Fatty Liver Disease

MedlinePlus

... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

PubMed

Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2014-02-01

Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Is alveolar hydatid disease of the liver incurable?

PubMed Central

Mosimann, F

1980-01-01

The etiologic agent of alveolar hydatid disease is Echinococcus multilocularis. Infestation of the liver by the larvae of this Cestode results in an infiltrative mass that behaves biologically very much like a malignant tumor. From 1955 to 1978, 13 patients with alveolar hydatid disease of the liver were investigated, operated and followed at the University Medical Center of Lausanne, Switzerland. Due to the extension of the lesions, six patients had exploratory laparotomy with biopsy only; the other seven were submitted to hepatic resection. Follow-up demonstrated that the disease progresses slowly and that a resection, even if incomplete, can afford long-lasting relief. However the present data suggest that surgical cure of alveolar hydatid disease must be very rare. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:7406556

Treatment of metastatic cutaneous Crohn disease with certolizumab.

PubMed

Kiuru, Maija; Camp, Brendan; Adhami, Katayun; Jacob, Vinita; Magro, Cynthia; Wildman, Horatio

2015-11-18

Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease.

Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival

PubMed Central

Desurmont, Thibault; Skrypek, Nicolas; Duhamel, Alain; Jonckheere, Nicolas; Millet, Guillaume; Leteurtre, Emmanuelle; Gosset, Pierre; Duchene, Belinda; Ramdane, Nassima; Hebbar, Mohamed; Van Seuningen, Isabelle; Pruvot, François-René; Huet, Guillemette; Truant, Stéphanie

2015-01-01

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities. PMID:25580640

Correlation between melphalan pharmacokinetics and hepatic toxicity following hyperthermic isolated liver perfusion for unresectable metastatic disease.

PubMed

Mocellin, Simone; Pilati, Pierluigi; Da Pian, Pierpaolo; Forlin, Marco; Corazzina, Susanna; Rossi, Carlo Riccardo; Innocente, Federico; Ori, Carlo; Casara, Dario; Ujka, Francesca; Nitti, Donato; Lise, Mario

2007-02-01

In the present work, we report on the results of our pilot study of hyperthermic isolated hepatic perfusion (IHP) with melphalan alone for patients with unresectable metastatic liver tumors refractory to conventional treatments, with particular regard to the correlation between pharmacokinetic findings and hepatic toxicity. Inclusion criteria were unresectable liver metastases, hepatic parenchyma replacement liver function, and previous failure of at least one conventional treatment. IHP was performed under hyperthermic conditions with melphalan (1.5 mg/kg body weight). Completeness of vascular isolation of the liver and drug distribution volumes of the perfusion circuit were assessed by a radiolabeled albumin-based method. Drug concentrations in perfusate and plasma were measured by means of high-performance liquid chromatography (HPLC). Twenty patients with unresectable liver metastases underwent IHP. No intraoperative mortality occurred. Treatment-related systemic toxicity was minimal and reversible. Three patients (15%) experienced grade 4 hepatic toxicity and died due to liver failure and subsequent multiorgan failure. Other six patients had significant (grade 3-4) but transitory hepatic toxicity. Complete and partial responses were observed in three and nine out of 17 evaluable patients, respectively (overall response rate = 70%). The pharmacokinetics study showed a 3% mean perfusate-to-plasma drug leakage (range 1-6%). Logistic regression analysis showed that drug concentration in the perfusate circuit, but not preoperative tests, significantly and independently correlated with hepatic toxicity (P = 0.028). Following melphalan-based IHP, objective tumor regression could be observed in a remarkable percentage of patients refractory to standard treatments. However, hepatic toxicity and related mortality were significant. Our findings suggest that drug dosage personalization based on the measurement of drug distribution volumes might minimize

Bisphenol A sulfonation is impaired in metabolic and liver disease

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

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results:more » In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.« less

Liver metastases

MedlinePlus

Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?

PubMed Central

Harrison-Findik, Duygu Dee

2009-01-01

Despite heavy consumption over a long period of time, only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors, besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver, which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes. It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-α signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease. PMID

Liver Diseases

MedlinePlus

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

Alcoholic Liver Disease and Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2016-08-01

Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver transplant for cholestatic liver diseases.

PubMed

Carrion, Andres F; Bhamidimarri, Kalyan Ram

2013-05-01

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

PubMed

Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

2016-03-01

Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.

PubMed

Desurmont, Thibault; Skrypek, Nicolas; Duhamel, Alain; Jonckheere, Nicolas; Millet, Guillaume; Leteurtre, Emmanuelle; Gosset, Pierre; Duchene, Belinda; Ramdane, Nassima; Hebbar, Mohamed; Van Seuningen, Isabelle; Pruvot, François-René; Huet, Guillemette; Truant, Stéphanie

2015-03-01

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients' outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02-50.92) vs 0.55 (0.07-3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00-7.85) vs 0.15 (0.01-7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

PubMed Central

Yamamoto, Yumiko; Kato, Yoshitake; Tabuchi, Hitoshi; Fukushima, Atsuki

2013-01-01

We report a case of cytomegalovirus (CMV) retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy. PMID:23467884

Effect of high-dose stereotactic body radiation therapy on liver function in the treatment of primary and metastatic liver malignancies using the Child-Pugh score classification system.

PubMed

Dyk, Pawel; Weiner, Ashley; Badiyan, Shahed; Myerson, Robert; Parikh, Parag; Olsen, Jeffrey

2015-01-01

The purpose of this study was to evaluate liver function after high-dose liver stereotactic body radiation therapy (SBRT) in the treatment of metastatic and primary malignancies of the liver using the Child-Pugh score classification system. This was a retrospective analysis of 46 patients treated with SBRT for metastatic and primary malignancies of the liver. Patient, disease, prior treatment, and SBRT dosimetric factors were analyzed to correlate with decline in Child-Pugh class after liver SBRT. Median follow-up was 11.0 months for patients alive at last follow-up. Twenty-three patients (50%) had primary liver malignancies. Median delivered dose was 55 Gy in 5 fractions (range, 36-60 Gy in 3-6 fractions) to 1 lesion (range, 1-4 lesions) measuring 4.0 cm (range, 1.3-12.4 cm). Forty-one patients (89%) received ≥50 Gy in 3 to 6 fractions. Child-Pugh score classification was A in 42 patients (91%). Seven patients (15%) received adjuvant chemotherapy or targeted therapy. Twenty-nine patients (63%) experienced an intrahepatic recurrence after treatment. Ten patients (22%) experienced a decline in Child-Pugh class at a median of 1.6 months (range, 0.2-6 months). Eighty percent experienced a one-category decline. Only the V20, V25, V30, and V50 were correlated with decline in Child-Pugh class on univariate analysis, with V25 being most significant (P = .027). A V25 >32% was associated with a 42% incidence of Child-Pugh class decline compared with 9% for V25 ≤32 (P = .029). For primary liver malignancies, a V25 >36% was associated with a 4-fold increase in the incidence of Child-Pugh class decline (60% vs 15%, P = .021). Approximately one-quarter of patients experience a decline in Child-Pugh class after high-dose liver SBRT. The V25 may be an important dosimetric parameter predicting decline in liver function after treatment. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Liver disease

MedlinePlus

... Coccidioidomycosis Delta agent (hepatitis D) Drug-induced cholestasis Fatty liver disease Hemochromatosis Hepatitis A Hepatitis B Hepatitis C ... abscess Reye syndrome Sclerosing cholangitis Wilson disease Images Fatty liver, CT scan Liver with disproportional fattening, CT scan ...

Liver Disease in Sri Lanka.

PubMed

Wijewantha, Hasitha S

2017-01-01

Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic and amebic liver abscesses and dengue infection are the other causes of liver disease. Some of the commonly used plants as traditional herbal medicine in Sri Lanka have been shown to have deleterious effects on the liver in animal studies. Considering the high popularity of traditional herbal medicine in the country, it is likely that herbal medicine is an etiological factor for liver disease in Sri Lanka, but no published data are available. Address reprint requests to: Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol 2017;7(1):78-81.

Treatment of metastatic uveal melanoma with intravenous fotemustine.

PubMed

Spagnolo, Francesco; Grosso, Marco; Picasso, Virginia; Tornari, Elena; Pesce, Marianna; Queirolo, Paola

2013-06-01

The purpose of the present study was to retrospectively evaluate the safety and activity of intravenous fotemustine in patients with metastatic uveal melanoma. We report on a series of 25 consecutive patients diagnosed with metastatic uveal melanoma. Fotemustine was administered intravenously as a first-line treatment to all patients. Thrombocytopenia and leukopenia (any grade) were observed in 60 and 52% of patients, respectively. Only two patients discontinued treatment because of toxicity (G3 thrombocytopenia), whereas all other patients were discontinued for progressive disease. Two partial responses were observed. Nine patients had stable disease (disease control rate=44%). The median survival duration was 13.9 months, and the 1-year survival rate was 60%. Intravenous fotemustine is well tolerated and could improve the outcome of metastatic uveal melanoma patients with or without liver involvement, although a randomized prospective trial is required to confirm these results.

Surgical Management of Metastatic Disease.

PubMed

Keung, Emily Z; Fairweather, Mark; Raut, Chandrajit P

2016-10-01

Sarcomas are rare cancers of mesenchymal cell origin that include many histologic subtypes and molecularly distinct entities. For primary resectable sarcoma, surgery is the mainstay of treatment. Despite treatment, approximately 50% of patients with soft tissue sarcoma are diagnosed with or develop distant metastases, significantly affecting their survival. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in select patients who receive multimodality therapy, including surgery, for their metastatic disease. This article provides an overview of the literature on surgical management of pulmonary and hepatic sarcoma metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

Coffee and Liver Disease.

PubMed

Wadhawan, Manav; Anand, Anil C

2016-03-01

Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

Senescence in chronic liver disease: Is the future in aging?

PubMed

Aravinthan, Aloysious D; Alexander, Graeme J M

2016-10-01

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

[Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

2015-08-01

Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

Liver function testing with nuclear medicine techniques is coming of age.

PubMed

Bennink, Roelof J; Tulchinsky, Mark; de Graaf, Wilmar; Kadry, Zakiyah; van Gulik, Thomas M

2012-03-01

Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease states. When the liver begins to fail in severely ill patients, it forecasts a terminal outcome. However, unlike the glomerular filtration rate which clearly quantifies the key renal function, at most practice sites, there is no clinically available quantitative test for liver function. Although it is commonplace to assess indirect evidence of that function (by measuring blood levels of its end products and by-products) and to detect an acute injury (by following rising transaminases), a widely available test that would directly measure hepatocellular function is lacking. This article reviews current knowledge on liver function studies and focuses on those nuclear medicine tests available to study the whole liver and regional liver function. The clinical application driving these tests, prediction of remnant liver function after partial hepatectomy for primary liver malignancy or metastatic disease, is addressed here in detail. The test was recently validated for this specific application and was shown to be better than the current standard of practice (computed tomography volumetry), particularly in patients with hepatic comorbidities like cirrhosis, steatosis, or cholestasis. Furthermore, early assessment of regional liver function increase after preoperative portal vein embolization becomes possible with this technology. The limiting factor to a wider acceptance of this test is based on the lack of clinical software that would allow calculation of liver function parameters. This article provides information that enables a clinical nuclear medicine facility to provide this test using readily available equipment. Furthermore, it addresses emerging clinical applications

Liver disease - resources

MedlinePlus

Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services (C.L.A.S.S.) -- www. ...

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

PubMed

Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

2018-02-01

Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Alcoholic liver disease: The gut microbiome and liver crosstalk

PubMed Central

Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

2015-01-01

Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

Addison's disease as a presentation of metastatic malignant melanoma.

PubMed

Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V

2016-01-01

Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Is Prophylactic Intervention More Cost-effective Than the Treatment of Pathologic Fractures in Metastatic Bone Disease?

PubMed

Blank, Alan T; Lerman, Daniel M; Patel, Neeraj M; Rapp, Timothy B

2016-07-01

Metastatic bone disease is a substantial burden to patients and the healthcare system as a whole. Metastatic disease can be painful, is associated with decreased survival, and is emotionally traumatic to patients when they discover their disease has progressed. In the United States, more than 250,000 patients have metastatic bone disease, with an estimated annual cost of USD 12 billion. Prior studies suggest that patients who receive prophylactic fixation for impending pathologic fractures, compared with those treated for realized pathologic fractures, have decreased pain levels, faster postoperative rehabilitation, and less in-hospital morbidity. However, to our knowledge, the relative economic utility of these treatment options has not been examined. We asked: (1) Is there a cost difference between a cohort of patients treated surgically for pathologic fractures compared with a cohort of patients treated prophylactically for impending pathologic lesions? (2) Do these cohorts differ in other ways regarding their utilization of healthcare resources? We performed a retrospective study of 40 patients treated our institution. Between 2011 and 2014, we treated 46 patients surgically for metastatic lesions of long bones. Of those, 19 (48%) presented with pathologic fractures; the other 21 patients (53%) underwent surgery for impending fractures. Risk of impending fracture was determined by one surgeon based on appearance of the lesion, subjective symptoms of the patient, cortical involvement, and location of the lesion. At 1 year postoperative, four patients in each group had died. Six patients (13%) were treated for metastatic disease but were excluded from the retrospective data because of a change in medical record system and inability to obtain financial records. Variables of interest included total and direct costs per episode of care, days of hospitalization, discharge disposition, 1-year postoperative mortality, and descriptive demographic data. All costs were

Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer.

PubMed

Ito, Daisuke; Yogosawa, Satomi; Mimoto, Rei; Hirooka, Shinichi; Horiuchi, Takashi; Eto, Ken; Yanaga, Katsuhiko; Yoshida, Kiyotsugu

2017-08-01

Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature.

PubMed

Gnanajothy, Rosana; Warren, Graham W; Okun, Sherry; Peterson, Lindsay L

2016-06-01

Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval.

Toxocariasis masquerading as liver and lung metastatic nodules in patents with gastrointestinal cancer: clinicopathologic study of five cases.

PubMed

Park, Sanghui; Kim, Yun Soo; Kim, Yu Jin; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Lee, Sang Pyo

2012-01-01

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

Impact of endoscopic ultrasound-guided fine-needle aspiration in prospective liver transplant recipients with hepatocellular carcinoma and lymphadenopathy.

