is exceedingly rare. The aim of the study was to report 3 cases of UELS, 2 of them being interesting because of their association with another neoplasm, vaginal embryonal rhabdomyosarcoma in a teenage girl and B-acute lymphoblastic leukemia in a middle-aged woman. Besides, one of our cases of UELS, in a 58-year-old woman, is an extremely rare presentation of such a tumor in a middle-aged adult. The patient's clinical features, therapy, and pathologic results were reviewed; immunohistochemical analysis and, in 2 cases, electron microscopy were performed. In this study, all 3 patients were females aged 13, 13, and 58 years. Histopathologic evaluation of resected liver tumors confirmed the diagnosis of UELS in all of them. In 2 of the cases, metachronous occurrence of UELS with vaginal embryonal rhabdomyosarcoma in a teenage girl and B-acute lymphoblastic leukemia in a middle-aged woman is described. Careful clinical analysis, histologic studies, and immunohistochemistry are mandatory to distinguish UELS from other hepatic malignancies with similar or overlapping features and to exclude the possibility of other tumors that may be considered in the differential diagnosis. The association of UELS with another neoplasm is exceedingly rare. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk factors associated with the presence of hepatitis E virus in livers and seroprevalence in slaughter-age pigs: a retrospective study of 90 swine farms in France.

PubMed

Walachowski, S; Dorenlor, V; Lefevre, J; Lunazzi, A; Eono, F; Merbah, T; Eveno, E; Pavio, N; Rose, N

2014-09-01

The frequency of sporadic cases of hepatitis E in humans in developed countries has increased in recent years. The consumption of raw or undercooked pig liver-based products has been identified as an important source of human infection. The question of possible massive human exposure to this zoonotic agent has been raised by the high prevalence of hepatitis E virus (HEV) in swine herds. However, little is known about the epidemiology of HEV on pig farms. A retrospective study, based on a previous prevalence study of 185 farms, was conducted on 90 farms located in Western France, randomly selected from this database, to identify factors associated with the presence of HEV in pig livers and HEV seroprevalence in slaughter-age pigs. At least one HEV RNA-positive liver was found in 30% of the sampled farms while seroprevalence in slaughter-age pigs at the farm level reached almost 75%. Different factors were associated with the two conditions. The risk of having HEV-positive livers was increased by early slaughter, genetic background, lack of hygiene measures and surface origin of drinking water. High HEV seroprevalence was associated with mingling practices at the nursery stage and hygiene conditions. These results can be used to determine on-farm measures to reduce within-farm HEV spread and infection of slaughter-age pigs.

Maternal coping with the prospect of liver transplant among their school-age children.

PubMed

Hiratsuka, Katsuhiro; Nakamura, Nobue; Sato, Naho

2017-06-01

The purpose of the current study was to describe the following: maternal coping with the prospect of becoming the living-donor liver transplant for their child; the daily lives of school-age children surviving biliary atresia with their native liver; and to explore the relationship between these individuals. Semistructured interviews were conducted with 6 school-age children surviving biliary atresia with their native liver and their mothers. The interviews were conducted from June to August 2014, and a qualitative content analysis was used. Results showed that mothers realized a possible need for transplantation in the future, which contributes to emotional and practical uncertainties. The mothers coexisted with this uncertainty and preferred to use a buffering strategy. In contrast, the children did not consider their illness and future and did not adhere to a therapeutic regimen. It is suggested that living with uncertainty about the health and survival of their children is advantageous for mothers. However, problems related to the psychosocial aspect and child's adherence may occur in the future. In addition, problem-solving coping strategies for mothers and the independence of chronically ill children with liver disease should be promoted. © 2017 John Wiley & Sons Australia, Ltd.

Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

PubMed

Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

2010-06-27

The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

PubMed

Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji

2017-09-01

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Ageing sensitized by iPLA2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

PubMed

Jiao, Li; Gan-Schreier, Hongying; Zhu, Xingya; Wei, Wang; Tuma-Kellner, Sabine; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

2017-12-01

Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA 2 β is a homeostatic PLA 2 by playing a role in phospholipid metabolism and remodeling. Global iPLA 2 β -/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA 2 β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA 2 β -/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA 2 β -/- mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA 2 β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA 2 β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis.

PubMed

Duarte, Tiago L; Caldas, Carolina; Santos, Ana G; Silva-Gomes, Sandro; Santos-Gonçalves, Andreia; Martins, Maria João; Porto, Graça; Lopes, José Manuel

2017-04-01

In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe -/- mice (an established model of human HFE-hemochromatosis). Wild-type, Nrf2 -/- , Hfe -/- and double knockout (Hfe/Nrf2 -/- ) female mice on C57BL/6 genetic background were sacrificed at the age of 6 (young), 12-18 (middle-aged) or 24 months (old) for evaluation of liver pathology. Despite the parenchymal iron accumulation, Hfe -/- mice presented no liver injury. The combination of iron overload (Hfe -/- ) and defective antioxidant defences (Nrf2 -/- ) increased the number of iron-related necroinflammatory lesions (sideronecrosis), possibly due to the accumulation of toxic oxidation products such as 4-hydroxy-2-nonenal-protein adducts. The engulfment of dead hepatocytes led to a gradual accumulation of iron within macrophages, featuring large aggregates. Myofibroblasts recruited towards the injury areas produced substantial amounts of collagen fibers involving the liver parenchyma of double-knockout animals with increased hepatic fibrosis in an age-dependent manner. The genetic disruption of Nrf2 promotes the transition from iron accumulation (siderosis) to liver injury in Hfe -/- mice, representing the first demonstration of spontaneous hepatic fibrosis in the long term in a mouse model of hereditary hemochromatosis displaying mildly elevated liver iron. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

HRQOL using SF36 (generic specific) in liver cirrhosis.

PubMed

Janani, K; Varghese, Joy; Jain, Mayank; Harika, Kavya; Srinivasan, Vijaya; Michael, Tom; Jayanthi, Venkataraman

2017-07-01

Health-related quality of life (HRQOL) is influenced by the disease state, associated complications and their management. In patients with liver cirrhosis co-morbidity, severity of liver disease and their complications are likely to affect the QOL. The aim of the study was to determine the factors that are likely to influence the domains of HRQOL using SF-36 in patients with liver cirrhosis. For the study, 149 patients with liver cirrhosis were compared with age-gender matched healthy controls for physical and mental components of SF-36 score and the effects of age, co-morbidity severity of liver disease and complications of liver cirrhosis on HRQOL were assessed using the same questionnaire. Results of the study showed that except for body pain, all the patients had a significantly low individual and composite domain score (p-value <0.0001) compared to age-gender matched controls. Patients below 45 years, Child-Turcotte-Pugh (CTP) C, a high model for end-stage liver disease (MELD) and higher rates of complication had low scores for body pain (KW p <0.005) and those above 55 years, for physical function (p <0.05). Both the physical components had a major impact on mental composite score (MCS) (KW p <0.05). Co-morbidity that included diabetes, hypertension and hypothyroid states in various combinations had no effect on SF-36 scores while co-morbid conditions like musculoskeletal pain, arthralgia etc. affected physical domains (physical function, body pain and role physical) and physical component score (PCS) (KW p <0.01 to <0.0001). By linear regression, MELD had a direct and significant association with overall PCS and mental component score (MCS).

Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain.

PubMed

Aoufi, S; Pascasio, J M; Sousa, J M; Sayago, M; Ferrer, M T; Gómez-Delgado, E; De la Cruz, M D; Alamo, J M; Gómez-Bravo, M A; Bernardos, A; Márquez, J L

2008-11-01

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients

Characterization of Hepatitis B and C Among Liver Transplant Recipients With Hepatocellular Carcinoma: An Analysis of the Nationwide Inpatient Sample Database.

PubMed

Lam, P H; Obirieze, A C; Ortega, G; Nwokeabia, I; Onyewu, S; Purnell, S D; Samimi, M M; Weeks, C B; Lee, E L; Shokrani, B; Frederick, W A I; Callender, C O; Wilson, L L

2016-01-01

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for most hepatocellular carcinoma (HCC) and subsequent liver transplant cases. Racial/ethnic disparities exist in access to liver transplantation and post-transplantation survival, and we sought to compare and explore potential disparities in HBV and HCV-related liver transplant populations. The Nationwide Inpatient Sample database was used (2001 to 2010). In this study, 2269 liver transplant recipients were included: 56% HCV, 6% HBV, and 37% non-HV. HBV and HCV patients were mostly Asian/Pacific Islander (API) and white, respectively. Within HBV transplant recipients, the mean age was youngest in black patients (P = .02); variation of mean age was not seen within HCV patients. Regarding the transplant recipients' income and insurance, most API and white patients were in the highest income quartile, whereas most black and Hispanic patients were in the lowest income group (P < .001). The most common form of payer across all racial/ethnic groupings was private insurance (P < .001). The mean length of hospitalization was longest in Hispanic patients (P = .008); they had a significantly longer stay compared with white patients (P = .02). The liver transplantations were mostly performed in teaching hospitals, located in urban areas in the West region of the United States (P < .001). Differences were found in the HBV and HCV-associated liver transplant populations. More work needs to be done to elucidate disparities regarding black and Hispanic liver transplant recipients as they receive transplants at younger mean ages, are in lower income quartiles, and have longer lengths of hospitalization compared with other racial/ethnic groupings. Copyright © 2016. Published by Elsevier Inc.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study.

PubMed

Zeng, Meng-Su; Ye, Hui-Yi; Guo, Liang; Peng, Wei-Jun; Lu, Jian-Ping; Teng, Gao-Jun; Huan, Yi; Li, Ping; Xu, Jian-Rong; Liang, Chang-Hong; Breuer, Josy

2013-12-01

Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. This was a single-arm, open-label, multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were evaluated by clinical study investigators and three independent, blinded radiologists. The primary efficacy endpoint was sensitivity in lesion detection. Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46% compared with pre-contrast imaging for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA vs pre-contrast, respectively). Improvements in detection were more pronounced in lesions less than 1 cm. Gd-EOB-DTPA improved diagnostic accuracy in lesion classification. This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly in those smaller than 1 cm. Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification, and furthermore, Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

Large splenic volume may be a useful predictor for partial splenic embolization-induced liver functional improvement in cirrhotic patients.

PubMed

Hayashi, Hiromitsu; Beppu, Toru; Masuda, Toshiro; Okabe, Hirohisa; Imai, Katsunori; Hashimoto, Daisuke; Ikuta, Yoshiaki; Chikamoto, Akira; Watanabe, Masayuki; Baba, Hideo

2014-01-01

Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients. From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count <10 × 10(4)/μl) underwent PSE. Of them, 71 patients with follow-up for more than one year after PSE were retrospectively investigated. In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response. Indeed, serum albumin and cholinesterase levels increased to 104 ± 14% and 130 ± 65% each of the pretreatment level at one year after PSE. In a multiple linear regression analysis, preoperative splenic volume was extracted as the predictive factor for the improvement in cholinesterase level after PSE. Cirrhotic patients with preoperative splenic volume >600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Normothermic ex-situ liver preservation: the new gold standard.

PubMed

Laing, Richard W; Mergental, Hynek; Mirza, Darius F

2017-06-01

Normothermic machine perfusion of the liver (NMP-L) is a novel technology recently introduced into the practice of liver transplantation. This review recapitulates benefits of normothermic perfusion over conventional static cold storage and summarizes recent publications in this area. The first clinical trials have demonstrated both safety and feasibility of NMP-L. They have shown that machine perfusion can entirely replace cold storage or be commenced following a period of cold ischaemia. The technology currently allows transplant teams to extend the period of organ preservation for up to 24 h. Results from the first randomized control trial comparing NMP-L with static cold storage will be available soon. One major advantage of NMP-L technology over other parallel technologies is the potential to assess liver function during NMP-L. Several case series have suggested parameters usable for liver viability testing during NMP-L including bile production and clearance of lactic acidosis. NMP-L allows viability testing of high-risk livers. It has shown the potential to increase utilization of donor organs and improve transplant procedure logistics. NMP-L is likely to become an important technology that will improve organ preservation as well as have the potential to improve utilization of extended criteria donor livers.