PubMed

Choudhary, Narendra S; Puri, Rajesh; Saigal, Sanjiv; Bhangui, Prashant; Saraf, Neeraj; Shah, Vinit; Nasa, Mukesh; Sarin, Haimanti; Guleria, Mridula; Sud, Randhir; Soin, Arvinder S

2016-11-01

Diagnosis of metastatic disease is important in patients with cirrhosis and hepatocellular carcinoma (HCC) to prevent futile liver transplantation. Some of these patients have metastatic lymphadenopathy; however, it is difficult to perform percutaneous fine-needle aspiration due to presence of collateral and anatomic location. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of lymph nodes offers several advantages like real-time vision, proximity to target, and avoidance of collaterals. The aim of this study was to look for metastatic lymphadenopathy by EUS-guided FNA (EUS-FNA) in prospective liver transplant recipients with HCC. A prospective study was conducted from January 2013 to January 2016 at a tertiary care center. All prospective liver transplant recipients with HCC had PET-CT and bone scan to look for metastatic disease. EUS-FNA was done in patients with abdominal or mediastinal lymphadenopathy and no evidence of extrahepatic disease. Data is shown as median (25-75 interquartile range). EUS-guided FNA was done for 50 patients (42 abdominal and 8 mediastinal lymph nodes), age 57 (53-62) years, Child-Turcotte-Pugh 7 (6-9), and model for end-stage liver disease 10 (7-16). FNA material was adequate in 92% patients, metastasis in 15 (30%), granulomatous lymphadenopathy in 4 (8%), and reactive change in 27 patients (54%). The material was inadequate for diagnosis in 4 (8%) patients. Thus, EUS-guided FNA precluded transplantation in 30% of patients with lymphadenopathy, and 4 (8%) patients received anti-tubercular therapy before liver transplantation. In patients with HCC and lymphadenopathy, EUS-guided FNA detected metastatic disease and precluded liver transplantation in approximately one third of patients.

Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease: Is the Liver Another Target?

PubMed Central

Mirrakhimov, Aibek E.; Polotsky, Vsevolod Y.

2012-01-01

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done. PMID:23087670

Metastatic breast disease from cutaneous malignant melanoma.

PubMed

Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

2014-01-01

Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prognostic significance of pattern and burden of metastatic disease in patients with stage 4 neuroblastoma: A study from the International Neuroblastoma Risk Group database.

PubMed

Morgenstern, Daniel A; London, Wendy B; Stephens, Derek; Volchenboum, Samuel L; Simon, Thorsten; Nakagawara, Akira; Shimada, Hiroyuki; Schleiermacher, Gudrun; Matthay, Katherine K; Cohn, Susan L; Pearson, Andrew D J; Irwin, Meredith S

2016-09-01

Neuroblastoma is a childhood cancer with remarkably divergent tumour behaviour and the presence of metastatic disease is a powerful predictor of adverse outcome. However, the importance of the involvement of specific metastatic sites or overall metastatic burden in determining outcome has not been fully explored. We analysed data from the International Neuroblastoma Risk Group database for 2250 patients with stage 4 disease treated from 1990 to 2002. Metastatic burden was assessed using a 'metastatic site index' (MSI), a score based on the number of metastatic systems involved. Overall, involvement of bone marrow, bone, lung, central nervous system, or other sites was associated with worse outcome. For patients aged ≥18 months, involvement of liver had the greatest impact on outcome and was associated with tumour MYCN amplification and adrenal primary and lung metastases. Increased MSI was associated with worse outcome and higher baseline ferritin/lactate dehydrogenase. We explored the impact of initial treatment approach on these associations. Limiting the analysis to patients allocated to protocols including stem cell transplant (SCT), there was no longer an association of outcome with metastatic involvement of any individual system or increasing MSI. Thus, treatment escalation with SCT (and the addition of differentiating agents to maintenance therapy) appears to have provided maximal benefit to patients with greatest metastatic disease burden. These findings underscore the importance of examining prognostic factors in the context of specific treatments since the addition of new therapies may change or even negate the predictive impact of a particular variable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

PubMed

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Gut microbiome and liver diseases.

PubMed

Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

2016-12-01

The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determinants of survival after liver resection for metastatic colorectal carcinoma.

PubMed

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases.

PubMed

Eckmann, Karen; Michaud, Laura B; Rivera, Edgardo; Madden, Timothy L; Esparza-Guerra, Laura; Kawedia, Jitesh; Booser, Daniel J; Green, Marjorie C; Hortobagyi, Gabriel N; Valero, Vicente

2014-04-01

Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

PubMed Central

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

Progression of Liver Disease

MedlinePlus

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When Less Is More: The indications for MIS Techniques and Separation Surgery in Metastatic Spine Disease.

PubMed

Zuckerman, Scott L; Laufer, Ilya; Sahgal, Arjun; Yamada, Yoshiya J; Schmidt, Meic H; Chou, Dean; Shin, John H; Kumar, Naresh; Sciubba, Daniel M

2016-10-15

Systematic review. The aim of this study was to review the techniques, indications, and outcomes of minimally invasive surgery (MIS) and separation surgery with subsequent radiosurgery in the treatment of patients with metastatic spine disease. The utilization of MIS techniques in patients with spine metastases is a growing area within spinal oncology. Separation surgery represents a novel paradigm where radiosurgery provides long-term control after tumor is surgically separated from the neural elements. PubMed, Embase, and CINAHL databases were systematically queried for literature reporting MIS techniques or separation surgery in patients with metastatic spine disease. PRISMA guidelines were followed. Of the initial 983 articles found, 29 met inclusion criteria. Twenty-five articles discussed MIS techniques and were grouped according to the primary objective: percutaneous stabilization (8), tubular retractors (4), mini-open approach (8), and thoracoscopy/endoscopy (5). The remaining 4 studies reported separation surgery. Indications were similar across all studies and included patients with instability, refractory pain, or neurologic compromise. Intraoperative variables, outcomes, and complications were similar in MIS studies compared to traditional approaches, and some MIS studies showed a statistically significant improvement in outcomes. Studies of mini-open techniques had the strongest evidence for superiority. Low-quality evidence currently exists for MIS techniques and separation surgery in the treatment of metastatic spine disease. Given the early promising results, the next iteration of research should include higher-quality studies with sufficient power, and will be able to provide higher-level evidence on the outcomes of MIS approaches and separation surgery. N/A.

Nonalcoholic fatty liver disease - A multisystem disease?

PubMed Central

Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

Metastatic breast cancer to the liver with hepatoid features and Hep Par 1 antibody positive mimicking hepatocellular carcinoma.

PubMed

Affleck, Authur; Lyman, William B; Jacobs, W Carl; Livasy, Chad A; Martinie, John B; Iannitti, David A; Vrochides, Dionisios

2018-05-09

The hepatocyte paraffin 1 antibody (Hep Par 1) has a high positive predictive value for differentiating hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma. 1 We report a case of metastatic breast cancer to the liver with hepatoid histology and strong positive staining for Hep Par 1 mimicking hepatocellular carcinoma. To our knowledge, primary breast carcinoma staining Hep Par 1 positive has not been reported in the setting of hepatic metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Biomechanics of metastatic disease in the vertebral column.

PubMed

Whyne, Cari M

2014-06-01

Metastatic disease in the vertebral column compromises the structural stability of the spine leading to increased risk of fracture. The complex patterns of osteolytic and osteoblastic disease within the bony spine have motivated a multimodal approach to better characterize the biomechanics of tumor-involved bone. This review presents our current understanding of the biomechanical behavior of metastatically involved vertebrae, and experimental and computational image-based approaches that have been employed to quantify structural integrity in preclinical models with translation to clinical data sets.

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence.

PubMed

O'Regan, Kevin; Breen, Micheál; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J; Hodi, F Stephen; Van den Abbeele, Annick D

2013-12-30

Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin.

Epidemiology and therapies for metastatic sarcoma

PubMed Central

Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

2013-01-01

Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

TNFRSF10C copy number variation is associated with metastatic colorectal cancer

PubMed Central

Tanenbaum, Daniel G.; Hall, William A.; Colbert, Lauren E.; Bastien, Amanda J.; Brat, Daniel J.; Kong, Jun; Kim, Sungjin; Dwivedi, Bhakti; Kowalski, Jeanne; Landry, Jerome C.

2016-01-01

Background Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). Methods Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. Results TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13–10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42–42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). Conclusions TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation

Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

PubMed Central

2012-01-01

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted. Methods A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c) who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL. Results Twenty patients (91%) underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14%) patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82%) patients. Twelve of 15 (80%) TIL tested were found to have in vitro tumor reactivity. Eleven patients (50%) received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45%) who received TIL, with one patient experiencing an ongoing complete response (32+ months). Conclusions Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma. PMID:22726267

gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver.

PubMed

Obrador, Elena; Carretero, Julian; Ortega, Angel; Medina, Ignacio; Rodilla, Vicente; Pellicer, José A; Estrela, José M

2002-01-01

B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/- 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3-fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5-fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver.

[Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

PubMed

Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

2016-07-01

We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

PubMed

Bae, Sun Hyun; Kim, Mi-Sook; Jang, Won Il; Cho, Chul Koo; Yoo, Hyung Jun; Kim, Kum Bae; Han, Chul Ju; Park, Su Cheol; Lee, Dong Han

2015-08-01

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV20Gy was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores≥6.

Management of end stage liver disease (ESLD): what is the current role of orthotopic liver transplantation (OLT)?

PubMed

Miró, José M; Laguno, Montserrat; Moreno, Asuncion; Rimola, Antonio

2006-01-01

Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Folate, Alcohol, and Liver Disease

PubMed Central

Medici, Valentina; Halsted, Charles H.

2013-01-01

Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

Autoimmune liver disease 2007.

PubMed

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

PubMed

Hara, Y; Ogata, Y; Shirouzu, K

2000-12-01

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

PubMed

Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-10

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females ( p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness ( p = 0.044). Tea consumption had no effect ( p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B

PubMed Central

Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-01

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044). Tea consumption had no effect (p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease. PMID:28075394

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Probiotics in Pediatric Liver Disease.

PubMed

Miloh, Tamir

2015-01-01

The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

[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.

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic findings.

PubMed

Pousa-Martínez, María; Alfageme, Fernando; González de Domingo, María Antonia; Suárez-Masa, Dolores; Calvo, Marta; Roustán, Gastón

2017-11-15

Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease characterized by skin lesions separated from the lesions of the gastrointestinal tract. The diagnosis of MCD is essentially histological,showing noncaseating granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD with vulvar involvement and clinical, histopathological, and ultrasonographic findings of this disease.

Interaction between periodontitis and liver diseases

PubMed Central

Han, Pengyu; Sun, Dianxing; Yang, Jie

2016-01-01

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence

PubMed Central

O’Regan, Kevin; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J.; Stephen Hodi, F.; Van den Abbeele, Annick D.

2013-01-01

Abstract Purpose: Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. Materials and methods: This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38–76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. Results: At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Conclusion: Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin. PMID:24434078

Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

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

Lin, Connie; Rountree, Carl B.; Department of Pediatrics, Bon Secour St. Mary's Hospital, 5801 Bremo Rd, Richmond, VA 23226

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed themore » ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor.« less

A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy.

PubMed

Aoyama, Mariko; Takizawa, Hiromitsu; Tsuboi, Mitsuhiro; Nakagawa, Yasushi; Tangoku, Akira

2017-12-28

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.

Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease?

PubMed Central

Brandl, Katharina

2016-01-01

Changes in the intestinal microbiota composition contribute to the pathogenesis of many disorders including gastrointestinal and liver diseases. Recent studies have broadened our understanding of the “gut-liver” axis. Dietary changes, other environmental and genetic factors can lead to alterations in the microbiota. Dysbiosis can further disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. In this article, the authors dissect the different steps involved in disease pathogenesis to further refine approaches for the medical management of liver diseases. The authors will specifically discuss the role of dysbiosis in inducing intestinal inflammation and increasing intestinal permeability. PMID:26088524

Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer.

PubMed

Takeshita, Nobuyoshi; Fukunaga, Toru; Kimura, Masayuki; Sugamoto, Yuji; Tasaki, Kentaro; Hoshino, Isamu; Ota, Takumi; Maruyama, Tetsuro; Tamachi, Tomohide; Hosokawa, Takashi; Asai, Yo; Matsubara, Hisahiro

2015-11-28

A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to

The Role of Akt in Chronic Liver Disease and Liver Regeneration.

PubMed

Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

2017-02-01

The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma

PubMed Central

Wadkin, James C. R.; Patten, Daniel A.; Kamarajah, Sivesh K.; Shepherd, Emma L.; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H.; Weston, Chris J.

2017-01-01

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

Metabonomics Research Progress on Liver Diseases.

PubMed

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

The 100 most cited articles in metastatic spine disease.

PubMed

Cohen, Jonathan; Alan, Nima; Zhou, James; Kojo Hamilton, D

2016-08-01

OBJECTIVE Despite the growing neurosurgical literature, a subset of pioneering studies have significantly impacted the field of metastatic spine disease. The purpose of this study was to identify and analyze the 100 most frequently cited articles in the field. METHODS A keyword search using the Thomson Reuters Web of Science was conducted to identify articles relevant to the field of metastatic spine disease. The results were filtered based on title and abstract analysis to identify the 100 most cited articles. Statistical analysis was used to characterize journal frequency, past and current citations, citation distribution over time, and author frequency. RESULTS The total number of citations for the final 100 articles ranged from 74 to 1169. Articles selected for the final list were published between 1940 and 2009. The years in which the greatest numbers of top-100 studies were published were 1990 and 2005, and the greatest number of citations occurred in 2012. The majority of articles were published in the journals Spine (15), Cancer (11), and the Journal of Neurosurgery (9). Forty-four individuals were listed as authors on 2 articles, 9 were listed as authors on 3 articles, and 2 were listed as authors on 4 articles in the top 100 list. The most cited article was the work by Batson (1169 citations) that was published in 1940 and described the role of the vertebral veins in the spread of metastases. The second most cited article was Patchell's 2005 study (594 citations) discussing decompressive resection of spinal cord metastases. The third most cited article was the 1978 study by Gilbert that evaluated treatment of epidural spinal cord compression due to metastatic tumor (560 citations). CONCLUSIONS The field of metastatic spine disease has witnessed numerous milestones and so it is increasingly important to recognize studies that have influenced the field. In this bibliographic study the authors identified and analyzed the most influential articles in the

Anesthesia for Patients With Liver Disease

PubMed Central

Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

2014-01-01

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above

The Relationship Between Fatty Liver Disease and Periodontal Disease

DTIC Science & Technology

2017-03-22

Periodontitis is a highly prevalent and destructive chronic disease. Numerous studies support an association between periodontal disease and other...systemic diseases (diabetes, cardiovascular disease, chronic kidney disease, adverse pregnancy outcome, etc.). Non-alcoholic fatty liver disease is a... chronic inflammatory disease that is characterized by accumulation of triglycerides and fat in the liver which may lead to fibrosis and even cirrhosis

Liver resection for colorectal cancer metastases

PubMed Central

Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

2013-01-01

Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens.

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen

2010-06-01

In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Stereotactic body radiotherapy for primary and metastatic liver tumors - the Mayo Clinic experience.

PubMed

Merrell, Kenneth W; Johnson, Jedediah E; Mou, Benjamin; Barney, Brandon M; Nelson, Kathryn E; Mayo, Charles S; Haddock, Michael G; Hallemeier, Christopher L; Olivier, Kenneth R

2016-01-01

To better understand the efficacy of liver SBRT we reviewed our prospectively collected institutional SBRT database. Between May 2008 and March 2013, 80 patients with 104 liver lesions received SBRT. The Kaplan-Meier method estimated local control (LC), overall survival (OS). Cox proportional hazards regression models identified factors associated with LC and OS. The median follow-up for living patients was 38.6 months. Patients had primary (n=17) or metastatic (n=63) tumors. The median tumor size was 2.7 cm (range, 0.6-14.0). The 1 and 4 year rates of LC were 89.4% and 88%, respectively. Colorectal (CRC) metastasis was associated with lower rates of LC (p=0.013). OS at 1 and 4 years was 78% and 25%, respectively. Patients with CRC metastases had higher rates of OS (p=0.03). The occurrence of severe acute and late toxicity was 3.8% and 6.3%, respectively. SBRT should be studied in prospective clinical trials compared with other liver-directed treatment modalities.

Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

PubMed Central

Völzke, Henry

2012-01-01

Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and “non-alcoholic” fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and “non-alcoholic” fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and “non-alcoholic” fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level. PMID:22826613

Fulminant abdominal gas gangrene in metastatic colon cancer.

PubMed

Bozkurt, Mustafa; Okutur, Kerem; Aydin, Kübra; Namal, Esat; Oztürk, Akin; Balci, Cem; Demir, Gökhan

2012-02-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms.

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

PubMed

Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

2017-08-01

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

PubMed

Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

2007-08-01

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Incremental value of live/real time three-dimensional transthoracic echocardiography over the two-dimensional technique in assessing carcinoid heart disease involving the aortic valve.

PubMed

Bulur, Serkan; Hsiung, Ming C; Nanda, Navin C; Hardas, Shalaka; Mohamed, Ahmed; ElKaryoni, Ahmed; Srialluri, Swetha; Barssoum, Kirolos; Elsayed, Mahmoud; Wei, Jeng; Yin, Wei-Hsian

2016-11-01

We present a case of an adult with metastatic carcinoid heart disease, in whom live/real time three-dimensional transthoracic echocardiography provided incremental value over two-dimensional transthoracic echocardiography in assessing involvement of the aortic valve. © 2016, Wiley Periodicals, Inc.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

PubMed

Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Re-irradiation of metastatic disease in the neck from xeroderma pigmentosum.

PubMed

Wei, C C; Sanfilippo, N J; Myssiorek, D

2010-06-01

Xeroderma pigmentosum, an autosomal recessive disease that occurs with a frequency of 1:250,000, is caused by a genetic defect in nucleotide excision repair enzymes. Mutation of these enzymes leads to the development of multiple basal cell and squamous cell carcinomas. We present a case of xeroderma pigmentosum in a patient with cervical and intraparotid metastatic disease from recurrent cutaneous squamous cell carcinomas of the face and scalp, treated with neck dissection and re-irradiation. With the illustrative case report, we include a literature review of diagnosis, prognostic factors, and treatment, with emphasis on surgical and radiation treatment of cervical metastatic disease from recurrent skin carcinomas. A xeroderma pigmentosum patient presented to our clinic with a 2-cm right submental and 1-cm right infra-auricular mass after resection of multiple squamous cell carcinomas of the scalp and face, and external-beam radiation therapy to the right face and neck. Fine-needle aspiration biopsy of the submental mass revealed poorly differentiated squamous cell carcinoma. The patient was brought to the operating room for a right modified radical neck dissection and excision of the right submental and intraparotid mass. Surgical pathology revealed 3 level ia and supraclavicular lymph nodes that were positive for metastatic squamous cell carcinoma. Re-irradiation to the entire right hemi-neck and left submandibular nodal region was performed using opposed oblique portals for the upper neck and a low anterior en face hemi-neck portal. The left parotid region was also included in the re-irradiation volume. Treatment was completed without delayed complications or recurrences to date. To our knowledge, this is the first case report in the literature of a patient with xeroderma pigmentosum who subsequently developed metastatic disease from recurrent cutaneous squamous cell carcinoma. Because of the rarity of xeroderma pigmentosum, this case report is also the first

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

PubMed

Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

2015-03-01

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P < 0.001; grade r = -0.54, P < 0.001; stage r = -0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P < 0.05) and grade (coefficient = -0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = -0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

Microbiota-Liver Axis in Hepatic Disease

PubMed Central

Chassaing, Benoit; Etienne-Mesmin, Lucie; Gewirtz, Andrew T.

2014-01-01

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive pro-inflammatory gene expression thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease. PMID:23703735

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

PubMed Central

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Fulminant abdominal gas gangrene in metastatic colon cancer

PubMed Central

BOZKURT, MUSTAFA; OKUTUR, KEREM; AYDIN, KÜBRA; NAMAL, ESAT; ÖZTÜRK, AKIN; BALCI, CEM; DEMIR, GÖKHAN

2012-01-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms. PMID:22740933

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of Melatonin on Liver Injuries and Diseases

PubMed Central

Zhang, Jiao-Jiao; Meng, Xiao; Li, Ya; Zhou, Yue; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2017-01-01

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action. PMID:28333073

Disseminated alveolar echinococcosis resembling metastatic malignancy: a case report.

PubMed

Caire Nail, Laura; Rodríguez Reimundes, Ezequiel; Weibel Galluzzo, Christelle; Lebowitz, Dan; Ibrahim, Yasmine Lucile; Lobrinus, Johannes Alexander; Chappuis, François

2017-04-18

Alveolar echinococcosis is a potentially lethal zoonosis caused by larval forms of the tapeworm Echinococcus multilocularis. Humans are aberrant intermediate hosts who become infected by ingestion of egg-contaminated food or water or via physical contact with domestic or wild animals that carry the parasite in their small intestine. In humans, the disease usually affects the liver and can spread to other organs causing metastatic infiltration. In this report, we describe an advanced presentation of human alveolar echinococcosis mimicking metastatic malignancy. A 62-year-old white woman was evaluated for fever, jaundice, and abdominal pain, associated with significant weight loss. She lived in a rural area in Switzerland and used to eat wild forest fruits and mushrooms. She owned cats that used to hunt rodents. On physical examination, she appeared severely ill with cachexia, altered mental status, jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with preserved liver function. An abdominal computed tomography scan showed an enlarged liver with a huge cystic mass in the right lobe extending into the left lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and occlusion of her right portal vein. A chest computed tomography scan showed multiple calcified bilateral pulmonary nodules. Her clinical and radiological presentation resembled an advanced neoplastic disease. Serologic tests for Echinococcus multilocularis were positive. The diagnosis of alveolar echinococcosis was established on her past history of exposure, imaging, and serology results. Clinical presentation and radiologic imaging findings of disseminated alveolar echinococcosis can mimic metastatic malignancy, and diagnosis can be challenging in atypically advanced cases. As the incidence of human alveolar echinococcosis appears to be increasing in Europe and Switzerland, physicians should be aware of alveolar echinococcosis, its epidemiology, and its clinical

Cirrhosis and autoimmune liver disease: Current understanding

PubMed Central

Liberal, Rodrigo; Grant, Charlotte R

2016-01-01

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

PubMed

Court, Colin M; Ankeny, Jacob S; Sho, Shonan; Winograd, Paul; Hou, Shuang; Song, Min; Wainberg, Zev A; Girgis, Mark D; Graeber, Thomas G; Agopian, Vatche G; Tseng, Hsian-Rong; Tomlinson, James S

2018-04-01

Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040). CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Targeting Dysbiosis for the Treatment of Liver Disease.

PubMed

Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

2016-02-01

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

Gastrointestinal Stromal Tumors: Management of metastatic disease and emerging therapies

PubMed Central

Vadakara, Joseph

2013-01-01

Synopsis Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Prior to the advent of tyrosine kinase inhibitors like imatinib, there were few treatment options available to patients with metastatic GIST. Surgery was the mainstay of treatment and the prognosis for patients with metastatic GIST was dismal. With the advent of imatinib the prognosis of metastatic GIST has improved dramatically. Second line tyrosine kinase inhibitors (TKI) such as sunitinib and regorafenib have further bettered prognosis, however there is still a need for therapies for patients with disease refractory to TKI therapy. Newer agents such as the Hsp90 inhibitors, PI3K-AKT-mTOR inhibitors and IGF1-R inhibitors are currently under investigation and may have promise. This review discusses the current standard of care in terms of pharmacotherapy, both standard and investigational (summarized in Box 1), in the management of metastatic GIST. PMID:24093167

Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance.

PubMed

Da Silva, Hannah E; Teterina, Anastasia; Comelli, Elena M; Taibi, Amel; Arendt, Bianca M; Fischer, Sandra E; Lou, Wendy; Allard, Johane P

2018-01-23

This study aimed to determine if there is an association between dysbiosis and nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin resistance (IR). This is a prospective cross-sectional study assessing the intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa was validated using quantitative PCR (qPCR). Metabolites in feces and serum were also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and 2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by qPCR for Ruminococcus, Faecalibacterium prausnitzii and Coprococcus. No difference was found between NASH and SS. This lower abundance in NAFLD (NASH+SS) was independent of BMI and IR. NAFLD patients had higher concentrations of fecal propionate and isobutyric acid and serum 2-hydroxybutyrate and L-lactic acid. These findings suggest a potential role for a specific IM community and functional profile in the pathogenesis of NAFLD.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

PubMed

Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

2011-02-01

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor

Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease.

PubMed

Adejumo, Adeyinka C; Ajayi, Tokunbo O; Adegbala, Oluwole M; Adejumo, Kelechi L; Alliu, Samson; Akinjero, Akintunde M; Onyeakusi, Nnaemeka E; Ojelabi, Ogooluwa; Bukong, Terence N

2018-01-17

Abusive alcohol use has well-established health risks including causing liver disease (ALD) characterized by alcoholic steatosis (AS), steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma (HCC). Strikingly, a significant number of individuals who abuse alcohol also use Cannabis, which has seen increased legalization globally. While cannabis has demonstrated anti-inflammatory properties, its combined use with alcohol and the development of liver disease remain unclear. The aim of this study was to determine the effects of cannabis use on the incidence of liver disease in individuals who abuse alcohol. We analysed the 2014 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (NIS) discharge records of patients 18 years and older, who had a past or current history of abusive alcohol use (n = 319 514). Using the International Classification of Disease, Ninth Edition codes, we studied the four distinct phases of progressive ALD with respect to three cannabis exposure groups: non-cannabis users (90.39%), non-dependent cannabis users (8.26%) and dependent cannabis users (1.36%). We accounted for the complex survey sampling methodology and estimated the adjusted odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use (SAS 9.4). Our study revealed that among alcohol users, individuals who additionally use cannabis (dependent and non-dependent cannabis use) showed significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55 [0.48-0.64], 0.57 [0.53-0.61], 0.45 [0.43-0.48] and 0.62 [0.51-0.76]). Furthermore, dependent users had significantly lower odds than non-dependent users for developing liver disease. Our findings suggest that cannabis use is associated with a reduced incidence of liver disease in alcoholics. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

One shot of carbon-ion radiotherapy cured a 6-cm chemo-resistant metastatic liver tumor: a case of breast cancer.

PubMed

Harada, Mayumi; Karasawa, Kumiko; Yasuda, Shigeo; Kamada, Tadashi; Nemoto, Kenji

2015-09-01

The standard treatment for metastatic liver tumor from breast cancer is systemic medical treatment, and there is controversy regarding the value of local treatment. However, there are some exceptional cases that do benefit from local therapy. We describe the case of a 54-year-old woman with systemic therapy-resistant liver metastasis from breast cancer successfully treated with a single shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without local recurrence. This case represents a good example of the usefulness and safety of carbon-ion radiotherapy, and who might benefit from local therapy.

High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity.

PubMed

Gutiérrez-Grobe, Ylse; Chávez-Tapia, Norberto; Sánchez-Valle, Vicente; Gavilanes-Espinar, Juan Gabriel; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez-Sánchez, Nahum

2012-01-01

Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p < 0.05, for all comparisons). There was no significant difference between groups in catalase (0.39 ± 0.74 vs. 0.28 ± 0.69 nM/min/mL), superoxide dismutase (5.4 ± 3.45 vs. 4.7 ± 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05 ± 1.87 vs. 3.94 ± 1.59 µM/mL). A high intake of coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Liver Disease in the HIV-Infected Individual

PubMed Central

Price, Jennifer C.; Thio, Chloe L.

2010-01-01

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. PMID:20851211

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life.

PubMed

Hagström, Hannes; Hemmingsson, Tomas; Discacciati, Andrea; Andreasson, Anna

2018-03-01

High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease. We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied. During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day. Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised. We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

PubMed Central

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-01-01

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Managing non-alcoholic fatty liver disease

PubMed Central

Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

2016-01-01

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

PubMed

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Health related quality of life assessment in metastatic disease of the spine: a systematic review.