Improvement of surgical margin with a coupled saline-radio-frequency device for multiple colorectal liver metastases.

PubMed

Ogata, Satoshi; Kianmanesh, Reza; Varma, Deepak; Belghiti, Jacques

2005-01-01

Complete resection of colorectal liver metastases (LM) has been the only curative treatment. However, when LM are multiple and bilobar, only a few patients are candidates for curative surgery. We report on a 53-year-old woman with synchronous multiple and bilobar LM from sigmoidal cancer who became resectable after a multimodal strategy including preoperative systemic chemotherapy and two-step surgery. The spectacular decrease in tumor size after systemic chemotherapy led us to perform two-step surgery, including right portal-vein ligation and left liver metastasectomies, with a coupled saline-radiofrequency device, in order to improve the surgical margin. An extended right hepatectomy was performed later to remove the remaining right liver lesions. The patient was discharged after 28 days without major complication and was recurrence-free 14 months later. We conclude that improving the surgical margin with a coupled saline-radiofrequency device is feasible and effective, avoiding small remnant liver even after multiple tumorectomies. The multimodal strategy, including preoperative chemotherapy, two-step surgery, and tumorectomies, using a coupled saline-radiofrequency device, could increase the number of patients with diffuse bilobar liver metastases who can benefit from liver resection.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

PubMed

Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

2017-04-01

A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Anatomic Peculiarities of Pig and Human Liver.

PubMed

Nykonenko, Andriy; Vávra, Petr; Zonča, Pavel

2017-02-01

Many investigations on surgical methods and medical treatment are currently done on pigs. This is possible because the pig is sufficiently close genetically to humans. In recent years, progress in liver surgery has opened new possibilities in surgical treatment of liver diseases. Because the methods are relatively novel, various improvements are still needed, and it is thus helpful to conduct experimental surgeries on pig livers. We reviewed the literature to compare the anatomic and functional features of pig and human livers, information that will be of great importance for improving surgical techniques. During the literature review, we used various sources, such as PubMed, Scopus, and veterinary journals. Our results were summarized in diagrams to facilitate understanding of the vascular structure and biliary systems. We conclude that, although the shapes of the human and pig livers are quite different, the pig liver is divided into the same number of segments as the human liver, which also shows a common structure of the vascular system. Thus, with the anatomic and structural features of the pig liver taken into account, this animal model can be used in experimental hepatic surgery.

[Contrast medium enhanced magnetic resonance tomography of liver metastases: positive versus negative contrast media].

PubMed

Hammerstingl, R M; Schwarz, W; Hochmuth, K; Staib-Sebler, E; Lorenz, M; Vogl, T J

2001-01-01

The development in oncologic liver surgery as well as modified interventional therapy strategies of the liver have resulted in improved diagnostic imaging. The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. In MRI contrast agents act indirectly by their effects on relaxation times. Contrast agents used for hepatic MR imaging can be categorized in those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. The first two result in a positive enhancement, the last one in a negative enhancement. Positive enhancers allow a better characterization of liver metastases using dynamic sequence protocols. Detection rate of liver metastases is increased using hepatobiliary contrast-enhanced MRI compared to unenhanced MRI. Negative enhancers, iron oxide particles, significantly increase tumor-to-liver contrast and allow detection of more lesions than other diagnostic methods. Iron-oxide enhanced MRI enables differential diagnosis of liver metastases comparing morphologic features using T2 and T1-weighted sequences.

Moro orange juice prevents fatty liver in mice.

PubMed

Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio

2012-08-07

To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Sex-specific mouse liver gene expression: genome-wide analysis of developmental changes from pre-pubertal period to young adulthood

PubMed Central

2012-01-01

Background Early liver development and the transcriptional transitions during hepatogenesis are well characterized. However, gene expression changes during the late postnatal/pre-pubertal to young adulthood period are less well understood, especially with regards to sex-specific gene expression. Methods Microarray analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the late postnatal/pre-pubertal period to young adulthood. Results A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p < E-76) in the set of genes positively regulated by the liver transcription factor HNF4α, as determined in a liver-specific HNF4α knockout mouse model, while genes down regulated during this developmental period showed significant enrichment (p < E-65) for negative regulation by HNF4α. Significant enrichment of the developmentally regulated genes in the set of genes subject to positive and negative regulation by pituitary hormone was also observed. Five sex-specific transcriptional regulators showed sex-specific expression at 4 wk (male-specific Ihh; female-specific Cdx4, Cux2, Tox, and Trim24) and may contribute to the developmental changes that lead to global acquisition of liver sex-specificity by 8 wk of age. Conclusions Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver. PMID:22475005

A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.

PubMed

Dinu, Monica; Whittaker, Anne; Pagliai, Giuditta; Giangrandi, Ilaria; Colombini, Barbara; Gori, Anna Maria; Fiorillo, Claudia; Becatti, Matteo; Casini, Alessandro; Benedettelli, Stefano; Sofi, Francesco

2018-04-13

KAMUT khorasan is an ancient grain with widely acclaimed health benefits. The aim of this study was to investigate the effects of a replacement diet with ancient khorasan wheat products in patients with NAFLD, in comparison to a similar replacement diet with control products made from organic semi-whole-grain modern wheat. Forty NAFLD patients (12 M/28 F; age 55.2 ± 10.4 years) with mild to moderate liver steatosis were included. The experimental design was a randomized, double-blind, parallel-arm study with 20 participants assigned to consume either KAMUT khorasan or control wheat products (pasta, bread, crackers, biscuits) over a 3-month period. Anthropometric measurements, blood analyses, and ultrasonography examination were performed at both the beginning and end of each dietary intervention. After the implementation of a general linear model for repeated measurements adjusted for baseline demographic details, risk factors, and medication, alanine aminotransferase (ALT) was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%, alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan group (p < 0.05 for all). Similarly, significant reductions in circulating proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were evident only in participants who consumed the khorasan products (p < 0.05 for all). Finally, significant improvements in the liver steatosis grading, Doppler perfusion index values, and reactive oxygen species (ROS) production were evident after consumption of both the khorasan and control products. This study suggests that a short-term replacement diet with ancient KAMUT khorasan products is most effective in reducing metabolic risk factors and ameliorating the liver profile in patients with NAFLD.

Impact of donor histology on survival following liver transplantation for chronic hepatitis C virus infection: a Scandinavian single-center experience.

PubMed

Ydreborg, Magdalena; Westin, Johan; Lagging, Martin; Castedal, Maria; Friman, Styrbjörn

2012-06-01

Survival following liver transplantation for hepatitis C virus (HCV) infection is affected by several factors. The aims of this single-center study were to evaluate survival from 1992 to 2006 in HCV-infected liver transplant recipients and to identify factors influencing patient and graft survival, with particular focus on donor liver histopathology. Survival among 84 patients transplanted for HCV-related liver disease at the Sahlgrenska University Hospital during the above period was evaluated. Median follow-up time was 57 months (range 28-87). A perioperative liver biopsy from the donor liver graft was available in 68 cases. Biopsies were assessed for fibrosis, necroinflammatory activity, and degree of steatosis. Patient and graft survival according to relevant factors including donor histopathology were analyzed by Kaplan-Meier analysis. We found an association between donor liver fibrosis and patient survival (p = 0.016) as well as between graft survival and portal inflammation in the donor liver (p = 0.026). Both these associations remained significant in multivariate analysis (p = 0.007 and 0.017 respectively). Moreover, recipient age over 60 was found predictive of patient survival and repeated steroid boluses or steroid-resistant rejection of graft survival. Donor age was high throughout the study period. Histopathological features, especially portal inflammation and stage of fibrosis, in the donor liver may deleteriously affect graft and patient survival following HCV-related liver transplantation. Thus, pretransplant evaluation of donor histopathology may be of value in the selection of donors for transplantation of HCV-positive individuals, especially among donors older than 60 years.

Pediatric liver transplantation

PubMed Central

Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

2009-01-01

In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

Exercise improves adipose function and inflammation and ameliorates fatty liver disease in obese diabetic mice.

PubMed

Haczeyni, Fahrettin; Barn, Vanessa; Mridha, Auvro R; Yeh, Matthew M; Estevez, Emma; Febbraio, Mark A; Nolan, Christopher J; Bell-Anderson, Kim S; Teoh, Narci C; Farrell, Geoffrey C

2015-09-01

Adipose inflammation and dysfunction underlie metabolic obesity. Exercise improves glycemic control and metabolic indices, but effects on adipose function and inflammation are less clear. Accordingly, it was hypothesized that exercise improves adipose morphometry to reduce adipose inflammation in hyperphagic obese mice. Alms1 mutant foz/foz mice housed in pairs were fed an atherogenic or chow diet; half the cages were fitted with a computer-monitored wheel for voluntary exercise. Insulin-induced AKT-phosphorylation, adipocyte size distribution, and inflammatory recruitment were studied in visceral versus subcutaneous depots, and severity of fatty liver disease was determined. Exercise prevented obesity and diabetes development in chow-fed foz/foz mice and delayed their onset in atherogenic-fed counterparts. Insulin-stimulated phospho-AKT levels in muscle were improved with exercise, but not in adipose or liver. Exercise suppressed adipose inflammatory recruitment, particularly in visceral adipose, associated with an increased number of small adipocyte subpopulations, and enhanced expression of beige adipocyte factor PRDM16 in subcutaneous fat. In atherogenic-fed foz/foz mice liver, exercise suppressed development of nonalcoholic steatohepatitis and related liver fibrosis. Exercise confers metabo-protective effects in atherogenic-fed hyperphagic mice by preventing early onset of obesity and diabetes in association with enhanced muscle insulin sensitivity, improved adipose morphometry, and suppressed adipose and liver inflammation. © 2015 The Obesity Society.

Prolactin improves hepatic steatosis via CD36 pathway.

PubMed

Zhang, Pengzi; Ge, Zhijuan; Wang, Hongdong; Feng, Wenhuan; Sun, Xitai; Chu, Xuehui; Jiang, Can; Wang, Yan; Zhu, Dalong; Bi, Yan

2018-06-01

Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9-10.3] µg/L; women: 8.7 [range, 6.1-12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8-13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2-16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4-9.5] µg/L vs. 9.7 [range, 7.1-12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2-10.6] µg/L vs. 9.8 [range, 8.2-15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content. Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway. Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR. Clinical trial number: NCT03296605. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hot topics in liver transplantation: organ allocation--extended criteria donor--living donor liver transplantation.

PubMed

Müllhaupt, Beat; Dimitroulis, Dimitrios; Gerlach, J Tilman; Clavien, Pierre-Alain

2008-01-01

Liver transplantation has become the mainstay for the treatment of end-stage liver disease, hepatocellular cancer and some metabolic disorders. Its main drawback, though, is the disparity between the number of donors and the patients needing a liver graft. In this review we will discuss the recent changes regarding organ allocation, extended donor criteria, living donor liver transplantation and potential room for improvement. The gap between the number of donors and patients needing a liver graft forced the transplant community to introduce an objective model such as the modified model for end-stage liver disease (MELD) in order to obtain a transparent and fair organ allocation system. The use of extended criteria donor livers such as organs from older donors or steatotic grafts is one possibility to reduce the gap between patients on the waiting list and available donors. Finally, living donor liver transplantation has become a standard procedure in specialized centers as another possibility to reduce the donor shortage. Recent data clearly indicate that center experience is of major importance in achieving good results. Great progress has been made in recent years. However, further research is needed to improve results in the future.

The healthcare burden imposed by liver disease in aging Baby Boomers.

PubMed

Davis, Gary L; Roberts, William L

2010-02-01

The Baby Boomer generation is composed of 78 million Americans who are just beginning to reach their retirement years. Most Boomers have at least one chronic health problem, and these significantly increase the expense of providing medical care. Liver disease is the 12th most common cause of death in the United States, representing a relatively small portion of overall healthcare costs compared with cardiovascular disease and malignancy. Nonetheless, hepatitis C and fatty liver disease are more common in the Boomers and may play a more dominant role as they age. As a consequence, primary liver cancer is likely to become more prevalent. As with most chronic illnesses, prevention rather than disease management is likely to have the greatest impact. For those already afflicted by chronic liver disease, recognition and treatment can reduce the incidence of late complications, as was clearly demonstrated with chronic hepatitis B and C. Perhaps obesity is the greatest threat to our future health, and fatty liver disease, although likely preventable, will probably become the disease that fills the waiting rooms of future hepatologists.

Delisting HCV-infected liver transplant candidates who improved after viral eradication: Outcome 2 years after delisting.

PubMed

Perricone, Giovanni; Duvoux, Christophe; Berenguer, Marina; Cortesi, Paolo A; Vinaixa, Carmen; Facchetti, Rita; Mazzarelli, Chiara; Rockenschaub, Susanne-Rasoul; Martini, Silvia; Morelli, Cristina; Monico, Sara; Volpes, Riccardo; Pageaux, Georges-Philippe; Fagiuoli, Stefano; Belli, Luca S

2018-05-11

Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary L-arginine supplement alleviates hepatic heat stress and improves feed conversion ratio of Pekin ducks exposed to high environmental temperature.

PubMed

Zhu, W; Jiang, W; Wu, L Y

2014-12-01

The current intensive indoor production system of commercial Pekin ducks never allows adequate water for swimming or wetting. Therefore, heat stress is a key factor affecting health and growth of ducks in the hot regions and season. Experiment 1 was conducted to study whether heat stress was deleterious to certain organs of ducks. Forty-one-day-old mixed-sex Pekin ducks were randomly allocated to four electrically heated battery brooders comprised of 10 ducks each. Ducks were suddenly exposed to 37 °C ambient temperature for 3 h and then slaughtered, in one brooder at 21 days and in another brooder at 49 days of age. The results showed that body weight and weight of immune organs, particularly liver markedly decreased in acute heat stress ducks compared with the control. Experiment 2 was carried out to investigate the influences of dietary L-arginine (Arg) supplement on weight and compositions of certain lymphoid organs, and growth performance in Pekin ducks, under daily cyclic hot temperature environment. A total of 151-day-old mixed-sex Pekin ducks were randomly divided into one negative control and two treatment groups, fed experimental diets supplemented with 0, 5, and 10 g L-Arginine (L-Arg)/kg to the basal diet respectively. Ducks were exposed to cyclic high temperature simulating natural summer season. The results showed that the addition of L-Arg improves feed conversion ratio (FCR) during a period of 7-week trial, as well as increases hepatic weight relative to body weight at 21 days, while decreases the hepatic water content at 49 days of age. This study indicated that the liver was more sensitive to acute heat stress, and the hepatic relative weight and chemical composition could be regulated by dietary L-Arg supplementation in Pekin ducks being reared at high ambient temperature. These beneficial effects of Arg on liver might be a cause of improved FCR. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Physiological, pharmacokinetic and liver metabolism comparisons between 3-, 6-, 12- and 18-month-old male Sprague Dawley rats under ketamine-xylazine anesthesia

PubMed Central

Giroux, Marie-Chantal; Santamaria, Raphael; Hélie, Pierre; Burns, Patrick; Beaudry, Francis; Vachon, Pascal

2015-01-01

The main objective of this study was to compare the physiological changes (withdrawal and corneal reflexes, respiratory and cardiac frequency, blood oxygen saturation, and rectal temperature) following intraperitoneal administration of ketamine (80 mg/kg) and xylazine (10 mg/kg) to 3-, 6-, 12- and 18-month-old male Sprague Dawley rats (n=6/age group). Plasma pharmacokinetics, liver metabolism, and blood biochemistry were examined for a limited number of animals to better explain anesthetic drug effects. Selected organs were collected for histopathology. The results for the withdrawal and corneal reflexes suggest a shorter duration and decreased depth of anesthesia with aging. Significant cardiac and respiratory depression, as well as decreased blood oxygen saturation, occurred in all age groups however, cardiac frequency was the most affected parameter with aging, since the 6-, 12-, and 18-month-old animals did not recuperate to normal values during recovery from anesthesia. Pharmacokinetic parameters (T1/2 and AUC) increased and drug clearance decreased with aging, which strongly suggests that drug exposure is associated with the physiological results. The findings for liver S9 fractions of 18-month-old rats compared with the other age groups suggest that following a normal ketamine anesthetic dose (80 mg/kg), drug metabolism is impaired, leading to a significant increase of drug exposure. In conclusion, age and related factors have a substantial effect on ketamine and xylazine availability, which is reflected by significant changes in pharmacokinetics and liver metabolism of these drugs, and this translates into shorter and less effective anesthesia with increasing age. PMID:26489361

Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

PubMed

Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

2016-08-01

Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.

PubMed

Salas, Alfonso Leija; Montezuma, Tania Díaz; Fariña, German Garrido; Reyes-Esparza, Jorge; Rodríguez-Fragoso, Lourdes

2008-01-01

To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease. (c) 2008 S. Karger AG, Basel.

Orthotopic Liver Transplantation in High-Risk Patients

PubMed Central

Gayowski, Timothy; Marino, Ignazio R.; Singh, Nina; Doyle, Howard; Wagener, Marilyn; Fung, John J.; Starzl, Thomas E.

2010-01-01

Background One of the most controversial areas in patient selection and donor allocation is the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing liver transplantation under primary tacrolimus-based immunosuppression. Methods Twenty-eight pre-liver transplant, operative, and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplants in 130 veterans (98% male; mean age, 47.3 years). Results Eighty-two percent of the patients had post-necrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% United Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (P=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (P<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with mortality by univariate analysis. Underlying liver disease, cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, ischemia time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV had a trend towards higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppression, post-transplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.001), pretransplant creatinine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurrence was of borderline significance (P=0.07). Conclusions Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling. PMID:9500623

Effect of Daisaikoto on Expressions of SIRT1 and NF-kappaB of Diabetic Fatty Liver Rats Induced by High-Fat Diet and Streptozotocin

PubMed Central

Qian, Weibin; Cai, Xinrui; Zhang, Xinying; Wang, Yingying; Qian, Qiuhai; Hasegawa, Junichi

2016-01-01

Background Daisaikoto (DSKT), a classical traditional Chinese herbal formula, has been used for treating digestive diseases for 1800 years in China. Therefore, in this study, we are going to investigate the effect of DSKT on diabetic fatty liver rats induced by a high-fat diet and streptozotocin (STZ), and the effects of DSKT on silent mating type information regulation 2 homolog 1 (SIRT1) and nuclear factor kappa B (NF-kappaB). Methods Diabetic fatty liver rat model was selected to establish a high-fat diet and STZ. Sixty Wistar rats were divided into six groups (n = 10): control group, high-fat diet + STZ group, simvastatin treatment group, DSKT low dose, medial dose and high dose treatment groups. After 8 weeks of drug intervention, body and liver weights, blood chemistry, blood glucose and insulin were examined. The expressions of sirtuin 1 and NF-kappaB in the liver were observed by RT-PCR and immunohistochemistry, respectively. Results A high-fat diet increased body, liver weights, and serum cholesterol concentrations. Intraperitoneal injection of STZ increased blood glucose and decreased body weights. DSKT improved them. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) indices were increased in the high-fat diet groups. DSKT improved them too. In histological examinations of the liver, we observed a significant improvement after treatment. Immunostaining expression of NF-kappaB in the liver was improved by DSKT and simvastatin. The mRNA expressions of SIRT1 in the liver were increased by DSKT and simvastatin. Conclusion We have demonstrated that DSKT is capable of reversing dyslipidemia and insulin resistance induced by a high-fat diet and STZ. High dose DSKT reveals a stronger effect than simvastatin on the expressions of SIRT1 and NF-kappaB. Furthermore, DSKT has shown a strong dose-depended protective effect on diabetic fatty liver. PMID:27493486

Acute-on-Chronic Liver Failure: Getting ready for prime-time.

PubMed

Bajaj, Jasmohan S; Moreau, Richard; Kamath, Patrick S; Vargas, Hugo E; Arroyo, Vicente; Reddy, K Rajender; Szabo, Gyongyi; Tandon, Puneeta; Olson, Jody; Karvellas, Constantine; Gustot, Thierry; Lai, Jennifer C; Wong, Florence

2018-04-24

Acute on chronic liver failure (ACLF) is a culmination of chronic liver disease and extra-hepatic organ failures, which is associated with a high short-term mortality and immense healthcare expenditure. There are varying definitions for organ failures and ACLF in Europe, North America and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multi-factorial and related to interactions between the immuno-inflammatory system, microbiota and the precipitating factors. Individual organ failures related to the kidney, brain, lungs and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by infections. Strategies to prevent and rapidly treat these organ failures are paramount in improving survival. With the aging population and paucity of organs for liver transplant, the prognosis of ACLF patients is poor, highlighting the need for novel therapeutic strategies. The role of liver transplant in ACLF is evolving and needs further investigation across large consortia. A role for early palliative care and management of frailty as approaches to alleviate disease burden and improve patient-reported outcomes is being increasingly recognized. ACLF is a clinically relevant syndrome that is epidemic worldwide and which requires a dedicated multi-national approach focused on prognostication and management. Investigations are underway worldwide to get ACLF ready for prime time. Compensated cirrhosis with >90% 1-year survival can transition into the decompensated stage with the onset of jaundice, ascites, variceal bleeding and hepatic encephalopathy (HE) (1)Acute on chronic liver failure (ACLF) is associated with rapid deterioration of liver function leading to liver failure, multiple extra-hepatic organ failures and high short-term mortality (2). Even if patients survive the acute insult, they may never return to their pre-episode functional state (3). The term "acute decompensation" has been used to characterize ascites, gastrointestinal bleeding, hepatic encephalopathy or infections without organ failure(4). There are several gaps in knowledge surrounding ACLF, which will be highlighted in this review. The prevalence of ACLF is difficult to assess due to varying regional definitions (5). ACLF, once thought to occur only in decompensated cirrhosis, has been recognized even in chronic liver disease without cirrhosis (5). ACLF occurs in approximately 10-30% of hospitalized cirrhotic patients (6-8). Because of its acuity, patients are frequently admitted into the intensive care unit (ICU), and every effort is made to stabilize these patients for liver transplantation (LT). This drives healthcare costs(9). Despite this intensive management, ACLF is associated with substantial morbidity and mortality. Because curative LT is only available to <10% of cirrhotic patients each year and ACLF patients are often delisted, the morbidity and mortality rates remain high, especially with an increasing number of organ failures (10). This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Differentiation between Malignant and Benign Solitary Lesions in the Liver with 18FDG PET/CT: Accuracy of Age-related Diagnostic Standard

PubMed Central

Xia, Qian; Feng, Yuanbo; Wu, Cheng; Huang, Gang; Liu, Jianjun; Chen, Tao; Sun, Xiaoguang; Song, Shaoli; Tong, Linjun; Ni, Yicheng

2015-01-01

Objective: This study was to determine the reliability of age-stratified diagnostic index in differential diagnosis of malignant and benign solitary lesions in the liver using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT). Methods: The enrolled 272 patients with solitary lesions in the liver were divided into three age groups, younger group (under 50 years), middle-aged group (50-69 years), and elderly group (70 years and above). Patients' ages were compared, and the optimal cut-offs of the standard uptake value (SUV) ratio (tumor-to-non-tumor ratio of the SUV), as well as areas under the curves (AUC), were evaluated in terms of malignant and benign lesions in each age group by using receiver operating characteristic (ROC) analysis. Based on optimal cut-offs, the sensitivity, specificity, accuracy were calculated, and the diagnostic accordance rate was compared between each age group and all patients, supported by 18FDG PET/CT imaging data. Results: There was a significant age difference between the malignant and benign groups (t=3.905 p=0.0001). ROC analysis showed that the optimal cut-off value in all patients, younger group, middle-aged group and elderly group was 1.25, 1.17, 1.45 and 1.25 for SUVratio, and 0.856, 0.962, 0.650, 0.973 for AUC. The chi-square test proved that diagnostic accordance rate of 18FDG PET/CT in younger group and elderly group were superior to that in all patients (χ2=13.352, P=0.0003) and (χ2=8.494, P=0.0036). Conversely, overall diagnostic accordance rate in all patient group was higher than that in middle-aged group (χ2=9.057, P=0.0026). Representative 18FDG PET/CT imaging findings are demonstrated. Conclusion: This study indicates that diagnostic optimal cut-offs of SUVratio of liver solitary lesions of 18FDG PET/CT were different in each age group. In addition, the diagnostic performance of SUVratio was better in younger and elderly groups than that in all patients, and was poorer in middle-aged group than that in all patients. Therefore, age difference appears to be one of the important factors for discriminating malignant liver lesions from benign ones using 18 FDG PET/CT. PMID:25553087

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

PubMed

Scorletti, Eleonora; Bhatia, Lokpal; McCormick, Keith G; Clough, Geraldine F; Nash, Kathryn; Hodson, Leanne; Moyses, Helen E; Calder, Philip C; Byrne, Christopher D

2014-10-01

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

PubMed

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic.