PubMed

Street, John; Berven, Sigurd; Fisher, Charles; Ryken, Timothy

2009-10-15

Systematic literature review. To examine the available literature on health related quality of life (HRQOL) assessment in metastatic disease of the spine and identify the optimal functional outcome scales to be used in developing a disease-specific tool. There is a lack of consensus in the use of HRQOL measures in patients with metastatic spine disease. A systematic review was conducted using MEDLINE, EMBASE, the Science Citation Index (ISI), the Cumulative Index to Nursing and Allied Health Literature, the PsycINFO, the Allied and Complementary Medicine (AMED), Cochrane Reviews and Global Health databases for clinical studies addressing metastatic spine disease from 1966 through 2008. The validity of outcome tools was established by linkage analysis with the International Classification of Functioning Disability and Health (ICF). One hundred forty-one clinical studies met inclusion criteria including 10,347 patients. Only 5 moderate grade and 1 high grade study were identified. Thirty- four studies used a patient self-assessment instrument to assess health status. None of the instruments were validated for metastatic spine patients. The most commonly used Pi-by-no tools were SF-36, SIP 5, and the ADL. None of the studies defined health related quality of life (HRQOL) or justified the choice of instrument. The most commonly used cancer-specific tools were ECOG, EORTC QCQ-C30, and EUROQOL 5D. Based on frequency of citation and on correlation with the International Classification of Functioning Disability and Health, the ECOG and SF36 were judged as most valid and reliable. A systematic review of the available evidence suggests that valid and reliable health related quality of life measures exist for the assessment of oncology patients; however, a disease-specific tool for metastatic spine disease awaits development. Until such time as a disease-specific tool is available, we recommend that the ECOG and SF-36 be considered for use in studies addressing the outcome

Liver recurrence in endometrial cancer: a multi-institutional analysis of factors predictive of postrecurrence survival.

PubMed

Toptas, Tayfun; Karalok, Alper; Ureyen, Isin; Tasci, Tolga; Erol, Onur; Bozkurt, Selen; Tulunay, Gokhan; Simsek, Tayup; Turan, Taner

2016-10-01

Predictive factors for survival following liver metastasis in endometrial cancer (EC) have not been studied to date. It is expected that patients who initially presented with liver metastasis or developed liver metastasis as the subsequent metastatic site of progressive disease are likely to have poor outcomes. However, patients developing liver metastasis as the first site of recurrence may have a chance of benefiting from the salvage therapies. Therefore, we aimed to determine factors influencing postrecurrence survival in EC patients who developed liver metastasis as the first site of recurrence. Patients with EC who underwent primary surgery at three centers between 1993 and 2013 were reviewed. Liver recurrence was defined as documentation of parenchymal liver metastasis either by radiologically or biopsy, after a disease-free interval of ≥3 months. Patients with liver metastasis at presentation, or liver metastasis as the subsequent metastatic site of progressive disease were excluded. Forty-six patients were identified. Median time to liver recurrence was 12 months, with 91.3 % of recurrences detected within 3 years. Most patients (73.9 %) had liver recurrence concomitant with extra-hepatic disease. Median survival after the diagnosis of liver recurrence was 9 months. While in univariate analysis, time to liver recurrence (p < 0.001) and presence of concomitant extra-hepatic metastasis (p = 0.048) were potential predictors of survival, multivariate analysis revealed that time to liver recurrence (p < 0.001) was the only independent predictor. This criterion may be used as a marker for stratifying patients into different prognostic risk groups and for selection of patients for salvage therapies.

Stereotactic body radiotherapy for primary and metastatic liver tumors — the Mayo Clinic experience

PubMed Central

Merrell, Kenneth W.; Johnson, Jedediah E.; Mou, Benjamin; Barney, Brandon M.; Nelson, Kathryn E.; Mayo, Charles S.; Haddock, Michael G.; Hallemeier, Christopher L.

2016-01-01

Introduction To better understand the efficacy of liver SBRT we reviewed our prospectively collected institutional SBRT database. Methods Between May 2008 and March 2013, 80 patients with 104 liver lesions received SBRT. The Kaplan-Meier method estimated local control (LC), overall survival (OS). Cox proportional hazards regression models identified factors associated with LC and OS. Results The median follow-up for living patients was 38.6 months. Patients had primary (n=17) or metastatic (n=63) tumors. The median tumor size was 2.7 cm (range, 0.6-14.0). The 1 and 4 year rates of LC were 89.4% and 88%, respectively. Colorectal (CRC) metastasis was associated with lower rates of LC (p=0.013). OS at 1 and 4 years was 78% and 25%, respectively. Patients with CRC metastases had higher rates of OS (p=0.03). The occurrence of severe acute and late toxicity was 3.8% and 6.3%, respectively. Conclusions SBRT should be studied in prospective clinical trials compared with other liver-directed treatment modalities. PMID:29296438

Management of alcohol misuse in patients with liver diseases

PubMed Central

Peng, Jennifer L; Patel, Milan Prakash; McGee, Breann; Liang, Tiebing; Chandler, Kristina; Tayarachakul, Sucharat; O’Connor, Sean; Liangpunsakul, Suthat

2017-01-01

Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence. PMID:27940551

Phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

PubMed Central

Sanchez-Pareja, Andrea; Clément, Sophie; Peyrou, Marion; Spahr, Laurent; Negro, Francesco; Rubbia-Brandt, Laura; Foti, Michelangelo

2016-01-01

AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease. METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical history. RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001). CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN

Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

PubMed Central

Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

2015-01-01

Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms.

PubMed

Miele, Luca; Cammarota, Giovanni; Vero, Vittoria; Racco, Simona; Cefalo, Consuelo; Marrone, Giuseppe; Pompili, Maurizio; Rapaccini, Gianlodovico; Bianco, Alessandro; Landolfi, Raffaele; Gasbarrini, Antonio; Grieco, Antonio

2012-12-01

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. Cross-sectional, case-control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76-6.36). Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

PubMed Central

Firneisz, Gábor

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

PubMed

Firneisz, Gábor

2014-07-21

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

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

The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

PubMed Central

Voican, Cosmin S.; Anty, Rodolphe; Saint-Paul, Marie-Christine; Rosenthal-Allieri, Maria-Alessandra; Agostini, Hélène; Njike, Micheline; Barri-Ova, Nadége; Naveau, Sylvie; Le Marchand-Brustel, Yannick; Veillon, Pascal; Calès, Paul; Perlemuter, Gabriel; Tran, Albert; Gual, Philippe

2012-01-01

Background Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis. Methodology/Principal Findings OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury. Conclusion/Significance OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the

Liver Disease and Pulmonary Hypertension

MedlinePlus

... Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that ... diagnosed? A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), ...

Periostin is identified as a putative metastatic marker in breast cancer-derived exosomes

PubMed Central

Vardaki, Ioulia; Ceder, Sophia; Rutishauser, Dorothea; Baltatzis, George; Foukakis, Theodoros; Panaretakis, Theocharis

2016-01-01

Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines. We found significant differences not only in the amount of secreted exosomes but most importantly in the protein content of exosomes secreted from metastatic versus non-metastatic ones. We identified periostin as a protein that is enriched in exosomes secreted by metastatic cells and validated its presence in a pilot cohort of breast cancer patient samples with localized disease or lymph node (LN) metastasis. PMID:27589561

Periostin is identified as a putative metastatic marker in breast cancer-derived exosomes.

PubMed

Vardaki, Ioulia; Ceder, Sophia; Rutishauser, Dorothea; Baltatzis, George; Foukakis, Theodoros; Panaretakis, Theocharis

2016-11-15

Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines. We found significant differences not only in the amount of secreted exosomes but most importantly in the protein content of exosomes secreted from metastatic versus non-metastatic ones. We identified periostin as a protein that is enriched in exosomes secreted by metastatic cells and validated its presence in a pilot cohort of breast cancer patient samples with localized disease or lymph node (LN) metastasis.

Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States.

PubMed

Wong, Robert J; Aguilar, Maria; Cheung, Ramsey; Perumpail, Ryan B; Harrison, Stephen A; Younossi, Zobair M; Ahmed, Aijaz

2015-03-01

Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States. However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on liver transplant waitlists in the United States. We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on liver transplant waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan-Meier and multivariate logistic regression models. Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2887 to 3291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among liver transplant waitlist registrants, after HCV. Patients with ALD had a significantly higher mean Model for End-Stage Liver Disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared with patients with NASH (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.67-0.89; P < .001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared with NASH patients. Compared with patients with NASH, patients with HCV (OR = 1.45; 95% CI: 1.35-1.55; P < .001), ALD (OR = 1.15; 95% CI: 1.06-1.24; P < .001), or HCV and ALD (OR = 1.29; 95% CI: 1.18-1.42; P < .001) had higher odds for 90-day survival. Based on data from US adult LT databases, since 2004 the number of

Nuclear Receptor Variants in Liver Disease

PubMed Central

Müllenbach, Roman; Weber, Susanne N.; Lammert, Frank

2012-01-01

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. PMID:22523693

Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

PubMed Central

Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

2014-01-01

Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular

Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

PubMed Central

Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

2014-01-01

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Ursodeoxycholic acid in chronic liver disease.

PubMed Central

de Caestecker, J S; Jazrawi, R P; Petroni, M L; Northfield, T C

1991-01-01

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID:1916492

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed Central

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-01-01

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice. PMID:6416437

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-11-12

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice.

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

PubMed

Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

2015-06-01

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Nutrition management in chronic liver disease.

PubMed

Bavdekar, Ashish; Bhave, Sheila; Pandit, Anand

2002-05-01

Liver has a central role in nutritional homeostasis and any liver disease leads to abnormalities in nutrient metabolism and subsequent malnutrition. All children with chronic liver disease (CLD) must undergo a periodic nutritional assessment--medical history, anthropometry esp. skinfold thickness and mid-arm circumference, and biochemical estimation of body nutrients. Nutritional rehabilitation is catered to the individual child but generally the caloric intake is increased to 130% of RDA by adding glucose polymers and/or MCT oil (coconut oil) with essential fatty acid supplementation (sunflower oil). The enteral route is preferred and occasionally nasogastric and/or nocturnal feeding are required to ensure an adequate intake. Proteins rich in branched chain amino acids are given in moderation (2-3 gm/kg/day) in compensated cirrhotics unless encephalopathy occurs when protein restriction may be necessary (1 gm/kg/day). Fat-soluble vitamins are supplemented in large quantities esp. in cholestasis along with other vitamins and minerals. Dietary therapy is the mainstay of management of some metabolic liver diseases and may be curative in disorders like galactosemia, fructosemia and glycogen storage disorders. Pre and postoperative nutritional support is an important factor in improving survival after liver transplantation.

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

Non-Alcoholic Fatty Liver Disease in HIV Infection.

PubMed

Macías, Juan; Pineda, Juan A; Real, Luis M

2017-01-01

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

Extracellular Matrix and Liver Disease

PubMed Central

Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

2014-01-01

Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

Investigation of the roles of exosomes in colorectal cancer liver metastasis.

PubMed

Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

2015-05-01

The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

PubMed

Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

The global burden of liver disease: the major impact of China.

PubMed

Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

2014-12-01

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. © 2014 by the American Association for the Study of Liver Diseases.

Betaine chemistry, roles, and potential use in liver disease.

PubMed

Day, Christopher R; Kempson, Stephen A

2016-06-01

Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease. Copyright © 2016 Elsevier B.V. All rights reserved.

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Filipec-Kanizaj, Tajana; Mijic, Maja; Jakopcic, Ivan; Milic, Sandra; Hrstic, Irena; Sobocan, Nikola; Stimac, Davor; Burra, Patrizia

2018-01-01

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of MetS and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population. PMID:29662288

Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

PubMed Central

Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Akita, Tomoyuki; Tanaka, Junko

2017-01-01

In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non‐liver‐related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non‐liver‐related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow‐up, but only nine deaths were due to liver‐related diseases. Of the remaining 170 patients who died due to non‐liver‐related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354‐3.457) and HR 4.814 (95% CI, 2.323‐9.977) for malignancies; HR 2.265 (95% CI, 1.141‐4.497) and HR 8.482 (95% CI, 3.558‐20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641‐6.303) and HR 5.558 (95% CI, 1.923‐16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non‐liver‐related causes in patients with NAFLD. (Hepatology Communications 2017;1:928–945) PMID:29404500

Periodontal disease and liver cirrhosis: A systematic review

PubMed Central

2015-01-01

Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

Percutaneous Hepatic Perfusion with Melphalan for Unresectable Metastatic Melanoma or Sarcoma to the Liver: A Single Institution Experience

PubMed Central

Forster, Meghan R.; Rashid, Omar M.; Perez, Matthew; Choi, Junsung; Chaudhry, Tariq; Zager, Jonathan S.

2015-01-01

Background Patients with unresectable melanoma or sarcoma hepatic metastasis have a poor prognosis with few therapeutic options. Percutaneous hepatic perfusion (PHP), isolating and perfusing the liver with chemotherapy, provides a promising minimally invasive management option. We reviewed our institutional experience with PHP. Methods We retrospectively reviewed patients with unresectable melanoma or sarcoma hepatic metastasis treated with PHP from 2008 to 2013 and evaluated therapeutic response, morbidity, hepatic progression free survival (hPFS), and overall survival (OS). Results Ten patients were treated with 27 PHPs (median 3). Diagnoses were ocular melanoma (n=5), cutaneous melanoma (n=3), unknown primary melanoma (n=1), and sarcoma (n=1). Median hPFS was 240 days, 9 of 10 patients (90%) demonstrated stable disease or partial response to treatment. At a median follow up of 11.5 months, 4 of 10 (40%) remain alive. There were no perioperative mortalities. Myelosuppresion was the most common morbidity, managed on an outpatient basis with growth factors. The median hospital stay was 3 days. Conclusions Patients with metastatic melanoma and sarcoma to the liver have limited treatment options. Our experience with PHP demonstrates promising results with minimal morbidity and should be considered (pending FDA approval) as a management option for unresectable melanoma or sarcoma hepatic metastasis. PMID:24249545

Chronic Liver Diseases in Children: Clinical Profile and Histology.

PubMed

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

Liver transplantation for Wilson disease.

PubMed

Catana, Andreea M; Medici, Valentina

2012-01-27

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

Liver transplantation for Wilson disease

PubMed Central

Catana, Andreea M; Medici, Valentina

2012-01-01

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model.