Hepatic Tissue Environment in NEMO-Deficient Mice Critically Regulates Positive Selection of Donor Cells after Hepatocyte Transplantation

PubMed Central

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Background Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Methods Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Results Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. Conclusion This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic. PMID:24979756

Correlation between liver iron concentration determined by magnetic resonance imaging and serum ferritin in adolescents with thalassaemia disease.

PubMed

Chuansumrit, Ampaiwan; Laothamathat, Jiraporn; Sirachainan, Nongnuch; Sungkarat, Witaya; Wongwerawattanakoon, Pakawan; Kumkrua, Patrapop

2016-08-01

MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease. To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters. An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease. Eighty-nine patients (48 males) with thalassaemia disease were enrolled. Seventy patients had been transfusion-dependent since a mean (SD) age of 3.8 (3.0) years, and 19 patients were not transfusiondependent. Mean (SD) haematocrit was 27.3 (2.9)%. Twenty-eight patients were splenectomized. Mean (SD) serum ferritin was 1673 (1506) μg/L. All transfusion-dependent patients received iron chelation at the mean (SD) age of 8.4 (3.5) years with either monotherapy of desferrioxamine, deferiprone, deferasirox or combined therapy of desferrioxamine and deferiprone, while only 5 of 19 patients who were not transfusion-dependent received oral chelation. The 89 patients underwent an MRI scan at the mean (SD) age of 14.8 (3.2) years. No patients had myocardial iron overload, but nine had severe liver iron overload, 27 had moderate liver iron overload, and 36 had mild liver iron overload. A significant correlation between liver T2* and serum ferritin was expressed as the equation: T2* (ms) = 28.080-7.629 log ferritin (μg/L) (r(2) 0.424, P = 0.0001). Patients with serum ferritin of >1000 to >2500 μg/L risked moderate and severe liver iron loading with the odds ratio ranging from 6.8 to 13.3 (95% CI 2.5-50.8). In thalassaemia, MRI is an alternative means of assessing iron stores, but when it is not available serum ferritin can be used to estimate liver T2*.

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

PubMed

Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

2017-03-28

Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1 df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.

PubMed

Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi

2016-01-01

3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats.

PubMed

Jagtap, A G; Patil, P B

2010-01-01

Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

PubMed Central

Razavi, Homie; Loomba, Rohit; Younossi, Zobair; Sanyal, Arun J.

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC) and increasingly an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available and validated using national surveillance data for incidence of NAFLD‐related HCC. Projected changes in NAFLD‐related cirrhosis, advanced liver disease, and liver‐related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 million (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 million to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015‐2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015‐2030, there are projected to be nearly 800,000 excess liver deaths. Conclusion: With continued high rates of adult obesity and DM along with an aging population, NAFLD‐related liver disease and mortality will increase in the United States. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. (Hepatology 2018;67:123‐133). PMID:28802062

Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis.

PubMed

Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh

2018-04-19

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Life-long spontaneous exercise does not prolong lifespan but improves health span in mice

PubMed Central

2013-01-01

Background Life expectancy at birth in the first world has increased from 35 years at the beginning of the 20th century to more than 80 years now. The increase in life expectancy has resulted in an increase in age-related diseases and larger numbers of frail and dependent people. The aim of our study was to determine whether life-long spontaneous aerobic exercise affects lifespan and healthspan in mice. Results Male C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (n = 72) or spontaneous wheel-runners (n = 72). We evaluated longevity and several health parameters including grip strength, motor coordination, exercise capacity (VO2max) and skeletal muscle mitochondrial biogenesis. We also measured the cortical levels of the brain-derived neurotrophic factor (BDNF), a neurotrophin associated with brain plasticity. In addition, we measured systemic oxidative stress (malondialdehyde and protein carbonyl plasma levels) and the expression and activity of two genes involved in antioxidant defense in the liver (that is, glutathione peroxidase (GPx) and manganese superoxide dismutase (Mn-SOD)). Genes that encode antioxidant enzymes are considered longevity genes because their over-expression may modulate lifespan. Aging was associated with an increase in oxidative stress biomarkers and in the activity of the antioxidant enzymes, GPx and Mn-SOD, in the liver in mice. Life-long spontaneous exercise did not prolong longevity but prevented several signs of frailty (that is, decrease in strength, endurance and motor coordination). This improvement was accompanied by a significant increase in the mitochondrial biogenesis in skeletal muscle and in the cortical BDNF levels. Conclusion Life-long spontaneous exercise does not prolong lifespan but improves healthspan in mice. Exercise is an intervention that delays age-associated frailty, enhances function and can be translated into the clinic. PMID:24472376

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

PubMed

Tag-Adeen, Mohammed; Sabra, Ahlam Mohamed; Akazawa, Yuko; Ohnita, Ken; Nakao, Kazuhiko

2017-01-01

Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication. The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0-F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p -value <0.05 was statistically significant. Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m 2 . Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of -5.8 occurred in F4 versus -2.79, -1.28 and +0.08 in F3, F2 and F0-F1 respectively ( p <0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 ( p <0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement ( p =0.01) and APRI improvement ( p =0.01) and 81% showed Fib-4 improvement ( p =0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement. Successful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo.

PubMed

Gonçalves, Patricia Lofego; Zago-Gomes, Maria da Penha; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

2013-01-01

To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2 ± 12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1 %), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1 %), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p = 0.052). Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

The association between content of the elements S, Cl, K, Fe, Cu, Zn and Br in normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by dual hierarchical clustering analysis.

PubMed

Laursen, Jens; Milman, Nils; Pind, Niels; Pedersen, Henrik; Mulvad, Gert

2014-01-01

Meta-analysis of previous studies evaluating associations between content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue samples. Normal liver samples from 45 Greenlandic Inuit, median age 60 years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27 Danes, median age 71 years. Element content was measured using X-ray fluorescence spectrometry. Dual hierarchical clustering analysis, creating a dual dendrogram, one clustering element contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure. One dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age. The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant associations with any other element. In contrast to simple statistical methods, which analyses content of elements separately one by one, dual hierarchical clustering analysis incorporates all elements at the same time and can be used to examine the linkage and interplay between multiple elements in tissue samples. Copyright © 2013 Elsevier GmbH. All rights reserved.

The overuse of serum ceruloplasmin measurement.

PubMed

Tapper, Elliot B; Rahni, David O; Arnaout, Ramy; Lai, Michelle

2013-10-01

Wilson disease is rare, found in 3 of 100,000 people (0.03%). Ceruloplasmin is often ordered to evaluate liver enzyme elevations. Because Wilson disease often presents before middle-age, the American Association for the Study of Liver Disease recommends screening patients between the ages of 3 and 55 years with liver abnormalities of uncertain cause. We evaluate guideline adherence and the clinical and economic impact of current clinical use of ceruloplasmin. We reviewed all ceruloplasmin measurements at a clinical laboratory that serves a large primary care network, specialty clinics, and a 600-bed tertiary referral center between January 1, 2003, and December 12, 2011. Ceruloplasmin was measured 5325 times in 5023 unique patients, resulting in 8 (0.16%) new Wilson disease diagnoses. Ceruloplasmin's positive predictive value was 8.4% (95% confidence interval, 7.7-9.3) and false-positive rate was 98.1% (95% confidence interval, 96.2-99.1). A total of 1109 ceruloplasmin levels (20.8%) were ordered in the 1066 patients aged more than 55 years (none with Wilson disease). A "shotgun" approach to liver disease diagnosis was found: Ceruloplasmin was ordered on the same day as hepatitis B (81.0%), hepatitis C (76.0%), autoimmune hepatitis (75.1%), and hemochromatosis (73.1%). Of 424 positive ceruloplasmin results, 91% were not pursued further. Guideline adherence restricts ceruloplasmin use to a population with a higher pre-test probability of Wilson disease: patients with chronic liver disease aged 3 to 55 years who have been tested for common causes of liver disease. The majority of the serum ceruloplasmin was measured in patients not indicated by the guidelines, resulting in poor test performance and wasted healthcare resources. Our data on ceruloplasmin use could serve as a touchstone for broader discussions on rational clinical decision making. Copyright © 2013 Elsevier Inc. All rights reserved.

Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.

PubMed

Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

2016-01-01

hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.

Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis.

PubMed

Petta, Salvatore; Adinolfi, Luigi Elio; Fracanzani, Anna Ludovica; Rini, Francesca; Caldarella, Rosalia; Calvaruso, Vincenza; Cammà, Calogero; Ciaccio, Marcello; Di Marco, Vito; Grimaudo, Stefania; Licata, Anna; Marrone, Aldo; Nevola, Riccardo; Pipitone, Rosaria Maria; Pinto, Antonio; Rinaldi, Luca; Torres, Daniele; Tuttolomondo, Antonino; Valenti, Luca; Fargion, Silvia; Craxì, Antonio

2018-07-01

Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ± 10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ± 0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ± 0.29 mm vs. 0.81 ± 0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Toxic and trace metal concentrations in liver and kidney of dogs: influence of diet, sex, age, and pathological lesions.

PubMed

Löpez-Alonso, Marta; Miranda, Marta; García-Partida, Paulino; Mendez, Adriana; Castillo, Cristina; Benedito, José Luis

2007-05-01

The aim of this study was to provide data on the main toxic and trace metals in the liver and kidney of domestic dogs in Galicia, NW Spain and to evaluate the influence of diet, sex, age, and pathological lesions on metal accumulation. Samples of the liver and kidney from 77 male and female dogs, aged between 6 mo and 18 yr, were collected during ordinary necropsy. Samples were acid-digested and metal concentrations determined by inductively coupled plasma (ICP)-mass spectrometry and ICP-atomic emission spectrometry. Mean toxic metal concentrations (geometric means for liver and kidney respectively) were 11.5 and 15.8 microg/kg wet weight for As, 56.3 and 166 microg/kg for Cd, 32.7 and 51.9 microg/kg for Hg, and 60.1 and 23.6 microg/kg for Pb. For the trace metals, these concentrations were respectively 16.3 and 21.0 microg/kg for Co, 57.6 and 43.9 microg/kg for Cr, 42.1 and 5.95 mg/kg for Cu, 394 mg/kg and 95.7 mg/kg for Fe, 2.39 and 0.956 mg/kg for Mn, 0.522 and 0.357 mg/kg for Mo, 23.8 and 26.8 microg/kg for Ni, 0.686 and 1.39 mg/kg for Se, and 46.7 and 26.0 mg/kg for Zn. Cd concentrations in the kidney significantly increased with age, and Co concentrations in the liver and kidney significantly decreased with age. Hepatic Pb concentrations were significantly higher in growing (<1 yr) and old (>10 yr) dogs. Animals with pathological lesions showed significantly higher Co and lower Mn and Zn concentrations in liver than animals without macroscopic abnormalities. Dogs that received commercial diets in general showed low variability in hepatic mineral status compared to animals that receive homemade feeds or a mixture of commercial and homemade feeds.

Liver grafts from selected older donors do not have significantly more ischaemia reperfusion injury

PubMed Central

Martins, Paulo N; Chang, Sue; Mahadevapa, Basant; Martins, Ann-Britt; Sheiner, Patricia

2011-01-01

Background There is a general concern that aged organs are more susceptible to ischaemia. In the light of recent proposals to change the liver allocation system by expanding regional sharing, it is feared that increased cold ischaemia time of grafts from older donors may reduce graft survival. The aim of this study was to correlate donor age and the patterns of ischaemia reperfusion injury and synthetic function early after liver transplantation. Methods We performed a retrospective study of first transplants using a single-centre electronic database. Patterns of liver injury (based on transaminases and post-reperfusion biopsy), synthetic function (international normalized ratio [INR]), and graft and patient survival in recipients receiving liver grafts from donors aged ≥65 years (group 1, n= 50) were compared with equivalent patterns in a matched cohort of recipients transplanted with grafts from donors aged <65 years (group 2, n= 50). Results There was no significant difference in transaminase levels from day 0 to day 6 after transplantation. When groups 1 and 2 were subdivided into two subgroups based on the duration of graft cold ischaemia time (<8 h and ≥8 h), there was no statistical difference in transaminase levels during the first 7 days. There were two cases (4%) of primary non-function in group 1 and one (2%) in group 2. Initial poor function did not differ significantly between the groups (26% vs. 24%; P= 0.81). In addition, there was no difference in histological changes in post-reperfusion biopsies (21% vs. 34%; P= 0.078) and rate of acute rejection episodes in the first year (30% vs. 32%; P= 0.99). There was no significant difference between groups 1 and 2 in 1-year patient and graft survivals (78% vs. 90% [P= 0.17]; 88% vs. 94% [P= 0.48], respectively). Conclusions Judiciously selected livers from aged donors are not associated with major increased susceptibility to ischaemia reperfusion injury. PMID:21309940

 Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

PubMed

Díaz, Francia C; Sáez-González, Esteban; Benlloch, Salvador; Álvarez-Sotomayor, Diego; Conde, Isabel; Polo, Begoña; García, María; Rodríguez, María; Prieto, Martín

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

PubMed

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

The impact of weight changes on nonalcoholic Fatty liver disease in adult men with normal weight.

PubMed

Cho, Ji-Young; Chung, Tae-Heum; Lim, Kyoung-Mo; Park, Hee-Jin; Jang, Jung-Mi

2014-09-01

Although it is known that losing weight has an effect on the treatment of non-alcoholic fatty liver disease, the studies that show how losing weight affects the non-alcoholic fatty liver disease for the normal weight male adults are limited so far. In this study, we set body mass index as criteria and investigated how the weight changes for 4 years makes an impact on the risk of non-alcoholic fatty liver disease for the male adults who have the normal body mass index. From January to December of 2004, among the normal weight male adults who had general check-up at the Health Promotion Center of Ulsan University Hospital, 180 people (average age, 47.4 ± 4.61 years) who were diagnosed with fatty liver through abdominal ultrasonography were included in this study and were observed according to the variety of data and ultrasonography after 4 years (2008). People who had a history of drinking more than 140 g of alcohol per week or who had a past medical history were excluded from the analysis. The weight change of subjects was calculated using the formula 'weight change = weight of 2008 (kg) - weight of 2004 (kg)' and classified into three groups, loss group (≤-3.0 kg), stable group (-2.9 to 2.9 kg), and gain group (≥3.0 kg). The odds for disappearance of non-alcoholic fatty liver disease in those three different groups were compared. Among 180 subjects, compared with stable group (67.2%, 121 subjects), loss group (11.7%, 21 subjects) showed 18.37-fold increase in the odds of disappearance of non-alcoholic fatty liver disease (95% confidence interval [CI], 4.34 to 77.80) and gain group (21.1%, 38 subjects) showed 0.28-fold decrease in the odds of disappearance of non-alcoholic fatty liver disease (95% CI, 0.10 to 0.83). Even for the normal weight people, losing weight has an effect on the improvement of non-alcoholic fatty liver disease.

Correlation between proton pump inhibitors and risk of pyogenic liver abscess.

PubMed

Lin, Hsien-Feng; Liao, Kuan-Fu; Chang, Ching-Mei; Lin, Cheng-Li; Lai, Shih-Wei

2017-08-01

Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n = 1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n = 1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30 days, between 31 to 90 days and ≥91 days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.

Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

PubMed

Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

2017-09-15

Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Levels of mercury in muscle and liver of star-spotted dogfish (Mustelus manazo) from the northern region of Japan: a comparison with spiny dogfish (Squalus acanthias).

PubMed

Endo, Tetsuya; Hisamichi, Yohsuke; Kimura, Osamu; Ogasawara, Hideki; Ohta, Chiho; Koga, Nobuyuki; Kato, Yoshihisa; Haraguchi, Koichi

2013-04-01

We analyzed mercury (Hg) concentrations in muscle and liver samples of star-spotted dogfish (Mustelus manazo) caught off the northern region of Japan and compared them with those of spiny dogfish (Squalus acanthias) caught in the same region. The average body length of male star-spotted dogfish specimens was significantly smaller than that of female specimens, reflecting the slower growth rate of male fish. Hg concentrations in liver and muscle increased with increases in body length and estimated age of both male and female star-spotted dogfish specimens. However, the relationships between Hg concentration in liver or muscle and body length or estimated age of male specimens differed markedly from those of female specimens, reflecting differences in growth rate and cessation of growth on reaching maturity. Marked increases in Hg concentration in liver of male and female star-spotted dogfish specimens were observed slightly later than increases in Hg concentration in muscle of those specimens due to growth cessation. These marked increases in Hg in liver may reflect increases in Hg due to the formation of mercury selenide. Similar results were previously reported in spiny dogfish specimens, except spiny dogfish showed only trace levels of Hg in liver (Endo et al., Chemosphere 77:1333-1337, 2009). The greater lipid content in liver and the larger liver size in spiny dogfish may explain the much lower levels of Hg observed in liver of spiny dogfish compared with those in the star-spotted dogfish.

Childhood Abuse, Nonadherence, and Medical Outcome in Pediatric Liver Transplant Recipients

ERIC Educational Resources Information Center

Shemesh, Eyal; Annunziato, Rachel A.; Yehuda, Rachel; Shneider, Benjamin L.; Newcorn, Jeffrey H.; Hutson, Carolyn; Cohen, Judith A.; Briere, John; Gorman, Jack M.; Emre, Sukru

2007-01-01

Objective: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. Method: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002.…

Epstein-Barr viral load before a liver transplant in children with chronic liver disease.

PubMed

Shakibazad, Nader; Honar, Naser; Dehghani, Seyed Mohsen; Alborzi, Abdolvahab

2014-12-01

Many children with chronic liver disease require a liver transplant. These patients are prone to various infections, including Epstein-Barr virus infection. This study sought to measure the Epstein-Barr viral load by polymerase chain reaction before a liver transplant. This cross-sectional study was done at the Shiraz University of Medical Sciences, Shiraz, Iran, in 2011. All patients were aged younger than 18 years with chronic liver disease and were candidates for a liver transplant at the Shiraz Nemazee Hospital Organ Transplant Center. They had been investigated regarding their demographic characteristics, underlying disease, laboratory findings, and Epstein-Barr viral load by real-time TaqMan polymerase chain reaction. Ninety-eight patients were studied and the mean age was 6.5 ± 5.9 years. Cryptogenic cirrhosis was the most-prevalent reason for liver transplant, and the death rate before a transplant was 15%. Among the study subjects, 6 had measurable Epstein-Barr viral load by polymerase chain reaction before the transplant, and 4 of them had considerably higher Epstein-Barr viral loads (more than 1000 copies/mL). With respect to the close prevalence of posttransplant lymphoproliferative disease (6%) and the high Epstein-Barr viral load in the patients before a transplant (4%), high pretransplant Epstein-Barr viral load can be considered a risk factor for posttransplant lymphoproliferative disorder.

Risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patient with component of metabolic syndrome.

PubMed

Cai, Shaohang; Ou, Zejin; Liu, Duan; Liu, Lili; Liu, Ying; Wu, Xiaolu; Yu, Tao; Peng, Jie

2018-05-01

We investigated whether metabolic syndrome exacerbated the risk of liver fibrosis among chronic hepatitis B patients and risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patients with components of metabolic syndrome. This study included 1236 chronic hepatitis B patients with at least one component of metabolic syndrome. The controlled attenuation parameter and liver stiffness, patient information and relevant laboratory data were recorded. Controlled attenuation parameter was increased progressively with the number of metabolic syndrome components ( p  < 0.001). Multivariate analysis indicated younger age, high gamma-glutamyltransferase level, high waist-hip ratio, and high body mass index were independent risk factors associated with nonalcoholic fatty liver disease among chronic hepatitis B patients with metabolic syndrome. In the fibrosis and non-fibrosis groups, most of blood lipid was relatively lower in fibrosis group. An increased proportion of chronic hepatitis B patients with liver fibrosis was found concomitant with an increasing number of components of metabolic syndrome. Male gender, older age, smoking, aspartate aminotransferase levels, high body mass index, and low platelet level were identified as independent risk factors associated with liver fibrosis. For chronic hepatitis B patients with coexisting components of metabolic syndrome, stratification by independent risk factors for nonalcoholic fatty liver disease and fibrosis can help with management of their disease.

Patent foramen ovale does not have a negative impact on early outcomes in patients undergoing liver transplantation.

PubMed

Alba, Ana Carolina; Verocai Flaman, F; Granton, J; Delgado, D H

2011-01-01

To identify the impact of the presence of patent foramen ovale (PFO) in patients undergoing liver transplantation. Twenty-seven pre-liver transplant patients who had a PFO (PFO group) were identified and compared with 61 patients without PFO (NoPFO group). Patients were matched according to age, gender and cause of liver disease. The diagnosis of PFO was made by transthoracic echocardiography prior to liver transplantation. Patient baseline characteristics and complications during the early post-transplant period were analyzed. The mean age in the PFO group was 47 ± 14 (range 18-68) yr and 50 ± 11 (range 12-65) yr in the NoPFO group. The PFO group had a mean model for end-stage liver disease (MELD) score of 15 ± 10 whereas in the NoPFO group the MELD score was 19 ± 10 (p = 0.08). There were non-significant differences in echocardiographic parameters between groups. Duration of mechanical ventilation and the incidence of neurological complications were similar. Thirty-day mortality rate was similar in both groups; only one patient in the NoPFO group died within the first 30 days post-transplantation. The presence of PFO in patients with end-stage liver disease undergoing liver transplantation does not appear to affect patient outcomes during the peri-operative period. © 2010 John Wiley & Sons A/S.

Sex, age, and tissue specific accumulation of eight metals, arsenic, and selenium in the European hedgehog (Erinaceus europaeus).

PubMed

Rautio, Anni; Kunnasranta, Mervi; Valtonen, Anu; Ikonen, Mirva; Hyvärinen, Heikki; Holopainen, Ismo J; Kukkonen, Jussi V K

2010-11-01

Many insectivores have been shown to be sensitive to heavy metals and therefore suitable for biomonitoring purposes. In Finland, the hibernation period of the European hedgehog (Erinaceus europaeus) is long, and during hibernation the stress caused by environmental toxins may be crucial. Concentrations of cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), arsenic (As), and selenium (Se) were measured in a population of hedgehogs in the town of Joensuu in eastern Finland during the summers of 2004 and 2005. The analyzed tissues were kidney, liver, hair, and spine. The sampled hedgehogs (n = 65) were mainly road-killed animals. As expected, the concentrations of heavy metals were low because the hedgehogs were living in a comparatively unpolluted area. Significant increases with age were found in Cd concentrations (kidney, liver, and spine) and some essential elements (Se in spine, kidney, and liver; Mo in kidney and liver; Cu in spine; Fe in liver; and Mn in spine). Age accumulation and correlations between Se and Cd and between Mo and Cd may indicate the protective roles of Se and Mo against Cd toxicity in hedgehogs, in which Cd is already at comparatively low concentrations. Sex had no significant effect on concentrations of the elements studied. In conclusion, age is an important parameter to be taken into account when studying heavy-metal concentrations in hedgehogs and other insectivores.