PubMed

Wang, Huan; Wu, Xia; Lezmi, Stephane; Li, Qian; Helferich, William G; Xu, Yueqing; Chen, Hong

2017-12-02

Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various bioactive compounds and it exerts beneficial effects including improvements in brain function and reduced risk of cardiovascular diseases. On the other hand, increased risk of thyroid and liver cancers by EGb have been reported in animals. A colon cancer metastasis model was established using intrasplenic injection of a human colon cancer cell line, SW620-luc in athymic mice to investigate the potential impact of EGb on colon cancer progression. After tumor establishment, EGb was intraperitonically injected daily for 5 wks. EGb significantly increased the rate of metastasis in mouse liver and decreased the number of necrotic and apoptotic cells in the metastatic liver when compared to the control. Meanwhile, EGb significantly induced proliferation of tumor cells in the metastatic liver, indicated by increased staining of Ki67 and H3S10p. mRNA expression of genes involved in cell cycle, metastasis, apoptosis, and oxidative stress were altered by EGb treatment in livers with tumors. Moreover, EGb activated the stress-responsive MAPK pathways in the liver with metastatic tumors. EGb exacerbated liver metastasis in a mouse colon cancer metastasis model. This is potentially due to the increased tumor cell proliferation involving stimulated MAPK pathways.

Hyaluronic acid concentration in liver diseases.

PubMed

Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

2016-11-01

The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

Interactions Between the Intestinal Microbiome and Liver Diseases

PubMed Central

Schnabl, Bernd; Brenner, David A.

2014-01-01

The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

PubMed Central

Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

2016-01-01

Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis. PMID:27128907

PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

PubMed

Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

2016-04-27

Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

[Oligometastatic bone disease. Can limited metastatic bone disease be cured? Is there room for local ablative treatments?].

PubMed

Thariat, J; Leysalle, A; Vignot, S; Marcy, P-Y; Lacout, A; Bera, G; Lagrange, J-L; Clezardin, P; Chiras, J

2012-09-01

Solitary metastases have been reported in up to 30% of cases in imaging series. Local treatment aims at consolidating the injured bone and to prevent neurologic complications. Since the prognosis of bony metastatic disease is about 30 months and includes some long survivors, the multisdisciplinary committee in charge of the patient should ask the question and decide on the type of radical/ablative intervention in case of oligometastases. A literature search was performed using MESH terms (bone, metastases, radiotherapy, radiology, cement, radiofrequency ablation, chemoembolisation). Local ablative treatments can yield symptomatic relief and local control rates of about 90%. Stereotactic hypofractionated irradiation and cementoplasty are increasingly used. In conclusion, local ablative treatment of bony oligometastases is an efficient treatment. Its potential impact on survival remains to be demonstrated prospectively in clinical trials. Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

PubMed

Stål, Per

2015-10-21

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

The Global Burden of Liver Disease: The Major Impact of China

PubMed Central

Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

2016-01-01

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus, HBV), nonalcoholic fatty liver disease and alcoholic liver disease affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines and drug development for liver diseases, and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003

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.

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

PubMed Central

Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

2014-01-01

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better

Endocannabinoids in liver disease and hepatic encephalopathy.

PubMed

Magen, Iddo; Avraham, Yosefa; Berry, Elliot; Mechoulam, Raphael

2008-01-01

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.

Klebsiella pneumoniae liver abscess and endophthalmitis

PubMed Central

Abdul-Hamid, Ayeshah; Bailey, Sarah-Jane

2013-01-01

A 36-year-old man was referred to the general medical team with endophthalmitis. He was noted to have raised inflammatory markers and deranged liver function tests on admission. Subsequent abdominal ultrasound scan revealed a liver abscess requiring percutaneous drainage. A common human pathogen, Klebsiella pneumoniae, was cultured from multiple sites. K pneumoniae has virulent serotypes (K1 and K2) that can cause primary liver abscess with metastatic infections. Cases have previously been predominantly reported in Southeast Asia but are increasing in prevalence in Europe and North America. The main known risk factor for the disease is diabetes mellitus. Swift antibiotic therapy, ophthalmology review and percutaneous drainage of any liver abscess are essential. Early recognition of the syndrome, despite potentially few initial symptoms, can significantly reduce morbidity and mortality. The authors report the first recorded case of K pneumoniae liver abscess with endophthalmitis in the UK. PMID:23559652

The emerging role of mast cells in liver disease.

PubMed

Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

[Liver involvement in coeliac disease].

PubMed

Riestra, S; Fernández, E; Rodrigo, L

1999-12-01

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

That liver lesion on MDCT in the oncology patient: is it important?

PubMed Central

Thakrar, Kiran H.; Wenzke, Daniel R.; Newmark, Geraldine M.; Mehta, Uday K.; Berlin, Jonathan W.

2012-01-01

Abstract Multidetector-row computed tomography (MDCT) has become the primary imaging test for the staging and follow-up of most malignancies that originate outside of the central nervous system. Technical advances in this imaging technique have led to significant improvement in the detection of metastatic disease to the liver. An unintended by-product of this improving diagnostic acumen is the discovery of incidental hepatic lesions in oncology patients that in the past remained undetected. These ubiquitous, incidentally identified hepatic lesions have created a management dilemma for both clinicians and radiologists: are these lesions benign or do they represent metastases? Naturally, the answer to this question has profound prognostic and therapeutic implications. In this review, guidelines concerning the diagnosis and management of some of the more common hepatic incidental lesions detected in patients with extrahepatic malignancies are presented. PMID:23023318

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

PubMed

Thakur, Archana; Bollig, Aliccia; Wu, Jiusheng; Liao, Dezhong J

2008-01-24

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

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

Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit.

PubMed

Geske, Michael J; Bloomer, Michele M; Kersten, Robert C; Vagefi, M Reza

Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist.

Gut-Liver Axis, Nutrition, and Non Alcoholic Fatty Liver Disease

PubMed Central

Kirpich, Irina A.; Marsano, Luis S.; McClain, Craig J.

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development. PMID:26151226

Liver Disease in Cystic Fibrosis: an Update

PubMed Central

Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

2013-01-01

Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

Nutritional Needs and Support for Children with Chronic Liver Disease

PubMed Central

Yang, Christine H.; Yoo, Eric R.; Kerner, John A.

2017-01-01

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional. PMID:29035331

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells.

PubMed

Bartucci, M; Dattilo, R; Moriconi, C; Pagliuca, A; Mottolese, M; Federici, G; Benedetto, A Di; Todaro, M; Stassi, G; Sperati, F; Amabile, M I; Pilozzi, E; Patrizii, M; Biffoni, M; Maugeri-Saccà, M; Piccolo, S; De Maria, R

2015-02-05

Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.

Liver metastasis of meningeal hemangiopericytoma: a study of 5 cases

PubMed Central

Lo, Regina C.; Suriawinata, Arief A.; Rubin, Brian P.

2016-01-01

Mesenchymal tumors in the liver, whether primary or metastatic, are rare. Meningeal hemangiopericytoma (HPC) is characteristically associated with delayed metastasis and the liver is one of the most common sites. Despite its consistent histological features, a pathological diagnosis of HPC in the liver is sometimes not straightforward due to its rarity and usually remote medical history of the primary meningeal tumor. In this report, the clinicopathological features of 5 cases of metastatic HPC to the liver were reviewed and described. PMID:27044772

Role of Gut Microbiota in Liver Disease.

PubMed

Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

2015-01-01

Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

PubMed

Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Limited Knowledge of Acetaminophen in Patients with Liver Disease.

PubMed

Saab, Sammy; Konyn, Peter G; Viramontes, Matthew R; Jimenez, Melissa A; Grotts, Jonathan F; Hamidzadah, Wally; Dang, Veronica P; Esmailzadeh, Negin L; Choi, Gina; Durazo, Francisco A; El-Kabany, Mohamed M; Han, Steven-Huy B; Tong, Myron J

2016-12-28

Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%-86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management.

Limited Knowledge of Acetaminophen in Patients with Liver Disease

PubMed Central

Saab, Sammy; Konyn, Peter G.; Viramontes, Matthew R.; Jimenez, Melissa A.; Grotts, Jonathan F.; Hamidzadah, Wally; Dang, Veronica P.; Esmailzadeh, Negin L.; Choi, Gina; Durazo, Francisco A.; El-Kabany, Mohamed M.; Han, Steven-Huy B.; Tong, Myron J.

2016-01-01

Abstract Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%–86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management. PMID:28097095

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

PubMed Central

Stål, Per

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

Discharge Disposition After Stroke in Patients With Liver Disease.

PubMed

Parikh, Neal S; Merkler, Alexander E; Schneider, Yecheskel; Navi, Babak B; Kamel, Hooman

2017-02-01

Liver disease is associated with both hemorrhagic and thrombotic processes, including an elevated risk of intracranial hemorrhage. We sought to assess the relationship between liver disease and outcomes after stroke, as measured by discharge disposition. Using administrative claims data, we identified a cohort of patients hospitalized with stroke in California, Florida, and New York from 2005 to 2013. The predictor variable was liver disease. All diagnoses were defined using validated diagnosis codes. Ordinal logistic regression was used to analyze the association between liver disease and worsening discharge disposition: home, nursing/rehabilitation facility, or death. Secondarily, multiple logistic regression was used to analyze the association between liver disease and in-hospital mortality. Models were adjusted for demographics, vascular risk factors, and comorbidities. We identified 121 428 patients with intracerebral hemorrhage and 703 918 with ischemic stroke. Liver disease was documented in 13 584 patients (1.7%). Liver disease was associated with worse discharge disposition after both intracerebral hemorrhage (global odds ratio, 1.28; 95% confidence interval, 1.19-1.38) and ischemic stroke (odds ratio, 1.23; 95% confidence interval, 1.17-1.29). Similarly, liver disease was associated with in-hospital death after both intracerebral hemorrhage (odds ratio, 1.33; 95% confidence interval, 1.23-1.44) and ischemic stroke (odds ratio, 1.60; 95% confidence interval, 1.51-1.71). Liver disease was associated with worse hospital discharge disposition and in-hospital mortality after stroke, suggesting worse functional outcomes. © 2016 American Heart Association, Inc.

Association of nonalcoholic fatty liver disease and liver cancer

PubMed Central

Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

2015-01-01

AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

Endocrine causes of nonalcoholic fatty liver disease

PubMed Central

Marino, Laura; Jornayvaz, François R

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

Genetics of nonalcoholic fatty liver disease.

PubMed

Dongiovanni, Paola; Valenti, Luca

2016-08-01

Epidemiological, familial, and twin studies indicate that non-alcoholic fatty liver disease, now the leading cause of liver damage in developed countries, has a strong heritability. The common I148M variant of PNPLA3 impairing hepatocellular lipid droplets remodeling is the major genetic determinant of hepatic fat content. The I148M variant has a strong impact on the full spectrum of liver damage related to fatty liver, encompassing non-alcoholic steatohepatitis, advanced fibrosis, and hepatocellular carcinoma, and influences the response to therapeutic approaches. Common variants in GCKR enhance de novo hepatic lipogenesis in response to glucose and liver inflammation. Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver. These and other recent findings reviewed here indicate that impaired lipid handling by hepatocytes has a major role in the pathogenesis of non-alcoholic fatty liver disease by triggering inflammation, fibrogenesis, and carcinogenesis. These discoveries have provided potential novel biomarkers for clinical use and have revealed intriguing therapeutic targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonalcoholic fatty liver disease is associated with cognitive function in adults

PubMed Central

Gottesman, Rebecca F.; Clark, Jeanne M.; Hernaez, Ruben; Chang, Yoosoo; Kim, Changsoo; Ha, Kyoung Hwa; Guallar, Eliseo; Lazo, Mariana

2016-01-01

Objective: We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence of cardiovascular disease (CVD) or its risk factors. Methods: This was a cross-sectional study of 4,472 adults aged 20–59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders. Results: Participants with NAFLD showed lower overall performance on the SDLT (β = 0.726, 95% confidence interval [CI] 0.105–1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (β = 0.018, 95% CI 0.006–0.030) and aspartate aminotransferase (β = 0.021, 95% CI 0.005–0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (β = 0.002, 95% CI 0.0001–0.004). Conclusions: NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications. PMID:26911638

Nonalcoholic fatty liver disease is associated with cognitive function in adults.

PubMed

Seo, Sang Won; Gottesman, Rebecca F; Clark, Jeanne M; Hernaez, Ruben; Chang, Yoosoo; Kim, Changsoo; Ha, Kyoung Hwa; Guallar, Eliseo; Lazo, Mariana

2016-03-22

We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence of cardiovascular disease (CVD) or its risk factors. This was a cross-sectional study of 4,472 adults aged 20-59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders. Participants with NAFLD showed lower overall performance on the SDLT (β = 0.726, 95% confidence interval [CI] 0.105-1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (β = 0.018, 95% CI 0.006-0.030) and aspartate aminotransferase (β = 0.021, 95% CI 0.005-0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (β = 0.002, 95% CI 0.0001-0.004). NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications. © 2016 American Academy of Neurology.

Metastatic spread pattern after curative colorectal cancer surgery. A retrospective, longitudinal analysis.

PubMed

Augestad, K M; Bakaki, P M; Rose, J; Crawshaw, B P; Lindsetmo, R O; Dørum, L M; Koroukian, S M; Delaney, C P

2015-10-01

The most common sites of colorectal cancer (CRC) recurrence are the local tissues, liver or lungs. The objective was to identify risk factors associated with the primary CRC tumor and cancer recurrence in these anatomical sites. Retrospective, longitudinal analyses of data on CRC survivors. Multivariable Cox regression analysis was performed to examine the association between possible cofounders with recurrence to various anatomical sites. Data for 10,398CRC survivors (tumor location right colon=3870, left colon=2898, high rectum=2569, low rectum=1061) were analyzed; follow up time was up to five years. Mean age at curative surgery was 71.5 (SD 11.8) years, 20.2% received radio-chemotherapy, stage T3 (64.4%) and N0 (65.1%) were most common. Overall 1632 (15.7%) had cancer recurrence (Isolated liver n=412, 3,8%;  isolated lung n=252, 2,4%; isolated local n=223, 2.1%). Risk factors associated with recurrent CRC were identified, i.e. isolated liver metastases (male: Adjusted Hazard Ratio (AHR) 1,45; colon left: AHR 1,63; N2 disease: AHR 3,35; T2 disease: AHR 2,82), isolated lung metastases (colon left: AHR 1,53; rectum high: AHR 2,48; rectum low: AHR 2,65; N2 disease 3,76), and local recurrence (glands examined<12: AHR 1,51; CRM <3mm: AHR 1,60; rectum high: AHR 2,15; N2 disease: AHR 2,58) (all p values <0001). Our study finds that the site of the primary CRC tumor is associated with location of subsequent metastasis. Left sided colon cancers have increased risk of metastatic spread to the liver, whereas rectal cancers have increased risk of local recurrence and metastatic spread to the lungs. These results, in combination with other risk factors for CRC recurrence, should be taken into consideration when designing risk adapted post-treatment CRC surveillance programs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

PubMed

Janjigian, Y Y; Werner, D; Pauligk, C; Steinmetz, K; Kelsen, D P; Jäger, E; Altmannsberger, H-M; Robinson, E; Tafe, L J; Tang, L H; Shah, M A; Al-Batran, S-E

2012-10-01

To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.