THE NATURAL HISTORY OF NONALCOHOLIC FATTY LIVER DISEASE WITH ADVANCED FIBROSIS OR CIRRHOSIS: AN INTERNATIONAL COLLABORATIVE STUDY

PubMed Central

Bhala, Neeraj; Angulo, Paul; van der Poorten, David; Lee, Eric; Hui, Jason M.; Saracco, Giorgio; Adams, Leon A.; Charatcharoenwitthaya, Punchai; Topping, Joanne H.; Bugianesi, Elisabetta; Day, Christopher P.; George, Jacob

2011-01-01

Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis. We conducted this prospective cohort study including 247 patients with NAFLD and 264 patients with HCV infection that were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced (stage 3) fibrosis or cirrhosis (stage 4) confirmed by liver biopsy at enrolment. In the NAFLD cohort, followed-up for 85.6 months mean (range 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed-up for 74.9 months mean (range 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (p=0.03), including incident hepatocellular cancer (6 vs 18; p=0.03), but that of cardiovascular events (p=0.17) and overall mortality (p=0.6) was similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, and serum levels of cholesterol and ALT were associated with liver-related complications; an AST/ALT ratio >1 and older age were associated with overall mortality; and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality. Conclusions Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict outcomes in patients with NAFLD. PMID:21688282

Estimation of standard liver volume in Chinese adult living donors.

PubMed

Fu-Gui, L; Lu-Nan, Y; Bo, L; Yong, Z; Tian-Fu, W; Ming-Qing, X; Wen-Tao, W; Zhe-Yu, C

2009-12-01

To determine a formula predicting the standard liver volume based on body surface area (BSA) or body weight in Chinese adults. A total of 115 consecutive right-lobe living donors not including the middle hepatic vein underwent right hemi-hepatectomy. No organs were used from prisoners, and no subjects were prisoners. Donor anthropometric data including age, gender, body weight, and body height were recorded prospectively. The weights and volumes of the right lobe liver grafts were measured at the back table. Liver weights and volumes were calculated from the right lobe graft weight and volume obtained at the back table, divided by the proportion of the right lobe on computed tomography. By simple linear regression analysis and stepwise multiple linear regression analysis, we correlated calculated liver volume and body height, body weight, or body surface area. The subjects had a mean age of 35.97 +/- 9.6 years, and a female-to-male ratio of 60:55. The mean volume of the right lobe was 727.47 +/- 136.17 mL, occupying 55.59% +/- 6.70% of the whole liver by computed tomography. The volume of the right lobe was 581.73 +/- 96.137 mL, and the estimated liver volume was 1053.08 +/- 167.56 mL. Females of the same body weight showed a slightly lower liver weight. By simple linear regression analysis and stepwise multiple linear regression analysis, a formula was derived based on body weight. All formulae except the Hong Kong formula overestimated liver volume compared to this formula. The formula of standard liver volume, SLV (mL) = 11.508 x body weight (kg) + 334.024, may be applied to estimate liver volumes in Chinese adults.

Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess

PubMed Central

Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei; Chen, Wen-Chi

2015-01-01

Abstract The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ≤7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess. After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance. Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem. PMID:26266369

[Effect of fenicaberan on liver function in patients with chronic noncalculous cholecystitis].

PubMed

Skroban, N V

1989-06-01

The author studied the effect of fenicaberan on the functional state of the liver in 34 patients with chronic noncalculous cholecystitis. It was found that fenicaberan favours improvement of the functional state of the liver but complete normalization of all liver values indicates necessity continuation of treatment in outpatient conditions.

Sexual dysfunction after liver transplantation.

PubMed

Burra, Patrizia

2009-11-01

1. The goal of liver transplantation is not only to ensure the survival of patients but also to offer patients the opportunity to achieve a good balance between the functional efficacy of the graft and their psychological and physical integrity. The quality of life after transplantation may be affected by unsatisfactory sexual activity and reproductive performance. 2. Sexual dysfunction and sex hormone disturbances are widely reported in men and women with chronic liver disease before liver transplantation. 3. Successful liver transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, therefore improving reproductive performance, but immunosuppressive drugs may interfere with hormone metabolism. 4. Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy, but fetal and maternal outcomes should be regularly assessed. 5. More detailed and comprehensive data are needed in the field of sexual function after transplantation, and new strategies are needed to support and inform patients on the waiting list and after liver transplantation. (c) 2009 AASLD.

Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.

PubMed

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh

2017-10-01

Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.

Adrenocortical carcinoma, an unusual cause of secondary hypertension.

PubMed

Veron Esquivel, Daniel; Batiz, Fernando; Farias Vega, Alfonso; Carrillo Gonzalez, Perla A

2016-12-07

We present the case of a female patient aged 39 years who was admitted to our hospital due to hypertension, severe hypokalaemia and metabolic alkalosis; physical examination was remarkable for plethoric moon face, centripetal obesity and bilateral lower extremity oedema. She was admitted for intravenous potassium replacement and further assessment of hypertension and associated clinical findings. Laboratory testing showed increased levels of aldosterone, renin, cortisol, testosterone and androstenedione. An abdominal CT revealed a large mass in the right adrenal gland with hepatic involvement. The patient was started on antihypertensive medications and underwent laparoscopic surgery for mass and liver biopsy. The pathological diagnosis was adrenocortical carcinoma with liver metastasis. Hyperaldosteronism is a cause of secondary hypertension and its diagnosis is usually benign. Adrenocortical carcinoma is a rare condition and aldosterone secreting tumours are even rarer; associated hypertension usually improves after tumour resection, but with the presence of metastasis, blood pressure control is difficult. 2016 BMJ Publishing Group Ltd.

Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox.

PubMed

Lescano, Manuel A; Tavares, Letícia C; Santos, Paulo C J L

2017-10-16

Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.

Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

PubMed Central

Lescano, Manuel A; Tavares, Letícia C; Santos, Paulo C J L

2017-01-01

Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms. PMID:29085829

An OX40/OX40L interaction directs successful immunity to hepatitis B virus

PubMed Central

Publicover, Jean; Gaggar, Anuj; Jespersen, Jillian M.; Halac, Ugur; Johnson, Audra J.; Goodsell, Amanda; Avanesyan, Lia; Nishimura, Stephen L.; Holdorf, Meghan; Mansfield, Keith G.; Judge, Joyce Bousquet; Koshti, Arya; Croft, Michael; Wakil, Adil E.; Rosenthal, Philip; Pai, Eric; Cooper, Stewart; Baron, Jody L.

2018-01-01

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB. PMID:29563320

Organ and tissue-dependent effect of resveratrol and exercise on antioxidant defenses of old mice.

PubMed

Tung, Bui Thanh; Rodriguez-Bies, Elisabet; Thanh, Hai Nguyen; Le-Thi-Thu, Huong; Navas, Plácido; Sanchez, Virginia Motilva; López-Lluch, Guillermo

2015-12-01

Oxidative stress has been considered one of the causes of aging. For this reason, treatments based on antioxidants or those capable of increasing endogenous antioxidant activity have been taken into consideration to delay aging or age-related disease progression. In this paper, we determine if resveratrol and exercise have similar effect on the antioxidant capacity of different organs in old mice. Resveratrol (6 months) and/or exercise (1.5 months) was administered to old mice. Markers of oxidative stress (lipid peroxidation and glutathione) and activities and levels of antioxidant enzymes (SOD, catalase, glutathione peroxidase, glutathione reductase and transferase and thioredoxin reductases, NADH cytochrome B5-reductase and NAD(P)H-quinone acceptor oxidoreductase) were determined by spectrophotometry and Western blotting in different organs: liver, kidney, skeletal muscle, heart and brain. Both interventions improved antioxidant activity in the major organs of the mice. This induction was accompanied by a decrease in the level of lipid peroxidation in the liver, heart and muscle of mice. Both resveratrol and exercise modulated several antioxidant activities and protein levels. However, the effect of resveratrol, exercise or their combination was organ dependent, indicating that different organs respond in different ways to the same stimulus. Our data suggest that physical activity and resveratrol may be of great importance for the prevention of age-related diseases, but that their organ-dependent effect must be taken into consideration to design a better intervention.

Survival and resource utilization in liver transplant recipients: the impact of admission to the intensive care unit.

PubMed

Aggarwal, A; Ong, J P; Goormastic, M; Nelson, D R; Arroliga, A C; Farquhar, L; Mayes, J; Younossi, Z M

2003-12-01

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P =.006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Combined liver resection and reconstruction of the supra-renal vena cava: the Paul Brousse experience.

PubMed

Azoulay, Daniel; Andreani, Paola; Maggi, Umberto; Salloum, Chadi; Perdigao, Fabiano; Sebagh, Mylène; Lemoine, Antoinette; Adam, René; Castaing, Denis

2006-07-01

Liver tumors with inferior vena cava (IVC) involvement may require combined resection of the liver and IVC. This approach, with its high surgical risks and poor long-term prognosis, was precluded until the development of neoadjuvant chemotherapy, portal vein embolization, reinforced vascular prostheses, and technical advances in liver transplantation. We reviewed 22 cases of hepatectomy with retrohepatic IVC resection and reconstruction. The patients had a median age of 51.5 years (range, 32.8-75.3 years). Indications for resection were: liver metastases (n = 9), cholangiocarcinoma (n = 8), hepatocellular carcinoma (n = 2), other cancers (n = 3). The liver resections carried out included 18 first, 3 second, and one third hepatectomy. Segment 1 (caudate lobe) was included in the specimen in 19 cases (86%). Resection concerned 1 to 6 liver segments (median = 5.0). Vascular control was achieved by vascular exclusion of the liver preserving the caval flow (n = 1), standard vascular exclusion of the liver (n = 12), in situ cold perfusion of the liver (n = 9). Ex situ surgery was not necessary in any case. Venovenous bypass was used in 12 cases. The IVC was reconstructed with a ringed Gore-Tex tube graft (n = 10), primarily (n = 8), or by caval plasty (n = 4). A main hepatic vein was reimplanted in 6 cases: into the native IVC (n = 4) or into a Gore-Tex tube graft (n = 2). One patient died (4.5%) due to catheter infection, 7 days after in situ cold perfusion with replacement of the vena cava. Eight patients (36%) had no complications and 14 patients (64%) had 23 complications. In all but 1 case, the complications were transient and successfully controlled. The patients stayed in intensive care for 3.3 +/- 2.0 days and in the hospital for 17.7 +/- 7.8 days. All vascular reconstructions were patent at last follow-up. With median follow-up of 19 months, 10 patients died of tumor recurrence and eleven were alive with (n = 5) or without (n = 6) disease. Actuarial 1-, 3-, and 5-year survival rates were 81.8%, 38.3%, and 38.3%, respectively. IVC resection and reconstruction combined with liver resection can be safely performed in selected patients. The lack of alternative treatments and the spontaneous poor prognosis justify this approach, provided that surgery is carried out at a center specialized in both liver surgery and liver transplantation. The development of adjuvant chemotherapy regimens is required to improve the long-term results of this salvage surgery.

Aging with HIV infection: a journey to the center of inflammAIDS, immunosenescence and neuroHIV.

PubMed

Nasi, Milena; Pinti, Marcello; De Biasi, Sara; Gibellini, Lara; Ferraro, Diana; Mussini, Cristina; Cossarizza, Andrea

2014-11-01

In the last years, a significant improvement in life expectancy of HIV+ patients has been observed in Western countries. The parallel increase in the mean age of these patients causes a parallel increase in the frequency of non-AIDS related complications (i.e., neurocognitive, cardiovascular, liver and kidney diseases, metabolic syndrome, osteoporosis, non-HIV associated cancers, among others), even when antiviral treatment is successful. Immune activation and persistent inflammation characterizes both HIV infection and physiological aging, and both conditions share common detrimental pathways that lead to early immunosenescence. Furthermore, HIV-associated neurocognitive disorders represent important consequences of the infection. The persistent systemic immune activation, the continuous migration of activated monocytes to the central nervous system and progressive patients' aging contribute to develop neuronal injuries, that are in turn linked to HIV-associated neurocognitive disorders, which can persist despite successful antiretroviral treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Poor Long-Term Outcomes of Adult Liver Transplantation Involving Elderly Living Donors.

PubMed

Tokodai, K; Kawagishi, N; Miyagi, S; Nakanishi, C; Hara, Y; Fujio, A; Kashiwadate, T; Maida, K; Goto, H; Kamei, T; Ohuchi, N

2016-05-01

Donor hepatectomy requires particular care to ensure the safety of the donor and the success of the liver transplantation. The aim of this study was to evaluate the effect of donor age on the postoperative outcomes of liver transplant donors and the long-term graft survival rates. We retrospectively reviewed 56 consecutive adult patients who underwent living donor liver transplantation at our institution between April 2001 and August 2010. Donors and recipients were divided into 2 groups, based on the age of the donor: the elderly donor group (donor age ≥50 years) and the younger donor group (donor age <50 years). Perioperative variables, postoperative complication rates, and long-term graft survival rates were compared between the 2 groups. The average ages in the elderly donor group and younger donor group were 58 years and 32 years, respectively. Baseline data excluding the age of the donor did not differ between the groups, nor did the overall complication rates of the donors. Hospital stays were longer in the elderly donor group than in the younger donor group (25 vs 18 days, P < .05). The 1-, 3-, and 5-year graft survival rates were 80%, 60%, and 50% in the elderly donor group, and 89%, 87%, and 82% in the younger donor group, respectively (P = .0002). Donor hepatectomy can be performed safely in elderly patients. However, compared with younger donors, their hospital stays were longer and the graft survival rates were shorter. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of natural ageing and antioxidant inhibition on liver antioxidant enzymes, glutathione system, peroxidation, and oxygen consumption in Rana perezi.

PubMed

López-Torres, M; Pérez-Campo, R; Barja de Quiroga, G

1991-01-01

A study of the physiological role of oxygen free radicals in relation to the ageing process was performed using the liver of Rana perezi, an animal with a moderate rate of oxygen consumption and a life span substantially longer than that of laboratory rodents. Among the five different antioxidant enzymes only superoxide dismutase (SOD) showed an age-dependent decrease. Cytochrome oxidase (COX), glutathione status, in vivo and in vitro liver peroxidation, and metabolic rate did not vary as a function of age. Long-term (2.5 months) treatment with aminotriazole and diethyldithiocarbamate depleted catalase (CAT) activity and did not change both glutathione peroxidases (GPx), COX, reduced (GSH) and oxidized (GSSG) glutathione, or metabolic rate. This treatment resulted in great compensatory increases in SOD (to 250-460% of controls) and glutathione reductase (GR) (to 200%) which are possibly responsible for the lack of increase of in vivo and in vitro liver peroxidation and for the absence of changes in survival rate. The comparison of these results with previous data from other species suggests the possibility that decreases in antioxidant capacity in old age are restricted to animal species with high metabolic rates. Nevertheless, ageing can still be due to the continuous presence of small concentrations of O2 radicals in the tissues throughout life in animals with either high or low metabolic rates, because radical scavenging can not be 100% effective. Compensatory homeostasis among antioxidants seems to be a general phenomenon in different species.

[Surgical techniques in liver transplantation].

PubMed

Chan, Carlos; Plata-Muñoz, Juan José; Franssen, Bernardo

2005-01-01

Liver transplantation (LT) is probably the biggest surgical aggression that a patient can endure. It was considered only as a last option in the era of experimental LT, yet it evolved into the definitive treatment for some types of acute and chronic end stage liver disease. In terms of technique LT is the most complex of all types of transplantations. The surgical procedure in itself is well established and has changed little through time. Liver transplantation owes its improvement to better and more systematic anesthetic procedures and to perioperative care more than being due to improvement of the surgical technique. The first surgical procedure was described by Thomas Starzl in 1969. His initial work has been strengthened with the development of venous bypass, the refinement in vascular and biliary reconstruction technique and the development of the split liver. Up to date technical aspects of orthotopic liver transplantation are described in the present article.

N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.

PubMed

McPheeters, Chelsey M; VanArsdale, Vanessa M; Weant, Kyle A

2016-01-01

This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.

Successful management of neonatal hemochromatosis by exchange transfusion and immunoglobulin: a case report.

PubMed

Babor, F; Hadzik, B; Stannigel, H; Mayatepek, E; Hoehn, T

2013-01-01

Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.

A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases.

PubMed

Zhao, Yingying; Xing, Huichun

2017-01-01

Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.

3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy.

PubMed

Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

2017-01-14

To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis ( P = 0.046) but also in those with decompensated cirrhosis ( P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume ( P = 0.002 and 0.005, respectively). Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

Elevated liver enzymes in women with a family history of diabetes.

PubMed

Inoue, Kazuo; Matsumoto, Masatoshi; Miyoshi, Yuji; Kobayashi, Yasuki

2008-03-01

Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9kg/m(2) vs. 23.4kg/m(2); p=0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67mmol/L vs. 5.22mmol/L; p<0.001), asparate aminotransferase (AST: 20.0IU/L vs. 19.2IU/L; p=0.049), alanine aminotransferase (ALT: 18.4IU/L vs. 16.7IU/L; p=0.004), gamma-glutamyltranspeptidase (GGT: 24.1IU/L vs. 20.5IU/L; p<0.001), and triglycerides (TG: 1.09mmol/L vs. 1.00mmol/L; p=0.011) for FHDM subjects, when adjusted for age and BMI. Multiple linear regression analysis revealed that FHDM, age, BMI, FPG, and TG were correlated with GGT (p=0.004 for FHDM; p<0.001 for age, BMI, FPG, and TG). Elevated liver enzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.

Donation after cardiac death liver transplantation: predictors of outcome.

PubMed

Mathur, A K; Heimbach, J; Steffick, D E; Sonnenday, C J; Goodrich, N P; Merion, R M

2010-11-01

We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver-only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post-DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African-American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Spontaneous and induced tolerance for liver transplant recipients.

PubMed

Feng, Sandy

2016-02-01

Transformative medical and surgical advances have remarkably improved short-term survival after liver transplantation. There is, however, pervasive concern that the cumulative toxicities of modern immunosuppression regimens severely compromise both quality and quantity of life for liver transplant recipients. The inherently tolerogenic nature of the liver offers the tantalizing opportunity to change the current paradigm of nonspecific and lifelong immunosuppression. Safe minimization or discontinuation of immunosuppression without damage to the liver allograft is an attractive strategy to improve long-term survival after liver transplantation. Recent prospective, multicenter clinical trials have demonstrated that immunosuppression can be safely withdrawn from selected liver transplant recipients with preservation of allograft histology. These successes have spurred multiple avenues of investigation to identify peripheral blood and/or tissue biomarkers and delineate mechanisms of tolerance. Concomitant advances in the ability to expand regulatory T cells in the laboratory have spawned clinical trials to facilitate immunosuppression minimization and/or discontinuation. This review will delineate the unique liver immunobiology that has driven the recent clinical trials to unmask spontaneous tolerance or induce tolerance for liver transplant recipients. The emerging results of these trials over the next 5 years hold promise to reduce the burden of lifelong immunosuppression and thereby optimize the long-term health of liver transplant recipients.

Damage to Liver and Skeletal Muscles in Marathon Runners During a 100 km Run With Regard to Age and Running Speed

PubMed Central

Jastrzębski, Zbigniew; Żychowska, Małgorzata; Radzimiński, Łukasz; Konieczna, Anna; Kortas, Jakub

2015-01-01

The purpose of this study was to determine: (1) whether damage to liver and skeletal muscles occurs during a 100 km run; (2) whether the metabolic response to extreme exertion is related to the age or running speed of the participant; (3) whether it is possible to determine the optimal running speed and distance for long-distance runners’ health by examining biochemical parameters in venous blood. Fourteen experienced male amateur ultra-marathon runners, divided into two age groups, took part in a 100 km run. Blood samples for liver and skeletal muscle damage indexes were collected from the ulnar vein just before the run, after 25, 50, 75 and 100 km, and 24 hours after termination of the run. A considerable increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was observed with the distance covered (p < 0.05), which continued during recovery. An increase in the mean values of lactate dehydrogenase (LDH), creatine kinase (CK) and C-reactive protein (CRP) (p < 0.05) was observed with each sequential course. The biggest differences between the age groups were found for the activity of liver enzymes and LDH after completing 75 km as well as after 24 hours of recovery. It can be concluded that the response to extreme exertion deteriorates with age in terms of the active movement apparatus. PMID:25964813

Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy

PubMed Central

Herrero, Astrid; Prigent, Julie; Lombard, Catherine; Rosseels, Valérie; Daujat-Chavanieu, Martine; Breckpot, Karine; Najimi, Mustapha; Deblandre, Gisèle; Sokal, Etienne M.

2017-01-01

There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag2−/-IL2Rg-/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery (n = 26) or following a critical 3-day period (n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved (p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair. PMID:27657746

Total body weight loss of ≥ 10 % is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis.

PubMed

Glass, Lisa M; Dickson, Rolland C; Anderson, Joseph C; Suriawinata, Arief A; Putra, Juan; Berk, Brian S; Toor, Arifa

2015-04-01

Given the rising epidemics of obesity and metabolic syndrome, nonalcoholic steatohepatitis (NASH) is now the most common cause of liver disease in the developed world. Effective treatment for NASH, either to reverse or prevent the progression of hepatic fibrosis, is currently lacking. To define the predictors associated with improved hepatic fibrosis in NASH patients undergoing serial liver biopsies at prolonged biopsy interval. This is a cohort study of 45 NASH patients undergoing serial liver biopsies for clinical monitoring in a tertiary care setting. Biopsies were scored using the NASH Clinical Research Network guidelines. Fibrosis regression was defined as improvement in fibrosis score ≥1 stage. Univariate analysis utilized Fisher's exact or Student's t test. Multivariate regression models determined independent predictors for regression of fibrosis. Forty-five NASH patients with biopsies collected at a mean interval of 4.6 years (±1.4) were included. The mean initial fibrosis stage was 1.96, two patients had cirrhosis and 12 patients (26.7 %) underwent bariatric surgery. There was a significantly higher rate of fibrosis regression among patients who lost ≥10 % total body weight (TBW) (63.2 vs. 9.1 %; p = 0.001) and who underwent bariatric surgery (47.4 vs. 4.5 %; p = 0.003). Factors such as age, gender, glucose intolerance, elevated ferritin, and A1AT heterozygosity did not influence fibrosis regression. On multivariate analysis, only weight loss of ≥10 % TBW predicted fibrosis regression [OR 8.14 (CI 1.08-61.17)]. Results indicate that regression of fibrosis in NASH is possible, even in advanced stages. Weight loss of ≥10 % TBW predicts fibrosis regression.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease.

PubMed

Akbulut, Ulas Emre; Emeksiz, Hamdi Cihan; Citli, Senol; Cebi, Alper Han; Korkmaz, Hatice Ayca Ata; Baki, Gaye

2018-05-05

The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. The study recruited 186 obese children aged 10-17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p<0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio 2.05, 95% confidence interval: 1.12-3.77, p=0.02). The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver

PubMed Central

Tien, Yun-Chen; Liu, Ke; Pope, Chad; Wang, Pengcheng; Ma, Xiaochao

2015-01-01

Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (<100 mg/kg) does not change expression and enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult mouse liver, whereas phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life. PMID:26400395

Effect of feed consumption levels on growth performance and carcass composition during the force-feeding period in foie gras production of male Mule ducks.