Alpha-1-antitrypsin phenotypes in adult liver disease patients

PubMed Central

Alempijevic, Tamara; Milutinovic, Aleksandra Sokic; Kovacevic, Nada

2009-01-01

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers. PMID:19961268

Current treatment for non-alcoholic fatty liver disease.

PubMed

Moctezuma-Velázquez, C

Non-alcoholic fatty liver disease is the most prevalent hepatopathy, estimated at 30% in the general population. In the coming years, it will likely be the most common indication for liver transplantation and the most frequent cause of hepatocellular carcinoma. Current treatment for non-alcoholic fatty liver disease is based on dietary and exercise interventions that have been shown to be efficacious, even for reverting fibrosis. Unfortunately, compliance with general measures involving lifestyle modifications is very poor, making pharmacologic strategies a necessary option. At present, there are no treatments for non-alcoholic fatty liver disease approved by regulatory agencies, and the only ones with sufficient evidence and recommended by international societies are treatments with pioglitazone and vitamin E, which are not exempt from adverse effects. We review herein the current management of non-alcoholic fatty liver disease, including dietary and physical activity interventions, available treatments, equivocal therapies, emerging treatments, and treatments presently in clinical trials. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Metastatic patterns and metastatic sites in mucosal melanoma: a retrospective study.

PubMed

Grözinger, Gerd; Mann, Steven; Mehra, Tarun; Klumpp, Bernhard; Grosse, Ulrich; Nikolaou, Konstantin; Garbe, Claus; Clasen, Stephan

2016-06-01

Melanomas arising from mucosa are rare and associated with a poor prognosis. This study aims to provide an analysis of metastatic pathways, time intervals, factors influencing metastatic spread and organs for distant metastases. A total of 116 patients with mucosal melanomas of different sites were included. The mean follow-up interval was 47 ± 52 months. Patients were assigned to two different metastatic pathways, either presenting loco-regional lymph node metastases as first spread or direct distant metastases. The distribution of distant metastases was assessed. Twenty-six patients presented with a pre-existing metastatic spread and were not assigned to pathways. Of the included patients, 44 developed metastases after treatment of the primary tumour; 25 patients directly developed distant metastases; 16 patients developed regional lymph node metastases prior to distant metastases. Location of the primary tumour in the upper airway or GI tract and advanced T stage were significant risk factors of direct distant metastases. Distant metastases are mainly located in the lung, the liver and non-regional lymph nodes. Mucosal melanomas show a high rate of direct distant metastases rather than regional lymph node metastases. Thus the follow-up should always include a whole-body cross-sectional imaging in high-risk tumours. • Mucosal melanomas show a high rate of direct distant metastases. • T stage and primary location are predictors for direct distant metastases. • Distant metastases were mainly found in lung, liver and lymph nodes. • Follow-up of a high-risk mucosal melanoma should include whole-body imaging.

Liver steatosis is a risk factor for hepatotoxicity in patients with inflammatory bowel disease under immunosuppressive treatment.

PubMed

Schröder, Torsten; Schmidt, Klaus J; Olsen, Vera; Möller, Steffen; Mackenroth, Tilo; Sina, Christian; Lehnert, Hendrik; Fellermann, Klaus; Büning, Jürgen

2015-06-01

In inflammatory bowel disease (IBD), hepatic disorders are frequently due to nonalcoholic fatty liver disease and drug-induced hepatotoxicity. Immunosuppressive treatment is known to exert hepatotoxic side effects by a still unknown mode. The relevance of liver steatosis for the development of drug-related hepatotoxicity in IBD is unknown. The charts of 259 patients with IBD under immunosuppression with either azathioprine, 6-mercaptopurine, or methotrexate were reviewed. The prevalence of liver steatosis was assessed by means of ultrasound reports. Aspartate transaminase and alanine transaminase above the normal range were used to indicate liver abnormalities. Liver steatosis on the basis of ultrasound criteria was observed in 73 patients (28.2%). In patients with liver steatosis, the presence of elevated liver enzymes (ELE) was found to be significantly more prevalent (28.8 vs. 14.5%, P=0.0095). The finding of liver steatosis was associated with higher age (44.1 vs. 34.5 years, P<0.0001) and body weight (BMI 26.7 vs. 23.4 kg/m, P<0.0001). Development of ELE under immunosuppression was seen in 50 patients (19.3%). Of the patients who developed ELE, 44.0% (vs. 24.4%, P=0.0095) showed liver steatosis. Logistic regression analysis revealed that male individuals showed an increased likelihood of developing ELE associated with steatosis (P=0.0118, odds ratio=3.93) and that patients who received steroids less often developed ELE in association with liver steatosis (P=0.0414, odds ratio=0.31). This study suggests that fatty liver represents a risk factor for hepatotoxicity in patients with IBD under immunosuppressive treatment and should be routinely considered in treatment strategies.

Sarcopenia in patients with advanced liver disease.

PubMed

Ponziani, Francesca Romana; Gasbarrini, Antonio

2017-04-28

Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-associated cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article.

PubMed

Vogl, Thomas J; Nour-Eldin, Nour-Eldin A; Hammerstingl, Renate Maria; Panahi, Bita; Naguib, Nagy N N

2017-11-01

Purpose  The locoregional interventional oncological treatment approach is an accepted modality for liver neoplasms, especially for hepatocellular carcinoma (HCC) and oligonodular liver metastases. Materials and Methods  The main aim of ablation therapies like microwave ablation (MWA) is to eradicate all malignant cells in a minimally invasive technique under imaging guidance while preserving the healthy tissue with a sufficient safety margin (at least 5 mm) surrounding the ablated lesion. Results  Ablation therapy can be performed via a percutaneous, laparoscopic or intraoperative approach under ultrasound, MRI or CT guidance for adequate localization and monitoring of the ablation process. Conclusion  Ablation is the method of choice for oligonodular HCCs ≤ 3 cm. The technical success rate varies from 88 % to 98 % and progression-free survival (PFS) at 3 years from 27 % to 91.7 %. The same criteria apply to the therapy of liver metastases. Key Points   · Careful selection of patients proves to be essential for optimum results of MWA. · Interventionists should be familiar with all aspects of complication and rapid assessment of imaging methods in order to evaluate induced damage by thermal ablation. · MWA seems to have some advantages over radiofrequency ablation, like shorter ablation time, less pain, less heat sink effect; however, scientific proof is needed. Citation Format · Vogl TJ, Nour-Eldin A, Hammerstingl RM et al. Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article. Fortschr Röntgenstr 2017; 189: 1055 - 1066. © Georg Thieme Verlag KG Stuttgart · New York.

Viewpoint: "Alcohol Consumption in Late Adolescence is Associated with an Increased Risk of Severe Liver Disease Later in Life".

PubMed

Tamburello, Adriana; Marando, Marco; Bellentani, Stefano

2018-04-09

Drinking alcohol during adolescence predispose to severe liver disease in the adult phase. This is the main message of this prospective study. Each daily gram of alcohol men consumed in their youth was linked with a two percent increase in the risk of severe liver disease. No threshold level emerged for liver damage and this is a warning for all the sociologists and politics. New legiferation and educational campaigns addressed to young people, with particular attention to the access to alcohol, prices and advertising are necessary.

Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

Intestinal fungi contribute to development of alcoholic liver disease.

PubMed

Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Xu, Jun; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene Ml; Hoffman, Hal M; Mehal, Wajahat Z; Garcia-Tsao, Guadalupe; Mutlu, Ece A; Keshavarzian, Ali; Brown, Gordon D; Ho, Samuel B; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E; Schnabl, Bernd

2017-06-30

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.

Pulmonary Vascular Complications of Liver Disease

PubMed Central

Fritz, Jason S.; Fallon, Michael B.

2013-01-01

Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary vascular complications of liver disease. The pathophysiology underlying each disorder is distinct, but patients with either condition may be limited by dyspnea. A careful evaluation of concomitant symptoms, the physical examination, pulmonary function testing and arterial blood gas analysis, and echocardiographic, imaging, and hemodynamic studies is crucial to establishing (and distinguishing) these diagnoses. Our understanding of the pathobiology, natural history, and treatment of these disorders has advanced considerably over the past decade; however, the presence of either still increases the risk of morbidity and mortality in patients with underlying liver disease. There is no effective medical treatment for hepatopulmonary syndrome. Although liver transplantation can resolve hepatopulmonary syndrome, there appears to be worse survival even with transplantation. Liver transplantation poses a very high risk of death in those with significant portopulmonary hypertension, where targeted medical therapies may improve functional status and allow successful transplantation in a small number of select patients. PMID:23155142

Metastatic ovarian tumors: a clinicopathologic study of 150 cases.

PubMed

Alvarado-Cabrero, Isabel; Rodríguez-Gómez, Adriana; Castelan-Pedraza, Jorge; Valencia-Cedillo, Raquel

2013-10-01

To determine the frequency of metastatic ovarian tumors and to identify their clinicopathologic features. A total of 150 patients with pathologically confirmed metastatic ovarian carcinoma who were treated between 1995 and 2011 at the Mexican Oncology Hospital were identified by retrospective review. Clinicopathologic data were analyzed. Metastatic ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%). Gynecologic primary sites were the uterine cervix (4%) and the uterine body (23%). Primary malignancies were detected first in 66 patients (44%) and simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass was the first manifestation of disease in 20.6% of the cases. The patients ranged in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35 patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid-cystic in 38, and multicystic in 44. Metastatic ovarian carcinomas are an important group of ovarian neoplasms, constituting 15.7% of all ovarian malignancies. Most of them arise from the gastrointestinal tract.

Weighted gene co-expression network analysis of colorectal cancer liver metastasis genome sequencing data and screening of anti-metastasis drugs.

PubMed

Gao, Bo; Shao, Qin; Choudhry, Hani; Marcus, Victoria; Dong, Kung; Ragoussis, Jiannis; Gao, Zu-Hua

2016-09-01

Approximately 9% of cancer-related deaths are caused by colorectal cancer (CRC). CRC patients are prone to liver metastasis, which is the most important cause for the high CRC mortality rate. Understanding the molecular mechanism of CRC liver metastasis could help us to find novel targets for the effective treatment of this deadly disease. Using weighted gene co-expression network analysis on the sequencing data of CRC with and with metastasis, we identified 5 colorectal cancer liver metastasis related modules which were labeled as brown, blue, grey, yellow and turquoise. In the brown module, which represents the metastatic tumor in the liver, gene ontology (GO) analysis revealed functions including the G-protein coupled receptor protein signaling pathway, epithelial cell differentiation and cell surface receptor linked signal transduction. In the blue module, which represents the primary CRC that has metastasized, GO analysis showed that the genes were mainly enriched in GO terms including G-protein coupled receptor protein signaling pathway, cell surface receptor linked signal transduction, and negative regulation of cell differentiation. In the yellow and turquoise modules, which represent the primary non-metastatic CRC, 13 downregulated CRC liver metastasis-related candidate miRNAs were identified (e.g. hsa-miR-204, hsa-miR-455, etc.). Furthermore, analyzing the DrugBank database and mining the literature identified 25 and 12 candidate drugs that could potentially block the metastatic processes of the primary tumor and inhibit the progression of metastatic tumors in the liver, respectively. Data generated from this study not only furthers our understanding of the genetic alterations that drive the metastatic process, but also guides the development of molecular-targeted therapy of colorectal cancer liver metastasis.

Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

PubMed

Wei, Shi; Siegal, Gene P

2017-03-01

It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications.

PubMed

Nguyen, Vi; George, Jacob

2015-08-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Laparoscopic management of cystic disease of the liver.

PubMed

Albrink, M H; McAllister, E W; Rosemurgy, A S; Karl, R C; Carey, L C

1994-04-01

Laparoscopic surgical procedures are increasing in scope and in variety. The benefits of decreased wound morbidity and pain have been well documented for multiple procedures that have traditionally required laparotomy. Although there are few controlled studies to document them, these benefits may be evident from simple clinical observation. Cystic disease of the liver is a condition that is treated largely for symptomatic reasons. The so-called noninvasive or radiographic guided methods of treatment for cystic disease of the liver are fraught with high recurrence rates. We present four cases of cystic disease of the liver treated laparoscopically, followed with pertinent discussion.

Autophagy in alcohol-induced liver diseases

PubMed Central

Dolganiuc, Angela; Thomes, Paul G.; Ding, Wen-Xing; Lemasters, John J.; Donohue, Terrence M.

2013-01-01

Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately-folded proteins and damaged high energy-generating intracellular organelles are prominent targets of autophagy in pathologic conditions. Coincidentally, inadequately-folded proteins accumulate and high energy-generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease. PMID:22551004

Review article: Probiotics in gastrointestinal and liver diseases.

PubMed

Jonkers, D; Stockbrügger, R

2007-12-01

Probiotics, defined as live micro-organisms with beneficial effects for the host, are widely applied in gastrointestinal and liver diseases. To review the available evidence of clinical trials on probiotics in gastrointestinal and liver diseases, with a major focus on irritable bowel syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases. Evidence for the therapeutic or preventive application of particular probiotic strains is available for antibiotic-associated diarrhoea, rota-virus-associated diarrhoea and pouchitis. Results are encouraging for irritable bowel syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori eradication therapies, but are less clear for Crohn's disease, lactose intolerance and constipation. In general, for most of these patient groups, more placebo-controlled methodologically well-designed studies that pay attention to both clinical outcome and mechanistic aspects are required. The application in liver disease and pancreatitis is promising, but more human trials have to be awaited. Possible mechanisms of probiotics include modulation of the intestinal microbiota and the immune system, but different bacterial may have different effects. Further insight into disease entities and the functioning of probiotic strains is required to be able to select disease-specific strains, which have to be tested in well-designed placebo-controlled studies.

Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.

PubMed

Poeta, Marco; Pierri, Luca; Vajro, Pietro

2017-08-02

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

Association between liver fibrosis and coronary heart disease risk in patients with nonalcoholic fatty liver disease.

PubMed

Dogan, Serkan; Celikbilek, Mehmet; Yilmaz, Yunus K; Sarikaya, Savas; Zararsiz, Gokmen; Serin, Halil I; Borekci, Elif; Akyol, Lütfi; Pirti, Ilyas; Davarci, Sena E

2015-03-01

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD in adults is associated with increased risk of coronary heart disease (CHD). Because of the limitations of liver biopsy, noninvasive scoring indexes such as the NAFLD fibrosis score (NFS) were developed. The Framingham risk score (FRS) provides an estimate of CHD risk. In our study we aimed to investigate whether the severity of liver fibrosis estimated with the NFS is associated with a higher risk of CHD among individuals with ultrasonography-diagnosed NAFLD. A total of 155 patients and controls (81 patients with NAFLD and 74 controls) with ages ranging from 18 to 70 years were enrolled in this cross-sectional prospective study. Demographic, anthropometric, clinical, and laboratory data were obtained from each individual. The NAFLD patients were divided into subgroups on the basis of the severity of fatty liver. The FRS and NFS were adopted to predict the risk of CHD and the severity of hepatic fibrosis. In our study, we found that the FRS was higher in NAFLD patients than in controls (P<0.05). According to the FRS category, NFSs were higher in the intermediate/high probability CHD risk group in NAFLD (P<0.05). In multiple models, only age, sex, cholesterol, and HDL were independently associated with intermediate/high CHD risk (P<0.05). We also found a positive correlation between the NFS and the FRS (r=0.373, P<0.001). The optimum NFS cutoff point for identifying intermediate/high CHD risk in NAFLD patients was -2.1284, with a sensitivity and specificity of 95.20 and 48.30%, respectively. The predictive performance of the NFS in the determination of intermediate/high CHD risk in NAFLD patients was found to be 72% based on the area under the curve value. The FRS is associated with the NFS in NAFLD. The assessment of liver fibrosis may be useful for the risk stratification of CHD in the absence of liver

[Non-alcoholic fatty liver disease--new view].

PubMed

Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

2008-06-01

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

Endocannabinoids in Liver Disease

PubMed Central

Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

2010-01-01

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

Epithelioid Haemangioendothelioma (EHE) of the Liver.

PubMed

Khan, Abidullah; Humayun, Mohammad; Haider, Iqbal; Khan, Wazir Muhammad; Ajmal, Fahad; Ayub, Maimoona

2016-06-01

A45-year previously known hypertensive lady presented with 2-year history of upper abdominal pain, heaviness, and weight loss. Her radiological assessment suggested the possibility of hepatoma or liver metastases. Considering her age, overall good health and absence of cirrhosis, a liver biopsy was taken which showed hepatic epithelioidhaemangioendothelioma (HEHE), a rare and unusual intermediate grade vascular tumor which can easily be confused with hepatoma or metastatic liver disease. To the best of their knowledge, the authors are most probably reporting the first ever case of HEHE from Pakistan with special emphasis on its clinical presentations, clinico-radiological diagnostic clues, and the management options in the light of the limited retrospective studies.

Crosstalk between the gut and the liver via susceptibility loci: Novel advances in inflammatory bowel disease and autoimmune liver disease.

PubMed

Li, Xinyang; Shen, Jun; Ran, Zhihua

2017-02-01

Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained. It has been found that HNF4-α, GPR35, MST1R, CARD9, IL2/IL21/IL2R, BACH2, TNFRSF14, MAdCAM-1, and FUT2 are the genes involved in tight junction formation, macrophage function, T helper cell or T reg cell cycle and function, TNF secretion, lymphocyte homing or intestinal dysbiosis, respectively. The intimate crosstalk between the gut and liver in immunity is also highlighted and discussed in this review. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

NASA Astrophysics Data System (ADS)

Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

1997-04-01

There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

PNPLA3 gene in liver diseases.

PubMed

Trépo, Eric; Romeo, Stefano; Zucman-Rossi, Jessica; Nahon, Pierre

2016-08-01

Genome-wide association studies (GWAS) in the field of liver diseases have revealed previously unknown pathogenic loci and generated new biological hypotheses. In 2008, a GWAS performed in a population-based sample study, where hepatic liver fat content was measured by magnetic spectroscopy, showed a strong association between a variant (rs738409 C>G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene and nonalcoholic fatty liver disease. Further replication studies have shown robust associations between PNPLA3 and steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma on a background of metabolic, alcoholic, and viral insults. The PNPLA3 protein has lipase activity towards triglycerides in hepatocytes and retinyl esters in hepatic stellate cells. The I148M substitution leads to a loss of function promoting triglyceride accumulation in hepatocytes. Although PNPLA3 function has been extensively studied, the molecular mechanisms leading to hepatic fibrosis and carcinogenesis remain unclear. This unsuspected association has highlighted the fact that liver fat metabolism may have a major impact on the pathophysiology of liver diseases. Conversely, alone, this locus may have limited predictive value with regard to liver disease outcomes in clinical practice. Additional studies at the genome-wide level will be required to identify new variants associated with liver damage and cancer to explain a greater proportion of the heritability of these phenotypes. Thus, incorporating PNPLA3 and other genetic variants in combination with clinical data will allow for the development of tailored predictive models. This attractive approach should be evaluated in prospective cohorts. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

PubMed Central

Tang, Zhao-You; Sun, Fan-Xian; Tian, Jian; Ye, Sheng-Long; Liu, Yin-Kun; Liu, Kang-Da; Xue, Qiong; Chen, Jie; Xia, Jing-Lin; Qin, Lun-Xiu; Sun, Hui-Chuan; Wang, Lu; Zhou, Jian; Li, Yan; Ma, Zeng-Chen; Zhou, Xin-Da; Wu, Zhi-Quan; Lin, Zhi-Ying; Yang, Bing-Hui

2001-01-01

Metastatic human HCC model is needed for the studies on mechanism and interven tion of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of hu man HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metasta sis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesio nmolecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis, antisense approach, metallopro teinase inhibitor, differentiation inducer, etc. It is concluded that the establ ishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence. PMID:11819839

Diet - liver disease

MedlinePlus

... of toxic waste products. Increasing your intake of carbohydrates to be in proportion with the amount of ... severe liver disease include: Eat large amounts of carbohydrate foods. Carbohydrates should be the major source of ...

Patient-Specific B-Cell Antibody Factories to Treat Metastatic Disease

DTIC Science & Technology

2013-08-01

Immortalization of these selected clones using Epstein - Barr viral transformation provides a method to maintain these antibody producing cell lines as a...2013 Please see next page. None provided. Patient-Specific B-Cell Antibody Factories to Treat Metastatic Disease Kevin Claffey University of

Gut Microbiota and Complications of Liver Disease

PubMed Central

Acharya, Chathur; Bajaj, Jasmohan

2016-01-01

Synopsis The epidemic of chronic liver disease and how to combat its complications has been a challenging aspect for many years. New laboratory techniques have made analysis of the human intestinal microbiome easier and also more detailed. With insight into dysbiosis and how this dysbiosis impacts liver disease, scientists have new targets in the intestine and liver. Dysbiosis is associated with endotoxemia and propagates liver injury in NASH and alcoholic cirrhosis. The composition of the microbiota changes with the development of cirrhosis and decompensation Apart from microbes, the role that bile acids play in this arena are also being discovered and newer treatments like FXR receptor agonists are coming into the picture. Altered gut microbiota plays an important role in cirrhosis and its modulation to prevent disease progression changes, and concomitantly bile acid physiology must be regulated or augmented to help prevent cirrhosis and its complications. PMID:28164848

Current and Future Burden of Chronic Nonmalignant Liver Disease.

PubMed

Udompap, Prowpanga; Kim, Donghee; Kim, W Ray

2015-11-01

Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

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

Anticoagulation and high dose liver radiation. A preliminary report

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

Lightdale, C.J.; Wasser, J.; Coleman, M.

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes onmore » liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.« less

Nonalcoholic fatty liver disease: Evolving paradigms

PubMed Central

Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

2017-01-01

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

The Natural Course of Non-Alcoholic Fatty Liver Disease

PubMed Central

Calzadilla Bertot, Luis; Adams, Leon Anton

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

Intrahepatic portal hypertension secondary to metastatic carcinoma of the prostate.

PubMed

Attila, Tan; Datta, Milton W; Sudakoff, Gary; Abu-Hajir, Majed; Massey, Benson T

2007-02-01

While the liver is a common site of metastasis, tumor metastases are not a common cause of portal hypertension. We report a case of a patient with symptomatic portal hypertension due to diffuse metastatic prostate carcinoma infiltration of liver parenchyma that was not appreciated with routine imaging.

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

Non-alcoholic fatty liver disease is not associated with a lower health perception.

PubMed

Mlynarsky, Liat; Schlesinger, Dalit; Lotan, Roni; Webb, Muriel; Halpern, Zamir; Santo, Erwin; Shibolet, Oren; Zelber-Sagi, Shira

2016-05-07

To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1

Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: Magnetic Resonance Imaging Is an Effective, Non-invasive Method to Evaluate Changes in the Liver Fat Fraction.

PubMed

Hedderich, Dennis M; Hasenberg, Till; Haneder, Stefan; Schoenberg, Stefan O; Kücükoglu, Özlem; Canbay, Ali; Otto, Mirko

2017-07-01

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease worldwide and is highly associated with obesity. The prevalences of both conditions have markedly increased in the Western civilization. Bariatric surgery is the most effective treatment for morbid obesity and its comorbidities such as NAFLD. Measure postoperative liver fat fraction (LFF) in bariatric patients by using in-opposed-phase MRI, a widely available clinical tool validated for the quantification of liver fat METHODS: Retrospective analyses of participants, who underwent laparoscopic Roux-Y-gastric-bypass (17) or laparoscopic sleeve gastrectomy (2) were performed using magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometric measurements 1 day before surgery, as well as 6, 12, and 24 weeks after surgery, LFF was calculated from fat-only and water-only MR images. Six months after surgery, a significant decrease of LFF and liver volume has been observed along with weight loss, decreased waist circumference, and parameters obtained by body fat measured by BIA. LFF significantly correlated with liver volume in the postoperative course. MRI including in-opposed-phase imaging of the liver can detect the quantitative decrease of fatty infiltration within the liver after bariatric surgery and thus could be a valuable tool to monitor NAFLD/NASH postoperatively.

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.

Alcoholic liver disease

MedlinePlus

... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:59-60. Carithers RL, McClain C. Alcoholic ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 86. Haines EJ, Oyama LC. ...

Portopulmonary Hypertension in Liver Disease Presenting in Childhood.

PubMed

Ecochard-Dugelay, Emmanuelle; Lambert, Virginie; Schleich, Jean-Marc; Duché, Mathieu; Jacquemin, Emmanuel; Bernard, Olivier

2015-09-01

Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature. Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients. In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively. POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk.

Spatiotemporal progression of metastatic breast cancer: a Markov chain model highlighting the role of early metastatic sites

PubMed Central

Newton, Paul K; Mason, Jeremy; Venkatappa, Neethi; Jochelson, Maxine S; Hurt, Brian; Nieva, Jorge; Comen, Elizabeth; Norton, Larry; Kuhn, Peter

2015-01-01

Background: Cancer cell migration patterns are critical for understanding metastases and clinical evolution. Breast cancer spreads from one organ system to another via hematogenous and lymphatic routes. Although patterns of spread may superficially seem random and unpredictable, we explored the possibility that this is not the case. Aims: Develop a Markov based model of breast cancer progression that has predictive capability. Methods: On the basis of a longitudinal data set of 446 breast cancer patients, we created a Markov chain model of metastasis that describes the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Progression is modeled as a random walk on a directed graph, where nodes represent anatomical sites where tumors can develop. Results: We quantify how survival depends on the location of the first metastatic site for different patient subcategories. In addition, we classify metastatic sites as “sponges” or “spreaders” with implications regarding anatomical pathway prediction and long-term survival. As metastatic tumors to the bone (main spreader) are most prominent, we focus in more detail on differences between groups of patients who form subsequent metastases to the lung as compared with the liver. Conclusions: We have found that spatiotemporal patterns of metastatic spread in breast cancer are neither random nor unpredictable. Furthermore, the novel concept of classifying organ sites as sponges or spreaders may motivate experiments seeking a biological basis for these phenomena and allow us to quantify the potential consequences of therapeutic targeting of sites in the oligometastatic setting and shed light on organotropic aspects of the disease. PMID:28721371

Immunology in the liver--from homeostasis to disease.

PubMed

Heymann, Felix; Tacke, Frank

2016-02-01

The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver disease, such as viral hepatitis, cholestasis or NASH, different triggers mediate immune-cell activation. Conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses in the liver. The inflammatory activation of hepatic stellate and Kupffer cells results in the chemokine-mediated infiltration of neutrophils, monocytes, natural killer (NK) and natural killer T (NKT) cells. The ultimate outcome of the intrahepatic immune response (for example, fibrosis or resolution) depends on the functional diversity of macrophages and dendritic cells, but also on the balance between pro-inflammatory and anti-inflammatory T-cell populations. As reviewed here, tremendous progress has helped to understand the fine-tuning of immune responses in the liver from homeostasis to disease, indicating promising targets for future therapies in acute and chronic liver diseases.

Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

PubMed

Ma, Jian; Yang, Quan-Liang; Ling, Yang

2017-02-14

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

PubMed Central

French, Samuel W.

2013-01-01

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

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

Functions of autophagy in normal and diseased liver

PubMed Central

Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

2013-01-01

Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

Hepatic protoporphyrin metabolism in patients with advanced protoporphyric liver disease.

PubMed Central

Bloomer, J. R.

1997-01-01

Protoporphyria is a genetic disorder in which liver damage is caused by the toxic effect of protoporphyrin accumulation in the liver. In this study protoporphyrin was measured in the resected livers of 7 patients who had liver transplantation and an additional patient from whom liver tissue was obtained post mortem. Comparison of liver, erythrocyte and serum protoporphyrin levels demonstrated a marked gradient between these compartments: erythrocyte, 5781 +/- 655 micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568 micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3 patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between liver and bile as well. Examination of the livers by polarization microscopy and electron microscopy demonstrated protoporphyrin pigment crystals. In one patient who had recurrent liver disease after transplantation, the protoporphyrin concentration in the graft at the time of death was similar to that in the resected liver. These data indicate that liver protoporphyrin levels in patients with advanced protoporphyric liver disease are much higher than levels in blood and bile, in part because protoporphyrin forms crystalline deposits in liver tissue. Thus, progressive hepatic accumulation of protoporphyrin occurs in the face of impaired biliary excretion. An intrinsic defect in hepatic excretion of protoporphyrin is probably not necessary for this condition to develop because liver disease can occur in the graft following transplantation. PMID:9626752

Clinical approaches to non-alcoholic fatty liver disease

PubMed Central

Schwenger, Katherine JP; Allard, Johane P

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

PubMed Central

Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

2015-01-01

Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effect of Liver Disease on Hepatic Transporter Expression and Function.

PubMed

Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

2017-09-01

Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma

PubMed Central

Glenn, Sean T.; Jones, Craig A.; Sexton, Sandra; LeVea, Charles M.; Caraker, Susan M.; Hajduczok, George; Gross, Kenneth W.

2014-01-01

Efforts to model human pancreatic neuroendocrine tumors (PanNET) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene while classically associated with expression in the kidney is also expressed in many other extra-renal tissues including the pancreas. To induce tumorigenesis within renin specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by the renin promoter. The primary neoplasm generated is a highly metastatic islet cell carcinoma of the pancreas. Lineage tracing identifies descendants of renin-expressing cells as pancreatic alpha cells despite a lack of active renin expression in the mature pancreas. Both primary and metastatic tumors express high levels of glucagon, furthermore an increased level of glucagon is found in the serum identifying the pancreatic cancer as a functional glucagonoma. This new model is highly penetrant and exhibits robust frequency of metastases to lymph nodes and liver, mimicking human disease and provides a useful platform for better understanding pancreatic endocrine differentiation and development, as well as islet cell carcinogenesis. The use of fluorescent reporters for lineage tracing of the cells contributing to disease initiation and progression provides a unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying co-operating mutations that are necessary for progression of disease. PMID:24292676

Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma.

PubMed

Glenn, S T; Jones, C A; Sexton, S; LeVea, C M; Caraker, S M; Hajduczok, G; Gross, K W

2014-12-11

Efforts to model human pancreatic neuroendocrine tumors (PanNETs) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene, although classically associated with expression in the kidney, is also expressed in many other extrarenal tissues including the pancreas. To induce tumorigenesis within rennin-specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by the renin promoter. The primary neoplasm generated is a highly metastatic islet cell carcinoma of the pancreas. Lineage tracing identifies descendants of renin-expressing cells as pancreatic alpha cells despite a lack of active renin expression in the mature pancreas. Both primary and metastatic tumors express high levels of glucagon; furthermore, an increased level of glucagon is found in the serum, identifying the pancreatic cancer as a functional glucagonoma. This new model is highly penetrant and exhibits robust frequency of metastases to the lymph nodes and the liver, mimicking human disease, and provides a useful platform for better understanding pancreatic endocrine differentiation and development, as well as islet cell carcinogenesis. The use of fluorescent reporters for lineage tracing of the cells contributing to disease initiation and progression provides an unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying cooperating mutations that are necessary for progression of disease.

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

PubMed Central

Povero, Davide; Eguchi, Akiko; Li, Hongying; Johnson, Casey D.; Papouchado, Bettina G.; Wree, Alexander; Messer, Karen; Feldstein, Ariel E.

2014-01-01

Background & Aim Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. Design Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. Results We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05), fibrosis (r2 = 0.66, p<0.05) and pathological angiogenesis (r2 = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. Conclusions These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD. PMID:25470250

[Coffee can be beneficial for patients with liver diseases].

PubMed

Kjærgaard, Maria; Thiele, Maja; Krag, Aleksander

2014-10-20

Coffee is one of the most commonly consumed beverages in the world. Consequently, it is important to consider the impact of coffee on health and disease. A daily intake of at least three cups of coffee is likely to have beneficial health effects, especially in patients at risk of liver diseases. Coffee has been associated with decreased liver inflammation, prevention of cirrhosis, reduced steatosis and lower incidence of hepatocellular carcinoma. It is not yet possible to make clear recommendations, but coffee can likely be included as part of a healthy diet for patients with liver diseases.

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

Non-Alcoholic Fatty Liver Disease.

PubMed

Engin, Atilla

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

Management of cytomegalovirus infection and disease in liver transplant recipients

PubMed Central

Bruminhent, Jackrapong; Razonable, Raymund R

2014-01-01

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.

PubMed

Evans, Christopher P; Higano, Celestia S; Keane, Thomas; Andriole, Gerald; Saad, Fred; Iversen, Peter; Miller, Kurt; Kim, Choung-Soo; Kimura, Go; Armstrong, Andrew J; Sternberg, Cora N; Loriot, Yohann; de Bono, Johann; Noonberg, Sarah B; Mansbach, Hank; Bhattacharya, Suman; Perabo, Frank; Beer, Tomasz M; Tombal, Bertrand

2016-10-01

Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195). Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease

Role of folate in nonalcoholic fatty liver disease.

PubMed

Sid, Victoria; Siow, Yaw L; O, Karmin

2017-10-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

Emerging roles of SIRT1 in fatty liver diseases

PubMed Central

Ding, Ren-Bo; Bao, Jiaolin; Deng, Chu-Xia

2017-01-01

Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD+) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family. Among seven mammalian sirtuins, sirtuin 1 (SIRT 1) is the most extensively studied one and is involved in both alcoholic and nonalcoholic fatty liver diseases. SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases. Here we summarize the latest advances of the biological roles of SIRT1 in regulating lipid metabolism, oxidative stress and inflammation in the liver, and discuss the potential of SIRT1 as a therapeutic target for treating alcoholic and nonalcoholic fatty liver diseases. PMID:28808418

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

PubMed Central

Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

2014-01-01

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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

Non-alcoholic fatty liver disease is not associated with a lower health perception

PubMed Central

Mlynarsky, Liat; Schlesinger, Dalit; Lotan, Roni; Webb, Muriel; Halpern, Zamir; Santo, Erwin; Shibolet, Oren; Zelber-Sagi, Shira

2016-01-01

AIM: To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity

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.

Mediterranean diet and nonalcoholic fatty liver disease.

PubMed

Anania, Caterina; Perla, Francesco Massimo; Olivero, Francesca; Pacifico, Lucia; Chiesa, Claudio

2018-05-21

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet (MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and anti-oxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.

Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers.

PubMed

Anavi, Sarit; Madar, Zecharia; Tirosh, Oren

2017-10-01

Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Monitoring of Total and Regional Liver Function after SIRT.

PubMed

Bennink, Roelof J; Cieslak, Kasia P; van Delden, Otto M; van Lienden, Krijn P; Klümpen, Heinz-Josef; Jansen, Peter L; van Gulik, Thomas M

2014-01-01

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)].

PubMed

Langness, U; Clausnitzer, H; Verspohl, M; Grasedyck, K

1978-08-25

100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.

Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

PubMed Central

Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS).

PubMed

Sheron, Nick; Moore, Michael; O'Brien, Wendy; Harris, Scott; Roderick, Paul

2013-10-01

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. A community feasibility study in nine general practice sites in Hampshire. Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives. Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.

Diagnosis and Management of Alcoholic Liver Disease.

PubMed

Dugum, Mohannad; McCullough, Arthur

2015-06-28

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

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.

Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

PubMed Central

Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

2013-01-01

Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

PubMed

Hashimoto, Takuzo; Itabashi, Michio; Ogawa, Shinpei; Hirosawa, Tomoichiro; Bamba, Yoshiko; Kaji, Sanae; Ubukata, Mamiko; Shimizu, Satoru; Sugihara, Kenichi; Kameoka, Shingo

2014-06-01

To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

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.

Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

PubMed

Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

2015-10-01

Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

[Various pathways leading to the progression of chronic liver diseases].

PubMed

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

Diabetes mellitus and renal involvement in chronic viral liver disease.

PubMed

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with

Should possible recurrence of disease contraindicate liver transplantation in patients with end-stage alveolar echinococcosis? A 20-year follow-up study.

PubMed

Bresson-Hadni, Solange; Blagosklonov, Oleg; Knapp, Jenny; Grenouillet, Frédéric; Sako, Yasuhito; Delabrousse, Eric; Brientini, Marie-Pascale; Richou, Carine; Minello, Anne; Antonino, Anca-Teodora; Gillet, Michel; Ito, Akira; Mantion, Georges André; Vuitton, Dominique Angèle

2011-07-01

Liver transplantation (LT) is currently contraindicated in patients with residual or metastatic alveolar echinococcosis (AE) lesions. We evaluated the long-term course of such patients who underwent LT and were subsequently treated with benzimidazoles. Clinical, imaging, serological, and therapeutic data were collected from 5 patients with residual/recurrent AE lesions who survived for more than 15 years. Since 2004, [(18) F]-2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) images were available, and the levels of serum antibodies (Abs) against Echinococcus multilocularis-recombinant antigens were evaluated. Median survival time after LT was 21 years. These patients were from a prospective cohort of 23 patients with AE who underwent LT: 5 of 8 patients with residual/recurrent AE and 4 of 9 patients without residual/recurrent AE were alive in September 2009. High doses of immunosuppressive drugs, the late introduction of therapy with benzimidazoles, its withdrawal due to side effects, and nonadherence to this therapy adversely affected the prognosis. Anti-Em2(plus) and anti-rEm18 Ab levels and standard FDG-PET enabled the efficacy of therapy on the growth of EA lesions to be assessed. However, meaningful variations in Ab levels were observed below diagnostic cutoff values; and in monitoring AE lesions, images of FDG uptake taken 3 hours after its injection were more sensitive than images obtained 1 hour after its injection. In conclusion, benzimidazoles can control residual/recurrent AE lesions after LT. Using anti-rEm18 or anti-Em2(plus) Ab levels and the delayed acquisition of FDG-PET images can improve the functional assessment of disease activity. The potential recurrence of disease, especially in patients with residual or metastatic AE lesions, should not be regarded as a contraindication to LT when AE is considered to be lethal in the short term. Copyright © 2011 American Association for the Study of Liver Diseases.

Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

PubMed

Williams, Tracy

2015-08-01

Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

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.

Clinical and radiological features of invasive Klebsiella pneumoniae liver abscess syndrome.

PubMed

Shin, Sung Ui; Park, Chang Min; Lee, Youkyung; Kim, Eui-Chong; Kim, Soo Jin; Goo, Jin Mo

2013-06-01

Recently, a striking new clinical manifestation of Klebsiella pneumoniae (KP) infection referred to as invasive KP liver abscess syndrome (IKPLAS), defined by liver abscess with contemporaneous metastatic KP infections at other body sites has been documented. Until now, however, there have been relatively few reports regarding its radiologic features. To describe the clinical and radiological features of IKPLAS patients, and to compare them with those with KP liver abscess without metastatic infections to ascertain possible predictors of IKPLAS. From January 2008 to May 2010, 35 patients (26 men and 9 women; mean age, 59.4 years) with both liver abscess and metastatic KP infections were diagnosed with IKPLAS. Their clinical and radiological features were retrospectively evaluated and compared with those of 25 contemporaneous non-metastatic patients to investigate predictive factors for metastatic infections. The rate of intensive care unit admissions and overall mortality was 34.3% and 17.1% in IKPLAS patients, and was significantly higher than those of the non-metastatic group (8% and 0%, respectively). As for metastatic infections, the lung was the most common site and multiple nodules or masses (n = 9) were the most common manifestations. Univariate analysis revealed that liver abscess ≤5.8 cm, bilobar involvement of abscess and altered mentality were significantly related with IKPLAS. At multivariate analysis, liver abscess ≤5.8 cm was proven to be a significant independent predictor of IKPLAS (OR, 3.6; P = 0.038). In addition, altered mentality was present solely in IKPLAS (25.7% vs. 0%) although its P value (P = 0.052) did not reach a statistical significance at multivariate analysis. IKPLAS has significantly worse prognosis than non-metastatic KP abscess patients. In patients with KP liver abscess, liver abscess ≤5.8 cm can be used as an independent predictor of IKPLAS and altered mentality as a very specific feature in diagnosing IKPLAS. © 2013 The

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease.

PubMed

Dou, Lei; Ono, Yoshihiro; Chen, Yi-Fa; Thomson, Angus W; Chen, Xiao-Ping

2018-05-01

The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pyogenic Liver Abscess as Endemic Disease, Taiwan

PubMed Central

Tsai, Feng-Chiao; Huang, Yu-Tsung; Chang, Luan-Yin

2008-01-01

Pyogenic liver abscess has become a health problem in Taiwanese society. However, the extent of this problem has remained unclear because of the lack of a population-based study. We therefore performed a nationwide analysis of pyogenic liver abscess in Taiwan from 1996 through 2004. We analyzed 29,703 cases from the Taiwan National Health Insurance database and 506 cases from National Taiwan University Hospital. Our analysis showed that the annual incidence of pyogenic liver abscess increased steadily from 11.15/100,000 population in 1996 to 17.59/100,000 in 2004. Diabetes, malignancy, renal disease, and pneumonia were associated with a higher risk for the disease. By contrast, death due to pyogenic liver abscess decreased over time, although population-based abscess-related death increased slightly. Renal disease, malignancy, pneumonia, and heart disease correlated with higher death rates; Klebsiella pneumoniae infection and therapeutic procedures were related to lower death rates. Diabetes did not significantly change death rates for the 506 patients from the hospital. PMID:18826824

Lower Muscle Endurance in Patients with Alcoholic Liver Disease

ERIC Educational Resources Information Center

Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

2012-01-01

Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

Nonalcoholic fatty liver disease and polycystic ovary syndrome.

PubMed

Vassilatou, Evangeline

2014-07-14

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Nonalcoholic fatty liver disease and polycystic ovary syndrome

PubMed Central

Vassilatou, Evangeline

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

Radiosurgery for metastatic disease at the craniocervical junction.

PubMed

Tuchman, Alexander; Yu, Cheng; Chang, Eric L; Kim, Paul E; Rusch, Mairead C; Apuzzo, Michael L J

2014-12-01