PubMed

Wen, Z G; Jiang, Y; Tang, J; Xie, M; Yang, P L; Hou, S S

2016-09-01

In order to avoid excess feed consumption during the force-feeding period in foie gras production, a dose-response experiment with seven feed consumption levels (450, 540, 630, 720, 810, 900, 990 g/day per bird) was conducted to evaluate the effects of feed consumption levels on growth performance and carcass composition of male Mule ducks from 91 to 102 days of age. One-day-old Mule ducklings (sterile and artificial hybrid of male Albatre Muscovy duck and female Pekin duck were fed a two-phase commercial diets for ad libitum intake from hatching to 91 days of age, followed by graded feeding levels of a corn diet by force-feeding from 91 to 102 days of age. Fifty-six 91-day-old male Mule ducks with similar BW were randomly assigned to seven treatments, with eight birds per treatment. Birds were housed in individual pens. At 102 days of age, final BW was measured and BW gain and feed conversion ratio of ducks from each treatment were calculated from day 91 to 102, and then all ducks were slaughtered to evaluate the yields of skin with subcutaneous fat, abdominal fat, breast meat (including pectoralis major and pectoralis minor), leg meat (including thigh and drum stick), and liver. Significant differences in BW gain, total liver weight and liver relative weight were observed among the treatments (P<0.001). According to the broken-line regression analysis, the optimal feed consumption levels of male Mule ducks from 91 to 102 days of age for maximum BW gain, total liver weight and liver relative weight were 217, 227 and 216 g feed/kg BW0.75·per day, respectively.

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay

2013-01-01

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease: More than 2-year Follow-up

PubMed Central

Zhang, Jin-Long; Yuan, Kai; Wang, Mao-Qiang; Yan, Jie-Yu; Xin, Hai-Nan; Wang, Yan; Liu, Feng-Yong; Bai, Yan-Hua; Wang, Zhi-Jun; Duan, Feng; Fu, Jin-Xin

2017-01-01

Background: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up. Methods: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0–72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 106.0 ± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P < 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P < 0.05). Conclusions: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume. PMID:28776546

Current Management of Neonatal Liver Tumors.

PubMed

Langham, Max R; Furman, Wayne L; Fernandez-Pineda, Israel

2015-01-01

This review is focused on the special issues and challenges confronting physicians and surgeons caring for an unborn child, or a newborn with a liver tumor. Liver tumors at this age are very rare and they make it difficult for pediatric surgeons to gain experience necessary to obtain good results. On the other hand, adult hepatobiliary surgeons faced with a fetus or infant with a liver mass are ill equipped to care for the patient even if they have done a high volume of adult liver surgery and are expert in the field. Often a team approach is the best solution.

Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years.

PubMed

Rabelo, A V; Alvarez, M J; Méndez, C S M; Villegas, M T; MGraneroa, K; Becerra, A; Dominguez, M; Raya, A M; Exposito, M; Suárez, Y F

2015-11-01

We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation

PubMed Central

Habib, Shahid; Khan, Khalid; Hsu, Chiu-Hsieh; Meister, Edward; Rana, Abbas; Boyer, Thomas

2017-01-01

Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated. PMID:28496531

"Immune activation, aging and gender" and progression of liver disease.

PubMed

Nasta, Paola

2011-08-01

Hepatitis C is the predominant cause of liver disease in the HIV-positive population and the most important of the non-AIDS-related causes of death. HCV disease tends to become chronic more frequently in HIV-positive subjects, and to evolve more rapidly into cirrhosis of the liver. The rapidity of the evolution varies considerably from one individual to the next and, if in HIV-negative subjects cirrhosis manifests itself after approx. 40-50 years of disease, in HIV-positive subjects it emerges 10-15 years earlier (1, 2). The severity of the fibrosis is not a gradual event and can be worsened by many factors. Age, sex, duration of the infection and assumption of alcohol are the most well-known variables; obesity, diabetes, steatosis and metabolic disorders are equally important factors that affect the progression of liver disease (3). The severity of the liver disease is very different in men compared to women. Being male is undoubtedly one of the factors most closely related to the gravity of fibrosis (4). In HCV mono-infected women, cirrhosis appears from the age of 60 onwards. With the onset of the menopause, in fact, the progression of liver disease accelerates and the risk of developing cirrhosis or cancer of the liver becomes particularly significant in women over 50. The conditions of menopause or of amenorrhea, irrespective of age, are therefore correlated with the progression of liver disease (5). This evidence led researchers to theorize on the possible anti-fibrogenic role of estrogens. In fact, estrogens in physiological doses in the plasma of women in fertile age contribute to controlling the progression of liver disease through antioxidant mechanisms and lipid peroxidation control mechanisms (6). The reduction of estrogens during the menopause is closely linked to the increase of metabolic disorders. During the menopause, steatosis and cardiovascular diseases increase in parallel with the increase of atherogenic lipoproteins, the accumulation ofintra-abdominal fat and the onset of insulin resistance (3, 7). Recent works have demonstrated how the concentration of HCV viremia in plasma correlates with the degree of insulin resistance and with the concentration of circulating triglycerides, demonstrating how the role of HCV in altering the hepatic lipid and glucide metabolism is functional to its replicative capacity. The correlation between the HCV viral load and the metabolic set-up is still unclear in the mono-infection and has been rarely studied in the HIV/HCV co-infection, where the picture is further altered by the metabolic impact of certain antiretroviral therapies. Over recent years, most of the HIV/HCV co-infected population, belonging - as is common knowledge - to the old intravenous drug user risk categories, have reached the age of 50 and have 20-25 years' history of liver disease. The women are reaching the menopause and are frequently characterized by prolonged states of amenorrhea. This conditions exposes HIV-positive women and the co-infected population, currently in care in our centres, to a sudden and rapid worsening of the liver condition. Over the last few years, we are also witnessing the launching on the market of new anti-HCV molecules which must, of necessity, find an outlet as new drug applications for HIV/HCV co-infected patients, as well as being used to the best advantage in populations with particular complications. (www.actabiomedica.it)

[Etiology and complications of liver cirrhosis: data from a German centre].

PubMed

Sivanathan, V; Kittner, J M; Sprinzl, M F; Weinmann, A; Koch, S; Wiltink, J; Nguyen-Tat, M; Marquardt, J U; Wörns, M A; Zimmermann, T; Lang, H; Galle, P R; Schattenberg, J M

2014-09-01

Liver cirrhosis develops as a terminal complication of chronic liver disease. The clinical course is determined by the underlying etiology and the accompanying risk factors, which are influenced by the geographic and cultural background. A total of 236 patients (159 men, 77 women, median age 57 [22-81] years) were included for retrospective analysis between July 2012 and February 2014 using standardized questionnaires during an outpatient visit at a hepatology clinic. The most common etiologies of liver cirrhosis were related to alcohol consumption (52 %), chronic hepatitis C (28 %) or hepatitis B (14 %) infection and NASH (nonalcoholic steatohepatitis, 6 %). At the time of presentation 55 % patients had compensated cirrhosis corresponding to Child-Turcotte-Pugh (CTP) stage A, while 45 % were in a decompensated stage (30 % CTP B and 15 % CTP C). Subgroups were analyzed for the incidence of complications and the emergence of infections. Most frequently esophageal varices (60 %) and ascites (49 %) were observed, followed by pleural effusion (14 %), hepatic encephalopathy (25 %) or hepatorenal syndrome (18 %). 16 % of patients exhibited infection based on clinical criteria. An infective agent was isolated in 38 % of all cases with infection and of those 50 % were gram positive bacteria. In multivariate analysis only the presence of ascites was an independent risk factor for infection. Despite improved medical therapies for viral hepatitis, these were the most frequent causes of liver cirrhosis, closely followed by alcoholic cirrhosis. The observed complications included bacterial infection and complication related to portal hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals

PubMed Central

Ferenci, Tamás; Makara, Mihály; Horváth, Gábor; Szlávik, János; Rupnik, Zsófia; Kormos, Luca; Gerlei, Zsuzsanna; Sulyok, Zita; Vályi-Nagy, István

2017-01-01

Background Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. Methods We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness. Results Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated. Discussion Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations. PMID:28097068

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

PubMed

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan; Skovgaard, Lene Theil; Moos, Torben

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

Assessment of liver volume with computed tomography and comparison of findings with ultrasonography.

PubMed

Bora, Aydın; Alptekin, Cem; Yavuz, Alpaslan; Batur, Abdussamet; Akdemir, Zülküf; Berköz, Mehmet

2014-12-01

In this study, we aimed to investigate the impact of non-alcoholic hepatic steatosis on the liver volume. As investigating hepatic steatosis, we utilized computed tomography (CT) to determine the degree of steatosis and we utilized hepatobiliary ultrasonography (USG) for densitometry and correlation. As hepatosteatosis group, 35 patients over 18 years of age and whose abdominal CT scans were requested by several clinics and performed routinely were included in this study, and as control group, 40 healthy subjects without hepatosteatosis (clinically and radiologically) and correlated with hepatosteatosis group in terms of age and gender were included in this study. CT densitometry and liver attenuation index (LAI) of all individuals who participated in our study were calculated, and contrast images of patients were transferred to CT-Volume Software (Siemens Syngo Multimodality Workplace; Version VE52A). In this study, interactive and automated volume measurement techniques were used together. The volumes were measured separately in patient and control group. In this study for each stage in USG, there was found a direct correlation in terms of LAI and volume, and this correlation was statistically significant (p < 0.01). Furthermore, statistical significance between size and USG stage draws attention (p < 0.05). A significance relationship between USG stage and age could not be determined. As a result, we have reached the conclusion that CT densitometry can be used as an assistive technique along with USG to determine the degree of steatosis in the non-alcoholic fatty liver disease, and there is a positive linear correlation between the liver size and volume, and liver volume increases in the non-alcoholic fatty liver disease.

Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer.

PubMed

Ryerson, A Blythe; Eheman, Christie R; Altekruse, Sean F; Ward, John W; Jemal, Ahmedin; Sherman, Recinda L; Henley, S Jane; Holtzman, Deborah; Lake, Andrew; Noone, Anne-Michelle; Anderson, Robert N; Ma, Jiemin; Ly, Kathleen N; Cronin, Kathleen A; Penberthy, Lynne; Kohler, Betsy A

2016-05-01

Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965. Overall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. Cancer 2016;122:1312-1337. © 2016 American Cancer Society. © 2016 American Cancer Society.

Prevalence and features of fatty liver detected by physical examination in Guangzhou

PubMed Central

Liao, Xian-Hua; Cao, Xu; Liu, Jie; Xie, Xiao-Hua; Sun, Yan-Hong; Zhong, Bi-Hui

2013-01-01

AIM: To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. METHODS: A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. RESULTS: The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P < 0.001). The overall prevalence of fatty liver increased with age, with the peak prevalence (39.5%) found in the 60 to 70-year-old age group. Among patients between the ages of 18 to 50-year-old, the prevalence of fatty liver was significantly higher in males (20.2% vs females: 8.7%, P < 0.001); the difference in prevalence between the two sexes in patients > 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and hyperuricemia were higher in males (hypertriglyceridemia, 36.0% vs females: 12.0%, P < 0.05; hyperuricemia, 17.3% vs females: 7.2%, P < 0.05); in contrast, however, the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females (mixed type hyperlipidemia, 18.7% vs females: 30.1%, P < 0.05, hypercholesterolemia, 9.5% vs females: 24.1%, P < 0.05). Finally, comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia were higher in the former (all P < 0.01). CONCLUSION: A high prevalence of fatty liver is detected upon physical examination in Guangzhou, and the primary associated clinical findings are hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia. PMID:23983438

Prevalence and features of fatty liver detected by physical examination in Guangzhou.

PubMed

Liao, Xian-Hua; Cao, Xu; Liu, Jie; Xie, Xiao-Hua; Sun, Yan-Hong; Zhong, Bi-Hui

2013-08-28

To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P < 0.001). The overall prevalence of fatty liver increased with age, with the peak prevalence (39.5%) found in the 60 to 70-year-old age group. Among patients between the ages of 18 to 50-year-old, the prevalence of fatty liver was significantly higher in males (20.2% vs females: 8.7%, P < 0.001); the difference in prevalence between the two sexes in patients > 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and hyperuricemia were higher in males (hypertriglyceridemia, 36.0% vs females: 12.0%, P < 0.05; hyperuricemia, 17.3% vs females: 7.2%, P < 0.05); in contrast, however, the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females (mixed type hyperlipidemia, 18.7% vs females: 30.1%, P < 0.05, hypercholesterolemia, 9.5% vs females: 24.1%, P < 0.05). Finally, comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia were higher in the former (all P < 0.01). A high prevalence of fatty liver is detected upon physical examination in Guangzhou, and the primary associated clinical findings are hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia.