Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: a case report.

PubMed

Motoki, T; Fukuda, M; Nakano, T; Matsukage, S; Fukui, A; Akiyoshi, S; Hayashi, Y K; Ishii, E; Nishino, I

2013-11-01

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

PubMed Central

Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

2016-01-01

Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

Drug-induced Liver Disease in Patients with Diabetes Mellitus.

PubMed

Iryna, Klyarytskaya; Helen, Maksymova; Elena, Stilidi

2015-01-01

The study presented here was accomplished to assess the course of drug-induced liver diseases in patient's rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with S-Adenosyl methionine was also evaluated. 13C-MBT: 13C-methacetin breath test; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartic transaminase; DILD: drug-induced liver disease; DM: diabetes mellitus; HE: hepatic encephalopathy; HFM: hepatic functional mass; SAMe: S-Adenosyl methionine; UDCA: ursodeoxycholic acid. Iryna K, Helen M, Elena S. Drug-induced Liver Disease in Patients with Diabetes Mellitus. Euroasian J Hepato-Gastroenterol 2015;5(2):83-86.

Adenoviral Gene Transfer of Hepatic Stimulator Substance Confers Resistance Against Hepatic Ischemia–Reperfusion Injury by Improving Mitochondrial Function

PubMed Central

Jiang, Shu-Jun; Li, Wen

2013-01-01

Abstract Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia–reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of HSS could attenuate hepatic ischemia–reperfusion injury and its possible mechanisms. Both in vivo hepatic I/R injury in mice and in vitro hypoxia–reoxygenation (H/R) in a cell model were used to evaluate the effect of HSS protection after adenoviral gene transfer. Moreover, a possible mitochondrial mechanism of HSS protection was investigated. Efficient transfer of the HSS gene into liver inhibited hepatic I/R injury in mice, as evidenced by improvement in liver function tests, the preservation of hepatic morphology, and a reduction in hepatocyte apoptosis. HSS overexpression also inhibited H/R-induced cell death, as detected by cell viability and cell apoptosis assays. The underlying mechanism of this hepatic protection might involve the attenuation of mitochondrial dysfunction and mitochondrial-dependent cell apoptosis, as shown by the good preservation of mitochondrial ultrastructure, mitochondrial membrane potential, and the inhibition of cytochrome c leakage and caspase activity. Moreover, the suppression of H/R-induced mitochondrial ROS production and the maintenance of mitochondrial respiratory chain complex activities may participate in this mechanism. This new function of HSS expands the possibility of its application for the prevention of I/R injury, such as hepatic resection and liver transplantation in clinical practice. PMID:23461564

Mistletoe hepatitis.

PubMed Central

Harvey, J; Colin-Jones, D G

1981-01-01

A 49-year-old woman presented with nausea, general malaise, and a dull ache in the right hypochondrium. Liver biopsy showed slight inflammatory-cell infiltration, and results of liver function tests suggested hepatitis. Hepatitis B surface antigen was not detected, and a cholecystogram was normal. Two years later she presented with similar symptoms, and both illnesses were found to have occurred after ingestion of a herbal remedy containing kelp, motherwort, skullcap, and mistletoe. A challenge test established this to be the cause of the illness. Mistletoe is the only constituent of the tablets known to contain any potential toxin and thus was probably the cause of the illness. Mistletoe is widely used in herbal remedies, whose ingestion may therefore cause hepatitis. Images FIG 1 FIG 2 PMID:6779941

Viscoelastic testing for hepatic surgery: a systematic review with meta-analysis-a protocol.

PubMed

McCrossin, Kate Elizabeth; Bramley, David Edmund Piers; Hessian, Elizabeth; Hutcheon, Evelyn; Imberger, Georgina

2016-09-06

Viscoelastic tests, including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), provide a global assessment of haemostatic function at the point of care. The use of a TEG or ROTEM system to guide blood product administration has been shown in some surgical settings to reduce transfusion requirements. The aim of this review is to evaluate all published evidence regarding viscoelastic testing in the setting of hepatic surgery. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials databases to identify randomised controlled trials examining the use of viscoelastic testing for hepatic surgery. Two reviewers will independently screen titles and abstracts of studies identified and will independently extract data. Any disagreements will be resolved by discussion with a third reviewer. A meta-analysis will be conducted if feasible. Viscoelastic devices such as TEG and ROTEM are increasingly available to clinicians as a bedside test. Patients undergoing hepatic surgery have a significant risk of blood loss and coagulopathy requiring transfusion. Theoretical benefits of use of a TEG or ROTEM system in the hepatic surgical setting include a rationalisation of blood products, a reduction in transfusion-related side effects, an improvement in patient outcomes including mortality, and a reduction in cost. This systematic review will summarise the current evidence regarding the use of viscoelastic testing for hepatic surgery. PROSPERO CRD42016036732.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

[Correlation between red blood cell count and liver function status].

PubMed

Xie, Xiaomeng; Wang, Leijie; Yao, Mingjie; Wen, Xiajie; Chen, Xiangmei; You, Hong; Jia, Jidong; Zhao, Jingmin; Lu, Fengmin

2016-02-01

To investigate the changes in red blood cell count in patients with different liver diseases and the correlation between red blood cell count and degree of liver damage. The clinical data of 1427 patients with primary liver cancer, 172 patients with liver cirrhosis, and 185 patients with hepatitis were collected, and the Child-Pugh class was determined for all patients. The differences in red blood cell count between patients with different liver diseases were retrospectively analyzed, and the correlation between red blood cell count and liver function status was investigated. The Mann-Whitney U test, Kruskal-Wallis H test, rank sum test, Spearman rank sum correlation test, and chi-square test were performed for different types of data. Red blood cell count showed significant differences between patients with chronic hepatitis, liver cancer, and liver cirrhosis and was highest in patients with chronic hepatitis and lowest in patients with liver cirrhosis (P < 0.05). In the patients with liver cirrhosis, red blood cell count tended to decrease in patients with a higher Child-Pugh class (P < 0.05). For patients with liver cirrhosis, red blood cell count can reflect the degree of liver damage, which may contribute to an improved liver function prediction model for these patients.

Review: Occult hepatitis C virus infection: still remains a controversy.

PubMed

Vidimliski, Pavlina Dzekova; Nikolov, Igor; Geshkovska, Nadica Matevska; Dimovski, Aleksandar; Rostaing, Lionel; Sikole, Aleksandar

2014-09-01

Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system. © 2014 Wiley Periodicals, Inc.

Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

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

D'Arienzo, A.; Celentano, L.; Scuotto, A.

1988-07-01

In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function testsmore » were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.« less

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

Previous hepatitis a virus infection is related to slower psychomotor speed in elderly adults.

PubMed

Hsieh, Cheng-Fang; Liu, Ching-Kuan; Fang, Tzu-Jung; Yu, Yau-Hua; Lai, Chiou-Lian; Kuo, Hsu-Ko

2009-10-01

Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function. From the National Health and Nutrition Examination Survey, 1999-2002, we selected study participants (> or =60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST). HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted beta coefficient of DSST score was -9.55 (95% confidence interval [CI] -9.57 to -9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted beta coefficient of DSST score was -2.48 (95% CI -2.49 to -2.46, p < .001) for the HAV-seropositive participants. HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.

Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression.

PubMed

Shaker, Mohamed E; Salem, Hatem A; Shiha, Gamal E; Ibrahim, Tarek M

2011-04-01

The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150mg/kg, twice weekly) for 12weeks. Daily treatments with imatinib (10mg/kg), nilotinib (10mg/kg), and silymarin (100mg/kg) were administered orally during the last 4weeks of TAA-administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA-induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4-HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA-treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA-treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti-fibrotic drug. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Hepatitis virus panel

MedlinePlus

Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

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

Shaker, Mohamed E., E-mail: mshaker2222@yahoo.com; Zalata, Khaled R.; Mehal, Wajahat Z.

2011-04-15

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl{sub 4}) rat model. Male Wistar rats received intraperitoneal injections of CCl{sub 4} twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) during the last 4 weeks of CCl{sub 4}-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stressmore » parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20 mg/kg) was the most effective treatment to counteract CCl{sub 4}-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10 mg/kg), nilotinib (20 mg/kg) and silymarin (100 mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl{sub 4}-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl{sub 4}-induced fibrosis was ameliorated significantly by nilotinib (20 mg/kg) and imatinib (20 mg/kg). Unlike nilotinib, imatinib (20 mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. - Graphical abstract: Display Omitted Research Highlights: > The anti-fibrotic effects of imatinib, nilotinib and silymarin were compared. > These effects were evaluated on CCl{sub 4}-induced hepatic fibrosis in rats. > Nilotinib was found to possess potent anti-fibrotic activity. > In addition, nilotinib did not show any signs of hepatotoxicity. > Thus, nilotinib may be valuable in the treatment of hepatic fibrosis in humans.« less

Rotating microgravity-bioreactor cultivation enhances the hepatic differentiation of mouse embryonic stem cells on biodegradable polymer scaffolds.

PubMed

Wang, Yingjie; Zhang, Yunping; Zhang, Shichang; Peng, Guangyong; Liu, Tao; Li, Yangxin; Xiang, Dedong; Wassler, Michael J; Shelat, Harnath S; Geng, Yongjian

2012-11-01

Embryonic stem (ES) cells are pluripotent cells that are capable of differentiating all the somatic cell lineages, including those in the liver tissue. We describe the generation of functional hepatic-like cells from mouse ES (mES) cells using a biodegradable polymer scaffold and a rotating bioreactor that allows simulated microgravity. Cells derived from ES cells cultured in the three-dimensional (3D) culture system with exogenous growth factors and hormones can differentiate into hepatic-like cells with morphologic characteristics of typical mature hepatocytes. Reverse-transcription polymerase chain-reaction testing, Western blot testing, immunostaining, and flow cytometric analysis show that these cells express hepatic-specific genes and proteins during differentiation. Differentiated cells on scaffolds further exhibit morphologic traits and biomarkers characteristic of liver cells, including albumin production, cytochrome P450 activity, and low-density lipoprotein uptake. When these stem cell-bearing scaffolds are transplanted into severe combined immunodeficient mice, the 3D constructs remained viable, undergoing further differentiation and maturation of hepatic-like cells in vivo. In conclusion, the growth and differentiation of ES cells in a biodegradable polymer scaffold and a rotating microgravity bioreactor can yield functional and organizational hepatocytes useful for research involving bioartificial liver and engineered liver tissue.

Modulatory role of kolaviron in phenytoin-induced hepatic and testicular dysfunctions in Wistar rats.

PubMed

Owoeye, Olatunde; Adedara, Isaac A; Adeyemo, Oluwatobi A; Bakare, Oluwafemi S; Egun, Christa; Farombi, Ebenezer O

2015-03-01

Phenytoin, an anticonvulsant agent used for the treatment of epilepsy has been reported to exhibit toxic side effects on the liver and testes. The present study investigated the protective effects of kolaviron (KV, a bioflavonoid from Garcinia kola seeds) against hepatic and testicular damage in rats exposed to phenytoin. The study consisted of four groups of six rats per group. Group I rats received 2 mL/kg of corn alone while group II received 75 mg/kg of phenytoin (PHT) alone. Groups III and IV were co-treated with kolaviron (200 mg/kg KV) and vitamin E (500 mg/kg VTE), respectively, for 14 days. The antioxidant status, hepatic and reproductive functional parameters were subsequently determined. PHT treatment significantly (p < 0.05) increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated lipid peroxidation (LPO) and hydrogen peroxide (H2O2) levels along with significant reduction in the hepatic and testicular levels of glutathione (GSH). Moreover, PHT exposure elicited significant increases in alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels. The significant reduction in seminal epithelium thickness and the diameter of seminiferous tubules was accompanied with marked decrease in sperm motility, sperm count, and viability in PHT-treated rats. However, antioxidant status and the functional indices of liver and testes were restored to near control levels in rats co-treated with KV and VTE. In conclusion, KV and VTE protect the liver and testes against functional impairment due to PHT treatment.

A phase II, randomized, controlled trial of S-adenosylmethionine in reducing serum alpha-fetoprotein (AFP) in patients with hepatitis C cirrhosis and elevated AFP

PubMed Central

Morgan, Timothy R.; Osann, Kathryn; Bottiglieri, Teodoro; Pimstone, Neville; Hoefs, John C.; Hu, Ke-Qin; Hassanein, Tarek; Boyer, Thomas D.; Kong, Lorene; Chen, Wen-Pin; Richmond, Ellen; Gonzalez, Rachel; Rodriguez, Luz M.; Meyskens, Frank L.

2015-01-01

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC while administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum AFP level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 grams/day, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. 110 subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury, or markers of oxidative stress or antioxidant potential. PMID:26130251

Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

PubMed

Driver, Todd H; Terrault, Norah; Saxena, Varun

2013-05-01

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

Diagnosis of viral hepatitis

PubMed Central

Easterbrook, Philippa J.; Roberts, Teri; Sands, Anita; Peeling, Rosanna

2017-01-01

Purpose of review Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV–HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016–2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics. Recent findings Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care. Summary Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for virological markers (nucleic acid testing and HCV core antigen), dried blood spot specimens used with different serological and nucleic acid test assays, multiplex and multi-disease platforms to enable testing for multiple analytes/pathogens and potential self-testing for viral hepatitis. PMID:28306597

p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

NASA Astrophysics Data System (ADS)

Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

1995-02-01

Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

Hepatitis C: What to Expect When Getting Tested

MedlinePlus

HEPATITIS C What to Expect When Getting Tested Getting tested for Hepatitis C • A blood test, called a Hepatitis C Antibody Test, is used to find out if someone has ever been infected with Hepatitis C. • The Hepatitis C Antibody Test, sometimes called the ...

Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

PubMed

Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

2013-06-01

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (p<0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p<0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p<0.05). A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Assessment of sulfasalazine and hydroxichloroqine hepatotoxicity in patients with rheumatic arthritis and isolated HBS-antigen positivity].

PubMed

Petrov, A V

2004-01-01

Findings were based on long-period survey (12-16 month) of 39 patients with rheumatoid arthritis (RA) and isolated persistent HBS-antigen. The patients were prescribed Hydroxichloroqine (H) and Sulfasolin (SF). Clinical data, laboratory tests, ultrasonic diagnostics to evaluate liver condition have been analyzed. HBs, Hbe-antigenes, DNA-virus B hepatitis blood test, nucleus dimensions, proliferative FGA response test and immune CD 8+, CD 14+ and CD 16+ cells to Fas-induced apoptosis were taken. SF therapy was found to be more hepatotoxic and likely to activate a latent virus B hepatitis as compared with Hydroxichloroqine and combine H and SF therapies. Triggering replication of virus B hepatitis occurs against a background of decreasing in functional activity of CD 14+ and CD 16+ cells. The immune critical level needed to activate VHB was determined.

[Acute hepatitis following amiodarone administration].

PubMed

Tagliamonte, E; Cice, G; Ducceschi, V; Mayer, M S; Iacono, A

1997-09-01

A 61 year old man, treated with amiodarone since 1993 for resistant supraventricular arrhythmias, developed acute hepatitis after an intravenous amiodarone administration. Kidney and liver function tests were performed and pointed out abnormal results. Symptoms ascribable to hepatotoxicity were absent. These changes returned to normal levels within 20 days from withdrawal of the drug. Amiodarone hepatotoxicity can be related to prolonged therapy with a high dose. Intravenous amiodarone may cause acute hepatic disease, but it is suggested that polysorbate 80, a solvent added to the intravenous infusion, is a more likely cause of this complication.

Postoperative course and clinical significance of biochemical blood tests following hepatic resection.

PubMed

Reissfelder, C; Rahbari, N N; Koch, M; Kofler, B; Sutedja, N; Elbers, H; Büchler, M W; Weitz, J

2011-06-01

Hepatic resection continues to be associated with substantial morbidity. Although biochemical tests are important for the early diagnosis of complications, there is limited information on their postoperative changes in relation to outcome in patients with surgery-related morbidity. A total of 835 consecutive patients underwent hepatic resection between January 2002 and January 2008. Biochemical blood tests were assessed before, and 1, 3, 5 and 7 days after surgery. Analyses were stratified according to the extent of resection (3 or fewer versus more than 3 segments). A total of 451 patients (54·0 per cent) underwent resection of three or fewer anatomical segments; resection of more than three segments was performed in 384 (46·0 per cent). Surgery-related morbidity was documented in 258 patients (30·9 per cent) and occurred more frequently in patients who had a major resection (P = 0·001). Serum bilirubin and international normalized ratio as measures of serial hepatic function differed significantly depending on the extent of resection. Furthermore, they were significantly affected in patients with complications, irrespective of the extent of resection. The extent of resection had, however, little impact on renal function and haemoglobin levels. Surgery-related morbidity caused an increase in C-reactive protein levels only after a minor resection. Biochemical data may help to recognize surgery-related complications early during the postoperative course, and serve as the basis for the definition of complications after hepatic resection. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Fontan-associated liver disease: Spectrum of US findings.

PubMed

Bae, Jung Min; Jeon, Tae Yeon; Kim, Jung Sun; Kim, Seokhwi; Hwang, Sook Min; Yoo, So-Young; Kim, Ji Hye

2016-04-01

To describe ultrasonography (US) findings of Fontan-associated liver disease (FALD) and to determine whether screening US examinations can identify FALD before biochemical hepatic dysfunction. This retrospective study included 55 patients who underwent Fontan procedure over a 20-year period. Hepatobiliary US findings (n=55), CT or MRI findings (n=19), biochemical hepatic function tests (n=49), and histopathological results (n=4) were analyzed. Images were reviewed focusing on the hepatic parenchymal changes, presence of focal lesions, and signs of portal hypertension. Hepatic parenchymal changes (either heterogeneous echotexture or surface nodularity) evident on US were present in 67% (37/55) and showed positive correlation with the Fontan duration. Hyper-echoic lesions were noted in 35% (19/55) and showed a predilection for multiplicity, small size, right lobe location, and irregular margin on high-frequency transducer. These lesions were not demonstrated by CT or MRI or by low-frequency transducer. Histopathological results of targeted biopsy for hyper-echoic lesions revealed lesser degree of patchy sinusoidal and portal fibrosis than seen in cases with surface nodularity. Abnormal parenchymal enhancement was commonly seen with CT or MRI in 63% (12/19) and hypervascular nodules in 21% (4/19). Most patients (82%, 40/49) showed normal biochemical hepatic function tests, despite the presence of hepatic parenchymal changes on imaging. The common US findings of FALD included heterogeneous parenchymal echotexture, surface nodularity, and hyper-echoic lesions. We suggest that hyper-echoic lesions without surface nodularity detected by high-frequency transducer may represent the early stage of fibrosis. US examination may be useful for identifying the progression of FALD before biochemical hepatic dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

PubMed

Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

2017-02-01

Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

[Abnormal hepatic function tests in pregnancy: causes and consequences].

PubMed

Nemesánszky, Elemér

2013-07-21

The well-known normal ranges of laboratory parameters are altered due to the broad spectrum of physiological changes as well as proinflammatory and procoagulant effects of pregnancy. Hepatic disorders of any aetiology can cause potential problems during gravidity. Most frequently toxic-effects, hepatotrop viruses (such as hepatitis B and C), metabolic syndrome and diseases with autoimmune background can be observed. When dealing with "pregnancy-specific hepatic syndromes", it is very important to consider the "timing-factors" of pathologic changes and deterioration of clinical pictures as well. Due to the progress in cholestasis management, early termination of pregnancy can be avoided in many cases. As the overlap is really broad between various hepatic disorders, a multidisciplinary cooperation of different sub-disciplines is emphasized in order to achieve proper diagnosis and curative measures at early phase.

Etiology, clinical features and outcome of fulminant hepatic failure in pregnancy.

PubMed

Brohi, Zahida Parveen; Sadaf, Aneela; Perveen, Uzma

2013-09-01

To determine the etiology, clinical features and outcome of fulminant hepatic failure in pregnancy. An observational hospital based study was conducted at Isra University hospital Hyderabad from 1st March 2009 to 28th February 2010. Total 1192 obstetric patients were admitted in obstetrics & gynaecology department during this period, of whom 52 were with Fulminant hepatic failure in pregnancy and were included in this study. A pre-designed structured proforma was used. All patients had clinical history and underwent a physical examination. Routine laboratory tests, liver function tests and viral serology were performed in all cases. All results were analyzed on statistical software SPSS version 11. Frequencies and percentages were calculated, the final outcome was recorded. Out of 52, 6 (11.5%) presented in the first trimester, 4 (7.6%) in the second trimester and 42 (80.7%) were in their 3rd trimester of pregnancy. Etiology of the disease was Hepatitis E in 28 (53.8%), Hepatitis B in 9 (17.3%), Hepatitis C in 7 (13.5%) HELLP syndrome in 7 (13.5%) and acute fatty liver of pregnancy in 1 (3.57%) case. Maternal mortality was 15 (28.8%) and foetal mortality was 40 (77%). Only 12 (23.1%) new born remained alive. Fulminant hepatic failure in pregnancy has very high foetal and maternal mortality which is mostly due to viral hepatitis E.

Qualifying and quantifying minimal hepatic encephalopathy.

PubMed

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin

2016-12-01

Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care-givers. It responds well to treatment with resolution of test abnormalities and the associated detrimental effects on quality of life, liver-related mortality and morbidity. Patients will only benefit in this way if they can be effectively diagnosed. Corporate efforts and consensus agreements are needed to develop effective diagnostic algorithms.

Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.

PubMed

Henkle, Emily; Lu, Mei; Rupp, Lora B; Boscarino, Joseph A; Vijayadeva, Vinutha; Schmidt, Mark A; Gordon, Stuart C

2015-02-15

Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Comparison of clinical and laboratory characteristics of viral hepatitis A and E in Montenegro].

PubMed

Terzić, Dragica; Mijović, Gordana; Dupanović, Brankica; Drasković, Nenad; Svirtlih, Neda

2010-01-01

Hepatitis E has many similarities in with hepatitis A concerning clinical picture, route of transmission and nonexistence of chronicity. Comparison of clinical and laboratory parameters of patients with hepatitis A and E to estimate characteristics of these diseases. Total of 54 patients divided into two groups was investigated: 27 had hepatitis A, others had hepatitis E. Detailed history past, clinical examination, liver function tests and ultrasonography of the upper abdomen, were done in all patients. Aetiology of viral hepatitis was investigated serologically by enzyme immunoassay (ELISA) using commercial kits for following viruses: Hepatitis A-E viruses, cytomegalovirus, and Epstein-Barr virus. Asymptomatic infections (29.6%) and clinical forms without jaundice (59.3%) were more frequent in patients with hepatitis E. Splenomegaly was found more frequent in patients with hepatitis A than in hepatitis E (66.7% vs. 33.3%). Patients with hepatitis E had significantly lower activity of aminotransferases than patients with hepatitis A. A significant increase of gamma-glutamyltranspeptidase was found in patients with hepatitis E (mean value: 120 IU/L). Our results are in concordance with other reports that hepatitis E virus infection is more common asymptomatic disease than hepatitis A. In addition, hepatocyte necrosis in hepatitis E is less extensive than in hepatitis A measured by the activity of aminotransferases. Contrary to that the value of gamma-glutamyltranspeptidase is more increased in hepatitis E than in hepatitis A without exact explanation so far: Viral hepatitis E and A have differences in some clinical features and laboratory parameters although both diseases principally have resolved without consequences after 6-8 weeks.

UCSF Center for HIV Information

MedlinePlus

... This patient educational brochure offers a primer on hepatitis C, including information on the liver's functions, laboratory tests, and treatment. HIV and Aging Toolkit Subscribe Subscribe to receive ...

Hepatitis Testing

MedlinePlus

... They include hepatitis A, hepatitis B, and hepatitis C. To diagnose hepatitis, your health care provider will ask you about your medical history and symptoms, do a physical exam, and order blood tests. There are blood tests ...

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

Levine, E.; Cook, L.T.; Grantham, J.J.

Hepatic CT findings were analyzed in 44 patients with autosomal-dominant polycystic kidney disease and were correlated with liver and renal function tests and liver, splenic, and renal CT volume measurements. CT showed many large liver cysts in 31.8% of patients, small liver cysts in 25%, and no liver cysts in 43.2%. Patients with many large cysts often showed increased liver volumes. There was no correlation between severity of liver involvement and extent of renal cystic disease as determined from urea nitrogen and creatinine levels and renal volumes. Liver function tests were normal except in two patients, one with a cholangiocarcinoma,more » which may have arisen from a cyst, and the other with an infected liver cyst and chronic active hepatitis. Accordingly, if liver function tests are abnormal, an attempt should be made to identify complications of polycystic liver disease such as tumor cyst infection, and biliary obstruction. CT is a useful method for detecting liver cysts and identifying patients at risk for these complications.« less

Acute hepatitis: a rare complication of Epstein-Barr virus (EBV) infection.

PubMed

Uluğ, Mehmet; Celen, Mustafa Kemal; Ayaz, Celal; Geyik, Mehmet Faruk; Hoşoğlu, Salih

2010-10-28

Infectious Mononucleosis (IM), a benign lymphoproliferative disease, is the best known clinical syndrome caused by Epstein-Barr Virus (EBV). It usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychological complications. In this report we describe a patient with acute hepatitis following EBV-IM in a previously healthy woman. A 26-year-old woman who presented with fever, generalized weakness, nausea, sore throat, yellowing of skin, and a generalized skin rash was admitted to our clinic. Tonsillar enlargement, pharyngeal erythema, palatal petechiae, lymphadenopathy, and jaundice were noted. Significant atypical lymphocytes ( > 10%) were seen on the peripheral blood smear. Liver function tests such as ALT: 303 U/L, AST: 172 U/L, ALP: 193 U/L and total bilirubin: 7.3 mg/dl were elevated. Serological tests for EBV infection were consistent with acute infection (EBV virus capsid antigen was reactive with IgM and IgG antibodies). The Monospot test was also positive. On the seventh day, liver function tests and bilirubin had risen to peak level and platelets were decreased. The patient was managed supportively and her critical condition improved and was finally stabilized. Although the prognosis for IM is very favorable, a variety of acute complications may occur.

Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids.

PubMed

Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, Hedwig S; Chen, Chen; Geijsen, Niels; Oosterhoff, Loes A; van Wolferen, Monique E; Pelaez, Nicolas; Fieten, Hille; Wubbolts, Richard W; Grinwis, Guy C; Chan, Jefferson; Huch, Meritxell; Vries, Robert R G; Clevers, Hans; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Schotanus, Baukje A

2015-11-10

The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Hepatic macrophage complement receptor clearance function following injury.

PubMed

Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

1986-03-01

Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

Evaluation of Hepatitis B Vaccination among Lichen Planus Patients.

PubMed

Balighi, K; Daneshpazhooh, M; Nasimi, M; Loloee, S; Asadi, A; Azizpour, A

2016-07-01

Lichen planus (LP) is an idiopathic chronic inflammatory mucocutaneous disease. Many reports in the literature have described hepatitis B vaccine as a predisposing factor for LP. This study was performed to determine the rate of previous vaccination against hepatitis B in LP patients. This was a cross sectional study on LP patients. Diagnosis of LP was confirmed by histological examination. Data were gathered by dermatology residents based on a checklist designed to guide their interview. Blood samples were tested for HBsAB titer, HBsAg, HCV Ab and liver function tests. One hundred & twenty four (124) patients entered the study. Females were 2.72 times more affected. The mean age of patients was 45.63 years (age range; 18-88). Forty-four (35.5%) patients had been vaccinated against hepatitis B. Lichen planus during the first six months of vaccination occurred in only one patient. Our findings bring into question the causative role of HBV vaccine in LP incidence in our population.

The efficacy of the Peginterferon treatment in chronic hepatitis HDV and compensate liver cirrhosis.

PubMed

Tugui, Letitia; Dumitru, M; Iacob, Speranta; Gheorghe, Liana; Preda, Carmen; Dinu, Ioana; Becheanu, G; Dumbrava, Mona; Nicolae, Ioana; Andrei, Adriana; Lupu, A; Diculescu, M

2014-01-01

To evaluate the efficiency of the treatment with Peginterferon alfa 2a 180 mcg/week, 48 weeks in patients with chronic hepatitis or compensated liver cirrhosis HDV and predictive factors of response to treatment. Prospective study that enrolled 50 patients with chronic hepatitis or compensated cirrhosis HDV between the 1st of January 2011 - 3st of December 2011. The diagnosis of chronic HDV infection was made based on the presence of detectable anti HDV IgG antibodies and HDV-RNA. Patients were evaluated at baseline by CBC, liver function tests, HBV profile, HDV RNA, and by liver biopsy/Fibrotest for evaluating fibrosis and necroinflammatory activity. At 24 weeks CBC (count blood cells), liver function tests, quantitative HBsAg and at 48 and 72 weeks biochemical tests, HDV RNA, HBV DNA, quantitative HBsAg, were performed. Adverse reactions to the treatment were recorded. SVR (sustained virologic response) was recorded in 12 patients (24%) and biochemical response in 28 patients (56%). SVR was correlated with low-grade fibrosis, age, the aminotransferase value and the value of HBsAg at the beginning of the treatment. In week 48 HDV RNA was undetectable in 20 patients (40%). The therapy was well tolerated, except two patients for whom the discontinuation of the treatment was decided for severe exacerbation of cytolysis, respectively hepatic decompensation. In a representative group of patients, the treatment with Peginterferon once again proves its efficacy in treating chronic HDV.

Hepatitis C: Information on Testing and Diagnosis

MedlinePlus

HEPATITIS C Information on Testing & Diagnosis What is Hepatitis C? Hepatitis C is a serious liver disease that results from infection with the Hepatitis C virus. Hepatitis C has been called a silent ...

The Prevalence of Hepatitis C Virus (HCV) among Lichen Planus Patients and Its Clinical Pattern at the University of Abuja Teaching Hospital (U.A.T.H), Gwagwalada, Abuja, Nigeria

PubMed Central

Bob, Ukonu Agwu; Augustine, Uhunmwangho

2012-01-01

Objective: The relationship between hepatitis C virus and Lichen Planus have been widely reported in the literature; although there are wide geographical variations in the reported prevalence of hepatitis C virus infection in patients with lichen planus. This study seeks to determine the prevalence of hepatitis C virus among lichen planus patients and its clinical morphological type in the University of Abuja Teaching Hospital, Gwagwalada Abuja, Nigeria. Materials/Methods: This study was conducted between January 2010 and December, 2011 at the out patients Dermatological unit of the department of medicine at the University of Abuja Teaching Hospital Gwagwalada Abuja, Nigeria. Consecutive patients who had body eruptions suspected to be lichen planus were recruited and histology done for confirmation. The control group included patients’ relations and some dermatology patients known to have low risk of hepatitis C virus infection and liver function tests done for both subjects and control after obtaining oral consent from them to participate in the study. Result: Anti- HCV antibodies were detected in nine cases (21.4%) and one case (3.3%) in the control group. This was statistically significant difference between the HCV antibody among the subject and control group (P<0.038). Hypertrophic lichen planus was the most frequent clinical type. Liver function test was not statistically significant among the subject and control group. Conclusion: Lichen planus and Hepatitis C virus appear to have a relationship and the prevalence rate was higher among the subject as compared to the control group in our environment. PMID:22980383

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

PubMed

Zaki, Maysaa El Sayed; Salama, Osama Saad; Mansour, Fathy Awaad; Hossein, Shaimaa

2008-06-01

Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.

In Vitro Hepatic Trans-Differentiation of Human Mesenchymal Stem Cells Using Sera from Congestive/Ischemic Liver during Cardiac Failure

PubMed Central

Bishi, Dillip Kumar; Mathapati, Santosh; Cherian, Kotturathu Mammen; Guhathakurta, Soma; Verma, Rama Shanker

2014-01-01

Cellular therapy for end-stage liver failures using human mesenchymal stem cells (hMSCs)-derived hepatocytes is a potential alternative to liver transplantation. Hepatic trans-differentiation of hMSCs is routinely accomplished by induction with commercially available recombinant growth factors, which is of limited clinical applications. In the present study, we have evaluated the potential of sera from cardiac-failure-associated congestive/ischemic liver patients for hepatic trans-differentiation of hMSCs. Results from such experiments were confirmed through morphological changes and expression of hepatocyte-specific markers at molecular and cellular level. Furthermore, the process of mesenchymal-to-epithelial transition during hepatic trans-differentiation of hMSCs was confirmed by elevated expression of E-Cadherin and down-regulation of Snail. The functionality of hMSCs-derived hepatocytes was validated by various liver function tests such as albumin synthesis, urea release, glycogen accumulation and presence of a drug inducible cytochrome P450 system. Based on these findings, we conclude that sera from congestive/ischemic liver during cardiac failure support a liver specific microenvironment for effective hepatic trans-differentiation of hMSCs in vitro. PMID:24642599

Phenotypic and in vivo functional characterization of immortalized human fetal liver cells.

PubMed

Patil, Pradeep B; Begum, Setara; Joshi, Meghnad; Kleman, Marika I; Olausson, Michael; Sumitran-Holgersson, Suchitra

2014-06-01

We report the establishment and characterization of immortalized human fetal liver progenitor cells by expression of the Simian virus 40 large T (SV40 LT) antigen. Well-characterized cells at various passages were transplanted into nude mice with acute liver injury and tested for functional capacity. The SV40LT antigen-immortalized fetal liver cells showed a morphology similar to primary cells. Cultured cells demonstrated stable phenotypic expression in various passages, of hepatic markers such as albumin, CK 8, CK18, transcription factors HNF-4α and HNF-1α and CYP3A/7. The cells did not stain for any of the tested cancer-associated markers. Albumin, HNF-4α and CYP3A7 expression was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry showed expression of some progenitor cell markers. In vivo study showed that the cells expressed both fetal and differentiated hepatocytes markers. Our study suggests new approaches to expand hepatic progenitor cells, analyze their fate in animal models aiming at cell therapy of hepatic diseases.

[Value of injection hepato-lymphography during percutaneous transhepatic cholangiography in patients with cholestasis].

PubMed

Sharipov, V Sh

2000-01-01

Injection hepatography (IH) was made in 278 patients with cholestasis to study the drainage function of the liver. In 208 cases. IH was performed as a test during percutaneous transhepatic cholangiography (PTHC). The hepatic lymph pathways were imaged in 167 (60%) patients. Images of the biliary tract were obtained in 245 (88.1%) patients with cholestasis, it being not dilated in 34 (12.2%) patients. The fact that hepatolymphography may be performed during PTHC as an independent test permits verification of hepatic lymph circulatory disorders that are an index of the rate of inflammation in the organ.

α-Antitrypsin Deficiency and Neonatal Hepatitis

PubMed Central

Porter, C. A.; Mowat, Alex P.; Cook, P. J. L.; Haynes, D. W. G.; Shilkin, K. B.; Williams, Roger

1972-01-01

Five out of 28 infants investigated in a regional survey of neonatal hepatitis were found to have genetically-determined deficiency of α1-antitrypsin (ZZ phenotype). The clinical course and pathological changes varied considerably. All five infants had an acute hepatitis-like illness, and although this subsided cirrhosis later developed in three cases. The remaining two infants had minimal abnormalities of the liver function tests at 12 and 18 months of age, and one had increased hepatic fibrosis. Australia antigen was found in the serum of three infants, and Australia antigen or antibody in one or both parents of these and of one further case whose serum was negative. It is suggested that the association of neonatal hepatitis with α1-antitrypsin deficiency may be commoner than previously realized and that Australia antigen acts as a trigger factor in these cases. ImagesFIG. 3FIG. 4FIG. 5FIG. 6 PMID:5069219

[Ketoconazole-induced hepatitis. Case report].

PubMed

Henning, H; Kasper, B; Lüders, C J

1983-12-01

Since Oct. 1981 a new systemic antifungal drug Ketoconazole is available in the Federal Republic of Germany that has proven effective even in severe cases with fungal infections. This case-study will call attention on a rare but important side effect, namely Ketoconazole induced hepatitis. As an acute icteric viral hepatitis, type Non-A-Non-B-hepatitis possibly misdiagnosed only a carefully compiled history of the recent intake of drugs points at the real cause of hepatitis. In our case-report we observed a considerable increase in serum enzymes, especially GOT, GPT and GLDH after a drug-challenge with two tablets. We recommend so-called liver functions tests 2 to 3 weeks after beginning of therapy and further-on in monthly intervals. Histologically at that time toxic hydropic changes of the liver cells and a mesenchymal reaction with portal and intralobular mainly eosinophilic infiltration could be established. The serum enzymes came to normal only after 12 weeks.

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling.

PubMed

Ning, Jia; Yang, Zhiying; Xie, Sheng; Sun, Yongliang; Yuan, Chun; Chen, Huijun

2017-10-01

To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast-enhanced MRI (DCE-MRI) using Gd-EOB-DTPA correlate with serum-based liver function tests, and compare the goodness of fit of the different output assumptions. A 6-min DCE-MRI protocol was performed in 38 patients. Four dual-input two-compartment models with different output assumptions and a published one-compartment model were used to calculate hepatic function parameters. The Akaike information criterion fitting error was used to evaluate the goodness of fit. Imaging-based hepatic function parameters were compared with blood chemistry using correlation with multiple comparison correction. The dual-input two-compartment model assuming venous flow equals arterial flow plus portal venous flow and no bile duct output better described the liver tissue enhancement with low fitting error and high correlation with blood chemistry. The relative uptake rate Kir derived from this model was found to be significantly correlated with direct bilirubin (r = -0.52, P = 0.015), prealbumin concentration (r = 0.58, P = 0.015), and prothrombin time (r = -0.51, P = 0.026). It is feasible to evaluate hepatic function by proper output assumptions. The relative uptake rate has the potential to serve as a biomarker of function. Magn Reson Med 78:1488-1495, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Impact of food on hepatic clearance of patients after endoscopic sphincterotomy.

PubMed

Chan, Hoi-Hung; Lai, Kwok-Hung; Lin, Chiun-Ku; Tsai, Wei-Lun; Peng, Nan-Jing; Hsu, Ping-I; Lo, Gin-Ho; Wei, Min-Ching; Wang, E-Ming; Chang, Hsueh-Wen

2009-01-01

The recurrence rate of common bile duct stones (CBDS) is around 3-21% after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to improve hepatic clearance in both patients with intact gallbladder and post-cholecystectomy after ES. This study tested the effects of different kinds of food on hepatic clearance by using quantitative cholescintigraphy (QC) in patients after ES. Forty-seven patients after ES with abnormal QC were enrolled in our study. Complete ablation of sphincter function was confirmed by sphincter of Oddi manometry. Fasting QC was done in every patient shortly after normalization of liver function, and then followed with low-fat and fatty-meal QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3 different levels of treatments (diets and fasting). Additionally, possible factors responsible for recurrent CBDS were investigated by means of logistic regression. Both fatty and low-fat meals could significantly improve hepatic clearance compared with fasting in most patients after ES. But the response to food types was individualized. All patients tolerated the meals well. There was no significant relationship between the recurrence of CBDS and sex, age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size, and improvement in hepatic clearance (> or = 5%) by food. Both fatty and low-fat meals improved hepatic clearance in most of the patients with CBDS after ES, but the response to meals was individualized. Therefore, there is no need to restrict the amount of fat intake for patients who have undergone ES.

Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.

PubMed

Shalev, Tamar; Aeed, Hussein; Sorin, Vladimir; Shahmurov, Mark; Didkovsky, Elena; Ilan, Yaron; Avni, Yona; Shirin, Haim

2010-06-01

Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate. OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

Toward preclinical predictive drug testing for metabolism and hepatotoxicity by using in vitro models derived from human embryonic stem cells and human cell lines - a report on the Vitrocellomics EU-project.

PubMed

Mandenius, Carl-Fredrik; Andersson, Tommy B; Alves, Paula M; Batzl-Hartmann, Christine; Björquist, Petter; Carrondo, Manuel J T; Chesne, Christophe; Coecke, Sandra; Edsbagge, Josefina; Fredriksson, J Magnus; Gerlach, Jörg C; Heinzle, Elmar; Ingelman-Sundberg, Magnus; Johansson, Inger; Küppers-Munther, Barbara; Müller-Vieira, Ursula; Noor, Fozia; Zeilinger, Katrin

2011-05-01

Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance. 2011 FRAME.

Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

PubMed

Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

2016-01-01

The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule out organic solvent-induced hepatitis.

Vaccinium bracteatum Thunb. Leaves' polysaccharide alleviates hepatic gluconeogenesis via the downregulation of miR-137.

PubMed

Qian, Hai-Feng; Li, Yan; Wang, Li

2017-11-01

Vaccinium bracteatum Thunb.(VBT) is a traditional Chinese herb that recorded has an effect of hypoglycemic. We previous discovered a dose-dependent anti-diabetic function of VBT. leaves' polysaccharide (VBTLP), but little is known about its underlying molecular mechanism. Therefore, we hypothesized that VBTLP would decrease hepatic gluconeogenesis to improve glucose metabolism in mice. To test this hypothesis, glucose tolerance test was performed to evaluate the effect of VBTLP on mice hepatic gluconeogenesis. Western blot and RT-PCR were performed to measure both in vivo and in vitro gene regulation under VBTLP treatment. Online bioinformatic analysis was performed to discover a target candidate, miR-137 of LKB1 and AMPK under VBTLP treatment, and the luciferase assay was conducted to validate it. Here we found that VBT. leaves' polysaccharide (VBTLP) decreased hepatic gluconeogenesis via activation of LKB1/AMPK axis in vivo and in vitro. Mechanistic studies reveal that miR-137 regulates hepatic glucose homeostasis by directly targeting AMPK and LKB1. Furthermore, we shown that VBTLP decreased hepatic miR-137 level, which might contribute to activation of LKB1/AMPK and downregulation of gluconeogenesis. Taken together, our study shown that the mechanisms might involve in VBTLP hypoglycemic effect, alleviates hepatic gluconeogenesis via the downregulation of miR-137. Our findings provide guidance in developing novel, safe and effective therapies for T2DM. Copyright © 2017. Published by Elsevier Masson SAS.

A fourth dimension in decision making in hepatology.

PubMed

Ilan, Yaron

2010-12-01

Today, the assessment of liver function in patients suffering from acute or chronic liver disease is based on liver biopsy and blood tests including synthetic function, liver enzymes and viral load, most of which provide only circumstantial evidence as to the degree of hepatic impairment. Most of these tests lack the degree of sensitivity to be useful for follow-up of these patients at the frequency that is needed for decision making in clinical hepatology. Accurate assessment of liver function is essential to determine both short- and long-term prognosis, and for making decisions about liver and non-liver surgery, TIPS, chemoembolization or radiofrequency ablation in patients with chronic liver disease. Liver function tests can serve as the basis for accurate decision-making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled (13) C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method for assessing liver function at the point-of-care. The (13) C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision-making. Our recent findings regarding the ability of point-of-care (13) C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders. © 2010 The Japan Society of Hepatology.

Improving the hepatitis cascade: assessing hepatitis testing and its management in primary health care in China.

PubMed

Wong, William C W; Lo, Ying-Ru; Jiang, Sunfang; Peng, Minghui; Zhu, Shanzhu; Kidd, Michael R; Wang, Xia-Chun; Chan, Po-Lin; Ong, Jason J

2018-05-08

The study aimed to decentralize hepatitis testing and management services to primary care in China. A nationwide representative provider survey amongst community health centres (CHCs) using randomized stratified sampling methods was conducted between September and December 2015. One hundred and eighty CHCs and frontline primary care practitioners from 20 cities across three administrative regions of Western, Central and Eastern China were invited to participate. One hundred and forty-nine clinicians-in-charge (79%), 1734 doctors and 1846 nurses participated (86%). Majority of CHCs (80%, 95% CI: 74-87) offered hepatitis B testing, but just over half (55%, 95% CI: 46-65) offered hepatitis C testing. The majority of doctors (87%) and nurses (85%) felt that there were benefits for providing hepatitis testing at CHCs. The major barriers for not offering hepatitis testing were lack of training (54%) and financial support (23%). Multivariate analysis showed that the major determinants for CHCs to offer hepatitis B and C testing were the number of nurses (AOR 1.1) and written policies for hepatitis B diagnosis (AOR 12.7-27.1), and for hepatitis B the availability of reproductive health service. Primary care providers in China could play a pivotal role in screening, diagnosing and treating millions of people with chronic hepatitis B and C in China.

Evaluation of a hepatitis B lay health worker intervention for Chinese Americans and Canadians.

PubMed

Taylor, Vicky M; Hislop, T Gregory; Tu, Shin-Ping; Teh, Chong; Acorda, Elizabeth; Yip, Mei-Po; Woodall, Erica; Yasui, Yutaka

2009-06-01

Hepatitis B testing is recommended for immigrants from countries where hepatitis B infection is endemic. However, only about one-half of Chinese in North America have received hepatitis B testing. We conducted a randomized controlled trial to evaluate the effectiveness of a hepatitis B lay health worker intervention for Chinese Americans/Canadians. Four hundred and sixty individuals who had never been tested for hepatitis B were identified from community-based surveys of Chinese conducted in Seattle, Washington, and Vancouver, British Columbia. These individuals were randomly assigned to receive a hepatitis B lay health worker intervention or a direct mailing of physical activity educational materials. Follow-up surveys were completed 6 months after randomization. Self-reported hepatitis B testing was verified through medical records review. A total of 319 individuals responded to the follow-up survey (69% response rate). Medical records data verified hepatitis B testing since randomization for 9 (6%) of the 142 experimental group participants and 3 (2%) of the 177 control group participants (P = 0.04). At follow-up, a higher proportion of individuals in the experimental arm than individuals in the control arm knew that hepatitis B can be spread by razors (P < 0.001) and during sexual intercourse (P = 0.07). Our findings suggest that lay health worker interventions can impact hepatitis B-related knowledge. However, our hepatitis B lay health worker intervention had a very limited impact on hepatitis B testing completion. Future research should evaluate other intervention approaches to improving hepatitis B testing rates among Chinese in North America.

Evaluation of a Hepatitis B Lay Health Worker Intervention for Chinese Americans and Canadians

PubMed Central

Taylor, Vicky M.; Hislop, T. Gregory; Tu, Shin-Ping; Teh, Chong; Acorda, Elizabeth; Yip, Mei-Po; Woodall, Erica; Yasui, Yutaka

2009-01-01

Hepatitis B testing is recommended for immigrants from countries where hepatitis B infection is endemic. However, only about one-half of Chinese in North America have received hepatitis B testing. We conducted a randomized controlled trial to evaluate the effectiveness of a hepatitis B lay health worker intervention for Chinese Americans/Canadians. Four hundred and sixty individuals who had never been tested for hepatitis B were identified from community-based surveys of Chinese conducted in Seattle, Washington, and Vancouver, British Columbia. These individuals were randomly assigned to receive a hepatitis B lay health worker intervention or a direct mailing of physical activity educational materials. Follow-up surveys were completed six months after randomization. Self-reported hepatitis B testing was verified through medical records review. A total of 319 individuals responded to the follow-up survey (69% response rate). Medical records data verified hepatitis B testing since randomization for nine (6%) of the 142 experimental group participants and three (2%) of the 177 control group participants (p=0.04). At follow-up, a higher proportion of individuals in the experimental arm than individuals in the control arm knew that hepatitis B can be spread by razors (p<0.001) and during sexual intercourse (p=0.07). Our findings suggest that lay health worker interventions can impact hepatitis B-related knowledge. However, our hepatitis B lay health worker intervention had a very limited impact on hepatitis B testing completion. Future research should evaluate other intervention approaches to improving hepatitis B testing rates among Chinese in North America. PMID:19127416

Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma

PubMed Central

Derambure, Céline; Coulouarn, Cédric; Caillot, Frédérique; Daveau, Romain; Hiron, Martine; Scotte, Michel; François, Arnaud; Duclos, Celia; Goria, Odile; Gueudin, Marie; Cavard, Catherine; Terris, Benoit; Daveau, Maryvonne; Salier, Jean-Philippe

2008-01-01

AIM: To look at a comprehensive picture of etiology-dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS: With a liver-oriented microarray, transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism, 12; hepatitis C, 10) and 5 controls. Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set (12 + 10) and a test set (6 + 7). RESULTS: A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism) or -2 (hepatitis C) and ontology indicated a predominant inflammatory response (alcoholism) or changes in cell cycle regulation, transcription factors and interferon responsiveness (hepatitis C). A stringent selection of 23 transcripts whose differences between etiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis. These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION: Etiology-specific abnormalities (chromosome preference; differences in transcriptomes and related functions) have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C. This may open novel avenues for differential therapies in this disease. PMID:18350606

Extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without malignancy: a case report.

PubMed

Yoon, Young-Min; Kang, Da-Yeong; Kim, Da-Young; Seo, Jun-Won; Lim, Hyun-Jong; Lee, Hee-Jeong; Park, Sang-Gon

2016-06-01

Alpha-fetoprotein is produced by a variety of tumors such as hepatocellular carcinoma, hepatoblastoma, and germ cell tumors of the ovary and testes. However, we present a case of significantly elevated serum alpha-fetoprotein without evidence of malignant disease in a patient who is a carrier of chronic hepatitis B. A 60-year-old Korean man presented with markedly increased alpha-fetoprotein (2350 ng/mL; normal <5 ng/mL). Various diagnostic evaluations, including computed tomography of the abdomen and thorax and ultrasonography of the abdomen and testes, showed liver cirrhosis and mild splenomegaly; however, no mass was detected in the liver, testes, or other organs scanned. The laboratory findings showed elevated liver function, positivity for hepatitis B e antigen, and a marked increase in hepatitis B virus deoxyribonucleic acid copy number (>7 × 105 IU/mL). Our patient was diagnosed with acute exacerbation of chronic hepatitis B, and we presumed that this condition might be related to extremely elevated alpha-fetoprotein. When our patient was treated with entecavir, the serum alpha-fetoprotein level immediately decreased, in parallel with the hepatitis B virus deoxyribonucleic acid copy number. We report a rare case of extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without any malignancy, and a decrease in this tumor marker simultaneous with a decrease in hepatitis B virus deoxyribonucleic acid copy number on entecavir treatment. This case report is important due to the rarity of the case; furthermore, it provides details of a diagnostic process for a variety of benign diseases and malignant tumors that should be considered in patients with elevated alpha-fetoprotein. Thus, we present a case report, along with a review, that will be helpful for diagnosis and treatment of patients with elevated alpha-fetoprotein.

KDR (VEGFR2) identifies a conserved human and murine hepatic progenitor and instructs early liver development

PubMed Central

Goldman, Orit; Han, Songyan; Sourrisseau, Marion; Dziedzic, Noelle; Hamou, Wissam; Corneo, Barbara; D’Souza, Sunita; Sato, Thomas; Kotton, Darrell N.; Bissig, Karl-Dimiter; Kalir, Tamara; Jacobs, Adam; Evans, Todd; Evans, Matthew J.; Gouon-Evans, Valerie

2013-01-01

SUMMARY Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like (hepatic) cells from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR, but when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR- hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells, and to support non-cell-autonomously the functional maturation of co-cultured KDR- hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts and subsequently adult hepatocytes and cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors, and a functional receptor instructing early liver development. PMID:23746980

Serum bile acid concentrations in dairy cattle with hepatic lipidosis.

PubMed

Garry, F B; Fettman, M J; Curtis, C R; Smith, J A

1994-01-01

This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition.

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves.

PubMed

Marinò, M; Morabito, E; Altea, M A; Ambrogini, E; Oliveri, F; Brunetto, M R; Pollina, L E; Campani, D; Vitti, P; Bartalena, L; Pincheral, A; Marcocci, C

2005-03-01

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.

Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.

PubMed

Eisenbach, Christoph; Longerich, Thomas; Fickenscher, Helmut; Schalasta, Gunnar; Stremmel, Wolfgang; Encke, Jens

2006-01-01

We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.

Abnormal scintigraphic evolution in AA hepatic amyloidosis

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

Lomena, F.; Rosello, R.; Pons, F.

1988-03-01

A patient with AA amyloidosis secondary to ankylosing spondylitis showed intense liver uptake of Tc-99m MDP on bone imaging. The biopsy showed hepatic amyloid deposition. A repeat bone scan with Tc-99m MDP 1 year later was negative, although the clinical signs and liver function tests of the patient had not changed. A mechanism might exist, other than the affinity of amyloid to calcium, which would explain the extraosseous uptake of pyrophosphates and diphosphonates in organs and soft tissues affected by systemic amyloidosis.

Silymarin-loaded Eudragit(®) RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats.

PubMed

Younis, N; Shaheen, Mohamed A; Abdallah, Marwa H

2016-07-01

Some nano-formulations of silymarin (SM), a drug commonly used for liver diseases, were developed to overcome its poor solubility and poor bioavailability; antifibrotic effect of these formulations has not been tested yet. In this study we aimed to formulate and evaluate silymarin-loaded Eudragit(®) RS100 nanoparticles (SMnps) and to test the capability of SMnps to reverse an established fibrosis model. SMnps were prepared by solvent evaporation and nano-precipitation techniques. The influence of drug:polymer ratio, concentration of surfactant in the aqueous phase on particle size, drug entrapment efficiency (EE) % and in vitro drug releases were investigated. For in vivo evaluation, bile duct ligated (BDL)-rats were treated with either SM or SMnps every other day (125mg/kg) orally for 3 weeks started 3 weeks after BDL. Liver function tests, oxidative stress and fibrosis/fibrogenesis process were evaluated using biochemical and histopathological techniques. The formulation No (F4) of SMnps showed an average particle size of 632.28±12.15nm, a drug EE% of 89.47±1.65% and released the drug in a prolonged manner over 24h. The prepared SMnps were nearly spherical with smooth surfaces. In BDL-rats, treatments with either SM or SMnps corrected liver function and oxidative stress. Only SMnps was able to reverse the induced fibrosis; SMnps significantly decreased serum tumor necrosis factor- α (TNF-α), serum transforming growth factor- β1 (TGF-β1), hepatic hydroxyproline and downregulated the hepatic expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and cytokeratin-19 (CK-19), whilst increased hepatic hepatocytes growth factor (HGF) and upregulated the hepatic expression of matrix metalloproteinase-2 (MMP-2) and increased MMP-2/TIMP-1 ratio at mRNA level. Livers of rats treated with SMnps showed very little collagen in ECM and restored hepatic architecture as compared to either BDL rats or rats treated with SM. Formulation of silymarin as nanoparticles improved its ability to resolve cholestasis-induced liver fibrosis by restoring hepatic regenerative capabilities. Therefore, formulation of SMnps may represent a step forward in the field of anti-fibrotic drug development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interaction between duck hepatitis virus and DDT in ducks

USGS Publications Warehouse

Ragland, W.L.; Friend, Milton; Trainer, D.O.; Sladek, N.E.

1971-01-01

Injections of duck hepatitis virus (DVH) decreased, and exposure to DDT increased, hepatic microsomal mixed-function oxidase activity. Injection of DFV prior to exposure to DDT did not prevent stimulation of hepatic microsomal mixed-function oxidase activity by DDT and may have enhanced it.

Survey of programmatic experiences and challenges in delivery of hepatitis B and C testing in low- and middle-income countries.

PubMed

Ishizaki, Azumi; Bouscaillou, Julie; Luhmann, Niklas; Liu, Stephanie; Chua, Raissa; Walsh, Nick; Hess, Sarah; Ivanova, Elena; Roberts, Teri; Easterbrook, Philippa

2017-11-01

There have been few reports on programmatic experience of viral hepatitis testing and treatment in resource-limited settings. To inform the development of the 2017 World Health Organization (WHO) viral hepatitis testing guidance and in particular the feasibility of proposed recommendations, we undertook a survey across a range of organisations engaged with hepatitis testing in low- and middle-income countries (LMICs). Our objective was to describe current hepatitis B and C testing practices across a range of settings in different countries, as well as key barriers or challenges encountered and proposed solutions to promote testing scale-up. Hepatitis testing programmes in predominantly LMICs were identified from the WHO Global Hepatitis Programme contacts database and through WHO regional offices, and invited to participate. The survey comprised a six-part structured questionnaire: general programme information, description of hepatitis testing, treatment and care services, budget and funding, data on programme outcomes, and perceptions on key barriers encountered and strategies to address these. We interviewed 22 viral hepatitis testing programmes from 19 different countries. Nine were from the African region; 6 from the Western Pacific; 4 from South-East Asia; and 3 from Eastern Europe. All but four of the programmes were based in LMICs, and 10 (45.5%) were supported by non-governmental or international organizations. All but two programmes undertook targeted testing of specific affected populations such as people living with HIV, people who inject drugs, sex workers, health care workers, and pregnant women. Only two programmes focussed on routine testing in the general population. The majority of programmes were testing in hospital-based or other health facilities, particularly HIV clinics, and community-based testing was limited. Nucleic acid testing (NAT) for confirmation of HCV and HBV viraemia was available in only 30% and 18% of programmes, respectively. Around a third of programmes required some patient co-payment for diagnosis. The most commonly identified challenges in scale-up of hepatitis testing were: limited community awareness about viral hepatitis; lack of facilities or services for hepatitis testing; no access to low cost treatment, particularly for HCV; absence of national guidance and policies; no dedicated budget for hepatitis; and lack of trained health care and laboratory workers. At this early stage in the global scale-up of testing for viral hepatitis, there is a wide variation in testing practices and approaches across different programmes. There remains limited access to NAT to confirm viraemia, and patient self-payment for testing and treatment is common. There was consensus from implementing organizations that scale-up of testing will require increased community awareness, health care worker training, development of national strategies and guidelines, and improved access to low cost NAT virological testing.

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

PubMed

Tutau, Federico; Rodríguez-Ortigosa, Carlos; Puche, Juan Enrique; Juanarena, Nerea; Monreal, Iñigo; García Fernández, María; Clavijo, Encarna; Castilla, Alberto; Castilla-Cortázar, Inma

2009-01-01

Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

Incidence and characteristics of hepatitis E virus infection in children in Assiut, Upper Egypt.

PubMed

Hasan, Gamal; Assiri, Asaad; Marzuuk, Naglaa; Daef, Enas; Abdelwahab, Sayed; Ahmed, Ahmed; Mohamad, Ismail; Al-Eyadhy, Ayman; Alhaboob, Ali; Temsah, Mohamad-Hani

2016-10-01

Objective To describe the characteristics of hepatitis E virus (HEV) infection in a cohort of children from Upper Egypt using data from a large multicentre prospective study of acute viral hepatitis (AVH). Methods Data from subjects aged 2-18 years with AVH or close contacts of those with AVH found to have asymptomatic AVH were included in the analysis. Information concerning medical history, clinical examination, liver function tests and screening for hepatotropic viruses was recorded and analysed. Results A total of 123 patients (73 boys, 50 girls) were included in the analysis. Of these, 33 (26.8%) had HEV infection, 17 (13.8%) had hepatitis A virus infection, 10 (8.1%) had hepatitis B virus infection, 14 (11.4%) had cytomegalovirus hepatitis, five (4.1%) had autoimmune hepatitis, 11 (8.9%) had hepatitis due to mixed viral infections and 33 (26.8%) had non A-E hepatitis. Overall, 38 (30.9%) had infection with HEV. HEV infection was significantly higher among those using underground wells as a water source compared with tap water. Liver enzymes were significantly raised in patients with non-HEV infection compared with those with HEV infection. Conclusions HEV is a significant cause of AVH among children in Upper Egypt. Contamination of drinking water appears to be a major source of infection. Screening for HEV should be considered in all Egyptian children with AVH.

Hepatic p38α regulates gluconeogenesis by suppressing AMPK.

PubMed

Jing, Yanyan; Liu, Wei; Cao, Hongchao; Zhang, Duo; Yao, Xuan; Zhang, Shengjie; Xia, Hongfeng; Li, Dan; Wang, Yu-cheng; Yan, Jun; Hui, Lijian; Ying, Hao

2015-06-01

It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38α in gluconeogenesis during fasting by applying a loss-of-function genetic approach. We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38α in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38α (p38α-AF) and the constitutively active mitogen-activated protein kinase 6, respectively. Adenoviral dominant-negative form of AMP-activated protein kinase α (DN-AMPKα) was employed to test our proposed model. Mice lacking hepatic p38α exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38α did not result in an alteration in CREB phosphorylation, but led to an increase in AMPKα phosphorylation. Adenoviral DN-AMPKα could abolish the effect of p38α-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor β-activated kinase 1 decreased the AMPKα phosphorylation induced by p38α-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKα phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38α-AF treatment ameliorated hyperglycemia in diabetic mice. Our study provides evidence that hepatic p38α functions as a negative regulator of AMPK signaling in maintaining gluconeogenesis, dysregulation of this regulatory network contributes to unrestrained gluconeogenesis in diabetes, and hepatic p38α could be a drug target for hyperglycemia. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

PubMed

Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

2016-12-01

Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

Lidocaine/monoethylglycinexylidide test, galactose elimination test, and sorbitol elimination test for metabolic assessment of liver cell bioreactors.

PubMed

Gerlach, Jörg C; Brayfield, Candace; Puhl, Gero; Borneman, Reiner; Müller, Christian; Schmelzer, Eva; Zeilinger, Katrin

2010-06-01

Various metabolic tests were compared for the performance characterization of a liver cell bioreactor as a routine function assessment of cultures in a standby for patient application in clinical studies. Everyday quality assessment (QA) is essential to ensure a continuous level of cellular functional capacity in the development of hepatic progenitor cell expansion systems providing cells for regenerative medicine research; it is also of interest to meet safety requirements in bioartificial extracorporeal liver support systems under clinical evaluation. Quality criteria for the description of bioreactor cultures were developed using primary porcine liver cells as a model. Porcine liver cells isolated by collagenase perfusion with an average of 3 x 10(9) primary cells were used in 39 bioreactors for culture periods up to 33 days. Measurements of monoethylglycinexylidide synthesis and elimination of lidocaine, galactose elimination, and sorbitol elimination proved to be useful for routine QA of primary liver cell cultures. We demonstrate two methods for dispensing test substances, bolus administration and continuous, steady-state administration. Bolus test data were grouped in Standard, Therapy, Infection/Contamination, and Cell-free control groups. Statistical analyses show significant differences among all groups for every test substance. Post hoc comparisons indicated significant differences between Standard and Cell-free groups for all elimination parameters. For continuous tests, results were categorized according to number of culture days and time-dependent changes were analyzed. Continuous administration enables a better view of culture health and the time dependency of cellular function, whereas bolus administration is more flexible. Both procedures can be used to define cell function. Assessment of cellular function and bioreactor quality can contribute significantly to the quality of experimental or clinical studies in the field of hepatic bioreactor development.

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

PubMed

Solomon, Marc M; Schechter, Mauro; Liu, Albert Y; McMahan, Vanessa M; Guanira, Juan V; Hance, Robert J; Chariyalertsak, Suwat; Mayer, Kenneth H; Grant, Robert M

2016-03-01

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Long-term culture of human liver tissue with advanced hepatic functions.

PubMed

Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

2017-06-02

A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

Prospective evaluation of FibroTest®, FibroMeter®, and HepaScore® for staging liver fibrosis in chronic hepatitis B: comparison with hepatitis C.

PubMed

Leroy, Vincent; Sturm, Nathalie; Faure, Patrice; Trocme, Candice; Marlu, Alice; Hilleret, Marie-Noëlle; Morel, Françoise; Zarski, Jean-Pierre

2014-07-01

Fibrosis blood tests have been validated in chronic hepatitis C. Their diagnostic accuracy is less documented in hepatitis B. The aim of this study was to describe the diagnostic performance of FibroTest®, FibroMeter®, and HepaScore® for liver fibrosis in hepatitis B compared to hepatitis C. 510 patients mono-infected with hepatitis B or C and matched on fibrosis stage were included. Blood tests were performed the day of the liver biopsy. Histological lesions were staged according to METAVIR. Fibrosis stages were distributed as followed: F0 n=76, F1 n=192, F2 n=132, F3 n=54, F4 n=56. Overall diagnostic performance of blood tests were similar between hepatitis B and C with AUROC ranging from 0.75 to 0.84 for significant fibrosis, 0.82 to 0.85 for extensive fibrosis and 0.84 to 0.87 for cirrhosis. Optimal cut-offs were consistently lower in hepatitis B compared to hepatitis C, especially for the diagnosis of extensive fibrosis and cirrhosis, with decreased sensitivity and negative predictive values. More hepatitis B than C patients with F ⩾3 were underestimated: FibroTest®: 47% vs. 26%, FibroMeter®: 24% vs. 6%, HepaScore®: 41% vs. 24%, p<0.01. Multivariate analysis showed that hepatitis B (0R 3.4, 95% CI 1.2-19.2, p<0.02) and low γGT (OR 7.3, 95% CI 2.0-27.0, p<0.003) were associated with fibrosis underestimation. Overall the diagnostic performance of blood tests is similar in hepatitis B and C. The risk of underestimating significant fibrosis and cirrhosis is however greater in hepatitis B and cannot be entirely corrected by the use of more stringent cut-offs. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes

PubMed Central

Klein, R; Zanger, U M; Berg, T; Hopf, U; Berg, P A

1999-01-01

Anti-liver-kidney microsome antibodies (anti-LKM) occur in autoimmune hepatitis (AIH) type II and in a subset of patients with hepatitis C. Anti-LKM1 in AIH are directed against cytochrome P4502D6 (CYP2D6), but conflicting data exist concerning the specificity of anti-LKM in hepatitis C. The aim of this study was to evaluate binding specificities of anti-LKM antibodies in both diseases using novel test antigens as well as their inhibitory capacity on CYP2D6 enzyme activity. Sera from 22 patients with AIH type II and 17 patients with hepatitis C being anti-LKM-positive in the immunofluorescence test were investigated for binding to native recombinant CYP2D6 and liver microsomes by ELISA and immunoblotting, and to synthetic peptides covering the region 254–339 (254–273, 257–269, 270–294, 291–310, 307–324, 321–339, 373–389) as well as the novel peptide 196–218 by ELISA. Furthermore, all sera were tested for inhibition of CYP2D6-dependent bufuralol 1′-hydroxylase activity. Twenty of the 22 AIH type II sera (91%) and nine of the 17 hepatitis C sera (53%) were positive for CYP2D6 by ELISA and/or immunoblotting. The previously described major peptide epitope comprising CYP2D6 amino acids 257–269 was recognized by 16 of the 22 AIH sera but by only one hepatitis C serum. A further epitope, 196–218, could be defined for the first time as another immunodominant epitope for AIH because it was recognized by 15 of the 22 AIH (68%) but only three of the 17 hepatitis C sera (18%). With the exception of the peptide 254–273, the other peptides showed no significant reactivity. Analysing the inhibitory properties of anti-LKM antibodies it emerged that 95% of AIH sera and 88% of hepatitis C sera inhibited enzyme function. These data indicate that anti-LKM antibodies in AIH and hepatitis C react with CYP2D6, as shown by their inhibitory activity, and that besides the known epitope 257–269 a further immunodominant epitope exists on CYP2D6 which is recognized by sera from patients with AIH II but hardly by sera from patients with hepatitis C. PMID:10540193

CDC Vital Signs: Hepatitis C: Testing Baby Boomers Saves Lives

MedlinePlus

... 6 MB] Read the MMWR Science Clips Hepatitis C Testing baby boomers saves lives Recommend on Facebook ... boomers got infected before the dangers of hepatitis C were well known. Anyone can get hepatitis C, ...

The clinical features of chronic hepatitis C are not affected by the coexistence of hepatitis B virus DNA in patients negative for hepatitis B surface antigen.

PubMed

Nirei, K; Kaneko, M; Moriyama, M; Arakawa, Y

2000-01-01

Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain reaction (PCR). The purpose of the present study was to clarify the clinical characteristics of patients with chronic hepatitis C who are negative for serum HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic hepatitis C who were negative for serum HBsAg and 119 blood donors who served as healthy controls. Serum samples were tested for the presence of HBV DNA by the nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic hepatitis C patients and in none (0%) of the 119 blood donors. Among the hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative for all HBV-associated markers and in 57.1% of those who were positive for one or more HBV-associated marker. The HBV DNA-positive rate among those in each F stage did not significantly differ. The liver function parameters of the HBV DNA-positive and the HBV DNA-negative chronic hepatitis C patients did not significantly differ. These results suggest that hepatitis C virus is frequently coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection in blood donors is low. However, it is considered that HBsAg-negative HBV infection does not modify the blood biochemical features of chronic hepatitis C. Copyright 2000 S. Karger AG, Basel

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Frey, Kirk A.

2013-08-01

Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF)more » images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.« less

Predictive models for regional hepatic function based on 99mTc-IDA SPECT and local radiation dose for physiologic adaptive radiation therapy.

PubMed

Wang, Hesheng; Feng, Mary; Frey, Kirk A; Ten Haken, Randall K; Lawrence, Theodore S; Cao, Yue

2013-08-01

High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage. Published by Elsevier Inc.

Preoperative galactose elimination capacity predicts complications and survival after hepatic resection.

PubMed

Redaelli, Claudio A; Dufour, Jean-François; Wagner, Markus; Schilling, Martin; Hüsler, Jürg; Krähenbühl, Lukas; Büchler, Markus W; Reichen, Jürg

2002-01-01

To analyze a single center's 6-year experience with 258 consecutive patients undergoing major hepatic resection for primary or secondary malignancy of the liver, and to examine the predictive value of preoperative liver function assessment. Despite the substantial improvements in diagnostic and surgical techniques that have made liver surgery a safer procedure, careful patient selection remains mandatory to achieve good results in patients with hepatic tumors. In this prospective study, 258 patients undergoing hepatic resection were enrolled: 111 for metastases, 78 for hepatocellular carcinoma (HCC), 21 for cholangiocellular carcinoma, and 48 for other primary hepatic tumors. One hundred fifty-eight patients underwent segment-oriented liver resection, including hemihepatectomies, and 100 had subsegmental resections. Thirty-two clinical and biochemical parameters were analyzed, including liver function assessment by the galactose elimination capacity (GEC) test, a measure of hepatic functional reserve, to predict postoperative (60-day) rates of death and complications and long-term survival. All variables were determined within 5 days before surgery. Data were subjected to univariate and multivariate analysis for two patient subgroups (HCC and non-HCC). The cutoffs for GEC in both groups were predefined. Long-term survival (>60 days) was subjected to Kaplan-Meier analysis and the Cox proportional hazard model. In the entire group of 258 patients, a GEC less than 6 mg/min/kg was the only preoperative biochemical parameter that predicted postoperative complications and death by univariate and stepwise regression analysis. A GEC of more than 6 mg/min/kg was also significantly associated with longer survival. This predictive value could also be shown in the subgroup of 180 patients with tumors other than HCC. In the subgroup of 78 patients with HCC, a GEC less than 4 mg/min/kg predicted postoperative complications and death by univariate and stepwise regression analysis. Further, a GEC of more than 4 mg/min/kg was also associated with longer survival. This prospective study establishes the preoperative determination of the hepatic reserve by GEC as a strong independent and valuable predictor for short- and long-term outcome in patients with primary and secondary hepatic tumors undergoing resection.

Preoperative Galactose Elimination Capacity Predicts Complications and Survival After Hepatic Resection

PubMed Central

Redaelli, Claudio A.; Dufour, Jean-François; Wagner, Markus; Schilling, Martin; Hüsler, Jürg; Krähenbühl, Lukas; Büchler, Markus W.; Reichen, Jürg

2002-01-01

Objective To analyze a single center’s 6-year experience with 258 consecutive patients undergoing major hepatic resection for primary or secondary malignancy of the liver, and to examine the predictive value of preoperative liver function assessment. Summary Background Data Despite the substantial improvements in diagnostic and surgical techniques that have made liver surgery a safer procedure, careful patient selection remains mandatory to achieve good results in patients with hepatic tumors. Methods In this prospective study, 258 patients undergoing hepatic resection were enrolled: 111 for metastases, 78 for hepatocellular carcinoma (HCC), 21 for cholangiocellular carcinoma, and 48 for other primary hepatic tumors. One hundred fifty-eight patients underwent segment-oriented liver resection, including hemihepatectomies, and 100 had subsegmental resections. Thirty-two clinical and biochemical parameters were analyzed, including liver function assessment by the galactose elimination capacity (GEC) test, a measure of hepatic functional reserve, to predict postoperative (60-day) rates of death and complications and long-term survival. All variables were determined within 5 days before surgery. Data were subjected to univariate and multivariate analysis for two patient subgroups (HCC and non-HCC). The cutoffs for GEC in both groups were predefined. Long-term survival (>60 days) was subjected to Kaplan-Meier analysis and the Cox proportional hazard model. Results In the entire group of 258 patients, a GEC less than 6 mg/min/kg was the only preoperative biochemical parameter that predicted postoperative complications and death by univariate and stepwise regression analysis. A GEC of more than 6 mg/min/kg was also significantly associated with longer survival. This predictive value could also be shown in the subgroup of 180 patients with tumors other than HCC. In the subgroup of 78 patients with HCC, a GEC less than 4 mg/min/kg predicted postoperative complications and death by univariate and stepwise regression analysis. Further, a GEC of more than 4 mg/min/kg was also associated with longer survival. Conclusions This prospective study establishes the preoperative determination of the hepatic reserve by GEC as a strong independent and valuable predictor for short- and long-term outcome in patients with primary and secondary hepatic tumors undergoing resection. PMID:11753045

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C.

PubMed

Valcour, Victor G; Rubin, Leah H; Obasi, Mary U; Maki, Pauline M; Peters, Marion G; Levin, Susanna; Crystal, Howard A; Young, Mary A; Mack, Wendy J; Cohen, Mardge H; Pierce, Christopher B; Adimora, Adaora A; Tien, Phyllis C

2016-07-01

Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

Hepatitis B & C and HIV

MedlinePlus

... HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis Testing Day ... Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People with HIV infection in the ...

Transverse myelitis caused by hepatitis E: previously undescribed in adults

PubMed Central

Sarkar, Pamela; Morgan, Catherine; Ijaz, Samreen

2015-01-01

We report the case of a 62-year-old Caucasian woman who was admitted with urinary retention and lower limb paraesthesia following a week's prodromal illness of headache and malaise. Liver function tests showed a picture of acute hepatocellular dysfunction. She developed reduced lower limb power, brisk reflexes, extensor plantars, a sensory level at T8 and reduced anal sphincter tone, establishing a clinical diagnosis of transverse myelitis. A spinal MRI showed no evidence of cauda equina or spinal cord compression. Cerebrospinal fluid (CSF) analysis showed raised protein and raised white cell count. Hepatitis E IgM and IgG were positive and hepatitis E virus was found in her CSF. She was treated with methylprednisolone and is slowly recovering with physiotherapy. PMID:26150621

The Oral Minimal Model Method

PubMed Central

Cobelli, Claudio; Dalla Man, Chiara; Toffolo, Gianna; Basu, Rita; Vella, Adrian; Rizza, Robert

2014-01-01

The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism. PMID:24651807

Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma.

PubMed

Ishikawa, Toru

2012-05-07

The prognosis of hepatocellular carcinoma (HCC) depends on tumor extension as well as hepatic function. Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC; the Child-Pugh classification system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease, using serum albumin level to achieve accurate assessment of the status of protein metabolism. However, insufficient attention has been given to the status of amino acid (AA) metabolism in chronic liver disease and HCC. Fischer's ratio is the molar ratio of branched-chain AAs (BCAAs: leucine, valine, isoleucine) to aromatic AAs (phenylalanine, tyrosine) and is important for assessing liver metabolism, hepatic functional reserve and the severity of liver dysfunction. Although this ratio is difficult to determine in clinical situations, BCAAs/tyrosine molar concentration ratio (BTR) has been proposed as a simpler substitute. BTR correlates with various liver function examinations, including markers of hepatic fibrosis, hepatic blood flow and hepatocyte function, and can thus be considered as reflecting the degree of hepatic impairment. This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

Hepatitis Associated Aplastic Anemia: A review

PubMed Central

2011-01-01

Hepatitis-associated aplastic anemia (HAAA) is an uncommon but distinct variant of aplastic anemia in which pancytopenia appears two to three months after an acute attack of hepatitis. HAAA occurs most frequently in young male children and is lethal if leave untreated. The etiology of this syndrome is proposed to be attributed to various hepatitis and non hepatitis viruses. Several hepatitis viruses such as HAV, HBV, HCV, HDV, HEV and HGV have been associated with this set of symptoms. Viruses other than the hepatitis viruses such as parvovirus B19, Cytomegalovirus, Epstein bar virus, Transfusion Transmitted virus (TTV) and non-A-E hepatitis virus (unknown viruses) has also been documented to develop the syndrome. Considerable evidences including the clinical features, severe imbalance of the T cell immune system and effective response to immunosuppressive therapy strongly present HAAA as an immune mediated mechanism. However, no association of HAAA has been found with blood transfusions, drugs and toxins. Besides hepatitis and non hepatitis viruses and immunopathogenesis phenomenon as causative agents of the disorder, telomerase mutation, a genetic factor has also been predisposed for the development of aplastic anemia. Diagnosis includes clinical manifestations, blood profiling, viral serological markers testing, immune functioning and bone marrow hypocellularity examination. Patients presenting the features of HAAA have been mostly treated with bone marrow or hematopoietic cell transplantation from HLA matched donor, and if not available then by immunosuppressive therapy. New therapeutic approaches involve the administration of steroids especially the glucocorticoids to augment the immunosuppressive therapy response. Pancytopenia following an episode of acute hepatitis response better to hematopoietic cell transplantation than immunosuppressive therapy. PMID:21352606

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

PubMed Central

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

2018-01-01

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

[Observation on the therapeutic effect of Lamivudin on chronic hepatitis B].

PubMed

Wen, Xiaofeng; Li, Xuemei; Xie, Houyu; Chen, Nian; Zeng, Wenfeng; Ru, Haiyun; Cui, Xaioping; Tang, Zhongmin

2002-12-01

To observe the therapeutic effect of Lamivudine on controlling hepatitis B virus DNA replication. The liver disease patients were divided into two groups, the treated group (n=64) was given Lamivudine 100 mg once a day for one year and was additionally given liver protection drugs according to their liver function, while the control group (n=30) was given common liver protection drugs. The blood routine test, liver function and the viral markers were detected at defined times. The results showed that after one year treatment of chronic hepatitis B with Lamivudine, the recovery rate of ALT was 90.7%, the negative conversion rate of HBV DNA was 73.1% showing a significant difference as compared with the control group (P<0.05). The negative seroconversion rate of HBeAg was 50%, HBeAg/anti HBe changing rate was 38.2%, that had no significant different as compared with the control group (P<0.05). The percentage for disease relapse and second elevation of ALT was 3.1% in therapeutic group that was significantly different from that of the control group (P<0.05). Two cases with severe hepatitis in the treated group were all alive. Lamivudine could effectively control HBV DNA replication, making ALT normal, it also could decrease the relapse rate of chronic hepatitis B and raise the survival rate of the patients with liver disease.

Minimal hepatic encephalopathy matters in daily life

PubMed Central

Bajaj, Jasmohan S

2008-01-01

Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients, estimated as high as 80% of the population tested. It is characterized by a specific, complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Although named “minimal”, minimal hepatic encephalopathy (MHE) can have a far-reaching impact on quality of life, ability to function in daily life and progression to overt hepatic encephalopathy. Importantly, MHE has a profound negative impact on the ability to drive a car and may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored in routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of care in patients with MHE. The lack of specific signs and symptoms, the preserved communication skills and lack of insight make MHE a difficult condition to diagnose. Diagnostic strategies for MHE abound, but are usually limited by financial, normative or time constraints. Recent studies into the inhibitory control and critical flicker frequency tests are encouraging since these tests can increase the rates of MHE diagnosis without requiring a psychologist. Although testing for MHE and subsequent therapy is not standard of care at this time, it is important to consider this in cirrhotics in order to improve their ability to live their life to the fullest. PMID:18595126

Randomized Controlled Trial of Hepatic Portal Reocclusion as a New Option for Detecting Bile Leakage during Hepatic Resection.

PubMed

Ma, Jun-Yong; Li, Xi-Feng; Yan, Zhen-Lin; Hasan, Mohammad Mahboob; Wang, Kui; Wang, Yu; Wang, Wen-Chao; Yan, Qiang; Shen, Feng; Shi, Le-Hua; Zhang, Xiao-Feng

2017-01-01

To explore the possibility and feasibility of hepatic portal reocclusion for detecting bile leakage during hepatectomy. Data were prospectively collected from 200 patients who underwent hepatectomy alone for removal of various benign or malignant tumors between March 2014 and November 2014. The surgical procedure used a conventional method for all patients, and one additional step (hepatic portal reocclusion) was included in group B. The postoperative outcomes of the patients in group A (subjected to the traditional procedure) and group B (subjected to hepatic portal reocclusion) were compared during the same period, and the incidence rates of postoperative bile leakage and other complications in the 2 groups were also analyzed. The incidence of postoperative bile leakage in group B was significantly lower than that in group A (1.0 vs. 9.2%, p = 0.009), although no significant differences in postoperative indicators of liver dysfunction and other complications were observed between the 2 groups (p > 0.05). Hepatic portal reocclusion effectively reduced the incidence of bile leakage compared to the traditional procedure, without significantly affecting liver function. Therefore, this method might be an alternative to other tests for bile leakage. © 2016 S. Karger AG, Basel.

Seroprevalence of HDV infection in HBsAg positive population in Ismailia, Egypt.

PubMed

Gomaa, Nahed I M; Metwally, Lobna A; Nemr, Nader; Younis, Soha

2013-01-01

Hepatitis D virus (HDV) is a defective RNA virus that needs hepatitis B surface antigen (HBsAg) from HBV for transmission. HDV can lead to fulminant hepatitis and the progression of chronic liver damage in patients with chronic hepatitis B. The aim of this study was to determine the seroprevalence of HDV among HBsAg positive individuals in Ismailia, Egypt. Serum samples were collected from 170 HBsAg positive healthy individuals from Suez Canal University blood bank over a one year period. All of them were seeking blood donation and found to be HBsAg positive during viral hepatitis screening workups which is routinely done prior to donation. Serum samples were screened for IgG antibodies to hepatitis delta virus (HDV) using enzyme-linked immunosorbent assay (ELISA) method. Anti-HDV antibodies were detected in 8 (4.7%) individuals aged from 29-43 years. Liver function tests showed that serum ALT and AST levels were elevated in the HBsAglanti-HDV positive cases. It is concluded that the rate of HDV infection in Ismailia is high and further investigation is needed to validate the findings and raise awareness about the risk of dual HBV and HDV infection.

Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system.

PubMed

Choi, Young-Jun; Kim, Hyemin; Kim, Ji-Woo; Yoon, Seokjoo; Park, Han-Jin

2018-05-01

The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism. Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (p < 0.001). Moreover, hepatocyte-specific functions, including albumin secretion and bile canaliculi formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of CES1 and BCHE, which encode hepatic esterases (p < 0.001). The enhanced activities of these hepatic esterases were confirmed by the cholinesterase activity assay and the increased susceptibility of HLCs to oseltamivir, which is metabolized by CES1. 3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.

A practice-changing culture method relying on shaking substantially increases mitochondrial energy metabolism and functionality of human liver cell lines.

PubMed

Adam, Aziza A A; van der Mark, Vincent A; Donkers, Joanne M; Wildenberg, Manon E; Oude Elferink, Ronald P J; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

2018-01-01

Practice-changing culturing techniques of hepatocytes are highly required to increase their differentiation. Previously, we found that human liver cell lines HepaRG and C3A acquire higher functionality and increased mitochondrial biogenesis when cultured in the AMC-Bioartificial liver (BAL). Dynamic medium flow (DMF) is one of the major contributors to this stimulatory effect. Recently, we found that DMF-culturing by shaking of HepaRG monolayers resulted in higher mitochondrial biogenesis. Here we further investigated the effect of DMF-culturing on energy metabolism and hepatic functionality of HepaRG and C3A monolayers. HepaRG and C3A DMF-monolayers were incubated with orbital shaking at 60 rpm during the differentiation phase, while control monolayers were maintained statically. Subsequently, energy metabolism and hepatic functionality were compared between static and DMF-cultures. DMF-culturing of HepaRG cells substantially increased hepatic differentiation; transcript levels of hepatic structural genes and hepatic transcription regulators were increased up to 15-fold (Cytochrome P450 3A4) and nuclear translocation of hepatic transcription factor CEBPα was stimulated. Accordingly, hepatic functions were positively affected, including ammonia elimination, urea production, bile acid production, and CYP3A4 activity. DMF-culturing shifted energy metabolism from aerobic glycolysis towards oxidative phosphorylation, as indicated by a decline in lactate production and glucose consumption, and an increase in oxygen consumption. Similarly, DMF-culturing increased mitochondrial energy metabolism and hepatic functionality of C3A cells. In conclusion, simple shaking of monolayer cultures substantially improves mitochondrial energy metabolism and hepatic differentiation of human liver cell lines. This practice-changing culture method may prove to prolong the in-vitro maintenance of primary hepatocytes and increase hepatic differentiation of stem cells.

Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

PubMed

Abdel-Rahman, Manal K

2011-07-07

The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels.

Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

PubMed Central

2011-01-01

Background and aims The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Methods and results Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. Conclusion This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels PMID:21736706

21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

PubMed

Brown, Jennifer; Plummer, Ruth; Bauer, Todd M; Anthony, Stephen; Sarantopoulos, John; De Vos, Filip; White, Mike; Schupp, Marco; Ou, Ying; Vaishampayan, Ulka

2017-01-01

Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m 2 doses. The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC 0-last , respectively (27 mg/m 2 dose); increases at the 56 mg/m 2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

21 CFR 660.4 - Potency test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.4 Potency test. To be satisfactory for release, each filling of Antibody to Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Surface Antigen Panel and shall be sufficiently potent...

21 CFR 660.4 - Potency test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.4 Potency test. To be satisfactory for release, each filling of Antibody to Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Surface Antigen Panel and shall be sufficiently potent...

21 CFR 660.43 - Potency test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.43 Potency test. To be satisfactory for release, each filling of Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Antiserum Panel and shall be sufficiently potent to be able to detect the...

21 CFR 660.43 - Potency test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.43 Potency test. To be satisfactory for release, each filling of Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Antiserum Panel and shall be sufficiently potent to be able to detect the...

21 CFR 660.4 - Potency test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.4 Potency test. To be satisfactory for release, each filling of Antibody to Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Surface Antigen Panel and shall be sufficiently potent...

21 CFR 660.43 - Potency test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.43 Potency test. To be satisfactory for release, each filling of Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Antiserum Panel and shall be sufficiently potent to be able to detect the...

21 CFR 660.4 - Potency test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.4 Potency test. To be satisfactory for release, each filling of Antibody to Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Surface Antigen Panel and shall be sufficiently potent...

21 CFR 660.43 - Potency test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.43 Potency test. To be satisfactory for release, each filling of Hepatitis B Surface Antigen shall be tested against the Reference Hepatitis B Antiserum Panel and shall be sufficiently potent to be able to detect the...

Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis.

PubMed

Mehta, Minal B; Shewale, Swapnil V; Sequeira, Raymond N; Millar, John S; Hand, Nicholas J; Rader, Daniel J

2017-06-23

Maintenance of whole-body glucose homeostasis is critical to glycemic function. Genetic variants mapping to chromosome 8p23.1 in genome-wide association studies have been linked to glycemic traits in humans. The gene of known function closest to the mapped region, PPP1R3B (protein phosphatase 1 regulatory subunit 3B), encodes a protein (G L ) that regulates glycogen metabolism in the liver. We therefore sought to test the hypothesis that hepatic PPP1R3B is associated with glycemic traits. We generated mice with either liver-specific deletion ( Ppp1r3b Δ hep ) or liver-specific overexpression of Ppp1r3b The Ppp1r3b deletion significantly reduced glycogen synthase protein abundance, and the remaining protein was predominantly phosphorylated and inactive. As a consequence, glucose incorporation into hepatic glycogen was significantly impaired, total hepatic glycogen content was substantially decreased, and mice lacking hepatic Ppp1r3b had lower fasting plasma glucose than controls. The concomitant loss of liver glycogen impaired whole-body glucose homeostasis and increased hepatic expression of glycolytic enzymes in Ppp1r3b Δ hep mice relative to controls in the postprandial state. Eight hours of fasting significantly increased the expression of two critical gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, above the levels in control livers. Conversely, the liver-specific overexpression of Ppp1r3b enhanced hepatic glycogen storage above that of controls and, as a result, delayed the onset of fasting-induced hypoglycemia. Moreover, mice overexpressing hepatic Ppp1r3b upon long-term fasting (12-36 h) were protected from blood ketone-body accumulation, unlike control and Ppp1r3b Δ hep mice. These findings indicate a major role for Ppp1r3b in regulating hepatic glycogen stores and whole-body glucose/energy homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Hepatitis C: Questions to Ask Your Doctor about Treatment

MedlinePlus

... Care » Viral Hepatitis » Veterans and Public Home » Hepatitis C » Questions to Ask Your Doctor about Treatment Viral ... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment ...

Simple and robust diagnosis of early, small and AFP-negative primary hepatic carcinomas: an integrative approach of serum fluorescence and conventional blood tests.

PubMed

Wang, Ting; Zhang, Kun-He; Hu, Piao-Ping; Huang, Zeng-Yong; Zhang, Pan; Wan, Qin-Si; Huang, De-Qiang; Lv, Nong-Hua

2016-09-27

The diagnosis of early, small and alpha-fetoprotein (AFP)-negative primary hepatic carcinomas (PHCs) remains a significant challenge. We developed a simple and robust approach to noninvasively detect these PHCs. A rapid, high-throughput and single-tube method was firstly developed to measure serum autofluorescence and cell-free DNA (cfDNA)-related fluorescence using a real-time PCR system, and both types of serum fluorescence were measured and routine laboratory data were collected in 1229 subjects, including 353 PHC patients, 331 liver cirrhosis (LC) patients, 213 chronic hepatitis (CH) patients and 332 normal controls (NC). The results showed that fluorescence indicators of PHC differed from those of NC, CH and LC to various extents, and all of them were not associated with age, gender, or AFP level. The logistic regression models established with the fluorescence indicators alone and combined with AFP, hepatic function tests and blood cell analyses were valuable for distinguishing early, small, AFP-negative and all PHC from LC, CH, NC and all non-PHC, with areas under the receiver operating characteristic curves 0.857-0.993 and diagnostic accuracies 80.2-97.7%. Conclusively, serum autofluorescence and cfDNA-related fluorescence are able to be rapidly and simultaneously measured by our simple method and valuable for diagnosing early, small and AFP-negative PHCs, especially integrating with AFP and conventional blood tests.

Hyperthyroidism and Jaundice

PubMed Central

Bal, CS; Chawla, Madhavi

2010-01-01

Development of hyperbilirubinemia, concurrent or subsequent to hyperthyroidism, can be due to thyrotoxicosis per se, or due to drug treatment of hyperthyroidism. Other rare conditions: autoimmune thyroid disease, or causes unrelated to hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, or as a side effect of certain medications. In this article, we review these causes of co-existent hyperthyroidism and jaundice. We also highlight the changes to be expected while interpreting thyroid function tests vis-a-vis liver function tests in this subgroup of patients. PMID:21713219

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

PubMed

Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Acute drug induced hepatitis secondary to a weight loss product purchased over the internet

PubMed Central

Joshi, Deepak; Cross, Tim JS; Wong, Voi Shim

2007-01-01

Background Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L). A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean), purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. Conclusion This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis. PMID:17597525

Hepatitis C: Mental Health

MedlinePlus

... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

Hepatitis C: Questions to Ask Your Doctor about Your Diagnosis

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Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986-90) and in the nationwide immunisation program.

PubMed

Peto, Thomas J; Mendy, Maimuma E; Lowe, Yamundow; Webb, Emily L; Whittle, Hilton C; Hall, Andrew J

2014-01-07

Gambian infants were not routinely vaccinated against hepatitis B virus (HBV) before 1986. During 1986-90 the Gambia Hepatitis Intervention Study (GHIS) allocated 125,000 infants, by area, to vaccination or not and thereafter all infants were offered the vaccine through the nationwide immunisation programme. We report HBV serology from samples of GHIS vaccinees and unvaccinated controls, and from children born later. During 2007-08, 2670 young adults born during the GHIS (1986-90) were recruited from 80 randomly selected villages and four townships. Only 28% (753/2670) could be definitively linked to their infant HBV vaccination records (255 fully vaccinated, 23 partially vaccinated [1-2 doses], 475 not vaccinated). All were tested for current HBV infection (HBV surface antigen [HBsAg]) and, if HBsAg-negative, evidence of past infection (HBV core-protein antibody [anti-HBc]). HBsAg-positive samples (each with two age- and sex-matched HBsAg-negative samples) underwent liver function tests. In addition, 4613 children born since nationwide vaccination (in 1990-2007) were tested for HBsAg. Statistical analyses ignore clustering. Comparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy. Among unvaccinated individuals, the prevalence was higher in males (p = 0.015) and in rural areas (p = 0.009), but adjustment for this did not affect estimated vaccine efficacy. Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001. Chronic active hepatitis was not common: the proportion of HBsAg-positive subjects with abnormal liver function tests (ALT > 2 ULN) was 4.1%, compared with 0.2% in those HBsAg-negative. The prevalence of antibodies to hepatitis C virus was low (0.5%, 13/2592). In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990-97, and 0.3% (9/35150) in those born between 1998-2007. Infant HBV vaccination achieves substantial protection against chronic carriage in early adulthood, even though approximately a quarter of vaccinated young adults have been infected. This protection persists past the potential onset of sexual activity, reinforcing previous GHIS findings of protection during childhood and suggesting no need for a booster dose. Nationwide infant HBV vaccination is controlling chronic infection remarkably effectively.

Cellular receptor traffic is essential for productive duck hepatitis B virus infection.

PubMed

Breiner, K M; Schaller, H

2000-03-01

We have investigated the mechanism of duck hepatitis B virus (DHBV) entry into susceptible primary duck hepatocytes (PDHs), using mutants of carboxypeptidase D (gp180), a transmembrane protein shown to act as the primary cellular receptor for avian hepatitis B virus uptake. The variant proteins were abundantly produced from recombinant adenoviruses and tested for the potential to functionally outcompete the endogenous wild-type receptor. Overexpression of wild-type gp180 significantly enhanced the efficiency of DHBV infection in PDHs but did not affect ongoing DHBV replication, an observation further supporting gp180 receptor function. A gp180 mutant deficient for endocytosis abolished DHBV infection, indicating endocytosis to be the route of hepadnaviral entry. With further gp180 variants, carrying mutations in the cytoplasmic domain and characterized by an accelerated turnover, the ability of gp180 to function as a DHBV receptor was found to depend on a wild-type-like sorting phenotype which largely avoids transport toward the endolysosomal compartment. Based on these data, we propose a model in which a distinct intracellular DHBV traffic to the endosome, but not beyond, is a prerequisite for completion of viral entry, i.e., for fusion and capsid release. Furthermore, the deletion of the two enzymatically active carboxypeptidase domains of gp180 did not lead to a loss of receptor function.

Relation of Insulin Resistance and Liver Fibrosis Progression in Patients with Chronic Hepatitis C Virus Infection

PubMed Central

Mohamed, Hassan R; Abdel-Azziz, Mohamed Yaqoot; Zalata, Kkaled Refaat; Abdel-Razik, Ahmed M M

2009-01-01

Background: Hepatitis C virus (HCV) infection can predispose to the development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicate that diabetes may be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. The aim of the study is to determine the prevalence of insulin resistance in non diabetic patients with chronic hepatitis C and its relation to liver fibrosis. Methods: Thirty eight patients with chronic liver diseases. They subdivided into 2 groups; chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Age and sex matched 12 healthy subjects as control group. All subjects were subjected to Careful history and copmlete examination with stress upon symptoms and signs of chronic liver diseases. Investigations include liver function tests; viral markers (Anti HCV antibodies & PCR for HCV). Serum fasting glucose; serum fasting insulin; homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound. Results: No correlation between viral load and hepatic fibrosis in HCV infected patients. Liver fibrosis is considerably higher among HCV patients with elevated serum transaminase levels. Insulin resistance is present in HCV infected cases compared with control group and it is positively correlated with liver fibrosis. Conclusion: The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non diabetic patients with chronic HCV. Follow up of hyperinsulinemia by serial measurement of HOMA test in non diabetic HCV infected patients may be a biochemical indicator for progression of liver fibrosis. PMID:21475535

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Hepatic functions of GLP-1 and its based drugs: current disputes and perspectives.

PubMed

Jin, Tianru; Weng, Jianping

2016-09-01

GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed "degradation" products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important. Postprandial GLP-1 release contributes to insulin secretion, which represses hepatic glucose production. This indirect effect of GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to determine whether GLP-1 and its analogs possess direct metabolic effects on the liver, as the determination of the existence of direct hepatic effects may advance the therapeutic theory and clinical practice on subjects with insulin resistance. Furthermore, recent investigations on the metabolic beneficial effects of previously assumed "degradation" products of GLP-1 in the liver and elsewhere, including GLP-128-36 and GLP-132-36, have drawn intensive attention. Such investigations may further improve the development and the usage of GLP-1-based drugs. Here, we have reviewed the current advancement and the existing controversies on the exploration of direct hepatic functions of GLP-1 and presented our perspectives that the direct hepatic metabolic effects of GLP-1 could be a GLP-1 receptor-independent event involving Wnt signaling pathway activation. Copyright © 2016 the American Physiological Society.

Reconstitution of hepatic tissue architectures from fetal liver cells obtained from a three-dimensional culture with a rotating wall vessel bioreactor.

PubMed

Ishikawa, Momotaro; Sekine, Keisuke; Okamura, Ai; Zheng, Yun-wen; Ueno, Yasuharu; Koike, Naoto; Tanaka, Junzo; Taniguchi, Hideki

2011-06-01

Reconstitution of tissue architecture in vitro is important because it enables researchers to investigate the interactions and mutual relationships between cells and cellular signals involved in the three-dimensional (3D) construction of tissues. To date, in vitro methods for producing tissues with highly ordered structure and high levels of function have met with limited success although a variety of 3D culture systems have been investigated. In this study, we reconstituted functional hepatic tissue including mature hepatocyte and blood vessel-like structures accompanied with bile duct-like structures from E15.5 fetal liver cells, which contained more hepatic stem/progenitor cells comparing with neonatal liver cells. The culture was performed in a simulated microgravity environment produced by a rotating wall vessel (RWV) bioreactor. The hepatocytes in the reconstituted 3D tissue were found to be capable of producing albumin and storing glycogen. Additionally, bile canaliculi between hepatocytes, characteristics of adult hepatocyte in vivo were also formed. Apart from this, bile duct structure secreting mucin was shown to form complicated tubular branches. Furthermore, gene expression analysis by semi-quantitative RT-PCR revealed the elevated levels of mature hepatocyte markers as well as genes with the hepatic function. With RWV culture system, we could produce functionally reconstituted liver tissue and this might be useful in pharmaceutical industry including drug screening and testing and other applications such as an alternative approach to experimental animals. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Enhancement of Programmed Death Ligand 2 on Hepatitis C Virus Infected Hepatocytes by Calcineurin Inhibitors

PubMed Central

Koike, Kazuko; Takaki, Akinobu; Yagi, Takahito; Iwasaki, Yoshiaki; Yasunaka, Tetsuya; Sadamori, Hiroshi; Shinoura, Susumu; Umeda, Yuzo; Yoshida, Ryuichi; Sato, Daisuke; Nobuoka, Daisuke; Utsumi, Masashi; Miyake, Yasuhiro; Ikeda, Fusao; Shiraha, Hidenori; Fujiwara, Toshiyoshi; Yamamoto, Kazuhide

2015-01-01

Background Post orthotopic liver transplantation (OLT) viral hepatitis is an immunological condition where immune cells induce hepatitis during conditions of immune-suppression. The immune-regulatory programmed death-1 (PD-1)/PD-ligand 1 system is acknowledged to play important roles in immune-mediated diseases. However, the PD-1/PD-L2 interaction is not well characterized, with PD-L2 also exhibiting an immunostimulatory function. We hypothesized that this atypical molecule could affect the recurrence of post-OLT hepatitis. To test this hypothesis, we conducted immunohistochemical staining analysis and in vitro analysis of PD-L2. Methods The expression of PD-L2 was evaluated in liver biopsy specimens from patients with chronic hepatitis B (n = 15), post-OLT hepatitis B (n = 8), chronic hepatitis C (n = 48), and post-OLT hepatitis C (CH-C-OLT) (n = 14). The effect of calcineurin inhibitors (CNIs) and hepatitis C virus (HCV) on PD-L2 expression was investigated in hepatoma cell lines. Results The PD-L2 was highly expressed on CH-C-OLT hepatocytes. Treatment of hepatoma cell lines with CNIs resulted in increased PD-L2 expression, especially in combination with HCV core or NS3 protein. Transfection of cell lines with PD-L2 containing plasmid resulted in high intercellular adhesion molecule-1 (ICAM-1) expression, which might enhance hepatitis activity. Conclusions The PD-L2 is highly expressed on CH-C-OLT hepatocytes, whereas HCV proteins, in combination with CNIs, induce high expression of PD-L2 resulting in elevated expression of ICAM-1. These findings demonstrate the effect of CNIs on inducing PD-L2 and subsequent ICAM-1 expression, effects that may produce inflammatory cell infiltration in post-OLT hepatitis C. PMID:25675203

Metabolic profile of liver damage in non-cirrhotic virus C and autoimmune hepatitis: A proton decoupled 31P-MRS study.

PubMed

Hakkarainen, Antti; Puustinen, Lauri; Kivisaari, Reetta; Boyd, Sonja; Nieminen, Urpo; Arkkila, Perttu; Lundbom, Nina

2017-05-01

To study liver 31 P MRS, histology, transient elastography, and liver function tests in patients with virus C hepatitis (HCV) or autoimmune hepatitis (AIH) to test the hypothesis that 31 P MR metabolic profile of these diseases differ. 25 patients with HCV (n=12) or AIH (n=13) underwent proton decoupled 31 P MRS spectroscopy performed on a 3.0T MR imager. Intensities of phosphomonoesters (PME) of phosphoethanolamine (PE) and phosphocholine (PC), phosphodiesters (PDE) of glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC), and γ, α and β resonances of adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide phosphate (NADPH) were determined. Liver stiffness was measured by transient elastography. Inflammation and fibrosis were staged according to METAVIR from biopsy samples. Activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALT) and thromboplastin time (TT) were determined from serum samples. PME had a stronger correlation with AST (z=1.73, p=0.04) and ALT (z=1.77, p=0.04) in HCV than in AIH patients. PME, PME/PDE, PE/GPE correlated positively and PDE negatively with inflammatory activity. PE, PC and PME correlated positively with liver function tests. 31 P-MRS suggests a more serious liver damage in HCV than in AIH with similar histopathological findings. 31 P-MRS is more sensitive in detecting inflammation than fibrosis in the liver. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

PubMed

Christenson, W R; Becker, B D; Wahle, B S; Moore, K D; Dass, P D; Lake, S G; Van Goethem, D L; Stuart, B P; Sangha, G K; Thyssen, J H

1996-02-01

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Evaluation of the Pharmacokinetics and Tolerance of Allopurinol Riboside in Human Volunteers.

DTIC Science & Technology

1984-08-06

hepatitis B "e" antigen. In addition, a mononucleosis screen was performed on serum. Urine and blood (buffy coat) were cultured for cytomegalovirus (CMV...study. His enzyme levels returned to norma, in two weeks, and remained normal one week thereafter. The following laboratory tests for infectious ...hepatitis were negative: hepatitis B surface antigen and antibody, hepatitis B core antibody, hepatitis A antibody, mononucleosis spot test, VDRL

75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor Deferral... Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus... Acid Test (NAT) and Hepatitis C Virus (HCV) NAT, on testing individual samples or pooled samples from...

Validity of injecting drug users' self report of hepatitis A, B, and C.

PubMed

Schlicting, Erin G; Johnson, Mark E; Brems, Christiane; Wells, Rebecca S; Fisher, Dennis G; Reynolds, Grace

2003-01-01

To test the validity of drug users self-reports of diseases associated with drug use, in this case hepatitis A, B, and C. Injecting drug users (n = 653) were recruited and asked whether they had been diagnosed previously with hepatitis A, B, and/or C. These self-report data were compared to total hepatitis A antibody, hepatitis B core antibody, and hepatitis C antibody seromarkers as a means of determining the validity of the self-reported information. Anchorage, Alaska. Criteria for inclusion included being at least 18-years old; testing positive on urinalysis for cocaine metabolites, amphetamine, or morphine; having visible signs of injection (track marks). Serological testing for hepatitis A, B, and C. Findings indicate high specificity, low sensitivity, and low kappa coefficients for all three self-report measures. Subgroup analyses revealed significant differences in sensitivity associated with previous substance abuse treatment experience for hepatitis B self-report and with gender for hepatitis C self-report. Given the low sensitivity, the validity of drug users, self-reported information on hepatitis should be considered with caution.

Costs of a public health model to increase receipt of hepatitis-related services for persons with mental illness.

PubMed

Slade, Eric P; Rosenberg, Stanley; Dixon, Lisa B; Goldberg, Richard W; Wolford, George L; Himelhoch, Seth; Tapscott, Stephanie

2013-02-01

This study examined the costs and impact on receipt of hepatitis and HIV testing and hepatitis immunization services of a public health intervention model that was designed for use by persons with serious mental illness and co-occurring substance use disorders. Between 2006 and 2008, a random sample of 202 nonelderly, predominantly African-American males with a psychotic or major depressive disorder and a co-occurring substance use disorder was recruited at four community mental health outpatient programs in a large metropolitan area. Participants were randomly assigned at each site to enhanced treatment as usual (N=97), including education about blood-borne diseases and referrals for testing and vaccinations, or to an experimental intervention (N=105) that provided on-site infectious disease education, screening of risk level, pretest counseling, testing for HIV and hepatitis B and C, vaccination for hepatitis A and B, and personalized risk-reduction counseling. The authors compared the two study groups to assess the average costs of improving hepatitis and HIV testing and hepatitis A and B vaccination in this population. The average cost per participant was $423 for the intervention and $24 for the comparison condition (t=52.7, df=201, p<.001). The costs per additional person tested was $706 for hepatitis C, $776 for hepatitis B, and $3,630 for HIV, and the cost per additional person vaccinated for hepatitis was $561. Delivery of hepatitis and HIV public health services to persons with serious mental illness in outpatient mental health settings can be as cost-effective as similar interventions for other at-risk populations.

Synthetic peptides for the immunodiagnosis of hepatitis A virus infection.

PubMed

Gauna, A; Losada, S; Lorenzo, M; Bermúdez, H; Toledo, M; Pérez, H; Chacón, E; Noya, O

2015-12-01

VP1, VP2 and VP3 molecules of hepatitis A virus are exposed capsid proteins that have shown to be antigenic and are used for diagnosis in recombinant-antigen commercial kits. In this study, we developed a sequence analysis in order to predict diagnostic peptide epitopes, followed by their spot synthesis on functionalized cellulose paper (Pepscan). This paper with synthetic peptides was tested against a sera pool of hepatitis A patients. Two peptide sequences, that have shown an antigenic recognition, were selected for greater scale synthesis on resin. A dimeric form of one of these peptides (IMT-1996), located in the C-Terminus region of protein VP1, was antigenic with a recognition frequency of 87-100% of anti-IgG antibodies and 100% of anti-IgM antibodies employing the immunological assays MABA and ELISA. We propose peptide IMT-1996, with less than twenty residues, as a cheaper alternative for prevalence studies and diagnosis of hepatitis A infection. Copyright © 2015 Elsevier B.V. All rights reserved.

[Mechanisms of spontaneous hypoglycaemia in the adult (author's transl)].

PubMed

Lubetzki, J; Duprey, J; Guillausseau, P J

1979-06-01

Hypoglycaemia increases hepatic glucose output; insulin release is suppressed and the secretion of counter regulatory hormones enhanced. Catecholamines and glucagon seem to play a major role. The brain energy content is initially preserved, but the neuronal activity exhibits a 40-60 % decrease. Neither cerebral blood flow, nor oxygen consumption are altered. In addition to glucose, other substrates are metabolized. Cerebral edema may occur. An insulin-storage defect seems to be the main abnormality in insulinoma beta cell function. The most accurate biological tests are the insulin/glucose ratio, stimulation tests and suppression tests such as fasting and insulin-induced hypoglycaemia. Ectopic release of ACTH, HCG, HLP, glucagon or gastrin, is observed in some malignant insulinomas. When inconclusive, classic localising procedures may be effected by selective venous-blood sampling. Hypoglycaemia of extra-pancreatic tumors results from glucose hyperconsumption and decreases in glucose hepatic output, lipolysis and ketogenesis, related to secretion of insulin-like peptides NSILAs or NSILAp. Rare cases of hypoglycaemia related to insulin auto-antibodies of unknown origin have been reported. Alcoholic hypoglycemia results from diminished hepatic glycogen content, alcohol dehydrogenase pathway blockade, reduction of gluconeogenesis defect in the alcohol catabolic catalase pathway and enhancement of peripheral glucose consumption.

The burden of minimal hepatic encephalopathy: from diagnosis to therapeutic strategies

PubMed Central

Ridola, Lorenzo; Cardinale, Vincenzo; Riggio, Oliviero

2018-01-01

Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). It affects the performance of psychometric tests focused on attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients. By being related to falls, an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life and their socioeconomic status. MHE is detected in clinically asymptomatic patients using appropriate psychometric tests and neurophysiological methods that highlight neuropsychological alterations, such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency-evoked cognitive potentials, and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment, including non-absorbable disaccharides, poorly absorbable antibiotics such as rifaximin, probiotics and branched-chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, the treatment of MHE is not currently recommended as routine, but only on a case-by-case basis. PMID:29507462

Study of Abnormal Liver Function Test during Pregnancy in a Tertiary Care Hospital in Chhattisgarh.

PubMed

Mishra, Nalini; Mishra, V N; Thakur, Parineeta

2016-10-01

Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. Eighty pregnant women with abnormal liver dysfunction were studied prospectively. Women with chronic liver disease and drug-induced abnormal liver function test were excluded. All available LFTs including LDH were studied along with some more definitive tests to aid identification of underlying cause. Foetomaternal outcome was noted in all. The incidence of abnormal LFT was 0.9 %. 13/80 (16.75 %) women had liver disorder not specific to pregnancy, whereas 67/80 (83.25 %) women had pregnancy-specific liver dysfunction. Of these, 65(81.25 %) women with liver dysfunction had pre-eclampsia including 11 (13.75 %) with HELLP and six women with eclampsia. 48/65 (60 %) women had pre-eclampsia in the absence of HELLP syndrome or eclampsia. The mean value for bilirubin (mg %) in hypertensive disorders of pregnancy ranged from 1.64 to 3.8, between 5 and 10 for ICP and AFLP and >10 in infective hepatitis. Transaminases were highest in infective hepatitis, whereas alkaline phosphate was highest in ICP. Total 27 (33.75 %) women suffered from adverse outcome with four (5 %) maternal deaths and 23 (28.75 %) major maternal morbidities. 33/80 (41.25 %) women had intrauterine death. 26.25 % babies were small for date. Pregnancy-specific disorders are the leading cause of abnormal liver function test during pregnant state particularly in the third trimester. Pre-eclampsia-related disorder is the commonest. Gestational age of pregnancy and relative values of various liver function tests in different pregnancy-specific and pregnancy nonspecific disorders appear to be the best guide to clinch the diagnosis.

Hepatitis C Testing Increased Among Baby Boomers Following The 2012 Change To CDC Testing Recommendations.

PubMed

Barocas, Joshua A; Wang, Jianing; White, Laura F; Tasillo, Abriana; Salomon, Joshua A; Freedberg, Kenneth A; Linas, Benjamin P

2017-12-01

In 2012 the Centers for Disease Control and Prevention recommended routine testing for hepatitis C for people born in the period 1945-65. Until now, the recommendation's impact on hepatitis C screening rates in the United States has not been fully understood. We used an interrupted time series with comparison group design to analyze hepatitis C screening rates in the period 2010-14 among 2.8 million commercially insured adults in the MarketScan database. Hepatitis C screening rates increased yearly between 2010 and 2014, from 1.65 to 2.59 per 100 person-years. A 49 percent increase in screening rates among people born during 1945-65 followed the release of the recommendation, but no such increase was observed among adults born after 1965. The effect among the target population was sustained, and by twenty-four months after the recommendation's release, screening rates had increased 106 percent. We conclude that the hepatitis C testing policy change resulted in significantly increased testing among the target population and may have decreased the magnitude of the hepatitis C epidemic.

[IgM class antibodies against hepatitis A viruses in the differentiation of viral hepatitis].

PubMed

Zivanović-Marinković, V; Stanković, D; Parabucki, S; Lazarov, A; Marinković, V; Krstić, L; Letica, Z

1982-01-01

The sera of 64 patients with acute viral hepatitis which were previously HbsAG negative by rPHA were tested by RIA methods for the presence of HBsAG and anti-HBc, by EIA method for HBc and anti-HBc and also by RIA method for the presence of IgM antibodies against hepatitis A virus. The pairs of sera were tested also for the presence of antibodies against cytomegalovirus and EB viruses. Of the total of 64 patients, markers of fresh HB viral infection were proved in 5 patients, sera positive to IgM antibodies to hepatitis A virus were found in 51 and no positive tests to any of the tested viruses were found in 8. The authors consider that they belonged to "non-A, non-B" viral hepatitis.

Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

PubMed

Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

2014-04-01

Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Hepatic TRAF2 Regulates Glucose Metabolism Through Enhancing Glucagon Responses

PubMed Central

Chen, Zheng; Sheng, Liang; Shen, Hong; Zhao, Yujun; Wang, Shaomeng; Brink, Robert; Rui, Liangyou

2012-01-01

Obesity is associated with intrahepatic inflammation that promotes insulin resistance and type 2 diabetes. Tumor necrosis factor receptor–associated factor (TRAF)2 is a key adaptor molecule that is known to mediate proinflammatory cytokine signaling in immune cells; however, its metabolic function remains unclear. We examined the role of hepatic TRAF2 in the regulation of insulin sensitivity and glucose metabolism. TRAF2 was deleted specifically in hepatocytes using the Cre/loxP system. The mutant mice were fed a high-fat diet (HFD) to induce insulin resistance and hyperglycemia. Hepatic glucose production (HGP) was examined using pyruvate tolerance tests, 2H nuclear magnetic resonance spectroscopy, and in vitro HGP assays. The expression of gluconeogenic genes was measured by quantitative real-time PCR. Insulin sensitivity was analyzed using insulin tolerance tests and insulin-stimulated phosphorylation of insulin receptors and Akt. Glucagon action was examined using glucagon tolerance tests and glucagon-stimulated HGP, cAMP-responsive element–binding (CREB) phosphorylation, and expression of gluconeogenic genes in the liver and primary hepatocytes. Hepatocyte-specific TRAF2 knockout (HKO) mice exhibited normal body weight, blood glucose levels, and insulin sensitivity. Under HFD conditions, blood glucose levels were significantly lower (by >30%) in HKO than in control mice. Both insulin signaling and the hypoglycemic response to insulin were similar between HKO and control mice. In contrast, glucagon signaling and the hyperglycemic response to glucagon were severely impaired in HKO mice. In addition, TRAF2 overexpression significantly increased the ability of glucagon or a cAMP analog to stimulate CREB phosphorylation, gluconeogenic gene expression, and HGP in primary hepatocytes. These results suggest that the hepatic TRAF2 cell autonomously promotes hepatic gluconeogenesis by enhancing the hyperglycemic response to glucagon and other factors that increase cAMP levels, thus contributing to hyperglycemia in obesity. PMID:22315325

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening test for HBsAg); and (4) Hepatitis C (e.g., FDA licensed screening test for anti-HCV). (b) In the case... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

PubMed Central

De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

2016-01-01

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

Orlistat-induced fulminant hepatic failure.

PubMed

Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

2014-12-01

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

Mineral metabolism in dimethylnitrosamine-induced hepatic fibrosis.

PubMed

George, Joseph

2006-10-01

Complications such as ascites during the pathogenesis of hepatic fibrosis and cirrhosis may lead to several abnormalities in mineral metabolism. In the present investigation, we have monitored serum and liver concentrations of calcium, magnesium, sodium and potassium during experimentally induced hepatic fibrosis in rats. The liver injury was induced by intraperitoneal injections of dimethylnitrosamine (DMN; N-nitrosodimethylamine, NDMA) in doses 1 mg/100 g body weight on 3 consecutive days of each week over a period of 21 days. Calcium, magnesium, sodium and potassium were measured by atomic absorption spectrophotometry in the serum and liver on days 7, 14 and 21 after the start of DMN administration. Negative correlations were observed between liver function tests and serum mineral levels, except with albumin. Calcium, magnesium, potassium and sodium concentrations in the serum were decreased after the induction of liver injury. The liver calcium content was increased after DMN treatment. No change occurred in liver sodium content. However, magnesium and potassium content was significantly reduced in the hepatic tissue. The results suggest that DMN-induced hepatic fibrosis plays certain role in the alteration of essential elements. The low levels of albumin and the related ascites may be one of the major causes of the imbalance of mineral metabolism in hepatic fibrosis and further aggravation of the disease.

Generation of Functional Human Hepatic Endoderm from Human iPS cells

PubMed Central

Sullivan, Gareth J.; Hay, David C.; Park, In-Hyun; Fletcher, Judy; Hannoun, Zara; Payne, Catherine M.; Dalgetty, Donna; Black, James R.; Ross, James A.; Samuel, Kay; Wang, Gang; Daley, George Q.; Lee, Je-Hyuk; Church, George M.; Forbes, Stuart J.; Iredale, John P.; Wilmut, Ian

2009-01-01

With the advent of induced pluripotent stem cell (iPSC) technology, it is now feasible to generate iPSCs with a defined genotype or disease state. When coupled with direct differentiation of defined lineage, such as hepatic endoderm (HE). iPSC would revolutionise the way we study human liver biology and generate efficient “off the shelf” models of human liver disease. Here we show the `proof of concept' that iPSC lines representing both male and female sexes and two ethnic origins can be differentiated to HE at efficiencies of between 70–90%, using a method mimicking a physiological condition. iPSC-derived HE exhibited hepatic morphology, and expressed the hepatic markers, Albumin and E-Cadherin as assessed by immuno-histochemistry. They also expressed alpha fetal protein (AFP), HNF4a, and a metabolic marker, Cyp7A1, demonstrating a definitive endodermal lineage differentiation. Furthermore, iPSC-derived hepatocytes produced and secreted the plasma proteins, fibrinogen, fibronectin, transthyretin (TTR) and AFP, an essential feature for functional HE. Additionally iPSC-derived HE supported both CYP1A2 and 3A4 metabolism, which is essential for drug and toxicology testing. Conclusion This work is first to demonstrate the efficient generation of hepatic endodermal lineage from human iPSC that exhibits key attributes of hepatocytes, and the potential application of iPSC-derived HE in studying human liver biology. In particular, iPSC from individuals representing highly polymorphic variants in metabolic genes and different ethnic groups will provide pharmaceutical development and toxicology studies a unique opportunity to revolutionise predictive drug toxicology assays and allow the creation of in vitro hepatic disease models. PMID:19877180

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

MedlinePlus

... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

Long-term and short-term effects of hemodialysis on liver function evaluated using the galactose single-point test.

PubMed

Hou, Yi-Chou; Liu, Wen-Chih; Liao, Min-Tser; Lu, Kuo-Cheng; Lo, Lan; Pan, Heng-Chih; Wu, Chia-Chao; Hu, Oliver Yoa-Pu; Tang, Hung-Shang

2014-01-01

The galactose single-point (GSP) test assesses functioning liver mass by measuring the galactose concentration in the blood 1 hour after its administration. The purpose of this study was to investigate the impact of hemodialysis (HD) on short-term and long-term liver function by use of GSP test. Seventy-four patients on maintenance HD (46 males and 28 females, 60.38 ± 11.86 years) with a mean time on HD of 60.77 ± 48.31 months were studied. The GSP values were compared in two groups: (1) before and after single session HD, and (2) after one year of maintenance HD. Among the 74 HD patient, only the post-HD Cr levels and years on dialysis were significantly correlated with GSP values (r = 0.280, P < 0.05 and r = -0.240, P < 0.05, resp.). 14 of 74 patients were selected for GSP evaluation before and after a single HD session, and the hepatic clearance of galactose was similar (pre-HD 410 ± 254 g/mL, post-HD 439 ± 298 g/mL, P = 0.49). GSP values decreased from 420.20 ± 175.26 g/mL to 383.40 ± 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean difference: 19.00 ± 37.66 g/mL, P < 0.05). Patients on maintenance HD for several years may experience improvement of their liver function. However, a single HD session does not affect liver function significantly as assessed by the GSP test. Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed.

Hepatotoxicity due to red bush tea consumption: a case report.

PubMed

Reddy, Shamantha; Mishra, Pragnyadipta; Qureshi, Sana; Nair, Singh; Straker, Tracey

2016-12-01

Many conventional drugs used today, including isoniazid, dapsone, and acetaminophen, are well recognized culprits of hepatotoxicity. With increasing use of complementary and alternative medical therapies, several herbal medicines, such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins. Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies when taken in excessive quantities. A myriad of liver dysfunctions may occur including transient liver enzyme abnormalities due to acute and chronic hepatitis. These herbal products are often overlooked as the causal etiologic agent during the evaluation of a patient with elevated liver function tests. We describe a case of hepatotoxicity due to ingestion of red bush tea diagnosed during preoperative assessment of a patient scheduled for laparoscopic appendectomy. Elevated liver enzymes and thrombocytopenia detected in the patient's laboratory work up confounded the initial diagnosis of acute appendicitis and additional investigations were required to rule out cholecystitis and other causes of hepatitis. Open appendectomy was done uneventfully under spinal anesthesia without any further deterioration of hepatic function. Copyright © 2016. Published by Elsevier Inc.

The first childhood case with coexisting Hashimoto thyroiditis, vitiligo and autoimmune hepatitis.

PubMed

Keskin, Melikşah; Savaş-Erdeve, Şenay; Özbay-Hoşnut, Ferda; Kurnaz, Erdal; Çetinkaya, Semra; Aycan, Zehra

2016-01-01

Hashimoto thyroiditis (HT) is the most common pediatric autoimmune endocrine disorder. It results in autoimmune-mediated thyroid gland destruction and is an organ-specific, typical autoimmune disease. The presence of antithyroid antibodies and the typical pattern on ultrasonography indicate the diagnosis. It is also frequently seen together with other autoimmune disorders including type 1 insulin-dependent diabetes, celiac disease, alopecia and vitiligo. Autoimmune hepatitis (AIH) is a chronic type of liver injury with an immune etiology that can frequently cause end-stage liver disease if left untreated. Autoimmune hepatitis patients may present with hepatitis, and the laboratory tests in the absence of other etiology usually reveal a positive immune serology together with elevated immunoglobulins and abnormal liver histology. It is interesting that HT and AIH are rarely seen together although both have an autoimmune etiology. 14-year-old male who was being followed-up for vitiligo presented with symptoms of a swelling at the neck and fatigue. He was diagnosed with HT after the tests and the liver enzymes were found to be high. The patient was also diagnosed with AIH after tests revealed that the liver enzyme elevation had continued for longer than six months. The thyroid functions and liver enzymes returned to normal and the symptoms decreased after sodium L-thyroxine replacement together with steroid and azathioprine treatment. We present this case as we believe it is the first pediatric patient diagnosed with HT, AIH and vitiligo.

Hepatitis A Test

MedlinePlus

... of immune globulin instead of the vaccine for post-exposure protection. Although hepatitis A IgM antibodies are considered diagnostic for acute infection with hepatitis A, there has been increasing use of the test in people who do not have signs and ...

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

PubMed

Wada, Yoshiko; Sato, Chikako; Tomita, Kyoko; Ishii-Aso, Rika; Haga, Hiroaki; Okumoto, Kazuo; Nishise, Yuko; Watanabe, Hisayoshi; Saito, Takafumi; Ueno, Yoshiyuki

2014-02-01

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.

The Safety of Tenofovir–Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B

PubMed Central

Schechter, Mauro; Liu, Albert Y.; McManhan, Vanessa M.; Guanira, Juan V.; Hance, Robert J.; Chariyalertsak, Suwat; Mayer, Kenneth H.; Grant, Robert M.

2016-01-01

Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. Methods: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Results: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. Conclusions: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered. PMID:26413853

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

PubMed

Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P < 0.05 was considered to be statistically significant. Of the 267 viral hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic?

PubMed

Stravitz, R Todd; Ilan, Yaron

2017-03-01

The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

Routine blood tests to predict liver fibrosis in chronic hepatitis C.

PubMed

Hsieh, Yung-Yu; Tung, Shui-Yi; Lee, Kamfai; Wu, Cheng-Shyong; Wei, Kuo-Liang; Shen, Chien-Heng; Chang, Te-Sheng; Lin, Yi-Hsiung

2012-02-28

To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C, compared with other noninvasive tests. This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting significant fibrosis score in chronic hepatitis C compared with other noninvasive tests. FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats.

PubMed

Wang, Zhenchang; Li, Quanqiang; Xiang, Mingpeng; Zhang, Fengying; Wei, Dongyu; Wen, Zhixi; Zhou, Ying

2017-01-01

Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl4 to a greater degree in diabetic animals. ELISA and Western Blot analysis were used to examine PAR2 signaling pathway in diabetic CCl4-rats and non-diabetic CCl4-rats. AGS inhibited the protein expression of PAR2 and its downstream pathway PKA and PKCɛ in CCl4-rats. Notably, the effects of AGS were greater in CCl4-rats with diabetes. AGS also significantly attenuated the CCl4-induced upregulations of pro-inflammatory cytokines, namely interleukin-1β, interleukin-6 and tumor necrosis factor-α accompanied with decreases of collagenic parameters such as hexadecenoic acid, laminin and hydroxyproline. Additionally, AGS improved the CCl4-induced exaggerations of liver index and functions including alanine aminotransferase, aspartate aminotransferase. Moreover, TGF-β1, a marker of hepatic fibrosis, was increased in CCl4-rats and AGS inhibited increases in TGF-β1 induced by CCl4. AGS alleviates hepatic fibrosis by inhibiting PAR2 signaling expression and its effects are largely enhanced in diabetic animals. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of hepatic fibrosis; and results of our study are likely to shed light on strategies for application of AGS because it has potentially greater therapeutic effectiveness for hepatic fibrosis in diabetes. © 2017 The Author(s)Published by S. Karger AG, Basel.

Epstein-Barr virus associated acute hepatitis with cross-reacting antibodies to other herpes viruses in immunocompetent patients: report of two cases.

PubMed

Gupta, Ekta; Bhatia, Vikram; Choudhary, Aashish; Rastogi, Archana; Gupta, Naveen L

2013-03-01

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM) which is characterized by the triad of fever, sore throat, and lymphadenopathy. Self-limited, mild liver function test abnormalities are seen in IM. Acute hepatitis in primary EBV infection is uncommon. Serum transaminases are elevated but are less than fivefold the normal levels in most cases and rarely exceed 10 times the normal levels in primary EBV infections especially in elderly. Laboratory diagnosis of acute EBV infection is by serological assays confirming the presence of EBV viral capsid antigen (VCA) IgM antibodies. Due to antigenic cross-reactivity with Herpes viruses, serological assays lack specificity; hence specific molecular diagnostic methods are required for confirmation of the etiology. The present report describes two cases of acute hepatitis caused by infection with EBV which had indistinguishable clinical features and biochemical markers from acute hepatitis caused by hepatotropic viruses such as hepatitis viruses A-E. The diagnosis of infection by EBV was confirmed by detection of EBV DNA in blood of both the patients and EBV DNA in the liver tissue of one of the patients. Copyright © 2013 Wiley Periodicals, Inc.

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.

PubMed

Lee, Hee Jae; Hong, Young-Shick; Jun, Woojin; Yang, Soo Jin

2015-11-01

Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.

Renal and Hepatic Functions after A Week of Controlled Ovarian Hyperstimulation during In Vitro Fertilization Cycles.

PubMed

Romito, Ilaria; Gulino, Ferdinando Antonio; Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Tuscano, Attilio; Leanza, Gianluca; Musmeci, Giulia; Leanza, Vito; Rapisarda, Agnese Maria Chiara; Palumbo, Marco Antonio

2017-01-01

One the main aspects of in vitro fertilization (IVF) cycle is to avoid any possible systemic damage on women undergoing a controlled ovarian hyperstimulation (COH). The aim of this work is to evaluate renal and hepatic function blood tests in patients undergoing controlled ovarian hyperstimulation during IVF cycles. We performed a prospective cohort analysis. All patients re- ceived a long stimulation protocol with gonadotropin-releasing hormone (GnRH) analogues by daily administration, since the twenty-first day of the previous ovarian cycle followed by COH with recombinant follicle-stimulating hormone (FSH). The daily dose of exogenous gonadotropins for every single patient was modified according to her follicular growth. The oocytes were retrieved during the oocyte pick up and fertilized by standard procedures of intracytoplasmic sperm injection (ICSI). The blood samples to evaluate renal and hepatic functions were taken at the 7 th day of ovarian stimulation. We enrolled 426 women aged between 19 and 44 years, with a mean body mass index (BMI) of 24.68 Kg/m 2 . The mean value of blood urea nitrogen was 14 ± 3.16 mg/ dl, creatinine: 1 ± 0.45 mg/dl, uric acid: 4 ± 1.95 mg/dl, total proteins: 7 ± 3.93 mg/dl, aspartate aminotransferase: 18 ± 6.29 mU/ml, alanine aminotransferase: 19 ± 10.41 mU/ ml, alkaline phosphatase: 81 ± 45.25 mU/ml, total bilirubin 1 ± 0.35 mg/dL. All of the results were considered as a normal range following the Medical Council of Canada. Our data suggest that, unlike ovarian hyperstimulation syndrome (OHSS), COH patients did not show any alteration to renal and hepatic functions.

Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

PubMed

Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

2015-12-01

Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Adiposity and family history of type 2 diabetes in an admixed population of adolescents: Associations with insulin sensitivity, beta-cell function, and hepatic insulin extraction in BRAMS study.

PubMed

Camilo, Daniella F; Vasques, Ana Carolina J; Hayashi, Keila; Tura, Andrea; da Silva, Cleliani de Cassia; Zambon, Mariana P; Antônio, Maria Ângela R de G Monteiro; Geloneze, Bruno

2018-03-01

Insulin resistance and beta-cell dysfunction manifest differently across racial/ethnic groups, and there is a lack of knowledge regarding the pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed adolescents. This study aimed to investigate the influence of adiposity and family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell function, and hepatic insulin extraction in Brazilian adolescents. A total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was defined as the presence of at least one known family member with T2DM. The hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and beta-cell function were obtained from C-peptide deconvolution. Analysis of covariance considered pubertal stage as a covariate. Both lean and overweight/obese adolescents had similar glycemic profiles and disposition indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of lean adolescents (1.1 ± 0.2 vs. 3.4 ± 0.3 mg·kg·min·pmol ∗ 1000), which was compensated by an increase around 2.5 times in basal (130 ± 7 vs. 52 ± 10 pmol·l·min) and total insulin secretion (130,091 ± 12,230 vs. 59,010 ± 17,522 pmol·l·min), and in the first and second phases of insulin secretion; respectively (p < 0.001). This increase was accompanied by a mean reduction in hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose sensitivity (p < 0.05). The positive FH of T2DM was not associated with derangements in insulin sensitivity, beta-cell function, and hepatic insulin extraction. In an admixed sample of adolescents, the hyperglycemic clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had no direct influence, in different aspects of glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronic parenteral nutrition induces hepatic inflammation, steatosis and insulin resistance in neonatal pigs

USDA-ARS?s Scientific Manuscript database

Prematurity and overfeeding in infants are associated with insulin resistance in childhood and may increase the risk of adult disease. Total parenteral nutrition (TPN) is a major source of infant nutrition support and may influence neonatal metabolic function. Our aim was to test the hypothesis that...

Liver failure in total artificial heart therapy.

PubMed

Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

PubMed Central

Chaya, D; Fougère-Deschatrette, C; Weiss, M C

1997-01-01

Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver. PMID:9343392

Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

PubMed

Chaya, D; Fougère-Deschatrette, C; Weiss, M C

1997-11-01

Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver.

Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea.

PubMed

Jeong, Jae Yoon; Jun, Dae Won; Bai, Daiseg; Kim, Ji Yean; Sohn, Joo Hyun; Ahn, Sang Bong; Kim, Sang Gyune; Kim, Tae Yeob; Kim, Hyoung Su; Jeong, Soung Won; Cho, Yong Kyun; Song, Do Seon; Kim, Hee Yeon; Jung, Young Kul; Yoon, Eileen L

2017-09-01

The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955). © 2017 The Korean Academy of Medical Sciences.

Hepatic fibrosis and carcinogenesis in α1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders.

PubMed

Perlmutter, David H; Silverman, Gary A

2011-03-01

In α1-antitrypsin (AT) deficiency, a point mutation renders a hepatic secretory glycoprotein prone to misfolding and polymerization. The mutant protein accumulates in the endoplasmic reticulum of liver cells and causes hepatic fibrosis and hepatocellular carcinoma by a gain-of-function mechanism. Genetic and/or environmental modifiers determine whether an affected homozygote is susceptible to hepatic fibrosis/carcinoma. Two types of proteostasis mechanisms for such modifiers have been postulated: variation in the function of intracellular degradative mechanisms and/or variation in the signal transduction pathways that are activated to protect the cell from protein mislocalization and/or aggregation. In recent studies we found that carbamazepine, a drug that has been used safely as an anticonvulsant and mood stabilizer, reduces the hepatic load of mutant AT and hepatic fibrosis in a mouse model by enhancing autophagic disposal of this mutant protein. These results provide evidence that pharmacological manipulation of endogenous proteostasis mechanisms is an appealing strategy for chemoprophylaxis in disorders involving gain-of-function mechanisms.

Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/−-IRS-1+/− Double Heterozygous (IR-IRS1dh) Mice

PubMed Central

Franko, Andras; Kunze, Alexander; Böse, Marlen; von Kleist-Retzow, Jürgen-Christoph; Paulsson, Mats; Hartmann, Ursula; Wiesner, Rudolf J.

2017-01-01

Mitochondria play a pivotal role in energy metabolism, but whether insulin signaling per se could regulate mitochondrial function has not been identified yet. To investigate whether mitochondrial function is regulated by insulin signaling, we analyzed muscle and liver of insulin receptor (IR)+/−-insulin receptor substrate-1 (IRS-1)+/− double heterozygous (IR-IRS1dh) mice, a well described model for insulin resistance. IR-IRS1dh mice were studied at the age of 6 and 12 months and glucose metabolism was determined by glucose and insulin tolerance tests. Mitochondrial enzyme activities, oxygen consumption, and membrane potential were assessed using spectrophotometric, respirometric, and proton motive force analysis, respectively. IR-IRS1dh mice showed elevated serum insulin levels. Hepatic mitochondrial oxygen consumption was reduced in IR-IRS1dh animals at 12 months of age. Furthermore, 6-month-old IR-IRS1dh mice demonstrated enhanced mitochondrial respiration in skeletal muscle, but a tendency of impaired glucose tolerance. On the other hand, 12-month-old IR-IRS1dh mice showed improved glucose tolerance, but normal muscle mitochondrial function. Our data revealed that deficiency in IR/IRS-1 resulted in normal or even elevated skeletal muscle, but impaired hepatic mitochondrial function, suggesting a direct cross-talk between insulin signaling and mitochondria in the liver. PMID:28556799

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PubMed

Siegel, Abby B; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Flaig, Thomas W; Tsai, Wei Yann; Wu, David P H; Lee, Valerie; Greenlee, Heather

2014-01-01

To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/--IRS-1+/- Double Heterozygous (IR-IRS1dh) Mice.

PubMed

Franko, Andras; Kunze, Alexander; Böse, Marlen; von Kleist-Retzow, Jürgen-Christoph; Paulsson, Mats; Hartmann, Ursula; Wiesner, Rudolf J

2017-05-30

Mitochondria play a pivotal role in energy metabolism, but whether insulin signaling per se could regulate mitochondrial function has not been identified yet. To investigate whether mitochondrial function is regulated by insulin signaling, we analyzed muscle and liver of insulin receptor (IR) +/- -insulin receptor substrate-1 (IRS-1) +/- double heterozygous (IR-IRS1dh) mice, a well described model for insulin resistance. IR-IRS1dh mice were studied at the age of 6 and 12 months and glucose metabolism was determined by glucose and insulin tolerance tests. Mitochondrial enzyme activities, oxygen consumption, and membrane potential were assessed using spectrophotometric, respirometric, and proton motive force analysis, respectively. IR-IRS1dh mice showed elevated serum insulin levels. Hepatic mitochondrial oxygen consumption was reduced in IR-IRS1dh animals at 12 months of age. Furthermore, 6-month-old IR-IRS1dh mice demonstrated enhanced mitochondrial respiration in skeletal muscle, but a tendency of impaired glucose tolerance. On the other hand, 12-month-old IR-IRS1dh mice showed improved glucose tolerance, but normal muscle mitochondrial function. Our data revealed that deficiency in IR/IRS-1 resulted in normal or even elevated skeletal muscle, but impaired hepatic mitochondrial function, suggesting a direct cross-talk between insulin signaling and mitochondria in the liver.

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.

PubMed

van Zutphen, Tim; Ciapaite, Jolita; Bloks, Vincent W; Ackereley, Cameron; Gerding, Albert; Jurdzinski, Angelika; de Moraes, Roberta Allgayer; Zhang, Ling; Wolters, Justina C; Bischoff, Rainer; Wanders, Ronald J; Houten, Sander M; Bronte-Tinkew, Dana; Shatseva, Tatiana; Lewis, Gary F; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M; Jonker, Johan W; Kim, Peter K; Bandsma, Robert H J

2016-12-01

Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. Peroxisomes and mitochondria play key roles in various hepatic metabolic functions including lipid metabolism and energy production. To investigate the involvement of these organelles in the mechanisms underlying malnutrition-induced hepatic dysfunction we developed a rat model of malnutrition. Weanling rats were placed on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Peroxisomal and mitochondrial structural features were characterized using immunofluorescence and electron microscopy. Mitochondrial function was assessed using high-resolution respirometry. A novel targeted quantitative proteomics method was applied to analyze 47 mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle and fatty acid β-oxidation pathways. Low protein diet-fed rats developed hypoalbuminemia and hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated peroxisomal dysfunction. This was followed by changes in mitochondrial ultrastructure and increased mitochondrial content. Mitochondrial function was impaired due to multiple defects affecting respiratory chain complex I and IV, pyruvate uptake and several β-oxidation enzymes, leading to strongly reduced hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial β-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. Malnutrition leads to severe impairments in hepatic peroxisomal and mitochondrial function, and hepatic metabolic dysfunction. We discuss the potential future implications of our findings for the clinical management of malnourished children. Severe malnutrition in children is associated with metabolic disturbances that are poorly understood. In order to study this further, we developed a malnutrition animal model and found that severe malnutrition leads to an impaired function of liver mitochondria which are essential for energy production and a loss of peroxisomes, which are important for normal liver metabolic function. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

76 FR 72950 - Draft Guidance for Industry: Use of Nucleic Acid Tests on Pooled and Individual Samples From...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... Hepatitis B Virus AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... Risk of Transmission of Hepatitis B Virus (HBV), and Requalification of Donors Who Test HBV NAT...-licensed nucleic acid tests (NAT) to screen blood donors for hepatitis B virus (HBV) deoxyribonucleic acid...

[Liver stiffness measured by acoustic radiation force impulse imaging in assessing hepatic functional reserve in patients with space-occupying lesions in the liver].

PubMed

Yan, Hui-tong; Luo, Yu-kun; Tang, Wen-bo; Jiao, Zi-yu; Yao, Chun-xiao; Lv, Fa-qin; Tang, Jie

2013-04-01

To investigate the value of liver stiffness measured by acoustic radiation force impulse imaging(ARFI) in assessing hepatic functional reserve in patients with space-occupying lesions in the liver. Sixty-three patients with space-occupying lesions in the liver were enrolled. Liver stiffness (LS) measurements with ARFI and indocyanine green(ICG) retention test were performed in the same day, and plasma clearance rate of indocyanine green(ICG-K), ICG retention at 15 minutes(ICGR15) as well as 10 effective values of LS were recorded. The correlation between Child-Pugh score, ICGR15, ICG-K, and LS were evaluated. The LS measurements with ARFI failed in one patient. A strong correlation between LS and ICGR15(r=0.789, P<0.01) and an inverse correlation between LS and ICG-K(r=-0.738, P<0.01) were observed. Besides, there was a significant correlation between LS measurements and Child-Pugh score(r=0.929, P<0.01) . The LS significantly differed among patients with Child-Pugh class A, B, and C(P<0.01) . ARFI is a simple, feasible and non-invasive method for assessing hepatic functional reserve in patients with space-occupying lesions in the liver.

Long-Term Health Effects of Repeated Exposure to Multiple Vaccines

DTIC Science & Technology

2004-01-01

0.945 Hepatits B surface antigen 0.0% 0.0% NT Anti-hepatitis C antibody 0.0% 2.0% 1.000 HLA - B27 9.8% 10.6% 0.868 NT, not tested. a Tests are two-tailed...536 The distribution of markers for hepatitis A, hepatitis B, hepatitis C, and HLA B27 was similar between groups (Table 1), supporting comparability

Technetium-99m NGA functional hepatic imaging: preliminary clinical experience

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

Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

1985-11-01

Technetium-99m galactosyl-neoglycoalbumin ( (Tc)NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis, and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and (Tc)sulfur colloid scintigraphy. Kinetic modeling of dynamic (Tc)NGA data produced estimates of standardizedmore » hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, (HBP). Significant rank correlation was obtained between (HBP) estimates and CTC scores. This correlation supports the hypothesis that (HBP) is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced (HBP) may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.« less

Resveratrol in Patients with Minimal Hepatic Encephalopathy

PubMed Central

Bertino, Gaetano; Motta, Massimo; Borzì, Antonio Maria; Vicari, Enzo; Bella, Rita; Drago, Filippo

2018-01-01

Background: Minimal Hepatic Encephalopathy (MHE) is characterized by an impairment of social interaction, emotional behavior, sleep disorders, physical and mental symptoms, and diminished Quality of Life (QoL). The aim of our study is evaluating the potential liver health promoting a perspective of Resveratrol (RV) activities and evaluate whether RV treatment may improve health related quality of life (HRQL) and reduce depression and anxiety in patients with MHE. Methods: We evaluated depression using the Beck Depression Inventory test, anxiety with State-trait anxiety inventory test, quality of life through SF-36 test, and ammonia serum levels in 70 MHE patients that were randomized into two groups. Results: In the comparison between RV group and placebo group we observed a decrease in Back Depression Inventory (BDI) (p < 0.001), in State-trait anxiety inventory (STAI) (p < 0.001), and improve in physical function (p < 0.001), in role physical (p < 0.05), in body pain (p < 0.05), in general health (p < 0.001), in vitality (p < 0.05), and in social function (p < 0.001). Conclusions: Resveratrol showed efficacy in the treatment of depression, anxiety, and ammonia serum levels, and improved the quality of life Of MHE patients. PMID:29522439

Adapting a computer-delivered brief alcohol intervention for veterans with Hepatitis C.

PubMed

Cucciare, Michael A; Jamison, Andrea L; Combs, Ann S; Joshi, Gauri; Cheung, Ramsey C; Rongey, Catherine; Huggins, Joe; Humphreys, Keith

2017-12-01

This study adapted an existing computer-delivered brief alcohol intervention (cBAI) for use in Veterans with the hepatitis C virus (HCV) and examined its acceptability and feasibility in this patient population. A four-stage model consisting of initial pilot testing, qualitative interviews with key stakeholders, development of a beta version of the cBAI, and usability testing was used to achieve the study objectives. In-depth interviews gathered feedback for modifying the cBAI, including adding HCV-related content such as the health effects of alcohol on liver functioning, immune system functioning, and management of HCV, a preference for concepts to be displayed through "newer looking" graphics, and limiting the use of text to convey key concepts. Results from usability testing indicated that the modified cBAI was acceptable and feasible for use in this patient population. The development model used in this study is effective for gathering actionable feedback that can inform the development of a cBAI and can result in the development of an acceptable and feasible intervention for use in this population. Findings also have implications for developing computer-delivered interventions targeting behavior change more broadly.

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

21 CFR 660.45 - Labeling.

Code of Federal Regulations, 2012 CFR

2012-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.45 Labeling. In... capable of transmitting hepatitis and should be handled accordingly. (d) The package shall include a... test methods, and (3) warnings as to possible hazards, including hepatitis transmitted in handling the...

21 CFR 660.45 - Labeling.

Code of Federal Regulations, 2014 CFR

2014-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.45 Labeling. In... capable of transmitting hepatitis and should be handled accordingly. (d) The package shall include a... test methods, and (3) warnings as to possible hazards, including hepatitis transmitted in handling the...

21 CFR 660.45 - Labeling.

Code of Federal Regulations, 2013 CFR

2013-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.45 Labeling. In... capable of transmitting hepatitis and should be handled accordingly. (d) The package shall include a... test methods, and (3) warnings as to possible hazards, including hepatitis transmitted in handling the...

21 CFR 660.45 - Labeling.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.45 Labeling. In... capable of transmitting hepatitis and should be handled accordingly. (d) The package shall include a... test methods, and (3) warnings as to possible hazards, including hepatitis transmitted in handling the...

21 CFR 660.45 - Labeling.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.45 Labeling. In... capable of transmitting hepatitis and should be handled accordingly. (d) The package shall include a... test methods, and (3) warnings as to possible hazards, including hepatitis transmitted in handling the...

Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling.

PubMed

Arlt, Volker M; Poirier, Miriam C; Sykes, Sarah E; John, Kaarthik; Moserova, Michaela; Stiborova, Marie; Wolf, C Roland; Henderson, Colin J; Phillips, David H

2012-09-03

Benzo[a]pyrene (BaP) is a widespread environmental carcinogen activated by cytochrome P450 (P450) enzymes. In Hepatic P450 Reductase Null (HRN) and Reductase Conditional Null (RCN) mice, P450 oxidoreductase (Por) is deleted specifically in hepatocytes, resulting in the loss of essentially all hepatic P450 function. Treatment of HRN mice with a single i.p. or oral dose of BaP (12.5 or 125mg/kg body weight) resulted in higher DNA adduct levels in liver (up to 10-fold) than in wild-type (WT) mice, indicating that hepatic P450s appear to be more important for BaP detoxification in vivo. Similar results were obtained in RCN mice. We tested whether differences between hepatocytes and non-hepatocytes in P450 activity may underlie the increased liver BaP-DNA binding in HRN mice. Cellular localisation by immunohistochemistry of BaP-DNA adducts showed that HRN mice have ample capacity for formation of BaP-DNA adducts in liver, indicating that the metabolic process does not result in the generation of a reactive species different from that formed in WT mice. However, increased protein expression of cytochrome b(5) in hepatic microsomes of HRN relative to WT mice suggests that cytochrome b(5) may modulate the P450-mediated bioactivation of BaP in HRN mice, partially substituting the function of Por. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Tc-NGA imaging in liver transplantation: preliminary clinical experience

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

Woodle, E.S.; Ward, R.E.; Stadalnik, R.C.

1989-03-01

Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver imaging agent that binds to hepatic-binding protein, a hepatocyte-specific membrane receptor. The purpose of this study was to determine the potential of Tc-NGA imaging in clinical liver transplantation. A total of 25 studies were performed in nine patients. Imaging studies performed in the early posttransplant period in patients with good hepatic allograft function revealed diffuse patchiness in tracer distribution, a manifestation of preservation damage. Left lobar infarction was demonstrated within a few hours of ischemic injury. Right posterior segmental infarction was seen in another patient. Comparison of kinetic, clinical, and biochemical data revealedmore » good correlation between hepatic allograft function and Tc-NGA kinetics. Major kinetic alterations were noted during periods of preservation injury, hepatic infarction, and acute rejection. These studies indicate: (1) major alterations in Tc-NGA kinetics occur during preservation injury, hepatic infarction, and acute rejection, and (2) Tc-NGA kinetic data appear to provide an accurate reflection of hepatic allograft function. Tc-NGA imaging has the advantages of being noninvasive and of utilizing standard nuclear medicine instrumentation, including portable imaging devices. In conclusion, Tc-NGA imaging provides a promising noninvasive approach for evaluation of liver function in patients undergoing hepatic transplantation.« less

Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma.

PubMed

Rajakannu, Muthukumarassamy; Cherqui, Daniel; Ciacio, Oriana; Golse, Nicolas; Pittau, Gabriella; Allard, Marc Antoine; Antonini, Teresa Maria; Coilly, Audrey; Sa Cunha, Antonio; Castaing, Denis; Samuel, Didier; Guettier, Catherine; Adam, René; Vibert, Eric

2017-10-01

Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506-0.907) and 0.71 (95% confidence interval, 0.646-0.917), respectively. Liver stiffness measurement ≥22 kPa had 42.9% sensitivity and 92.6% specificity and hepatic venous pressure gradient ≥10 mm Hg had 28.6% sensitivity and 96.3% specificity. In selected patients undergoing liver resection for hepatocellular carcinoma, transient elastography is an easy and effective test to predict persistent hepatic decompensation preoperatively. Copyright © 2017 Elsevier Inc. All rights reserved.

Syphilitic hepatitis: clinical, immunological and morphological aspects.

PubMed

Fehér, J; Somogyi, T; Timmer, M; Józsa, L

1975-01-01

In 17 out of 176 cases of early syphilis (seropositive syphillis I; syphilis II) liver function tests yielded a positive result. In these patients a significant increase in the serum IgG, IgM and coeruloplasmin levels and a decrease in t4e transferrin level was found. The concentrations of alpha-2-macroglobulin and of beta-1-C-globulin were practically uneffected. Liver biopsy revealed hepatitis of variable severity in 13 patients with focal necroses or a proliferative process effecting the walls of the central veins, the arterioles and the branches of the portal vein. In 7 cases the presence of Treponema in the liver was demonstrated.

Evaluation of knowledge resources for public health reporting logic: Implications for knowledge authoring and management

PubMed Central

Staes, Catherine J; Altamore, Rita; Han, EunGyoung; Mottice, Susan; Rajeev, Deepthi; Bradshaw, Richard

2011-01-01

To control disease, laboratories and providers are required to report conditions to public health authorities. Reporting logic is defined in a variety of resources, but there is no single resource available for reporters to access the list of reportable events and computable reporting logic for any jurisdiction. In order to develop evidence-based requirements for authoring such knowledge, we evaluated reporting logic in the Council of State and Territorial Epidemiologist (CSTE) position statements to assess its readiness for automated systems and identify features that should be considered when designing an authoring interface; we evaluated codes in the Reportable Condition Mapping Tables (RCMT) relative to the nationally-defined reporting logic, and described the high level business processes and knowledge required to support laboratory-based public health reporting. We focused on logic for viral hepatitis. We found that CSTE tabular logic was unnecessarily complex (sufficient conditions superseded necessary and optional conditions) and was sometimes true for more than one reportable event: we uncovered major overlap in the logic between acute and chronic hepatitis B (52%), acute and Past and Present hepatitis C (90%). We found that the RCMT includes codes for all hepatitis criteria, but includes addition codes for tests not included in the criteria. The proportion of hepatitis variant-related codes included in RCMT that correspond to a criterion in the hepatitis-related position statements varied between hepatitis A (36%), acute hepatitis B (16%), chronic hepatitis B (64%), acute hepatitis C (96%), and past and present hepatitis C (96%). Public health epidemiologists have the need to communicate parameters other than just the name of a disease or organism that should be reported, such as the status and specimen sources. Existing knowledge resources should be integrated, harmonized and made computable. Our findings identified functionality that should be provided by future knowledge management systems to support epidemiologists as they communicate reporting rules for their jurisdiction. PMID:23569619

Hepatitis Panel: MedlinePlus Lab Test Information

MedlinePlus

... this page: https://medlineplus.gov/labtests/hepatitispanel.html Hepatitis Panel To use the sharing features on this page, please enable JavaScript. What is a Hepatitis Panel? Hepatitis is a type of liver disease. ...

Influence of hepatic impairment on the pharmacokinetics of the dopamine agonist rotigotine.

PubMed

Cawello, Willi; Fichtner, Andreas; Boekens, Hilmar; Braun, Marina

2014-09-01

The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function and nine with moderate hepatic impairment (Child-Pugh class B) received one rotigotine transdermal patch (providing a dose of 2 mg/24 h) daily for 3 days with a 24-h patch-on period. Blood and urine samples were collected to evaluate pharmacokinetic parameters characterizing drug bioavailability and elimination. Primary variables included plasma and urine concentrations of unconjugated rotigotine (active parent compound) and total rotigotine (unconjugated rotigotine plus sulfate and glucuronide conjugates) under steady-state (SS) conditions. For unconjugated rotigotine, point estimates for the ratios of AUC(0-24)SS and C max,SS between the two groups (normal vs. impaired hepatic function) were near 1: AUC(0-24)SS, 0.90 (90 % CI 0.59, 1.38) and C max,SS, 0.94 (90 % CI 0.66, 1.35); t max,SS and t 1/2 were lower in subjects with hepatic impairment, while renal clearance was unaffected and overall clearance was higher. For total rotigotine, C max,SS was higher in subjects with hepatic impairment compared with those with normal hepatic function (P = 0.0239, ANOVA). A tendency to reduced non-renal clearance was observed in subjects with hepatic impairment, consistent with their higher plasma concentrations of total rotigotine. Thus, moderate hepatic impairment did not influence the pharmacokinetics of unconjugated rotigotine under steady-state conditions suggesting that dose adjustment will not be required for patients with mild or moderate hepatic insufficiency. In addition, the rotigotine patch was well tolerated in subjects with moderate hepatic impairment.

Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

PubMed

Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

2014-01-01

It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate.

CLINICAL STUDIES ON KALMEGH (ANDROGRAPHIS PANICULATA NEES) IN INFECTIVE HEPATITIS

PubMed Central

Chturvedi, G. N.; Tomar, G. S.; Tiwari, S. K.; Singh, K. P.

1983-01-01

Infective hepatitis ia an acute inflamatory condition of liver. It is usually manifested in the form of Jaundice. In this clinical study Kalmegh(Andrographis paniculata Nees) was given in the decoction form to the patients of infective hepitis. The results were assessed on the basis of clinical and biochemical parameters. A marked symptomatic improvement in majority of the cases was observed. A statistically highly significant decrease was noted in various liver function tests viz., serum bilirubin, thymol turbidity, alkaline phosphatase, S.G.O.T.; S.G.P.T. and serum globulin fraction of protein. Moreover it increased significantly total serum globulin fraction of protien. Moreover it increased significantly total serum protein level along with albumin fraction. On the total assessment 80% cases of this series were cured and 20% patients were relieved. Therefore, Kalmegh appears to be a useful remedy for the treatment of infective hepatitis. PMID:22556984

Clinical studies on kalmegh (andrographis paniculata nees) in infective hepatitis.

PubMed

Chturvedi, G N; Tomar, G S; Tiwari, S K; Singh, K P

1983-04-01

Infective hepatitis ia an acute inflamatory condition of liver. It is usually manifested in the form of Jaundice. In this clinical study Kalmegh(Andrographis paniculata Nees) was given in the decoction form to the patients of infective hepitis. The results were assessed on the basis of clinical and biochemical parameters. A marked symptomatic improvement in majority of the cases was observed. A statistically highly significant decrease was noted in various liver function tests viz., serum bilirubin, thymol turbidity, alkaline phosphatase, S.G.O.T.; S.G.P.T. and serum globulin fraction of protein. Moreover it increased significantly total serum globulin fraction of protien. Moreover it increased significantly total serum protein level along with albumin fraction. On the total assessment 80% cases of this series were cured and 20% patients were relieved. Therefore, Kalmegh appears to be a useful remedy for the treatment of infective hepatitis.

Polycystic Liver Disease

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

Linda, Nguyen, E-mail: nguyenli@einstein.edu

A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations.more » The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.« less

Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients.

PubMed

Hønge, Bl; Jespersen, S; Medina, C; Té, Ds; da Silva, Zj; Ostergaard, L; Laursen, Al; Wejse, C; Krarup, H; Erikstrup, C

2014-10-01

In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation. © 2014 British HIV Association.

Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.

PubMed

Alessandrino, F; Tirumani, S H; Krajewski, K M; Shinagare, A B; Jagannathan, J P; Ramaiya, N H; Di Salvo, D N

2017-07-01

The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. The recent arrival of immune checkpoint inhibitors in oncology has introduced a new range of immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. High-dose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome. Management of hepatic toxicity depends on the clinical scenario, the drug in use, and the severity of the findings. In this article, we will (1) present the most common types of oncological drugs associated with hepatic toxicity and associated liver injuries; (2) illustrate imaging findings of hepatic toxicities and the possible differential diagnosis; and (3) provide a guide for management of these conditions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Physiologic and Metabolic Benefits of Formulated Diets and Mangifera indica in Fluoride Toxicity.

PubMed

Karn, Sanjay S; Narasimhacharya, A V R L

2015-06-01

Fluorosis is a major health problem affecting normal physiological and metabolic functions in people living in endemic fluoride areas. The present work was aimed at investigating the role of basal, high carbohydrate low protein (HCLP) and high protein low carbohydrate (HPLC) diets and Mangifera indica fruit powder as a food supplement in fluoride-induced metabolic toxicity. Exposure to fluoride resulted in elevation of plasma glucose levels, ACP, ALP, SGPT, SGOT, and hepatic G-6-Pase activities, plasma and hepatic lipid profiles with decreased plasma protein, HDL-C, hepatic glycogen content and hexokinase activity in basal, HCLP and HPLC diet fed albino rats. However among the three diets tested, HPLC diet was found to be relatively, a better metabolic regulator. All the three formulated diets (basal, HCLP and HPLC) supplemented with mango fruit powder (5 and 10 g), decreased plasma glucose content, ACP, ALP, SGPT, SGOT and hepatic G-6-Pase activities and plasma as well as hepatic lipid profiles. These diets also elevated the hepatic glycogen content and hexokinase activities. These effects however, were prominent with the HPLC diet supplemented with mango fruit powder and, among the two doses of mango fruit powder, the higher dose (10 g) yielded more promising results. It is surmised that the micronutrients and phytochemicals present in the diets and the mango fruit could be responsible for attenuation of fluoride-induced metabolic toxicity.

Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells.

PubMed

Zhang, Zhenzhen; Liu, Jianfang; Liu, Yang; Li, Zheng; Gao, Wei-Qiang; He, Zuping

2013-02-01

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end-stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end-stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra-hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra-hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Characterization of European-ancestry NAFLD-Associated Variants in Individuals of African and Hispanic Descent

PubMed Central

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon LR; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-01-01

Nonalcoholic Fatty Liver Disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European-ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African and/or Hispanic Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African-American (n=3124) and one Hispanic-American (n=849) cohorts. All analyses controlled for variation in age, age2, gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African-American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9kg/m2, respectively. Hepatic steatosis was 0.20–0.34 heritable in African-and Hispanic-American families (p<0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Conclusions We show for the first time that multiple genetic variants are associated with hepatic steatosis across ancestries and explain a substantial proportion of the genetic predisposition in African and Hispanic Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. PMID:23564467

Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent.

PubMed

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon L R; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-09-01

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age(2) , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m(2) , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families (P < 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. © 2013 by the American Association for the Study of Liver Diseases.

Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl.

PubMed

Della Corte, Claudia; Carlucci, Antonio; Francalanci, Paola; Alisi, Anna; Nobili, Valerio

2011-06-24

In the last years numerous reports describing a possible association between administration of vaccines and development of autoimmune phenomena and overt autoimmune disease were published. Possible mechanisms of induction of autoimmune phenomena by vaccines and their excipients are probably similar to those implicated in induction by infectious agents. Here we report the case of an 11-year-old girl who developed autoimmune hepatitis type II after four weeks from vaccination against human papillomavirus. The possible relationships between the use of adjuvated vaccine against papillomavirus and autoimmune hepatitis are discussed. Although we do not provide evidence for a causal link, we suggest that the occurrence of the autoimmune hepatitis may be related to the stimulation of immune system by adjuvated-vaccine, that could have triggered the disease in a genetically predisposed individual. Therefore a monitoring of liver function test following administration of vaccine against papillomavirus may be useful in adolescent girl with signs of hepatopathy, as jaundice, dark urine or hepatomegaly, to early identify and to promptly treat autoimmune liver disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multiple factors contribute to positive results for hepatitis A virus immunoglobulin M antibody.

PubMed

Alatoom, Adnan; Ansari, M Qasim; Cuthbert, Jennifer

2013-01-01

In the United States, a successful vaccination program for hepatitis A virus (HAV) infection has decreased both its incidence and the true positive rate for diagnostic immunoglobulin M (IgM) antibody to HAV in acute hepatitis. To survey positive results of HAV IgM tests and determine the effect of changing ordering options. We reviewed all positive results for IgM antibody to HAV between January 2007 and December 2010. Patient demographics, clinical history, and laboratory data were recorded and the encounter, order, and reason for test reviewed. Each result was categorized as indicating acute, recent, resolved, or indeterminate HAV infection. A total of 10,735 tests were performed; 35 patients had 49 positive results. Most positive test results were associated with outpatient visits and were ordered in the assessment of patients with liver disease, but not clinical acute hepatitis. In the final analysis, 4 patients had acute hepatitis A and 20 individual patients had recent and/or resolved hepatitis. All but 1 of the remaining 11 patients had another established cause of liver disease with a positive IgM HAV antibody test result; data to determine causality were insufficient. The total number of tests requested annually decreased more than 35% with the introduction of computerized physician order entry. Current assays for IgM HAV antibodies are overused in the absence of clinical acute hepatitis; future clinical decision support may improve patterns of order entry. Most patients have findings consistent with HAV exposure but not acute hepatitis; dormant viral infection may be a continuing source of antigen.

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan.

PubMed

Deng, J F; Wang, J D; Shih, T S; Lan, F L

1987-01-01

Three workers from a color printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure and pulmonary edema. An investigation was subsequently conducted at the plant to determine the etiology of the outbreak and the prevalence of liver disease among the remaining workers. Comprehensive medical evaluations were conducted, which included physical examinations, liver function tests, and serological screening for hepatitis. Seventeen of 25 workers from the plant had abnormal liver function tests 10 days after the outbreak, and a significant association was found between the presence of abnormal liver function tests and a history of recently having worked inside any of three rooms in which an interconnecting air conditioning system had been installed to cool the printing machines. After further investigation, it was determined that the incident occurred following inadvertent use of carbon tetrachloride to clean a pump in the printing machine. A simulation of the pump cleaning operation revealed ambient air levels of carbon tetrachloride of 300-500 ppm. Ultimately, it was concluded that the outbreak was in all likelihood due to the combined use of carbon tetrachloride and isopropyl alcohol in the cleaning operation. This outbreak underscores the importance of adopting appropriate industrial hygiene measures in a rapidly industrializing nation such as Taiwan.

Molar Tooth Sign with Deranged Liver Function Tests: An Indian Case with COACH Syndrome.

PubMed

Sanjeev, Rama Krishna; Kapoor, Seema; Goyal, Manisha; Kapur, Rajiv; Gleeson, Joseph Gerard

2015-01-01

We report the first genetically proven case of COACH syndrome from the Indian subcontinent in a 6-year-old girl who presented with typical features of Joubert syndrome along with hepatic involvement. Mutation analysis revealed compound heterozygous missense mutation in the known gene TMEM67 (also called MKS3).

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

PubMed Central

Honda, Koichi; Seike, Masataka; Oribe, Junya; Endo, Mizuki; Arakawa, Mie; Syo, Hiroki; Iwao, Masao; Tokoro, Masanori; Nishimura, Junko; Mori, Tetsu; Yamashita, Tsutomu; Fukuchi, Satoshi; Muro, Toyokichi; Murakami, Kazunari

2016-01-01

AIM: To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS: A total of 123 patients with hepatitis B virus- or hepatitis C virus-related hepatocellular car-cinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS: CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as signi-ficant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION: Long-term liver function following RFA was dependent on liver functional reserve, the degree of fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. PMID:27168872

Corticosteroid therapy in a case of severe cholestasic hepatitis associated with amoxicillin-clavulanate.

PubMed

Herrero-Herrero, José-Ignacio; García-Aparicio, Judit

2010-12-01

Amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillin-clavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3-4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin-clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin-clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

Hepatic Encephalopathy

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... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

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

Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.

Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4}more » in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic hepatic injury. • Carvedilol is an antioxidant β-blocker used for prophylaxis of portal hypertension. • Carvedilol suppresses the elevated serum and hepatic IL-6 levels. • Carvedilol could protect against hepatocarcinogenesis of chronically damaged liver.« less

17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B.

PubMed

Galmés-Pascual, Bel M; Nadal-Casellas, Antonia; Bauza-Thorbrügge, Marco; Sbert-Roig, Miquel; García-Palmer, Francisco J; Proenza, Ana M; Gianotti, Magdalena; Lladó, Isabel

2017-02-01

Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17β-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects. In ovariectomized (OVX) rats (half of which were treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and function, increased oxidative stress, and defective lipid metabolism, but was counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing mitochondrial biogenesis and function was confirmed. These effects were unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was knocked down by specific siRNA. Our results reveal a widespread protective role of E2 in hepatocytes, which is explained by enhanced mitochondrial content and oxidative capacity, lower hepatic lipid accumulation, and a reduction of oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a modulator of E2 effects on mitochondrial biogenesis and function supporting activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders. © 2017 Society for Endocrinology.

"Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

PubMed

Jorgensen, Cynthia; Carnes, C Amanda; Downs, Alycia

2016-01-01

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions.

77 FR 37912 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

.... Project: Enhancing Substance Abuse Treatment Services To Address Hepatitis Infection Among Intravenous Drug Users Hepatitis Testing and Vaccine Tracking Form (OMB No. 0930-0300)--Reinstatement and Extension... Treatment (CSAT), is responsible for the Hepatitis Testing and Vaccine Tracking Form for the prevention of...

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness two years after treatment with Ombitasvir/Paritaprevir/Ritonavir ±Dasabuvir ±Ribavirin in the AMBER, real-world experience study.

PubMed

Flisiak, Robert; Janczewska, Ewa; Łucejko, Mariusz; Karpińska, Ewa; Zarębska-Michaluk, Dorota; Nazzal, Khalil; Bolewska, Beata; Białkowska, Jolanta; Berak, Hanna; Fleischer-Stępniewska, Katarzyna; Tomasiewicz, Krzysztof; Karwowska, Kornelia; Simon, Krzysztof; Piekarska, Anna; Tronina, Olga; Tuchendler, Ewelina; Garlicki, Aleksander

2018-06-11

We followed for 2 years patients treated with Direct Acting Agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction of liver stiffness (LS), and risk of hepatocellular carcinoma (HCC).The study included patients from 16 hepatologic centers involved in the AMBER, investigators initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. A total of 204 patients among 209 from the primary study were enrolled; 200 with available testing at 2 years follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 non-responders retreated). During 2yFU 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses was lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, two-years follow-up confirmed durability of virologic response after treatment of HCV infection with Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics, that support the need for longer than 2-year monitoring for possible disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

PubMed Central

Li, Yi-Ming; Lv, Fan; Xu, Xin; Ji, Hong; Gao, Wen-Tao; Lei, Tuan-Jie; Ren, Gui-Bing; Bai, Zhi-Lan; Li, Qiang

2003-01-01

AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and Child-Pugh’s classification, and to discuss its value of clinical application. METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a history of haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia. A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4 times before and after intravenous D-sorbitol infusion. The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QTOTAL) and intrahepatic shunt (RINS) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively. RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358 ± 0.064) mmol·L-1 in cirrhotic group and (0.189 ± 0.05) mmol·L-1 in control group (P < 0.01). CLH = (812.7 ± 112.4) mL·min-1, QTOTAL = (1280.6 ± 131.4) mL·min-1, and RINS = (36.54 ± 10.65)% in cirrhotic group and CLH = (1248.3 ± 210.5) mL·min-1, QTOTAL = (1362.4 ± 126.9) mL·min-1, and RINS = (8.37 ± 3.32)% in control group (P < 0.01). The liver volume of cirrhotic group was 1057 ± 249 cm3, 851 ± 148 cm3 and 663 ± 77 cm3 in Child A, B and C group respectively with significant difference (P < 0.001). The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P < 0.001). The patient, whose liver volume decreased by 40% with the CLH below 600 mL·min-1, would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CLH, liver volume and Child-Pugh’s classification. CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh’s classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time. PMID:12970913

Systematic review with meta-analysis: neuroimaging in hepatitis C chronic infection.

PubMed

Oriolo, G; Egmond, E; Mariño, Z; Cavero, M; Navines, R; Zamarrenho, L; Solà, R; Pujol, J; Bargallo, N; Forns, X; Martin-Santos, R

2018-05-01

Chronic hepatitis C is considered a systemic disease because of extra-hepatic manifestations. Neuroimaging has been employed in hepatitis C virus-infected patients to find in vivo evidence of central nervous system alterations. Systematic review and meta-analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C. Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer-reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis C patients without cirrhosis or encephalopathy, with control group. Meta-analyses were performed when possible. The final sample comprised 25 studies (magnetic resonance spectroscopy [N = 12], perfusion weighted imaging [N = 1], positron emission tomography [N = 3], single-photon emission computed tomography [N = 4], functional connectivity in resting state [N = 1], diffusion tensor imaging [N = 2] and structural magnetic resonance imaging [N = 2]). The whole sample was of 509 chronic hepatitis C patients, with an average age of 41.5 years old and mild liver disease. A meta-analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference [MD] 0.12, 95% confidence interval [CI] 0.06-0.18), creatine (MD 0.85, 95% CI 0.42-1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39-2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07-0.19) in chronic hepatitis C patients compared with healthy controls. Photon emission tomography studies meta-analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis C patients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies. Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances. © 2018 John Wiley & Sons Ltd.

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis.

PubMed

Takahashi, Hideaki; Shigefuku, Ryuta; Yoshida, Yoshihito; Ikeda, Hiroki; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2014-12-07

To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC). The subjects included 35 patients with AL-LC (34 men, 1 woman; mean age, 58.9 ± 10.7 years; median age, 61 years; range: 37-76 years). All patients were enrolled in this study after obtaining written informed consent. Liver function was measured with tests measuring albumin (Alb), prothrombin time (PT), brain natriuretic peptide (BNP), branched amino acid and tyrosine ratio (BTR), branched chain amino acid (BCAA), tyrosine, ammonia (NH3), cholinesterase (ChE), immunoreactive insulin (IRI), total bile acid (TBA), and the retention rate of indocyanine green 15 min after administration (ICG R15). Hepatic blood flow, hepatic arterial tissue blood flow (HATBF), portal venous tissue blood flow (PVTBF), and total hepatic tissue blood flow (THTBF) were simultaneously calculated using xenon computed tomography. PVTBF, HATBF and THTBF were 30.2 ± 10.4, 20.0 ± 10.7, and 50.3 ± 14.9 mL/100 mL/min, respectively. Alb, PT, BNP, BTR, BCAA, tyrosine, NH3, ChE, IRI, TBA, and ICG R15 were 3.50 ± 0.50 g/dL, 72.0% ± 11.5%, 63.2 ± 56.7 pg/mL, 4.06 ± 1.24, 437.5 ± 89.4 μmol/L, 117.7 ± 32.8 μmol/L, 59.4 ± 22.7 μg/dL, 161.0 ± 70.8 IU/L, 12.8 ± 5.0 μg/dL, 68.0 ± 51.8 μmol/L, and 28.6% ± 13.5%, respectively. PVTBF showed a significant negative correlation with ICG R15 (r = -0.468, P <0.01). No significant correlation was seen between ICG 15R, HATBF and THTBF. There was a significant correlation between PVTBF and Alb (r = 0.2499, P < 0.05), and NH₃ tended to have an inverse correlation with PVTBF (r = -0.2428, P = 0.0894). There were also many significant correlations between ICG R15 and liver function parameters, including Alb, NH3, PT, BNP, TBA, BCAA, and tyrosine (r = -0.2156, P < 0.05; r = 0.4318, P < 0.01; r = 0.4140, P < 0.01; r = 0.3610, P < 0.05; r = 0.5085, P < 0.001; r = 0.4496, P < 0.01; and r = 0.4740, P < 0.05, respectively). Our investigation showed that there is a close correlation between liver function and hepatic blood flow.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

Thyroidectomy in a patient with thyroid storm: report of a case.

PubMed

Uchida, Naotaka; Suda, Takako; Ishiguro, Kiyosuke

2015-01-01

Thyroid storm is a life-threatening condition that is generally considered to be a contradiction to surgical intervention. We herein describe the case of a 37-year-old patient with a history of Graves' disease who was transferred to Tottori University Hospital with thyroid storm. She had been followed by her family doctor since 2006, but she had stopped taking her medication of her own volition in 2010. About ten days prior to her admission at our hospital, she consulted her family doctor with complaints of dyspnea, palpitations and general fatigue. Subsequent thyroid function tests showed TSH < 0.01 μU/ml, FT3 25.0 pg/ml and FT4 8.0 ng/dl. She also had acute heart failure, atrial fibrillation and hepatic failure. A diagnosis of thyroid storm was made and she was transferred to our hospital. She received steroids, beta blockade, potassium iodide, and plasma exchange, but her hepatic failure did not resolve and her clinical condition deteriorated. The decision was made to proceed with thyroidectomy. Postoperatively, her hepatic function normalized. Thus, thyroidectomy is a potential therapeutic choice for cases of thyroid storm refractory to medical management.

Intraoperative factors associated with delayed recovery of liver function after hepatectomy: analysis of 1969 living donors.

PubMed

Choi, S-S; Cho, S-S; Ha, T-Y; Hwang, S; Lee, S-G; Kim, Y-K

2016-02-01

The safety of healthy living donors who are undergoing hepatic resection is a primary concern. We aimed to identify intraoperative anaesthetic and surgical factors associated with delayed recovery of liver function after hepatectomy in living donors. We retrospectively analysed 1969 living donors who underwent hepatectomy for living donor liver transplantation. Delayed recovery of hepatic function was defined by increases in international normalised ratio of prothrombin time and concomitant hyperbilirubinaemia on or after post-operative day 5. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with delayed recovery of hepatic function after living donor hepatectomy. Delayed recovery of liver function after donor hepatectomy was observed in 213 (10.8%) donors. Univariate logistic regression analysis showed that sevoflurane anaesthesia, synthetic colloid, donor age, body mass index, fatty change and remnant liver volume were significant factors for prediction of delayed recovery of hepatic function. Multivariate logistic regression analysis showed that independent factors significantly associated with delayed recovery of liver function after donor hepatectomy were sevoflurane anaesthesia (odds ratio = 3.514, P < 0.001), synthetic colloid (odds ratio = 1.045, P = 0.033), donor age (odds ratio = 0.970, P = 0.003), female gender (odds ratio = 1.512, P = 0.014) and remnant liver volume (odds ratio = 0.963, P < 0.001). Anaesthesia with sevoflurane was an independent factor in predicting delayed recovery of hepatic function after donor hepatectomy. Although synthetic colloid may be associated with delayed recovery of hepatic function after donor hepatectomy, further study is required. These results can provide useful information on perioperative management of living liver donors. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Viral hepatitis in a homeless shelter in Hawai'i.

PubMed

Boyce, Daniel E C; Tice, Alan D; Ona, Fernando V; Akinaka, Kenneth T; Lusk, Heather

2009-06-01

It is estimated that as many as 21,000 people in the state of Hawai'i may be infected with HCV Most of those infected with viral hepatitis are unaware they are infected. Complications from viral hepatitis include liver cirrhosis and hepatocellular carcinoma. Hawai'i has the highest incidence of hepatocellular carcinoma in the United States. In 2003 there were over 6000 homeless and over 155,000 people at-risk of becoming homeless living in the state of Hawai'i. Risk factors for hepatitis, such as drug use, tattoos, sexual contact, and sharing of personal hygiene equipment are more prevalent in the homeless population. To determine the incidence of hepatitis B and C among a population of homeless individuals, a health fair was held at a Honolulu area homeless shelter with approximately 200 residents. The incidence of hepatitis B and C was determined by anti-HCV and HBsAg blood tests. A survey was also conducted regarding risk factors and basic demographics. Fifty-nine homeless adults volunteered for testing and took the survey. Thirty-one (52%) volunteers were born in Micronesia, twenty-four (41%) were born in the United States, two (3%) were born in Samoa, one (2%) was born in the Philippines, and one (2%) was born in the Marshall Islands. Forty adults were tested for Hepatitis C antibody, three of which tested positive. The primary risk factor among this group was jail time (100%), followed by illegal drug injection (67%), tattoos (67%), ear/body piercing (67%), snorting drugs (33%), blood transfusions (33%), and a sex partner with hepatitis (33%). Forty adults were also tested for HBsAg, One of which tested positive. This was a recent immigrant from Micronesia. Homeless people in Hawai'i are more likely to have hepatitis B or C because risk factors are common among this population. Additionally a large proportion of Hawai'i's homeless people come from the Pacific Islands, where the prevalence of hepatitis B is one of the highest in the world. In addition there are significant risks of hepatitis spread among the homeless and into the general population as many homeless do not realize they are infected. The health fair approach was an effective means for screening homeless people for hepatitis B and C. Our preliminary information suggests homeless shelters may be a good place for education, screening, and possibly interventions as well.

Variation in the Viral Hepatitis and HIV Policies and Practices of Methadone Maintenance Programs.

PubMed

Jessop, Amy B; Hom, Jeffrey K; Burke, Monika

Patients prescribed methadone maintenance treatment (MMT) demonstrate elevated prevalence of hepatitis B virus (HBV), hepatitis C virus, and HIV. Government agencies recommend testing for these infections in MMT programs, but uptake is limited. We audited infection-related policies and practices of all 14 MMT programs in Philadelphia, Pennsylvania, in 2015. Results were tabulated and compared with the results from a 2010 audit of 10 of 12 MMT programs. The audit focused on which patients are tested, timing and frequency, specific tests ordered, vaccination, and communication of test results. Written policies were nonspecific, offering little guidance on appropriate testing. The principal change in policy between 2010 and 2015 involved adding clearer guidance for communication of results to patients. In 2010 and 2015, all MMT programs tested new patients for hepatitis C virus antibodies, although retesting of existing patients varied. HBV testing increased from 2010 to 2015, though it was not uniform, with 5 programs testing for HBV surface antibodies and 10 programs testing for HBV surface antigens. Six programs assessed hepatitis vaccination status, but only 1 administered vaccines. In 2010, city-sponsored HIV antibody testing was available at all MMT programs. Without this program in 2015, few MMT programs conducted HIV testing. Despite limited hepatitis and HIV screening in MMT programs nationally, this study shows that testing can be incorporated into routine procedures. MMT programs are positioned to play an integral role in the identification of patients with chronic infections, but additional guidance and resources are required to maximize their impact.

Donating Blood Questions and Answers

MedlinePlus

... isolated laboratory test results should not be considered equivalent to a history of viral hepatitis. In particular, ... transfusion. This test was intended as a surrogate non-specific test for hepatitis C (formerly called non- ...

The Epoxyeicosatrienoic Acid Pathway Enhances Hepatic Insulin Signaling and is Repressed in Insulin-Resistant Mouse Liver*

PubMed Central

Schäfer, Alexander; Neschen, Susanne; Kahle, Melanie; Sarioglu, Hakan; Gaisbauer, Tobias; Imhof, Axel; Adamski, Jerzy; Hauck, Stefanie M.; Ueffing, Marius

2015-01-01

Although it is widely accepted that ectopic lipid accumulation in the liver is associated with hepatic insulin resistance, the underlying molecular mechanisms have not been well characterized. Here we employed time resolved quantitative proteomic profiling of mice fed a high fat diet to determine which pathways were affected during the transition of the liver to an insulin-resistant state. We identified several metabolic pathways underlying altered protein expression. In order to test the functional impact of a critical subset of these alterations, we focused on the epoxyeicosatrienoic acid (EET) eicosanoid pathway, whose deregulation coincided with the onset of hepatic insulin resistance. These results suggested that EETs may be positive modulators of hepatic insulin signaling. Analyzing EET activity in primary hepatocytes, we found that EETs enhance insulin signaling on the level of Akt. In contrast, EETs did not influence insulin receptor or insulin receptor substrate-1 phosphorylation. This effect was mediated through the eicosanoids, as overexpression of the deregulated enzymes in absence of arachidonic acid had no impact on insulin signaling. The stimulation of insulin signaling by EETs and depression of the pathway in insulin resistant liver suggest a likely role in hepatic insulin resistance. Our findings support therapeutic potential for inhibiting EET degradation. PMID:26070664

Know Hepatitis B Questions and Answers for Asian Americans and Pacific Islanders (AAPIs)

MedlinePlus

... Campaign About our Partner Spread the Word Know Hepatitis B Questions and Answers Recommend on Facebook Tweet ... Overview Transmission Symptoms Testing Treatment Overview What is Hepatitis B? Hepatitis B is a liver disease. It ...

Molindone and hepatotoxicity.

PubMed

Bhatia, S C; Banta, L E; Ehrlich, D W

1985-10-01

An adolescent male with chronic schizophrenic disorder, paranoid type, was treated with molindone. He developed hepatotoxicity in the early treatment phase as evidenced by flu-like symptoms and laboratory abnormalities of liver functions. These symptoms and his hepatic functions improved on discontinuing molindone. Similar liver function trends were seen on reintroduction and subsequent withdrawal of the drug. Hepatic hypersensitivity has not been reported previously with the use of this drug. It is suggested that clinicians should be aware of this association and should assess hepatic functions in patients who develop a prodromal flu-like syndrome with this drug, especially in the early treatment phase.

Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer.

PubMed

Raut, V; Takaori, K; Kawaguchi, Y; Mizumoto, M; Kawaguchi, M; Koizumi, M; Kodama, S; Kida, A; Uemoto, S

2011-11-01

Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico-duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT scan. © 2011 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Blackwell Publishing Asia Pty Ltd.

The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing.

PubMed

Tucker, Joseph D; Meyers, Kathrine; Best, John; Kaplan, Karyn; Pendse, Razia; Fenton, Kevin A; Andrieux-Meyer, Isabelle; Figueroa, Carmen; Goicochea, Pedro; Gore, Charles; Ishizaki, Azumi; Khwairakpam, Giten; Miller, Veronica; Mozalevskis, Antons; Ninburg, Michael; Ocama, Ponsiano; Peeling, Rosanna; Walsh, Nick; Colombo, Massimo G; Easterbrook, Philippa

2017-11-01

Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7). The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed.

Initial report of a hepatitis investigation in rural Belize.

PubMed

Hoffman, K J; Gaydos, J C; Krieg, R E; Duncan, J F; MacArthy, P O; Ticehurst, J R; Jaramillo, R; Reyes, L G; Sjogren, M H; Legters, L J

1993-01-01

In spring 1991, Belizian health officials expressed concern about a possible hepatitis outbreak in a banana farming district. A study was designed to identify cases and to address the serological prevalence of hepatitis virus markers. Three populations were studied: (i) persons meeting a clinical case definition for hepatitis; (ii) designated banana workers; and (iii) people in a random sample of households in the community. Information was collected using questionnaires and sera were collected for laboratory testing. This report presents the preliminary results of a study conducted in June 1991. Among people who met the clinical case definition, 24% of 42 tested had immunoglobulin M antibody to hepatitis B virus (HBV) core antigen (anti-HBc IgM). In the worker and household survey populations, 284 and 280 people, respectively, were tested for anti-HBc IgM. In each group, 4% were positive. HBV surface antigen was found in 37% of 43 clinical cases, 18% of workers, and 13% of people in the household survey. Among the 3 study populations, the prevalence of HBV core antibody (anti-HBc) ranged from 73% to 81%. Almost all tested persons had evidence of prior hepatitis A virus infection. Evidence of prior infection with hepatitis viruses A and B was widespread, but an aetiology could not be established for most of the clinical cases. However, the prevalence of hepatitis B markers in this population was very high compared to other reports from the Caribbean.

Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre.

PubMed

Majumdar, Kaushik; Sakhuja, Puja; Puri, Amarender Singh; Gaur, Kavita; Haider, Aiman; Gondal, Ranjana

2018-05-01

Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described. To assess the histological spectrum of 'coeliac hepatitis' and possibility of reversal of such features after a GFD. Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible. Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score. Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in 'coeliac hepatitis'. Trial of a GFD may result in clinicopathological improvement of 'coeliac hepatitis'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

PubMed Central

Russell, Jacquelyn O.; Monga, Satdarshan P.

2018-01-01

The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. The Wnt/β-catenin pathway plays a role in almost every facet of liver biology. Furthermore, its aberrant activation is also a hallmark of various hepatic pathologies. In addition to its signaling function, β-catenin also plays a role at adherens junctions. Wnt/β-catenin signaling also influences the function of many different cell types. Due to this myriad of functions, Wnt/β-catenin signaling is complex, context-dependent, and highly regulated. In this review, we discuss the Wnt/β-catenin signaling pathway, its role in cell-cell adhesion and liver function, and the cell type–specific roles of Wnt/β-catenin signaling as it relates to liver physiology and pathobiology. PMID:29125798

Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA.

PubMed

Sekiba, Kazuma; Otsuka, Motoyuki; Ohno, Motoko; Yamagami, Mari; Kishikawa, Takahiro; Suzuki, Tatsunori; Ishibashi, Rei; Seimiya, Takahiro; Tanaka, Eri; Koike, Kazuhiko

2018-06-07

Hepatitis B virus (HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host miRNAs and may deregulate miRNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viral-derived miRNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBV-derived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBV-induced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.

A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

PubMed Central

Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

2013-01-01

Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

The future of viral hepatitis testing: innovations in testing technologies and approaches.

PubMed

Peeling, Rosanna W; Boeras, Debrah I; Marinucci, Francesco; Easterbrook, Philippa

2017-11-01

A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most people with hepatitis remain unaware of their infection. Advances in rapid detection technology have created new opportunities for enhancing access to testing and care, as well as monitoring of treatment. This article examines a range of other technological innovations that can be leveraged to provide more affordable and simplified approaches to testing for HBV and HCV infection and monitoring of treatment response. These include improved access to testing through alternative sampling methods (use of dried blood spots, oral fluids, self-testing) and combination rapid diagnostic tests for detection of HIV, HBV and HCV infection; more affordable options for confirmation of virological infection (HBV DNA and HCV RNA) such as point-of-care molecular assays, HCV core antigen and multi-disease polyvalent molecular platforms that make use of existing centralised laboratory based or decentralised TB and HIV instrumentation for viral hepatitis testing; and finally health system improvements such as integration of laboratory services for procurement and sample transportation and enhanced data connectivity to support quality assurance and supply chain management.

Routine screening of blood donations at Qingdao central blood bank, China, for hepatitis B virus (HBV) DNA with a real-time, multiplex nucleic acid test for HBV, hepatitis C virus, and human immunodeficiency virus Types 1 and 2.

PubMed

Yang, Zhongsi; Xu, Lei; Liu, Li; Feng, Qiuxia; Zhang, Longmu; Ma, Weijuan; Saldanha, John; Wang, Mingmin; Zhao, Lin

2013-10-01

The Roche cobas TaqScreen MPX test was used to evaluate the rate of hepatitis B surface antigen (HBsAg)-negative donations that were hepatitis B virus (HBV) DNA reactive from June 2010 to January 2011 in Qingdao, China. HBsAg-negative samples from 65,800 voluntary blood donors were tested with the cobas TaqScreen MPX test in pools of 6 on the Roche cobas s 201 blood screening platform. Samples positive for HBV DNA and negative for HBsAg were quantitated with the Roche COBAS AmpliPrep/COBAS TaqMan HBV test. In addition, serologic tests for HBsAg, hepatitis B surface antibody, anti-hepatitis B core antigen (anti-HBc), anti-hepatitis B e antigen (anti-HBe), and hepatitis B e antigen (HBe) were done using the Roche electrochemiluminescence immunoassay. A total of 80 nucleic acid amplification technology (NAT) test-reactive pools were identified and 59 pools (74%) resolved to a reactive sample. All samples were HBV DNA reactive and the viral load in each sample was quantitated. The viral loads of the samples ranged from less than 20 to 34,600 IU/mL; 13 samples (22%) had viral loads of more than 20 IU/mL, 27 samples (45.8%) had viral loads of less than 20 IU/mL, and 19 samples (32.2%) had undetectable viral loads. Of the 59 NAT-reactive samples, 40 (67.8%) were anti-HBc positive. Fifteen of the 59 samples could not be confirmed as NAT reactive either by an alternative NAT test or by serology. The HBV NAT yield in blood donors in Qingdao is 0.06% (38/65,800). This study confirmed the value of NAT for interdicting HBV-positive donations and preventing transfusion-transmitted HBV infections. © 2013 American Association of Blood Banks.

Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

PubMed

Mohamed, Omar E; Jones, Julie; Osman, Husam; Huissoon, Aarnoud P

2017-08-09

Data from recent studies suggest rising incidence rate of hepatitis E virus (HEV) infection in the UK. HEV infection may take a severe and persistent course in immunocompromised patients, including transplant recipients on immunosuppressives, patients with HIV, haematological malignancies and in idiopathic CD4 + T lymphocytopenia. The prevalence of HEV in primary antibody deficiency (PAD) disorders is still unknown. The aim of this study was to investigate HEV infection in 27 patients with PAD with unexplained, persistently elevated liver enzymes. Although all the 27 patients tested negative for HEV-RNA, we would still strongly recommend that HEV should be considered in any immunodeficient patient with impaired liver function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The natural history of autoimmune hepatitis presenting with jaundice.

PubMed

Panayi, Vasilis; Froud, Oliver J; Vine, Louisa; Laurent, Paul; Woolson, Kathy L; Hunter, Jeremy G; Madden, Richard G; Miller, Catherine; Palmer, Jo; Harris, Nicola; Mathew, Joe; Stableforth, Bill; Murray, Iain A; Dalton, Harry R

2014-06-01

Forty percent of patients with autoimmune hepatitis (AIH) present with acute jaundice/hepatitis. Such patients, when treated promptly, are thought to have a good prognosis. The objective of this study was to describe the natural history of AIH in patients presenting with jaundice/hepatitis and to determine whether the diagnosis could have been made earlier, before presentation. This study is a retrospective review of 2249 consecutive patients who presented with jaundice to the Jaundice Hotline clinic, Truro, Cornwall, UK, over 15 years (1998-2013) and includes a review of the laboratory data over a 23-year period (1990-2013). Of the 955 patients with hepatocellular jaundice, 47 (5%) had criterion-referenced AIH: 35 female and 12 male, the median age was 65 years (range 15-91 years); the bilirubin concentration was 139 μmol/l (range 23-634 μmol/l) and the alanine transaminase level was 687 IU/l (range 22-2519 IU/l). Among the patients, 23/46 (50%) were cirrhotic on biopsy; 11/47 (23%) died: median time from diagnosis to death, 5 months (range 1-59); median age, 72 years (range 59-91 years). All 8/11 patients who died of liver-related causes were cirrhotic. Weight loss (P=0.04) and presence of cirrhosis (P=0.004) and varices (P=0.015) were more common among those who died. Among patients who died from liver-related causes, 6/8 (75%) died less than 6 months from diagnosis. Cirrhosis at presentation and oesophageal varices were associated with early liver-related deaths (P=0.011, 0.002 respectively). Liver function test results were available in 33/47 (70%) patients before presentation. Among these patients, 16 (49%) had abnormal alanine transaminase levels previously, and eight (50%) were cirrhotic at presentation. AIH presenting as jaundice/hepatitis was mainly observed in older women: 50% of the patients were cirrhotic, and liver-related mortality was high. Some of these deaths were potentially preventable by earlier diagnosis, as the patients had abnormal liver function test results previously, which had not been investigated.

Phoenix dactylifera protects against oxidative stress and hepatic injury induced by paracetamol intoxication in rats.

PubMed

Salem, Gamal A; Shaban, Ahmed; Diab, Hussain A; Elsaghayer, Wesam A; Mjedib, Manal D; Hnesh, Aomassad M; Sahu, Ravi P

2018-05-16

The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group. These PCM-induced effects were associated with oxidative stress as demonstrated by increased levels of malondialdehyde (MDA) and reduced levels of hepatic antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Pretreatment of PLME decreased ALT and AST by 78.2% and tissue MDA by 54.1%, and increased hepatic GPx (3.5 folds), CAT (7 folds) and SOD (2.5 folds) compared to PCM group. These PLME-mediated effects were comparable to NAC pretreatment. Histological analysis demonstrates that PLME conserved hepatic tissues against lesions such as inflammation, centrilobular necrosis, and hemorrhages induced by PCM. In contrast, PLAE-mediated effects were less effective in reducing levels of liver function enzymes, oxidative stress, and liver histopathological profiles, and restoring antioxidant defenses against PCM-induced intoxication. These findings indicate that PLME exerts protective effects against PCM-induced hepatotoxicity via scavenging free radicals and restoring hepatic antioxidant enzymes. Thus, PLME and its bioactive components could further be evaluated for their pharmacological properties against drug-induced deleterious effects. Copyright © 2018. Published by Elsevier Masson SAS.

Hepatic expression of spermatogenic genes and their transiently remarkable downregulations in Wistar-Kyoto rats in response to lead-nitrate administration: strain-difference in the gene expression patterns.

PubMed

Nemoto, Kiyomitsu; Ito, Sei; Yoshida, Chiaki; Miyata, Misaki; Kojima, Misaki; Degawa, Masakuni

2011-06-01

Administration of lead ion (Pb) to rats and mice affects hepatic functions such as the induction of hepatic cell proliferation and upregulation of cholesterol biosynthesis. To identify the genes for which expression changes in response to Pb-administration, we analyzed hepatic gene expression patterns in stroke-prone spontaneously hypertensive rat (SHRSP), its normotensive control, Wistar-Kyoto rat (WKY), and Spraque-Dawley (SD) rat strains, 3, 6, and 12 hr later after single i.v. injection of lead nitrate (LN) at a dose of 100 µmol using a DNA microarray technique. The data analysis demonstrated that the expression of a great number of genes was transiently and remarkably downregulated 3 hr after LN-injection, and then recovered to control levels only in LN-injected WKY. These normal hepatic expression levels in WKY and SHRSP were much higher than those in SD rats. Furthermore, most of these genes were ones thought to be expressed specifically in the spermatids and/or testes; i.e. genes encoding protamin 1, transition protein 1, and transition protein 2. These findings suggest that the regulation system common to expression of all of these genes could be a target site of Pb-toxic action, at least, in the liver of WKY, and that this system might be similar to the system essential for spermatogenesis, especially spermiogenesis, in the testis. In addition, it appears that clarifying the cause of the difference between the systems of WKY and SHRSP might aid in identifying the pathologic genes in SHRSP. Finally, it will be an important to clarify how the products of the genes related to spermatogenesis, including spermiogenesis, are functional in the livers of WKY and SHRSP.

Impact of contrast-enhanced ultrasound in the study of hepatic artery hypoperfusion shortly after liver transplantation: contribution to the diagnosis of artery steal syndrome.

PubMed

García-Criado, Angeles; Gilabert, Rosa; Bianchi, Luis; Vilana, Ramón; Burrel, Marta; Barrufet, Marta; Oliveira, Rafael; García-Valdecasas, Juan Carlos; Brú, Concepción

2015-01-01

To assess the value of contrast-enhanced ultrasound (CEUS) in the absence of hepatic artery signal on Doppler ultrasound (DUS) in the immediate postoperative period after liver transplant. This prospective study included 675 consecutive liver transplants. Patients without hepatic artery signal by DUS within 8 days post-transplant were studied with CEUS. If it remained undetectable, a thrombosis was suspected. In patent hepatic artery, a DUS was performed immediately after CEUS; if low resistance flow was detected, an arteriography was indicated. Patients with high resistance waveform underwent DUS+/CEUS follow-up. Arteriography was indicated when abnormal flow persisted for more than 5 days or liver dysfunction appeared. Thirty-four patients were studied with CEUS. In 11 patients CEUS correctly diagnosed hepatic artery thrombosis. In two out of 23 non-occluded arteries, a low resistance flow lead to a diagnosis of stenosis/proximal thrombosis. Twenty-one patients had absence of diastolic flow, which normalized in the follow-up in 13 patients. In the remaining eight patients, splenic artery steal syndrome (ASS) was diagnosed. CEUS allows us to avoid invasive tests in the diagnostic work-up shortly after liver transplant. It identifies the hepatic artery thrombosis and points to a diagnosis of ASS. • CEUS is useful in the diagnostic work-up shortly after liver transplant • CEUS identifies the hepatic artery thrombosis with reliability • There is little information about DUS and CEUS findings in the ASS • DUS and CEUS offer functional information useful in the diagnosis of ASS.

Prevalence of HBsAg, knowledge, and vaccination practice against viral hepatitis B infection among doctors and nurses in a secondary health care facility in Lagos state, South-western Nigeria.

PubMed

Abiola, Abdul-Hakeem Olatunji; Agunbiade, Adebukola Bola; Badmos, Kabir Bolarinwa; Lesi, Adenike Olufunmilayo; Lawal, Abdulrazzaq Oluwagbemiga; Alli, Quadri Olatunji

2016-01-01

Hepatitis B Virus, a highly infectious blood-borne virus poses a major threat to public health globally due to its high prevalence rate and grave consequence in causing liver cirrhosis and hepatocelullar carcinoma, the third cause of cancer death worldwide. The aim is determine the prevalence of HBsAg, knowledge, and vaccination practices against viral hepatitis B infection among doctors and nurses in a health care facility. Study design was a descriptive cross-sectional study among all the doctors and nurses in the health care facility. Data was collected using pre-tested, structured, self-administered questionnaire and blood samples were taken from respondents and tested using commercial enzyme-linked immunosorbent assay (ELIZA) test kit to determine prevalence of hepatitis B surface antigen after informed consent. Ethical approval was obtained from Health Research and Ethics Committee of the Lagos University Teaching Hospital. Responses of the respondents to the knowledge and vaccination practices against viral hepatitis B infection were scored and graded as poor (<50%), fair (50-74%) and good (≥75%). The study was carried out in January, 2014. A total of 134 out of the 143 recruited respondents participated in the study. Prevalence of HBsAg was 1.5%. Among the respondents, 56.7% had good knowledge and 94.8% reported poor practice of vaccination against viral hepatitis B infection. Mean knowledge and vaccination practices scores (%) were 72.54+7.60 and 29.44+14.37 respectively. Only 29% of the respondents did post vaccination testing for anti HBsAg. Prevalence of HBsAg was low. Knowledge of viral hepatitis B was fair, and practice of post hepatitis B vaccination testing was poor. It is therefore recommended that the state ministry of health should organise further health education programme, institute compulsory occupational hepatitis B vaccination programme and post vaccination anti-HBS testing to ensure adequate antibody level in this adult population.

Expression of hepatic lipid droplets is decreased in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Takahashi, Hiromizu; Kutasy, Balazs; Friedmacher, Florian; Takahashi, Toshiaki; Puri, Prem

2016-02-01

Prenatal mortality in newborn infants with congenital diaphragmatic hernia (CDH) has been attributed to increased amounts of liver hernia ion through the diaphragmatic defect. Antenatal studies in human and rodent fetus with CDH further demonstrated a contribution of the developing liver in the pathogenesis of CDH. The abnormal hepatic growth in experimental animal models, therefore, indicates a disruption of normal liver development in CDH. However, the underlying structural, histological and functional changes in the liver of animals with CDH remain unclear. We design this study to test the hypothesis that the morphological and cellular liver development is altered in the nitrogen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Livers and chest were harvested on D21 and divided into two groups: control (n = 8), nitrofen with CDH (CDH, n = 8). Haematoxylin-eosin (Straub et al. Histopathology 68:617-631, 2013) staining was performed to evaluate underlying morphological changes. Apoptosis was checked by using TUNEL staining and apoptotic cell number was counted on 16-16 slides in 25 fields by two independent viewers. Hepatic lipid droplet expressions were evaluated by hepatic adipose differentiation-related protein (ARDP) expression. Compared to controls markedly increased hypertrophy was seen in CDH group. Significantly increased apoptotic cell numbers were detected in CDH group compared to controls (5.1 ± 1.5 vs 2.1 ± 0.6) (p < 0.05). The relative mRNA expression levels of ARDP were significantly reduced in CDH group compared to controls. Immunohistochemistry showed markedly decreased hepatic ADRP immunoreactivity in CDH fetuses compared to controls. Our findings provide strong evidence of hepatic hypertrophy and increased cell apoptosis in the liver of nitrofen-induced CDH. These morphological changes may affect liver lipid droplet expression function.

Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.

PubMed

Gish, Robert G; Given, Bruce D; Lai, Ching-Lung; Locarnini, Stephen A; Lau, Johnson Y N; Lewis, David L; Schluep, Thomas

2015-09-01

The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

PubMed

Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

2015-07-01

Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Diagnosis of liver involvement in early syphilis. A critical review.

PubMed

Veeravahu, M

1985-01-01

The diagnosis of liver involvement in early syphilis has always posed problems because of its rarity and the difficulty of excluding coincidental liver disease caused by a multitude of pathogens. Case reports deal predominantly with jaundiced homosexual men in whom syphilis is discovered later, and the prospective studies of patients with early syphilis disclose only mild biochemical abnormalities in liver function test results. There is no single characteristic feature attributable to early syphilitic hepatitis. Even liver histologic findings are variable. At least in those patients who have jaundice, there is a likelihood of coincidental viral hepatitis. Therefore, the evidence to implicate Treponema pallidum as a liver pathogen in early syphilis is not convincing.

Hepatitis A virus: a test method for virucidal activity.

PubMed

Wolff, M H; Schmitt, J; Rahaus, M; König, A

2001-08-01

Hepatitis A virus (HAV) is closely related to the genus enterovirus. HAV is very stable and resistant to acid pH and elevated temperature, as well as to chemicals and environmental influences. Human poliovirus is still one of the model viruses for testing disinfectants but there are discussions about changing to hepatitis A virus. The purpose of this study was to develop a method for using adapted hepatitis A virus to test hand disinfectants. Using HAV strains HM175/24a and FRhK-4 cytopathic effects were visible rarely, and not before 14 days. To verify virus growth in cells a RT-PCR was developed. Two disinfectants tested did not show the required virucidal activity to satisfy current German guidelines.

Nadolol for lithium tremor in the presence of liver damage.

PubMed

Dave, M; Langbart, M M

1994-03-01

Lithium-induced tremor classically responds to treatment with propranolol. Since it is metabolized in the liver, propranolol may not be the drug of choice in those patients who have compromised liver function or who are recovering from prior liver diseases. Another nonselective beta-adrenergic blocker, nadolol, has no hepatic biotransformation. We present here the first case report of successful treatment of lithium-induced tremor with nadolol, which was selected because the patient had compromised liver function. The patient's liver function tests remained stable with the therapy.

Insulin protects against hepatic damage postburn.

PubMed

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.

Insulin Protects against Hepatic Damage Postburn

PubMed Central

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes. PMID:21267509

Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies

PubMed Central

Ju, Cynthia; Tacke, Frank

2016-01-01

Macrophages represent a major cell type of innate immunity and have emerged as a critical player and therapeutic target in many chronic inflammatory diseases. Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. Hepatic macrophages play a central role in maintaining homeostasis of the liver and in the pathogenesis of liver injury, making them an attractive therapeutic target for liver diseases. However, the various populations of hepatic macrophages display different phenotypes and exert distinct functions. Thus, more research is required to better understand these cells to guide the development of macrophage-based therapeutic interventions. This review article will summarize the current knowledge on the origins and composition of hepatic macrophages, their functions in maintaining hepatic homeostasis, and their involvement in both promoting and resolving liver inflammation, injury, and fibrosis. Finally, the current strategies being developed to target hepatic macrophages for the treatment of liver diseases will be reviewed. PMID:26908374

Acute hepatitis after amiodarone infusion.

PubMed

Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

2015-10-16

Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.

Models and methods for in vitro testing of hepatic gap junctional communication.

PubMed

Maes, Michaël; Yanguas, Sara Crespo; Willebrords, Joost; Vinken, Mathieu

2015-12-25

Inherent to their pivotal roles in controlling all aspects of the liver cell life cycle, hepatocellular gap junctions are frequently disrupted upon impairment of the homeostatic balance, as occurs during liver toxicity. Hepatic gap junctions, which are mainly built up by connexin32, are specifically targeted by tumor promoters and epigenetic carcinogens. This renders inhibition of gap junction functionality a suitable indicator for the in vitro detection of nongenotoxic hepatocarcinogenicity. The establishment of a reliable liver gap junction inhibition assay for routine in vitro testing purposes requires a cellular system in which gap junctions are expressed at an in vivo-like level as well as an appropriate technique to probe gap junction activity. Both these models and methods are discussed in the current paper, thereby focusing on connexin32-based gap junctions. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatic encephalopathy

PubMed Central

2017-01-01

Abstract Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients. PMID:28533911

The role of T2*-weighted gradient echo in the diagnosis of tumefactive intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse hepatic iron overload: a case report and review of the literature.

PubMed

Belay, Abel A; Bellizzi, Andrew M; Stolpen, Alan H

2018-01-15

Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been previously described. A 52-year-old white man with myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic lesion on ultrasound during workup for bone marrow transplantation. Magnetic resonance imaging revealed diffuse hepatic iron overload and non-visualization of the lesion on T2* gradient-echo sequence suggesting the presence of iron deposition within the lesion similar to that in background hepatic parenchyma. Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary hematopoiesis. Six months later, while still being evaluated for bone marrow transplant, our patient was found to have poor pulmonary function tests. Follow-up computed tomography angiogram showed a mass within his right main pulmonary artery. Bronchoscopic biopsy of this mass once again revealed extramedullary hematopoiesis. He received radiation therapy to his chest. However, 2 weeks later, he developed mediastinal hematoma and died shortly afterward, secondary to respiratory arrest. Mass-forming extramedullary hematopoiesis is rare; however, our report emphasizes that it needs to be considered in the initial differential diagnosis of hepatic lesions arising in the setting of bone marrow disorders. We also show that in the setting of diffuse hepatic iron overload, tumefactive extramedullary hematopoiesis appeared isointense to background liver on T2* gradient-echo sequence, while adenoma, hepatoma, and hepatic metastasis appear hyperintense. Thus, T2*-weighted gradient-echo sequence may have a potential role in the imaging diagnosis of mass-forming hepatic extramedullary hematopoiesis arising in the setting of diffuse iron overload.

Co-infection by hepatitis B virus and hepatitis C virus in renal transplantation: morbidity and mortality in 1098 patients.

PubMed

Pouteil-Noble, C; Tardy, J C; Chossegros, P; Mion, F; Chevallier, M; Gérard, F; Chevallier, P; Megas, F; Lefrançois, N; Touraine, J L

1995-01-01

The aim of the study was to analyse the influence of co-infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) as compared with HCV infection alone in 1098 patients who received a kidney transplant between 1 January and 31 December 1991. At transplantation, the prevalence of anti-HCV antibodies was 21.40% (235/1098) while the prevalence of HBV infection was 9.85% (108/1096); 46 patients were co-infected with HBV and HCV, either 19.70% of HCV-infected patients and 42.60% of HBV-infected patients. Liver tests, galactose clearance and liver biopsy were compared in the 46 co-infected patients (HCV+HBV+) and in the 189 HCV-infected patients (HCV+HBV-). At the time of transplantation, cytolysis was present in 31.45% of HCV+HBV- patients (50/159) and in 40% of HCV+HBV- patients (16/40); cholestasis was present in 34.18% of HCV+HBV- patients (34/158) and 42.11% of HCV+HBV+ patients (16/38). At 6 months the incidence of biological abnormalities increased to 37% in HCV+HBV- patients (55/150) and to 52.5% in HCV+HBV+ patients (21/40), suggesting a more deleterious effect of the immunosuppressive therapy in the co-infected group. Over the course of transplantation, chronic hepatitis was present in 50% of HCV+HBV- patients and in 64.1% of HCV+HBV+ patients. Liver failure occurred in 7% of HCV+HBV- patients (12/156) and 17% of HCV+HBV+ patients (7/41). Galactose clearance was performed as a functional test in 68 patients: it was not significantly different in either group. Liver biopsy was performed in 108 patients at least once.(ABSTRACT TRUNCATED AT 250 WORDS)

Prodromal fever indicates a high risk of liver failure in acute hepatitis B.

PubMed

Du, Wen-Jun; Liu, Li; Sun, Chao; Yu, Jin-Hong; Xiao, Di; Li, Qiang

2017-04-01

The role of prodromal fever in the clinical course of acute hepatitis B virus (HBV) infection is still largely unclear. This study was conducted to investigate the factors associated with prodromal fever and its role in the development of acute liver failure (ALF) in patients with acute hepatitis B (AHB). Inpatients with AHB diagnosed between January 2006 and December 2010 were evaluated and followed. Clinical manifestations, results of laboratory tests, and outcomes were compared between patients with and without prodromal fever. The diagnosis of AHB was based on the discrete onset of symptoms, jaundice, abnormal liver function tests, the detection of high-titer IgM antibody to hepatitis B core antigen (anti-HBc), and a compatible clinical history. A total of 618 AHB inpatients were identified during the study period, of whom 102 (16.5%) had prodromal fever and 41 (6.6%) developed ALF. Prodromal fever indicated more severe liver injury and was independently associated with hepatitis B e antigen (HBeAg) negativity. The occurrence of ALF was more common in febrile patients than in non-febrile patients (18.6% vs. 4.3%, p<0.001). Multivariate logistic regression showed prodromal fever and temperature >38.0°C to be independently associated with the risk of ALF, with an odds ratio (95% confidence interval) of 3.5 (1.4-8.6) and 7.1 (2.6-19.7), respectively. AHB patients with prodromal fever, which is associated with a lack of HBeAg due to HBV mutation, are at high risk of ALF. Febrile patients with AHB should be managed with particular care. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

PubMed

Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

2016-03-29

Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

PubMed Central

Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

2016-01-01

AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria. PMID:27217699

Restorative effects of hydroxysafflor yellow A on hepatic function in an experimental regression model of hepatic fibrosis induced by carbon tetrachloride

PubMed Central

Li, Yanuo; Shi, Yan; Sun, Yan; Liu, Luying; Bai, Xianyong; Wang, Dong; Li, Hongxing

2017-01-01

Hepatic fibrosis is a reversible pathological process, in which fibrotic tissue is excessively deposited in the liver during the repair process that follows hepatic injury. Early prevention or treatment of hepatic fibrosis has great significance on the treatment of chronic hepatic diseases. Hydroxysafflor yellow A (HSYA) is a water-soluble monomer extracted from safflower, which serves numerous pharmacological roles. However, it remains to be elucidated how HSYA regulates hepatic fibrogenesis. The aim of the present study was to reveal the possible mechanisms underlying the effects of HSYA on the prevention and treatment of hepatic fibrosis. A rat model of hepatic fibrosis was established in the present study, and the rats were administered various doses of HSYA. The effects of HSYA on pathological alterations of the liver tissue in rats with hepatic fibrosis were observed using hematoxylin-eosin staining and Masson staining. In order to explore the anti-hepatic fibrosis effects and underlying mechanisms of HSYA, serum levels, and hepatic function and hepatic fibrosis indices were evaluated. The results demonstrated that HSYA can improve the general condition of rats with hepatic fibrosis and relieve cellular swelling of the liver, fatty degeneration, necrosis, inflammatory cell infiltration and fibroplastic proliferation. Subsequent to administration of HSYA, globulin was increased during hepatic fibrosis caused by tetrachloromethane. However, total cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase and levels of hyaluronic acid, laminin, procollagen III N-terminal peptide, collagen type IV and hydroxyproline were significantly reduced. The results additionally demonstrated that HSYA could enhance superoxide dismutase activity and reduce malondialdehyde levels, inhibiting lipid peroxidation caused by free radicals. PMID:27909717

Risk factors of hepatic dysfunction in patients with Graves’ hyperthyroidism and the efficacy of 131iodine treatment

PubMed Central

Wang, Renfei; Tan, Jian; Zhang, Guizhi; Zheng, Wei; Li, Chengxia

2017-01-01

Abstract Hepatic dysfunction is often observed in patients with Graves’ hyperthyroidism. The aims of this study were to investigate the risk factors for hepatic dysfunction and to analyze the efficacy of 131I (radioactive iodine-131) treatment. In total, 2385 patients with Graves’ hyperthyroidism (478 males, 1907 females; age 42.8 ± 13.5 years) were involved in our study. Of these, 1552 cases with hepatic dysfunction received 131I treatment. All clinical data were retrospectively reviewed to explore the risk factors associated with hepatic dysfunction using logistic regression analysis. Furthermore, we observed thyroid and liver function indices for the 1552 subjects at 3, 6 and 12 months after 131I treatment, in order to evaluate efficacy. Overall, 65% patients were affected by hepatic dysfunction. The most common abnormality was elevated alkaline phosphatase (ALP), of which the prevalence was 52.3%. The percentages of hepatocellular injury type, bile stasis, and mixed type were 45.8%, 32.4%, and 21.8%, respectively. Both univariate and multivariate analyses demonstrated that age, duration of Graves hyperthyroidism, free triiodothyronine (FT3)level, and thyrotrophin receptor antibody (TRAb) concentration were the most significant risk factors predicting hepatic dysfunction. Additionally, the patients with mild hepatic dysfunction, or hepatocellular injury type were more likely to attain normal liver function after 131I treatment. Furthermore, after 131I treatment, liver function was more likely to return to normal in the cured group of patients compared with the uncured group. Older patients and cases with a longer history of Graves’ hyperthyroidism, higher FT3 or TRAb concentration were more likely to be associated with hepatic dysfunction, and the prognosis of hepatic dysfunction was closely associated with the outcomes of Graves’ hyperthyroidism after 131I treatment. PMID:28151911

2017 European guideline for the screening, prevention and initial management of hepatitis B and C infections in sexual health settings.

PubMed

Brook, Gary; Brockmeyer, Norbert; van de Laar, Thijs; Schellberg, Sven; Winter, Andrew J

2018-01-01

This guideline updates the 2010 European guideline for the management of hepatitis B and C virus infections. It is primarily intended to provide advice on testing, prevention and initial management of viral hepatitis B and C for clinicians working in sexual health clinical settings in European countries. The guideline is in a new question and answer format based on clinical situations, from which population/intervention/comparison/outcome questions were formulated. Updates cover areas such as epidemiology, point-of-care tests for hepatitis B, hepatitis C risk and 'chemsex', and HIV pre-exposure prophylaxis and hepatitis B. We have also included a short paragraph on hepatitis E noting there is no evidence for sexual transmission. The guideline has been prepared in accordance with the Europe protocol for production available at http://www.iusti.org/regions/europe/pdf/2017/ProtocolForProduction2017.pdf.

Case-finding for hepatitis C in primary care: a mixed-methods service evaluation

PubMed Central

Datta, Shivani; Horwood, Jeremy; Hickman, Matthew; Sharp, Debbie

2014-01-01

Background Hepatitis C is often asymptomatic, presenting with liver failure and cancer decades after infection. People who inject drugs (PWID) and immigrant populations from countries with a moderate-to-high prevalence of hepatitis C virus (HCV) are the main risk groups. Deaths and hospital admissions due to HCV cirrhosis tripled between 1998 and 2010, but the majority of people with chronic HCV are unaware of it. Aim To identify patients at risk of developing hepatitis C using routine GP data, to determine the proportion not tested, and to explore GPs’ views regarding testing. Design and setting Mixed-methods service evaluation (density-based selection of PWID) in six NHS practices in Bristol. Method Patients at risk of HCV were identified. The Health Protection Agency laboratory (now part of Public Health England) provided test results. Semi-structured interviews with 17 GPs were audiorecorded and thematic analyses conducted on anonymised transcripts. Results Of 3765 patients identified as being at risk of developing hepatitis C, 3051 (81%) had no test result, including 53% of PWID and 93% of the ‘ethnicity’ group. All GPs said they usually test PWID. Most GPs test for HIV and hepatitis B in immigrants more often than they test for HCV. Barriers to testing included not questioning patients about risk factors, competing priorities, the chaotic lifestyle of PWID, difficulty extracting information from computerised records, and forgetting to address HCV. Conclusion Computer prompts and GP education on whom to test are warranted. Ensuring that country of origin and drug use is included on the new-patient questionnaire might also aid case-finding for HCV. PMID:24567619

Case-finding for hepatitis C in primary care: a mixed-methods service evaluation.

PubMed

Datta, Shivani; Horwood, Jeremy; Hickman, Matthew; Sharp, Debbie

2014-02-01

Hepatitis C is often asymptomatic, presenting with liver failure and cancer decades after infection. People who inject drugs (PWID) and immigrant populations from countries with a moderate-to-high prevalence of hepatitis C virus (HCV) are the main risk groups. Deaths and hospital admissions due to HCV cirrhosis tripled between 1998 and 2010, but the majority of people with chronic HCV are unaware of it. To identify patients at risk of developing hepatitis C using routine GP data, to determine the proportion not tested, and to explore GPs' views regarding testing. Mixed-methods service evaluation (density-based selection of PWID) in six NHS practices in Bristol. Patients at risk of HCV were identified. The Health Protection Agency laboratory (now part of Public Health England) provided test results. Semi-structured interviews with 17 GPs were audiorecorded and thematic analyses conducted on anonymised transcripts. Of 3765 patients identified as being at risk of developing hepatitis C, 3051 (81%) had no test result, including 53% of PWID and 93% of the 'ethnicity' group. All GPs said they usually test PWID. Most GPs test for HIV and hepatitis B in immigrants more often than they test for HCV. Barriers to testing included not questioning patients about risk factors, competing priorities, the chaotic lifestyle of PWID, difficulty extracting information from computerised records, and forgetting to address HCV. Computer prompts and GP education on whom to test are warranted. Ensuring that country of origin and drug use is included on the new-patient questionnaire might also aid case-finding for HCV.

Liver Function Assessment by Magnetic Resonance Imaging.

PubMed

Ünal, Emre; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver function assessment by hepatocyte-specific contrast-enhanced magnetic resonance imaging is becoming a new biomarker. Liver function can be assessed by T1 mapping (reduction rate) and signal intensity measurement (relative enhancement ratio) before and after GD-EOB-DTPA (gadoxetic acid) administration, as alternative to Tc-99m galactosyl serum albumin scintigraphy, 99m Tc-labeled mebrofenin scintigraphy, and indocyanine green clearance test. Magnetic resonance imaging assessment of liver function can enable diagnosis of cirrhosis, nonalcoholic fatty liver disease associated fibrosis and steatohepatitis, primary sclerosing cholangitis, toxic hepatitis, and chemotherapy and radiotherapy-related changes, which may be only visible on hepatobiliary phase images. Simple visual assessment of signal intensity at hepatobiliary phase images is important for the diagnosis of different patterns of liver dysfunction including diffuse, lobar, segmental, and subsegmental forms. Furthermore, preoperative assessment of liver function is feasible before oncologic hepatic surgery, which may be important to prevent posthepatectomy liver failure and to estimate future remnant volume. Functional magnetic resonance cholangiography obtained by T1-weighted images at hepatobiliary phase can allow diagnosis of acalculous cholecystitis, biliary leakage, bile reflux to the stomach, sphincter of oddi dysfunction, and lesions with communication to biliary tree. Functional information can be easily obtained when Gd-EOB-DTPA is used for liver magnetic resonance imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic performance of T lymphocyte subpopulations in assessment of liver fibrosis stages in hepatitis C virus patients: simple noninvasive score.

PubMed

Toson, El-Shatat A; Shiha, Gamal E; El-Mezayen, Hatem A; El-Sharkawy, Aml M

2016-08-01

Evaluation of liver fibrosis in patients infected with hepatitis C virus is highly useful for the diagnosis of the disease as well as therapeutic decision. Our aim was to develop and validate a simple noninvasive score for liver fibrosis staging in chronic hepatitis C (CHC) patients and compare its performance against three published simple noninvasive indexes. CHC patients were divided into two groups: an estimated group (n=70) and a validated group (n=52). Liver fibrosis was tested in biopsies using the Metavair score system. CD4 and CD8 count/percentage were assayed by fluorescence-activated cell sorting analysis. The multivariate discriminant analysis selects a function on the basis of absolute values of five biochemical markers: immune fibrosis index (IFI); score=3.07+3.06×CD4/CD8+0.02×α-fetoprotein (U/l)-0.07×alanine aminotransferase ratio-0.005×platelet count (10/l)-1.4×albumin (g/dl). The IFI score produced areas under curve of 0.949, 0.947, and 0.806 for differentiation of all patient categories [significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4)]. The IFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage in CHC patients. Our score was more efficient than aspartate aminotransferase to platelet ratio index, fibrosis index, and fibroQ and more suitable for use in Egyptian hepatitis C virus patients.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.

PubMed

Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

2005-12-07

To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. After one course of treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio of CD4(+)/CD8(+) increased as compared to those before the treatment but the level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

PubMed Central

Saludes, Verónica; González, Victoria; Planas, Ramon; Matas, Lurdes; Ausina, Vicente; Martró, Elisa

2014-01-01

Hepatitis C virus (HCV) infection represents a major public health issue. Hepatitis C can be cured by therapy, but many infected individuals are unaware of their status. Effective HCV screening, fast diagnosis and characterization, and hepatic fibrosis staging are highly relevant for controlling transmission, treating infected patients and, consequently, avoiding end-stage liver disease. Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays. Additionally, the use of point-of-care tests can increase HCV screening opportunities. However, active HCV infection must be confirmed by direct diagnosis methods. Additionally, HCV genotyping is required prior to starting any treatment. Increasingly, high-volume clinical laboratories use different types of automated platforms, which have simplified sample processing, reduced hands-on-time, minimized contamination risks and human error and ensured full traceability of results. Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods, such as imaging techniques and serum-based tests. However, no single test is currently available that is able to completely replace liver biopsy. This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests. PMID:24707126

Ammonia Test

MedlinePlus

... of hepatic encephalopathy, but there is not widespread agreement on its clinical utility. Since hepatic encephalopathy can ... more clinically useful, but there is not widespread agreement on this. Is ammonia testing used to detect ...

Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

PubMed

Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

2014-09-01

We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

In vitro hepatic differentiation of human endometrial stromal stem cells.

PubMed

Yang, Xin-yuan; Wang, Wei; Li, Xu

2014-02-01

Human endometrial stromal stem cells (hESSCs) can differentiate into mesodermal and ectodermal cellular lineages in the endometrium. However, whether hESSCs can differentiate into functional hepatic-like cells is unknown. In this study, we developed a multiple-step induction protocol to differentiate hESSCs into functional hepatic-like cells in vitro. Endometrial stromal cells were isolated by magnetic affinity sorting using anti-epithelial cell adhesion molecule-coated Dynabeads. The enriched hESSCs were analyzed by flow cytometry and were able to differentiate into osteoblasts or adipocytes under proper induction media. To differentiate into hepatic-like cells, hESSCs were cultured in a stepwise system containing hepatocyte growth factor, fibroblast growth factor-4, oncostatin M, and trichostatin A for a total of 24 d. The hepatic-like cell differentiation was analyzed by confocal microscopy and immunocytochemical staining. Glycogen storage, cellular urea synthesis, and ammonia concentrations were measured. Hepatic-like cells were successfully generated from hESSCs and were identified by their epithelial-like shape characteristics and expression of specific biomarkers albumin and cytokeratin 8 accompanied with a reduction of alpha-fetoprotein and alpha-smooth muscle actin expression. The hepatic-like cells generated were functional as evidenced by urea synthesis and glycogen storage. Our study demonstrated that hESSCs were able to differentiate into hepatic-like cells in vitro. Thus, endometrial stromal cells may be used as an easily accessible alternative source of stem cells for potential therapeutic applications in liver disease.

Development of an ESL curriculum to educate Chinese immigrants about hepatitis B.

PubMed

Taylor, Victoria M; Coronado, Gloria; Acorda, Elizabeth; Teh, Chong; Tu, Shin-Ping; Yasui, Yutaka; Bastani, Roshan; Hislop, T Gregory

2008-08-01

Chinese immigrants to North America have substantially higher rates of chronic hepatitis B infection than the general population. One area for strategic development in the field of health education is the design and evaluation of English-as-a-Second language (ESL) curricula. The theoretical perspective of the Health Behavior Framework, results from a community-based survey of Chinese Canadian immigrants with limited English proficiency, and findings from focus groups of ESL instructors as well as Chinese ESL students were used to develop a hepatitis B ESL educational module. This research was conducted in Vancouver, BC. Survey data showed that less than three-fifths of the respondents had been tested for hepatitis B, and documented some important hepatitis B knowledge deficits. Further, only about one-quarter had ever received a physician recommendation for hepatitis B serologic testing. The ESL curriculum aims to both promote hepatitis B testing and improve knowledge, and includes seven different ESL exercises: Warm-up, vocabulary cards, information-gap, video, jigsaw, guided discussion, and problem/advice cards. Our quantitative and qualitative methods for curriculum development could be replicated for other health education topics and in other limited English speaking populations.

Epidemiology of hepatitis B and hepatitis C in Lebanon.

PubMed

Abou Rached, Antoine; Abou Kheir, Selim; Saba, Jowana; Ammar, Walid

2016-03-01

Hepatitis B and C are two potentially life threatening liver infections. Lebanon is ranked as a zone of moderate endemicity. This study aimed to determine the prevalence of hepatitis B and C in Lebanon and their distribution according to age, region and sex. This national prospective cross-sectional study was conducted from January 2011 till December 2012 in the six Lebanese Governorates in collaboration with municipalities, the Ministry of Public Health, Health Centres and dispensaries. An upcoming screening for hepatitis B and C was announced? in different districts of each Governorate. All individuals presenting to local laboratory, not known to have chronic hepatitis, were asked for a blood sample and answered a questionnaire addressing sex, age, place of birth and residence. Screening tests were "Abbots" for hepatitis B and "Human Hexagon" for hepatitis C. PCR testing was used to confirm the positivity of the previous tests. Of 31147 individuals screened, 542 had a rapid test positive for HBV (prevalence 1.74%, 95% CI 1.6-1.89) with a male to female ratio of 1.08. This prevalence was higher in the South and Nabatieh (1.9%) compared to Beirut (0.73%). Of 31,147 individuals screened, 64 had a rapid test positive for HCV (prevalence 0.21%, 95% CI 0.16-0.27) with a male to female ratio of 0.85. This prevalence was higher in Nabatieh (0.61%) compared to Mount Lebanon (0.08%). The prevalence of HBV and HCV in Lebanon is 1.74% and 0.21%, respectively with a higher prevalence in South and Nabatieh districts. These data rank Lebanon amongst countries with low endemicity for both viruses. Decrease in the prevalence of HBV is due to awareness campaign as well as success of the MOPH National Hepatitis Program in vaccinating all new born since 1998 and in screening and vaccinating high risk groups. Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. 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.

[Data analysis on hepatitis B through pilot surveillance reporting system in Henan province, 2012-2016].

PubMed

Guo, Y H; Lyu, Y Y; Yang, J H; Xu, J; Li, J; Ye, Y; Zhang, Y Y

2018-04-10

Objective: To standardize the reporting system on hepatitis B in order to improve the quality of monitoring program in Henan province. Methods: A total of 6 sites of Hepatitis B pilot surveillance were selected in Xinzheng of Zhengzhou city, Linzhou of Anyang city, Shanyang district of Jiaozuo city, Shaoling district of Luohe city, Yongcheng of Shangqiu city, Pingqiao district of Xinyang city in Henan province. Subjects under study were those reported hepatitis B cases, from 2012 to 2016. Cases diagnosed in 2011 were chosen as controls. Data on classification of hepatitis B, time that HBsAg became positive and ALT value of the cases were analyzed annually. 5 ml venous blood was collected and anti-HBc IgM confirmed test was made for those suspected acute cases on hepatitis B. Based on the 2016 data from the monitoring system, the incidence of acute hepatitis B in Henan province was estimated. Results: The number of reported hepatitis B cases had declined in 6 sites of Hepatitis B pilot surveillance substantially. A total of 17 436 hepatitis B reported in 2011 but only 2 632 cases were reported in 2016, with a reduction of 84.90%(14 804/17 436) in these six monitoring sites. The number of unclassified hepatitis B cases also dropped sharply. In 2011, 36.87% of the cases were unclassified, but the figure reduced to 0.08% in 2016, from the six sites. The rate on ALT detection also gradually improved. The rate of misdiagnosis on HBV carrier from hepatitis B almost disappeared. From 2013 to 2016, 777 blood samples were collected from six pilot sites. 29.34% (228/777) of the blood samples were tested positive for anti-HBc IgM after confirmed by the hepatitis laboratory of the China Center for Disease Control and Prevention. Conclusions: Since the development of the pilot surveillance program, the quality of reporting system on hepatitis B had been improved, as well as the accuracy of diagnosis. Rate on the accuracy of reporting on hepatitis B and the methods of testing should be improved at the monitoring sites.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Histoplasmosis Presenting as Granulomatous Hepatitis: Case Report and Review of the Literature

PubMed Central

Rihana, Nancy A.; Kandula, Manasa; Velez, Ana; Dahal, Kumud; O'Neill, Edward B.

2014-01-01

Background. Histoplasma capsulatum is the most common endemic mycosis in the United States and is a frequent cause of opportunistic infection in immunodeficient hosts. Histoplasmosis is most often self-limiting and goes unrecognized in the immunocompetent population but can progress to disseminated histoplasmosis in patients with an impaired immune system. Liver involvement as a part of disseminated histoplasmosis which usually originates in the lung is well known. However, extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare. Case Presentation. We report a rare case of histoplasmosis that presented as persistent fever and abnormal liver function tests in a 66-year-old female with rheumatoid arthritis, receiving infliximab. Conclusion. Emphasizing histoplasmosis as a major cause of acute granulomatous hepatitis and fever of unknown origin in cell mediated immunodeficient population, this case highlights the need for high index of suspicion and the importance of prompt diagnosis since any delay of treatment can be life threatening in this population. PMID:25013413

Histoplasmosis presenting as granulomatous hepatitis: case report and review of the literature.

PubMed

Rihana, Nancy A; Kandula, Manasa; Velez, Ana; Dahal, Kumud; O'Neill, Edward B

2014-01-01

Background. Histoplasma capsulatum is the most common endemic mycosis in the United States and is a frequent cause of opportunistic infection in immunodeficient hosts. Histoplasmosis is most often self-limiting and goes unrecognized in the immunocompetent population but can progress to disseminated histoplasmosis in patients with an impaired immune system. Liver involvement as a part of disseminated histoplasmosis which usually originates in the lung is well known. However, extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare. Case Presentation. We report a rare case of histoplasmosis that presented as persistent fever and abnormal liver function tests in a 66-year-old female with rheumatoid arthritis, receiving infliximab. Conclusion. Emphasizing histoplasmosis as a major cause of acute granulomatous hepatitis and fever of unknown origin in cell mediated immunodeficient population, this case highlights the need for high index of suspicion and the importance of prompt diagnosis since any delay of treatment can be life threatening in this population.

Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces specific immune responses in mice

PubMed Central

Weigand, Kilian; Voigt, Franziska; Encke, Jens; Hoyler, Birgit; Stremmel, Wolfgang; Eisenbach, Christoph

2012-01-01

AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole “viral surface” induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cells directed against HCV. Furthermore, T-cell responses confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further. PMID:22371638

Antioxidant and Hepatoprotective Efficiency of Selenium Nanoparticles Against Acetaminophen-Induced Hepatic Damage.

PubMed

Amin, Kamal Adel; Hashem, Khalid Shaban; Alshehri, Fawziah Saleh; Awad, Said T; Hassan, Mohammed S

2017-01-01

Overdoses of acetaminophen (APAP), a famous and widely used drug, may have hepatotoxic effects. Nanoscience is a novel scientific discipline that provides specific tools for medical science problems including using nano trace elements in hepatic diseases. Our study aimed to assess the hepatoprotective role of selenium nanoparticles (Nano-Se) against APAP-induced hepatic injury. Twenty-four male rats were classified into three equal groups: a control group that received 0.9 % NaCl, an APAP-treated group (oral administration), and a group treated with Nano-Se (10-20 nm, intraperitoneal (i.p.) injection) and APAP (oral administration). APAP overdose induced significant elevations in liver function biomarkers, hepatic lipid peroxidation, hepatic catalase, and superoxide dismutase (SOD), decreased the reduced glutathione (GSH) content and glutathione reductase (GR) activity, and stimulated significant DNA damage in hepatocytes, compared to control rats. Nano-Se administration improved the hepatic antioxidant protection mechanism and decreased cellular sensitivity to DNA fragmentation. Nano-Se exhibits a protective effect against APAP-induced hepatotoxicity through improved liver function and oxidative stress mediated by catalase, SOD, and GSH and decreases hepatic DNA fragmentation, a hepatic biomarker of cell death. Nano-Se could be a novel hepatoprotective strategy to inhibit oxidative stress.

Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function.

PubMed

Item, Flurin; Wueest, Stephan; Lemos, Vera; Stein, Sokrates; Lucchini, Fabrizio C; Denzler, Rémy; Fisser, Muriel C; Challa, Tenagne D; Pirinen, Eija; Kim, Youngsoo; Hemmi, Silvio; Gulbins, Erich; Gross, Atan; O'Reilly, Lorraine A; Stoffel, Markus; Auwerx, Johan; Konrad, Daniel

2017-09-07

Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.

Reticulocyte Count Test

MedlinePlus

... Acid-Fast Bacillus (AFB) Testing Activated Clotting Time Acute Viral Hepatitis Panel Adenosine Deaminase Adrenocorticotropic Hormone (ACTH) ... Guillain-Barré Syndrome Hashimoto Thyroiditis Heart Attack and Acute Coronary Syndrome Heart Disease Hemochromatosis Hemoglobin Abnormalities Hepatitis ...

Correlation of four potential biomarkers of liver fibrosis with liver function and grade of hepatic fibrosis in a neonatal cholestatic rat model.

PubMed

Tang, Ning; Zhang, Yaping; Liu, Zeyu; Ai, Xuemei; Liang, Qinghong

2017-07-01

The present study investigated the correlation between four serum biomarkers of liver fibrosis, liver function and pathological hepatic fibrosis grade in neonatal cholestatic rats. A total of 38 Sprague‑Dawley rats, aged 3 weeks, were randomly assigned to the experimental group (EG), control group (CG) and the blank control group (BCG). EG received intragastric administration of 1% α‑naphthylisothiocyanate, 75 mg/kg, to induce acute cholestasis liver injury, CG and BCG were set as control groups. Blood samples from all groups were collected 48 h following the procedure. The levels of liver function markers, and four biomarkers of liver fibrosis in serum, were measured and sections of liver tissue were stained for pathological analysis. The results of the present study demonstrated that the degree of hepatic fibrosis in EG, in the serum levels or by pathological analysis, was markedly more evident compared with the CG. Several indices of four biomarkers for liver fibrosis in serum were identified and correlated with the levels of liver function markers. The pathological hepatic fibrosis grade was correlated with γ‑glutamyl transferase (γ‑GT) and Hyaluronic acid (HA). Therefore, HA and γ‑GT were positively correlated with the grade of hepatic fibrosis, indicating their efficacy as biomarkers of infantile cholestatic hepatic fibrosis.

Antisense apolipoprotein B therapy: where do we stand?

PubMed

Akdim, Fatima; Stroes, Erik S G; Kastelein, John J P

2007-08-01

Antisense oligonucleotides are novel therapeutic agents that reduce the number of specific mRNAs available for translation of the encoded protein. ISIS 301012 is an antisense oligonucleotide developed to reduce the hepatic synthesis of apolipoprotein B-100. Apolipoprotein B-100 is made in the liver, and antisense oligonucleotides preferentially distribute to that organ, so antisense apolipoprotein B-100 may have potential as an efficacious lipid-lowering agent. Recently, in healthy volunteers and in mild dyslipidaemic patients, this strategy as monotherapy or in conjunction with statins has shown unparalleled efficacy in reducing apolipoprotein B-100 and LDL-cholesterol. Tolerance for this novel therapy is encouraging and safety concerns currently only relate to mild injection-site reactions and rare liver-function test abnormalities. It should be noted, however, that these safety results were obtained in relatively few individuals. ISIS 301012 has initially shown promising results in experimental animal models, and in clinical trials in humans. Besides the effect of reducing apolipoprotein B-100 and LDL-cholesterol, this compound also significantly lowers plasma triglycerides. Safety concerns related to the drug include increased liver-function tests. To date no evidence of hepatic steatosis has been reported. Nonetheless, clinical trials of longer duration are required to demonstrate further safety.

Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

PubMed

Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

2004-07-01

Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to hypertriglyceridemia of nephrotic syndrome.

Anti-smooth muscle antibody

MedlinePlus

... be due to: Chronic active autoimmune hepatitis Cirrhosis Infectious mononucleosis The test also helps distinguish autoimmune hepatitis from ... Editorial team. Cirrhosis Read more Hepatitis Read more Infectious Mononucleosis Read more A.D.A.M., Inc. is ...

Hepatitis C: Why Baby Boomers Should Get Tested

MedlinePlus

... C can cause serious health problems. In fact, hepatitis C is a leading cause of liver cancer and the leading cause of liver transplants. Treatments are now available that can cure hepatitis C. ...

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats.

PubMed

Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton

2013-11-01

Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.

BCR-ABL1: Test

MedlinePlus

... Acid-Fast Bacillus (AFB) Testing Activated Clotting Time Acute Viral Hepatitis Panel Adenosine Deaminase Adrenocorticotropic Hormone (ACTH) ... Guillain-Barré Syndrome Hashimoto Thyroiditis Heart Attack and Acute Coronary Syndrome Heart Disease Hemochromatosis Hemoglobin Abnormalities Hepatitis ...

HEPATITIS B AWARENESS, TESTING, AND KNOWLEDGE AMONG VIETNAMESE AMERICAN MEN AND WOMEN

PubMed Central

Taylor, Victoria M.; Choe, John H.; Yasui, Yutaka; Li, Lin; Burke, Nancy; Jackson, J. Carey

2006-01-01

Southeast Asians have higher rates of liver cancer than any other racial/ethnic group in the United States. Chronic carriage of hepatitis B virus (HBV) is the most common underlying cause of liver cancer in the majority of Asian populations. Our objectives were to describe Vietnamese Americans’ awareness of hepatitis B, levels of HBV testing, and knowledge about hepatitis B transmission; and to compare the HBV knowledge and practices of men and women. A community-based, in-person survey of Vietnamese men and women was conducted in Seattle during 2002. Seven hundred and fifteen individuals (345 men and 370 women) completed the questionnaire. Eighty-one percent of the respondents had heard of hepatitis B (76% of men, 86% of women) and 67% reported HBV testing (66% of men, 68% of women). A majority of the participants knew that HBV can be transmitted during sexual intercourse (71% of men, 68% of women), by sharing toothbrushes (67% of men, 77% of women), and by sharing razors (59% of men, 67% of women). Less than one-half knew that hepatitis B is not spread by eating food prepared by an infected person (46% of men, 27% of women), nor by coughing (39% of men, 25% of women). One-third of our respondents did not recall being tested for HBV. Important knowledge deficits about routes of hepatitis B transmission were identified. Continued efforts should be made to develop and implement hepatitis B educational campaigns for Vietnamese immigrant communities. These efforts might be tailored to male and female audiences. PMID:16370056

[Clinical, hemodynamic and angiographic results of total cavo-pulmonary connection].

PubMed

Jimenez, A C; Neville, P; Chamboux, C; Crenn, R; Vaillant, M C; Marchand, M; Chantepie, A

1998-05-01

The aim of the study was to assess the short and medium term results of total cavo-pulmonary connection based on analysis of the functional status, the cavo-pulmonary circulation and the surgical techniques, and the hepatic consequences. Fifteen patients with congenital defects beyond repair were treated by total cavo-pulmonary connection at Tours between March 1st 1992 and July 30th 1996. There were 12 children (mean age: 6.3 years) and 3 adults aged 25 to 28. Results were assessed by clinical examination, hepatic function tests and cardiovascular investigations including right heart catheterisation with angiography in 14 patients. There were no fatalities. Seven patients were in functional Class I and 8 in Class II at medium term (average follow-up of 33 months). Hepatic function was mildly abnormal in all patients with an increase in serum bilirubin and gamma GT, and a decrease in the coagulation factors. The mean pressures in the atrial channel were 12 mmHg (9-16 mmHg), in the superior vena 13.2 mmHg (10-18 mmHg), in the right pulmonary artery 9.5 mmHg (7-15 mmHg) and 11.6 mmHg (8-16 mmHg) in the left pulmonary artery. Significant residual stenosis of a pulmonary branch was observed in 2 cases. The cavo-pulmonary anastomoses were out of line, one from the other, in all cases. The atrial channel was tubular in 9 cases and dilated with slight stagnation of the contrast medium in its inferior region in 5 cases. Total cavo-pulmonary connection transformed the clinical status of these patients but was associated with minor abnormalities of liver function. The quality of the cavo-pulmonary circulation and the surgical anastomoses was estimated to be satisfactory in the majority of cases.

Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk.

PubMed

Bergeron, Nathalie; Phan, Binh An P; Ding, Yunchen; Fong, Aleyna; Krauss, Ronald M

2015-10-27

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk. © 2015 American Heart Association, Inc.

N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers.

PubMed

Medina, Scott H; Tekumalla, Venkatesh; Chevliakov, Maxim V; Shewach, Donna S; Ensminger, William D; El-Sayed, Mohamed E H

2011-06-01

There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH₂) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis-Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

PubMed Central

Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

2005-01-01

AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B. PMID:16437674

Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests).

PubMed

Kappus, Matthew R; Bajaj, Jasmohan S

2012-02-01

Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of Patatin-Like Phospholipase Domain-Containing 3 on Lipid-Induced Hepatic Steatosis and Insulin Resistance in Rats

PubMed Central

Kumashiro, Naoki; Yoshimura, Toru; Cantley, Jennifer L; Majumdar, Sachin K; Guebre-Egziabher, Fitsum; Kursawe, Romy; Vatner, Daniel F; Fat, Ioana; Kahn, Mario; Erion, Derek M; Zhang, Xian-Man; Zhang, Dongyan; Manchem, Vara Prasad; Bhanot, Sanjay; Gerhard, Glenn S; Petersen, Kitt F; Cline, Gary W; Samuel, Varman T; Shulman, Gerald I

2013-01-01

Genome-wide array studies have associated the patatin-like phospholipase domain-containing 3 (PNPLA3) gene polymorphisms with hepatic steatosis. However, it is unclear whether PNPLA3 functions as a lipase or a lipogenic enzyme and whether PNPLA3 is involved in the pathogenesis of hepatic insulin resistance. To address these questions we treated high-fat-fed rats with specific antisense oligonucleotides to decrease hepatic and adipose pnpla3 expression. Reducing pnpla3 expression prevented hepatic steatosis, which could be attributed to decreased fatty acid esterification measured by the incorporation of [U-13C]-palmitate into hepatic triglyceride. While the precursors for phosphatidic acid (PA) (long-chain fatty acyl-CoAs and lysophosphatidic acid [LPA]) were not decreased, we did observe an ∼20% reduction in the hepatic PA content, ∼35% reduction in the PA/LPA ratio, and ∼60%-70% reduction in transacylation activity at the level of acyl-CoA:1-acylglycerol-sn-3-phosphate acyltransferase. These changes were associated with an ∼50% reduction in hepatic diacylglycerol (DAG) content, an ∼80% reduction in hepatic protein kinase Cε activation, and increased hepatic insulin sensitivity, as reflected by a 2-fold greater suppression of endogenous glucose production during the hyperinsulinemic-euglycemic clamp. Finally, in humans, hepatic PNPLA3 messenger RNA (mRNA) expression was strongly correlated with hepatic triglyceride and DAG content, supporting a potential lipogenic role of PNPLA3 in humans. Conclusion: PNPLA3 may function primarily in a lipogenic capacity and inhibition of PNPLA3 may be a novel therapeutic approach for treatment of nonalcoholic fatty liver disease-associated hepatic insulin resistance. ((Hepatology 2013;57:1763-1772)) PMID:23175050

Effect of hepatic impairment on the pharmacokinetics of a single dose of cilostazol.

PubMed

Bramer, S L; Forbes, W P

1999-01-01

The pharmacokinetic profiles of cilostazol and its metabolites following a single oral dose of cilostazol 100 mg were compared between individuals with impaired and normal liver function. The study was conducted as a single-centre, open-label, single dose pharmacokinetic and tolerability trial. 12 patients with impaired and compensated liver function were compared with 12 volunteers with normal liver function. Participants in each group were matched for gender, age and weight. Of the 12 patients with hepatic impairment examined in this study, 10 had mild impairment (Child-Pugh class A) and 2 had moderate impairment (Child-Pugh class B). Blood and urine were collected up to 144 hours after drug administration. Pharmacokinetics were determined by noncompartmental methods. Protein binding did not differ between the groups (95.2% healthy volunteers, 94.6% hepatically impaired patients). Mean +/- SD unbound oral clearance of cilostazol decreased by 8.6% because of hepatic impairment (3380 +/- 1400 ml/min in healthy volunteers, 3260 +/- 2030 ml/min in hepatically impaired patients). Total urinary excretion of metabolites was significantly higher in healthy volunteers (26 vs 17% of dose). Overall, the pharmacokinetics of cilostazol and its metabolites, OPC-13213 and OPC-13015, were not substantially different in those with mild and moderate hepatic disease compared with values in healthy volunteers. Except for terminal-phase disposition half-life and apparent terminal-phase volume of distribution for cilostazol, the ratios of geometric means of pharmacokinetic parameters for plasma cilostazol, OPC-13213 and OPC-13015 in those with hepatic impairment versus healthy volunteers were close to 100%. Based on the results of the pharmacokinetic analysis, dose adjustment in patients with mild hepatic impairment is not necessary. However, caution should be exercised when cilostazol is administered to patients with moderate or severe hepatic impairment.

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis

PubMed Central

Bleau, Christian; Filliol, Aveline; Samson, Michel

2016-01-01

ABSTRACT Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. PMID:27489277

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis.

PubMed

Bleau, Christian; Filliol, Aveline; Samson, Michel; Lamontagne, Lucie

2016-10-15

Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

PubMed

Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

2017-04-01

To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Novel Index (Hepatic Receptor: IHR) to Evaluate Hepatic Functional Reserve Using (99m)Tc-GSA Scintigraphy.

PubMed

Hasegawa, Daisuke; Onishi, Hideo; Matsutomo, Norikazu

2016-02-01

This study aimed to evaluate the novel index of hepatic receptor (IHR) on the regression analysis derived from time activity curve of the liver for hepatic functional reserve. Sixty patients had undergone (99m)Tc-galactosyl serum albumin ((99m)Tc-GSA) scintigraphy in the retrospective clinical study. Time activity curves for liver were obtained by region of interest (ROI) on the whole liver. A novel hepatic functional predictor was calculated with multiple regression analysis of time activity curves. In the multiple regression function, the objective variables were the indocyanine green (ICG) retention rate at 15 min, and the explanatory variables were the liver counts in 3-min intervals until end from beginning. Then, this result was defined by IHR, and we analyzed the correlation between IHR and ICG, uptake ratio of the heart at 15 minutes to that at 3 minutes (HH15), uptake ratio of the liver to the liver plus heart at 15 minutes (LHL15), and index of convexity (IOC). Regression function of IHR was derived as follows: IHR=0.025×L(6)-0.052×L(12)+0.027×L(27). The multiple regression analysis indicated that liver counts at 6 min, 12 min, and 27 min were significantly related to objective variables. The correlation coefficient between IHR and ICG was 0.774, and the correlation coefficient between ICG and conventional indices (HH15, LHL15, and IOC) were 0.837, 0.773, and 0.793, respectively. IHR had good correlation with HH15, LHL15, and IOC. The finding results suggested that IHR would provide clinical benefit for hepatic functional assessment in the (99m)Tc-GSA scintigraphy.

[Behaviour of the LAP (leucine-amino-peptidase) in the serum of blood in subjects affected of cirrhosis of the liver in stage ascitical (author's transl)].

PubMed

Pace, M; Fernandes, D

1980-12-01

The AA. have studied behaviour of the LAP (leucine-amino-peptidase) in the serum of blood in subjects affected of cirrhosis of the liver in stage ascitical, of cause toxic-alcoholic excluding about of the casuistry the cirrhosis of the another cause and the cirrhosis that are compled white an obstruction in and extrahepatic standard biliary cirrhosis 1 degree e 2 degree. After the exposition of the casuistry in the registred normality of the test (seric-LAP) in some cases of hepatic-alcoholic cirrhosis, the AA. concluded considering the LAP an indicator only of the obstruction in and extra-hepatic, consistent with hepatic-organ well operating; do not be a secure test to follow development of a chronic hepatitis of any kind, even if in the hepatic disease is present an infiltration and an overturning of the hepatic-lobule, like it is normally in the hepatic alcoholic diseases.

A Perspective on Efflux Transport Proteins in the Liver

PubMed Central

Kock, K; Brouwer, K.L.R

2013-01-01

Detailed knowledge regarding the influence of hepatic transport proteins on drug disposition has advanced at a rapid pace over the past decade. Efflux transport proteins located in the basolateral and apical (canalicular) membranes of hepatocytes play an important role in the hepatic elimination of many endogenous and exogenous compounds, including drugs and metabolites. This review focuses on the role of these efflux transporters in hepatic drug excretion. The impact of these proteins as underlying factors for disease is highlighted, and the importance of hepatic efflux proteins in the efficacy and toxicity of drugs is discussed. In addition, a brief overview of methodology to evaluate the function of hepatic efflux transport proteins is provided. Current challenges in predicting the impact of altered efflux protein function on systemic, intestinal and hepatocyte exposure to drugs and metabolites are highlighted. PMID:22948894

21 CFR 660.4 - Potency test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Potency test. 660.4 Section 660.4 Food and Drugs... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.4 Potency test. To be satisfactory for release, each filling of Antibody to Hepatitis B Surface Antigen...

21 CFR 610.40 - Test requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; (3) Hepatitis B virus; (4) Hepatitis C virus; (5) Human T-lymphotropic virus, type I; and (6) Human T-lymphotropic virus, type II. (b) Testing using one or more approved screening tests. To test for evidence of... single identified recipient under paragraphs (a), (b), and (e) of this section; except that, if the donor...

Frequent hepatitis E in the Netherlands without traveling or immunosuppression.

PubMed

Koot, H; Hogema, B M; Koot, M; Molier, M; Zaaijer, H L

2015-01-01

In several Western countries, silent endemic hepatitis E virus (HEV) infection is common among blood donors. Immunocompromised persons may develop chronic hepatitis E, but the relevance of endemic HEV for immunocompetent persons remains largely unknown. We investigated the immune status and travel history in cases of hepatitis E in the Netherlands. Between January 2009 and May 2014, physicians throughout the Netherlands submitted samples from 4067 hepatitis patients to Sanquin Diagnostic Services for HEV antibody testing. For the 144 patients testing positive for HEV IgM and HEV RNA, travel behavior and immune status were assessed. Complete information was obtained for 81 patients. Surprisingly, the majority of patients (52/81, 64%) were immunocompetent and did not travel outside Europe. HEV genotyping was obtained for 47 non-traveling patients, all concerned HEV genotype 3. Our findings suggest that currently in Western countries the impact of hepatitis E for non-traveling, immunocompetent persons is underestimated. Historically cases of hepatitis A, B and C, but not cases of hepatitis E, are notifiable and warrant preventive measures. However, in parts of Western Europe HEV may have become the most important source of viral hepatitis, in immunocompetent and in immunosuppressed persons. Pending measures against the ongoing transmission of HEV genotype 3 in parts of Europe, physicians should consider hepatitis E in dealing with new hepatitis patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Control of leptin by metabolic state and its regulatory interactions with pituitary growth hormone and hepatic growth hormone receptors and insulin like growth factors in the tilapia (Oreochromis mossambicus).

PubMed

Douros, Jonathan D; Baltzegar, David A; Mankiewicz, Jamie; Taylor, Jordan; Yamaguchi, Yoko; Lerner, Darren T; Seale, Andre P; Grau, E Gordon; Breves, Jason P; Borski, Russell J

2017-01-01

Leptin is an important cytokine for regulating energy homeostasis, however, relatively little is known about its function and control in teleost fishes or other ectotherms, particularly with regard to interactions with the growth hormone (GH)/insulin-like growth factors (IGFs) growth regulatory axis. Here we assessed the regulation of LepA, the dominant paralog in tilapia (Oreochromis mossambicus) and other teleosts under altered nutritional state, and evaluated how LepA might alter pituitary growth hormone (GH) and hepatic insulin-like growth factors (IGFs) that are known to be disparately regulated by metabolic state. Circulating LepA, and lepa and lepr gene expression increased after 3-weeks fasting and declined to control levels 10days following refeeding. This pattern of leptin regulation by metabolic state is similar to that previously observed for pituitary GH and opposite that of hepatic GHR and/or IGF dynamics in tilapia and other fishes. We therefore evaluated if LepA might differentially regulate pituitary GH, and hepatic GH receptors (GHRs) and IGFs. Recombinant tilapia LepA (rtLepA) increased hepatic gene expression of igf-1, igf-2, ghr-1, and ghr-2 from isolated hepatocytes following 24h incubation. Intraperitoneal rtLepA injection, on the other hand, stimulated hepatic igf-1, but had little effect on hepatic igf-2, ghr1, or ghr2 mRNA abundance. LepA suppressed GH accumulation and gh mRNA in pituitaries in vitro, but had no effect on GH release. We next sought to test if abolition of pituitary GH via hypophysectomy (Hx) affects the expression of hepatic lepa and lepr. Hypophysectomy significantly increases hepatic lepa mRNA abundance, while GH replacement in Hx fish restores lepa mRNA levels to that of sham controls. Leptin receptor (lepr) mRNA was unchanged by Hx. In in vitro hepatocyte incubations, GH inhibits lepa and lepr mRNA expression at low concentrations, while higher concentration stimulates lepa expression. Taken together, these findings indicate LepA gene expression and secretion increases with fasting, consistent with the hormones function in promoting energy expenditure during catabolic stress. It would also appear that LepA might play an important role in stimulating GHR and IGFs to potentially spare declines in these factors during catabolism. Evidence also suggests for the first time in teleosts that GH may exert important regulatory effects on hepatic LepA production, insofar as physiological levels (0.05-1 nM) suppresse lepa mRNA accumulation. Leptin A, may in turn exert negative feedback effects on basal GH mRNA abundance, but not secretion. Copyright © 2016 Elsevier Inc. All rights reserved.

[Genome organization and life cycle of the hepatitis c virus].

PubMed

Kalinina, O V; Dmitriev, A V

2015-01-01

The review summarizes the current data about the hepatitis C viral genome and polyprotein organization. The functional role of the structural and non-structural viral proteins including their interaction with cellular regulatory proteins and cell structural elements is discussed. Specific peculiarities of the life cycle of the hepatitis C virus important for the understanding of the viral hepatitis C pathogenesis are summarized.

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

PubMed

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism

PubMed Central

Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound–multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs. PMID:29391777

[Parenteral S-adenosylmethionine compared to placebos in the treatment of alcoholic liver diseases].

PubMed

Diaz Belmont, A; Dominguez Henkel, R; Uribe Ancira, F

1996-01-01

The improvements in the knowledge of the action of ethanol over the hepatic cell, its direct action over the cell, and the intracytoplasmatic structures membranes, point out the possibilities of use of sulfo-adenosil-L-metionina (SAMe); as an util drug inn the treatment of the altered metilation reactions, that take place in those membranes, facilitating their physiological functions. The primary end point in this study was to demonstrate the therapeutic worth os SAMe, by parenteral route in 45 patients with alcoholic liver disease, which were determined by clinical laboratory and hepatic function test, label qith 32 points or more of the discriminatory function index. Divided into two groups, placebo-SAMe, randomized, double blind. As well as total plasmatic and reduced glutation and lipoperoxidation index, indirect form as malondehaldehyde. Were determined at the first visit anf after 8 and 15 days of treatment. Comparing the results of both groups there were a significative favorable results for the group treatment with SAMe and this confirms the utility of this drug in the treatment of patients with alcoholic liver disease with a discriminatory function index (Maddrey index), of 32 points or more.

Low prevalence of hepatitis E in Iceland: a seroepidemiological study.

PubMed

Löve, Arthur; Björnsdottir, Thora B; Olafsson, Sigurdur; Björnsson, Einar S

2018-03-01

Hepatitis E virus (HEV) infection has been reported to be more prevalent in the developed countries than previously thought. HEV infection is an important differential diagnosis in patients with drug-induced liver injury (DILI). The prevalence of hepatitis E was investigated in the general population of Iceland, among pig farmers and patients with DILI. Serum samples were tested for hepatitis E IgG, with two commercial ELISA tests: Diagnostic Bioprobes Srl. (Dia Pro) and the Wantai HEV IgG and subjects repeatedly reactive were tested with an immunoblot assay (RecomLINE). Three groups were tested: (1) healthy volunteers (HV), (2) pig farm workers (PFWs) and (3) patients participating in a nationwide prospective study on DILI. Overall 291 individuals were tested, HV (n = 195), PFW (n = 21) and DILI (n = 75). Only 6/291 (2.1%) tested positive for IgG antibodies to HEV in all three tests. Three HV were HEV IgG antibody positive and three in the DILI group. One PFW tested positive in the Dia Pro and Wantai tests but not in the immunoblot assay. All but one of the positive individuals in all three tests was either of foreign national origin or had spent extended period of time outside of Iceland. The seroprevalence of hepatitis E appears to be lower in Iceland than majority of recent studies in other western countries have demonstrated. This may be due to relative isolation and severe restriction on import of livestock from other countries.

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI.

PubMed

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

2010-10-01

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C(max) , T(max) and T(1/2) ), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child-Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child-Pugh scores. Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. © 2010 International Hepato-Pancreato-Biliary Association.

Review of hepatitis B surveillance in China: improving information to frame future directions in prevention and control.

PubMed

Cui, Fuqiang; Drobeniuc, Jan; Hadler, Stephen C; Hutin, Yvan J; Ma, Fubao; Wiersma, Steve; Wang, Fuzhen; Wu, Jiang; Zheng, Hui; Zhou, Liwei; Zuo, Shuyan

2013-12-27

As the WHO verified that China reached the target of 1% prevalence of chronic hepatitis B infection among children targeted by universal hepatitis B immunization of newborns, the country considered new options for hepatitis B prevention and control. We reviewed hepatitis B surveillance in the broader context of viral hepatitis surveillance to propose recommendations to improve the system. We described surveillance for viral hepatitis in China with a specific focus on hepatitis B. We assessed critical attributes of the system, including data quality, predictive positive value and usefulness. While remarkable progress in hepatitis B immunization of infants and children has likely almost eliminated transmission in younger age groups, reported rates of hepatitis B increased steadily in China between 1990 and 2008, probably because of a failure to distinguish acute from chronic infections. Elements that prevented a clearer separation between acute and chronic cases included (1) missed opportunity to report cases accurately among clinicians, (2) low availability and use of tests to detect IgM against the hepatitis B core antigen (IgM anti-HBc) and (3) lack of systems to sort, manage and analyze surveillance data. To improve hepatitis B surveillance, China may consider (1) training clinicians to diagnose acute cases and to use IgM anti-HBc to confirm them, (2) improving access and use of validated IgM anti-HBc tests and (3) developing data management and analysis techniques that sort out acute from chronic cases. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Diagnostic tests for hepatitis C: Recent trends in electrochemical immunosensor and genosensor analysis

PubMed Central

Uliana, Carolina V; Riccardi, Carla S; Yamanaka, Hideko

2014-01-01

Hepatitis C is a liver disease that is transmitted through contact with the blood of an infected person. An estimated 150 million individuals worldwide have been chronically infected with the hepatitis C virus (HCV). Hepatitis C shows significant genetic variation in the global population, due to the high rate of viral RNA mutation. There are six variants of the virus (HCV genotypes 1, 2, 3, 4, 5, and 6), with 15 recorded subtypes that vary in prevalence across different regions of the world. A variety of devices are used to diagnose hepatitis C, including HCV antibody test, HCV viral load test, HCV genotype test and liver biopsy. Rapid, inexpensive, sensitive, and robust analytical devices are therefore essential for effective diagnosis and monitoring of disease treatment. This review provides an overview of current electrochemical immunosensor and genosensor technologies employed in HCV detection. There are a limited number of publications showing electrochemical biosensors being used for the detection of HCV. Due to their simplicity, specificity, and reliability, electrochemical biosensor devices have potential clinical applications in several viral infections. PMID:25400433

A novel multiplex real-time PCR assay for the concurrent detection of hepatitis A, B and C viruses in patients with acute hepatitis.

PubMed

Park, Yongjung; Kim, Beom Seok; Choi, Kyu Hun; Shin, Dong Ho; Lee, Mi Jung; Cho, Yonggeun; Kim, Hyon-Suk

2012-01-01

A novel multiplex real-time PCR assay for concurrent detection of hepatitis viruses was evaluated for its clinical performance in screening patients with acute hepatitis. A total of 648 serum samples were collected from patients with acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV and HCV was performed using the Magicplex™ HepaTrio Real-time Detection test. Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas® AmpliPrep/Cobas® TaqMan® (CAP/CTM) HBV and HCV tests. Patients' medical records were also reviewed. Concordance rates between the results from the HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k = 0.88) and 99.2% (k = 0.98), respectively. The cycle threshold values with the HepaTrio test were also correlated well with the levels of HBV DNA (r = -0.9230) and HCV RNA (r = -0.8458). The sensitivity and specificity of the HepaTrio test were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and 100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test demonstrated good clinical performance and produced results that agreed well with those of the CAP/CTM assays, especially for the detection of HCV. This assay was also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore, this new multiplex PCR assay could be useful for the concurrent detection of the three hepatitis viruses.

Role of pretest counseling sessions on increasing subjective knowledge about HIV and hepatitis transmission among the beneficiaries of a free of charge, voluntary counseling and testing program in Constanta, Romania.

PubMed

Schweitzer, A-M; Bogdan, M; Corduneanu, A; Ciocea, I

2018-02-01

To describe the characteristics of clients who enrolled into of an opt-in, HIV, HBV & HCV Voluntary Counseling and Testing Program in Dobrogea Region, Romania (VCT) and to identify the utility of the pre-test counseling sessions in increasing subjective perception regarding transmission knowledge for the clients attending the VCT program. Cross sectional data collection, between August 2015 and September 2016. Sociodemographic and behavioral information were collected for the clients who enrolled at two Baylor centers. Counselors were trained regarding the delivery of standardized information during the session, to reduce variation. After the pre-test session clients evaluated the subjective level of knowledge (SK) increase regarding viral transmission. 3065 clients were screened at the two centers and completed the SK increase assessment after the pre-test session. About 9% of all persons tested had reactive results to any of the infections in the context of high exposure risks for 62% and low hepatitis B vaccination rates (8%). 78% of attendees perceived that their knowledge regarding HIV and viral hepatitis transmission increasing with more than 60% as the result of the pretest counselling; more information was gained about hepatitis transmission compared with HIV. Cumulative prevalence in Dobrogea community is high. The NGO-run VCT program is helping the healthcare system to efficiently screen for undiagnosed HIV and hepatitis cases. Pre-test counselling is directly contributing to increasing SK among attendees. Routine HIV and hepatitis integrated pre-test counseling should be considered as a good-practice even in settings where it is not compulsory by law. © 2018 British HIV Association.

Measuring the Consistency in Change in Hepatitis B Knowledge among Three Different Types of Tests: True/False, Multiple Choice, and Fill in the Blanks Tests.

ERIC Educational Resources Information Center

Sahai, Vic; Demeyere, Petra; Poirier, Sheila; Piro, Felice

1998-01-01

The recall of information about Hepatitis B demonstrated by 180 seventh graders was tested with three test types: (1) short-answer; (2) true/false; and (3) multiple-choice. Short answer testing was the most reliable. Suggestions are made for the use of short-answer tests in evaluating student knowledge. (SLD)

Comparative evaluation of western blotting in hepatic and pulmonary cystic echinococcosis.

PubMed

Akisu, C; Delibas, S B; Bicmen, C; Ozkoc, S; Aksoy, U; Turgay, N

2006-12-01

Many serological tests are widely used in the diagnosis of cystic echinococcosis (CE), caused by the larval stages of Echinococcus granulosus. The present study was carried for differentiation between hepatic and pulmonary cystic echinococcosis by Western Blotting (WB). A total of 121 sera from patients with hepatic CE (37), pulmonary CE (31) and controls (53; consisting of six healthy, seven Hymenolepis nana infection, 20 hepatic and 20 pulmonary diseases other than CE) were examined. In all of the CE patients, E. gronulosus infection was confirmed by surgical intervention. Sera were previously tested using IHA and ELISA to detect the E. gronulosus specific antibodies. Sera from hepatic cases of CE reacted with 16 polypeptides of 6-116 kDa and sera from pulmonary cases of CE reacted with 14 polypeptides of 4-130 kDa by Western Blotting. The WB test enabled the detection of antibodies in the hepatic CE samples for proteins of 24, 32 34, 44-46 and 52-54 kDa in molecular weight in 78.4%, 75.7%, 78.4% and 89.2% of the patients, respectively. In the pulmonary CE samples sera WB test enabled the detection of antibodies 24, 44-46, 100, 110, 116 and 120 124 kDa in molecular weight in 81.3%, 75.0%, 87.5%, 71.9%, 84.4% and 65.6% of the patients, respectively. We indicated that the antigenic components of high molecular weight can be good candidates for differentiation of hepatic CE from pulmonary CE.

Hepatitis C performance measure on hepatitis A and B vaccination: missed opportunities?

PubMed

Hernandez, Bridget; Hasson, Noelle K; Cheung, Ramsey

2009-08-01

Prevention of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection in patients with chronic hepatitis C (CHC) through vaccination is endorsed by all major professional societies. This study was conducted to determine adherence to the recently adopted physician performance measure on HAV and HBV vaccination. This was a retrospective study. Hepatitis A and B serology data and immunization records between 2000 and 2007 from CHC patients with detectable hepatitis C virus (HCV) RNA were analyzed. A total of 2,968 CHC patients were included in the study. Of these, 2,143 patients (72%) were tested for susceptibility to HAV, of which 53% had immunity. Of the non-immune patients, 746 (74%) were vaccinated as well as an additional 218 without prior testing. For HBV, 2,303 patients (78%) were tested for immunity and 782 (34%) were immune. Of the susceptible patients, 1,086 (71%) were vaccinated as well as an additional 197 patients without prior testing. The overall vaccination performance measure adherence rate was 71% for HAV, 70% for HBV, and 62% for both HAV and HBV. Random review of 176 charts found the major reasons for non-adherence were missed opportunity (41%), change of health care system (31%), and documented vaccination outside our health care system (22%). Our study found a high and improved adherence to the recommendations, but missed opportunity was still the main reason of non-adherence. This study also supported the strategy of selective vaccination in the veteran population.

Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells.

PubMed

Catani, Lucia; Sollazzo, Daria; Bianchi, Elisa; Ciciarello, Marilena; Antoniani, Chiara; Foscoli, Licia; Caraceni, Paolo; Giannone, Ferdinando Antonino; Baldassarre, Maurizio; Giordano, Rosaria; Montemurro, Tiziana; Montelatici, Elisa; D'Errico, Antonia; Andreone, Pietro; Giudice, Valeria; Curti, Antonio; Manfredini, Rossella; Lemoli, Roberto Massimo

2017-12-01

Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133 + stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133 + cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133 + and LX-2 hepatic stellate cells. We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133 + SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133 + SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. We demonstrated that the interaction between CD133 + SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis

PubMed Central

Tomiyama, C; Watanabe, H; Izutsu, Y; Watanabe, M; Abo, T

2011-01-01

Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-Alow B220+); however, conventional DC were CD11c+ I-Ahigh B220–. At an early stage (3–6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12–24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b- cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function. PMID:21985372

Effect of Post-Traumatic Stress Disorder on Cognitive Function and Covert Hepatic Encephalopathy Diagnosis in Cirrhotic Veterans.

PubMed

Burroughs, Thomas K; Wade, James B; Ellwood, Michael S; Fagan, Andrew; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2018-02-01

In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients. Outpatient veterans with cirrhosis underwent two separate modalities for CHE cognitive testing [Psychometric Hepatic Encephalopathy Scale (PHES) and Inhibitory Control Test (ICT)]. ICT tests for inhibitory control and response inhibition, while PHES tests for attention and psychomotor speed. Comparisons were made between patients with/without PTSD. Multivariable logistic regression with CHE on PHES and CHE on ICT as dependent variables including prior OHE, demographics, PTSD and psychotropic medications was performed. Of 402 patients with cirrhosis, 88 had evidence of PTSD. Fifty-five of these were on psychoactive medications, 15 were undergoing psychotherapy, while no specific PTSD-related therapy was found in 28 patients. Cirrhotic patients with/without PTSD were statistically similar on demographics and cirrhosis severity, but cirrhotic subjects with PTSD had a higher frequency of alcoholic cirrhosis etiology and psychotropic drug use. PTSD cirrhosis had higher ICT lure and switching errors (NCT-B response), but on regression, there was no significant impact of PTSD on CHE diagnosis using either the ICT or PHES. Veterans with cirrhosis and PTSD have a higher frequency of psychotropic drug use and alcoholic cirrhosis etiology. CHE diagnosis using PHES or ICT is not affected by concomitant PTSD.

[The clinical features and natural history of post-transfusion hepatitis C].

PubMed

Chong, Yu-tian; Lin, Chao-shuang; Zhao, Zhi-xin; Lin, Guo-li; Li, Jian-guo; Gao, Zhi-liang

2006-03-01

To study the clinical features and natural history of post-transfusion hepatitis C (PTHC). Ninety-nine post-transfusion hepatitis C patients were analyzed using retrospective and prospective study and follow-up. (1) Ninety-nine post-transfusion HCV patients were infected during 1989-1994, mostly between 1990-1992. (2) Ninety patients were diagnosed as chronic hepatitis C, and 9 as hepatic cirrhosis (period of compensation). (3) The intervals between their transfusions and their initial diagnoses of PTHC were 7.4+/-6.6 years in all 99 patients, and the intervals in 9 cirrhosis patients were 12.7+/-5.8 years. (4) Among 63 male patients, 59 cases were chronic hepatitis C and 4 were cirrhosis while among 36 female patients, 31 were chronic hepatitis C and 5 were cirrhosis. There was no significant difference of the ratio for hepatitis C and cirrhosis between the male and female patients (P>0.05). (5) Repeat abnormal liver function occurred accompanied with a fluctuation of ALT elevation in those patients with cirrhosis. (6) No patient developed hepatic carcinoma during the study period. (1) The possibility of HCV infection by transfusion has declined greatly since 1995 in Guangzhou. (2) Nine of the 99 (9.1%) chronic HCV-infected patients developed a compensated cirrhosis after 12.7+/-5.8 years. (3) For those PTHC patients with repeat abnormal liver functions, interferon combined with ribavirin is recommended to prevent the development of cirrhosis.

Characterization of hepatitis E virus from sporadic hepatitis cases and sewage samples from Vellore, south India

PubMed Central

Vivek, Rosario; Zachariah, Uday G.; Ramachandran, Jeyamani; Eapen, Chundamannil E.; Rajan, Deva P.; Kang, Gagandeep

2017-01-01

Background Hepatitis E virus (HEV) is endemic in India and causes epidemics and sporadic cases. However, the exact transmission route for sporadic hepatitis E remains unclear. This study investigated HEV in sporadic hepatitis cases and sewage samples, as sewage is the major source of contamination of water in developing countries. Methods Monthly sampling and testing for HEV in sewage samples from Vellore, India was carried out for 1 year (November 2009–October 2010) and plasma and/or fecal samples from sporadic hepatitis cases presenting to a hospital in Vellore during 2006–2010 were tested for HEV RNA. A total of 144 raw sewage samples and 94 samples from sporadic hepatitis cases were tested for HEV RNA using RT-PCR. Results The prevalence of HEV RNA in sewage and sporadic cases was 55.6% and 9.6%, respectively. HEV strains isolated from sewage showed 94–100% nucleotide sequence similarity with the HEV strains isolated from the sporadic hepatitis cases. HEV RNA in sewage was identified more often during the summer (81.2%) than the monsoon season (14.5%) (p < 0.001). Conclusion This study indicates that sewage may be a source of contamination for sporadic hepatitis and also underscores the need for preventive measures to protect drinking water from sewage contamination, particularly in the summer. GenBank accession numbers HEV strains isolated from this study were deposited in GenBank under accession numbers JF972766–JF972773, JN705651–JN705659 and JN705660–JN705662. PMID:23677583

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

PubMed

Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

2017-07-15

Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis

PubMed Central

Kim, Hyunbae; Zheng, Ze; Walker, Paul D.; Kapatos, Gregory

2017-01-01

ABSTRACT Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. PMID:28461393

Performance of the OraQuick HCV rapid antibody test for screening exposed patients in a hepatitis C outbreak investigation.

PubMed

Gao, Fengxiang; Talbot, Elizabeth A; Loring, Carol H; Power, Jill J; Dionne-Odom, Jodie; Alroy-Preis, Sharon; Jackson, Patricia; Bean, Christine L

2014-07-01

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Differential Location and Distribution of Hepatic Immune Cells

PubMed Central

Freitas-Lopes, Maria Alice; Mafra, Kassiana; David, Bruna A.; Carvalho-Gontijo, Raquel; Menezes, Gustavo B.

2017-01-01

The liver is one of the main organs in the body, performing several metabolic and immunological functions that are indispensable to the organism. The liver is strategically positioned in the abdominal cavity between the intestine and the systemic circulation. Due to its location, the liver is continually exposed to nutritional insults, microbiota products from the intestinal tract, and to toxic substances. Hepatocytes are the major functional constituents of the hepatic lobes, and perform most of the liver’s secretory and synthesizing functions, although another important cell population sustains the vitality of the organ: the hepatic immune cells. Liver immune cells play a fundamental role in host immune responses and exquisite mechanisms are necessary to govern the density and the location of the different hepatic leukocytes. Here we discuss the location of these pivotal cells within the different liver compartments, and how their frequency and tissular location can dictate the fate of liver immune responses. PMID:29215603

Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

PubMed

Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.

Transforming growth factor beta1 gene variation Leu10Pro affects secretion and function in hepatic cells.

PubMed

Gu, Xing; Ji, Xin; Shi, Le-Hua; Yi, Chang-Hong; Zhao, Yun-Peng; Wang, Ai-Hua; Lu, Lun-Gen; Yu, Wen-Bo; Gao, Chun-Fang

2012-11-01

Our previous work revealed transforming growth factor beta1 (TGFβ1) gene polymorphisms are associated with susceptibility to hepatocellular carcinoma and liver cirrhosis. However, no further study of functional substitution in hepatic cells has yet been reported. This study was designed to uncover the functional mechanisms of TGFβ1 gene polymorphisms in the pathogenesis of liver diseases. Two recombinant TGFβ1 expression plasmids containing TGFβ1 codon 10 Leu/Pro variation were constructed with CMV promoter and transfected into human hepatoma cell lines (HepG2 and SMMU 7721), hepatic stellate cells (LX-2), and immortalized hepatocytes (L02). The secretion capacities of TGFβ1 protein in the transfected cells were determined by ELISA. Apoptosis, proliferative activity, and expression of CD 105, CD83, and CD80 were also measured by use of flow cytometry. The ELISA results showed that cells transfected with CMV-Pro10 were more capable of TGFβ1 secretion than those transfected with CMV-Leu10. Functionally, CMV-Pro10 was more apoptosis-protective and induced more proliferation than CMV-Leu10 in transfected hepatic cells. Pro10 up-regulated expression of CD105 and down-regulated expression of CD83. TGFβ1 gene Leu10Pro variation in signal peptide has significant effects on TGFβ1 secretion and functions in hepatic cells.

Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia.

PubMed

Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

2018-05-08

Glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unclear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. SIRT1 is a NAD + -dependent deacetylase that can deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial integrity, biogenesis, and function. We hypothesized that downregulation of hepatic SIRT1 signaling in G6Pase-α-deficient livers impairs PGC-1α activity, leading to mitochondrial dysfunction. Here we show that the G6Pase-α-deficient livers display defective PGC-1α signaling, reduced numbers of functional mitochondria, and impaired oxidative phosphorylation. Overexpression of hepatic SIRT1 restores PGC-1α activity, normalizes the expression of electron transport chain components, and increases mitochondrial complex IV activity. We have previously shown that restoration of hepatic G6Pase-α expression normalized SIRT1 signaling. We now show that restoration of hepatic G6Pase-α expression also restores PGC-1α activity and mitochondrial function. Finally, we show that HCA/HCC lesions found in G6Pase-α-deficient livers contain marked mitochondrial and oxidative DNA damage. Taken together, our study shows that downregulation of hepatic SIRT1/PGC-1α signaling underlies mitochondrial dysfunction and that oxidative DNA damage incurred by damaged mitochondria may contribute to HCA/HCC development in GSD-Ia.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

[Differential chronic hepatitis diagnosis].

PubMed

Hinterberger, W

2000-01-01

Chronic hepatitis comprises a group of disorders of the liver exhibiting a chronic necroinflammatory process that differs in etiology, clinical course and treatment strategies. A diagnosis of chronic hepatitis is usually made when inflammation and liver cell necrosis persist for longer than 6 months. Clinical manifestations range from asymptomatic patients to those with advanced hepatic failure. Both sexes and all age groups are affected. Chronic hepatitis may emerge as a sequelae of hepatitis C and less often after hepatitis B. Both diseases are treatable and require rapid and exact diagnosis. The differential diagnosis must exclude autoimmune hepatitis, chronic steatohepatitis, congenital metabolic hepatopathies and drug-induced hepatopathies. Laboratory tests, histologic investigations and clinical differential diagnosis must exclude other causes of chronic liver disease.

Physiological and biochemical basis of clinical liver function tests: a review.

PubMed

Hoekstra, Lisette T; de Graaf, Wilmar; Nibourg, Geert A A; Heger, Michal; Bennink, Roelof J; Stieger, Bruno; van Gulik, Thomas M

2013-01-01

To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

Hepatitis A, B, C, D, E, G: an update.

PubMed

Hall, Gairy F

2007-01-01

Acute and chronic liver diseases are an assortment of disorders brought to the clinician's attention by abnormal liver function tests or specific signs and symptoms. The differential diagnosis includes disorders that have primary or secondary liver involvement. This paper will be limited to the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the different viral liver diseases: A, B, C, D, E and G.

Hepatic encephalopathy secondary to a splenorenal shunt that manifested a long time after a liver transplantation.

PubMed

Tomás Pujante, Paula; Jiménez Sánchez, Andrés Francisco; Iglesias Jorquera, Elena; Pons Miñano, José Antonio

2018-04-24

Splenorenal shunts are a rare cause of hyperammonemia and hepatic encephalopathy in the absence of cirrhosis. We report the case of a woman, who presented hepatic encephalopathy, with a normal functioning graft, after 14 years of liver transplantation, confirmed by liver biopsy.

77 FR 15761 - Office of the Assistant Secretary for Health, Statement of Organization, Functions, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... hepatitis, other infectious diseases of public health significance, and blood safety and availability. The..., including viral hepatitis and HIV/AIDS, across HHS and monitors progress toward achieving established goals... to promote effective prevention and advancement of research for HIV/AIDS, viral hepatitis, and other...

Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda

PubMed Central

Van Geertruyden, J.P.; Ssenyonga, R.; Opio, C.K.; Kaducu, J.M.; Sempa, J.B.; Colebunders, R.; Ocama, P.

2017-01-01

Background Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. Methods We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. Results We recruited 612 mothers, median age 23 years (IQR 20–28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6–7.0) IU/mL with 9 (17.6%) having levels ≥105 IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. Conclusion Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission. PMID:28434689

Low rates of hepatitis A and B vaccination in patients with chronic hepatitis C at an urban methadone maintenance program.

PubMed

Felsen, Uriel R; Fishbein, Dawn A; Litwin, Alain H

2010-10-01

Patients with chronic hepatitis C virus (HCV) are at increased risk for complications of liver disease if they become infected with the hepatitis A (HAV) or hepatitis B (HBV) viruses. The authors examined the rates of testing for HAV, HBV, and HCV, as well as rates of vaccination against HAV and HBV in patients with chronic HCV in a random sample (N = 207) of medical records of patients enrolled in a methadone maintenance program. Almost all patients reviewed were tested for HAV, HBV, and HCV. Of the 111 patients with chronic HCV, 53 (48.6%) and 68 (63%) lacked immunity to HAV and HBV, respectively. Of those lacking immunity, 29 (54.7%) and 2 (2.9%) were vaccinated for HAV and HBV, respectively. Despite high rates of testing for HAV, HBV, and HCV at a methadone maintenance program, approximately half of those with chronic HCV eligible for the HAV vaccine received it, and few of those eligible for HBV vaccine received it.

Serological markers for hepatitis types A and B among U.S. Arym soldiers, Germany.

PubMed Central

James, J J; Smith, L

1979-01-01

Viral hepatitis rates among U.S. Army soldiers in Europe have been found to be two to three times higher than corresponding rates for soldiers stationed in the U.S. Sera from 89 per cent of a representative Army unit with 865 members and a known hepatitis problem were tested for HBsAg, anti-HBs, anti-HBc, and anti-HA. The prevalence of HB markers was 20 per cent, and hepatitis A antibody was present in 25 per cent. A six-month follow-up, conducted on 260 individuals initially negative for all four tests, revealed that 11 of these were now HB seropositive, whereas none had seroconverted to anti-HA positive. The HB virus was the principal agent responsible for hepatitis in the unit surveyed. PMID:228562

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012-2014.

PubMed

Linde, Ann C; Sweet, Kristin A; Nelson, Kailey; Mamo, Blain; Chute, Sara M

2016-01-01

The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees.

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012–2014

PubMed Central

Sweet, Kristin A.; Nelson, Kailey; Mamo, Blain; Chute, Sara M.

2016-01-01

Objective The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. Methods MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. Results In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). Conclusion In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees. PMID:27168670

Could JC virus provoke metastasis in colon cancer?

PubMed Central

Sinagra, Emanuele; Raimondo, Dario; Gallo, Elena; Stella, Mario; Cottone, Mario; Orlando, Ambrogio; Rossi, Francesca; Orlando, Emanuele; Messina, Marco; Tomasello, Giovanni; Lo Monte, Attilio Ignazio; La Rocca, Ennio; Rizzo, Aroldo Gabriele

2014-01-01

AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test. RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ2 = 9.55, P = 0.002). CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors. PMID:25400458

Clues for minimal hepatic encephalopathy in children with noncirrhotic portal hypertension.

PubMed

D'Antiga, Lorenzo; Dacchille, Patrizia; Boniver, Clementina; Poledri, Sara; Schiff, Sami; Zancan, Lucia; Amodio, Piero

2014-12-01

In children with noncirrhotic extrahepatic portal vein obstruction (EHPVO), minimal hepatic encephalopathy (MHE) was reported in a few series, but neither is it routinely investigated nor does consensus about its diagnosis exist. In this prospective observational study we aimed at detecting the prevalence of MHE in children with EHPVO and providing a practical diagnostic protocol. A consecutive sample of 13 noncirrhotic children (age range 4-18 years) with EHPVO underwent a screening for MHE based on level of fasting ammonia, quantified electroencephalogram (EEG) evaluation, and a wide battery of 26 psychometric tests exploring learning ability, abstract reasoning, phonemic and semantic fluency, selective attention, executive functions, short-term verbal and visual memory, long-term verbal memory, and visuopractic ability. Five children had at least 2 altered psychometric tests. Selective attention, executive function, and short-term visual memory were the domains more frequently altered, and 4 tests were enough to detect 80% of these children. Fasting ammonia plasma level was increased in 6 children. EEG mean dominant frequency adjusted for age was associated with serum ammonia concentration (β = -0.44 ± 0.19, P < 0.05). As a whole, children with EHPVO showed trends for lower α (median 41% vs 49%) and higher θ power than controls (median 41% vs 49% and 29% vs 20%, respectively). MHE affects approximately 50% of children with EHPVO and, therefore, is worthwhile to be investigated. Three simple tools, serum ammonia, quantified EEG, and neuropsychological examination, focused on selective attention, executive function, and short-term visual memory can be used effectively in the evaluation of MHE in this setting.

Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis.

PubMed

Czaja, A J; Manns, M P; Homburger, H A

1992-10-01

To assess the frequency of antibodies to liver/kidney microsome type 1 (anti-LKM1) in patients with chronic active hepatitis, 131 such patients were tested by an indirect immunofluorescence assay. Of 62 patients with type 1 autoimmune hepatitis, none were seropositive. In contrast, 3 of 11 patients with autoimmune hepatitis and antimitochondrial antibodies (27%) were seropositive for anti-LKM1. Each had responded to corticosteroid therapy, and retesting of sera confirmed that each had been misclassified as antimitochondrial antibody positive. None of the patients with chronic active hepatitis B (14 patients) or C (24 patients) had anti-LKM1. Similarly, none of the 20 patients with cryptogenic disease had these antibodies. It is concluded that anti-LKM1 is specific for type 2 autoimmune hepatitis and is infrequent in adult patients seen at a referral center in the United States for chronic active hepatitis. Anti-LKM1 reactivity may be misinterpreted as antimitochondrial antibody reactivity by indirect immunofluorescence. Chronic hepatitis B and C virus infections are not important stimuli for the production of anti-LKM1, and testing for anti-LKM 1 is unlikely to clarify the nature of cryptogenic disease.

A historical perspective on the discovery and elucidation of the hepatitis B virus.

PubMed

Block, Timothy M; Alter, Harvey J; London, W Thomas; Bray, Mike

2016-07-01

The discovery in 1965 of the "Australia antigen," subsequently identified as the hepatitis B virus surface antigen (HBsAg), was such a watershed event in virology that it is often thought to mark the beginning of hepatitis research, but it is more accurately seen as a critical breakthrough in a long effort to understand the pathogenesis of infectious hepatitis. A century earlier, Virchow provided an authoritative explanation of "catarrhal jaundice," which did not consider an infectious etiology, but the transmission of jaundice by human serum was clearly identified in two outbreaks in 1885, and the distinction between "infectious" and "serum" hepatitis was recognized by the early 1920s. The inability to culture a virus or reproduce either syndrome in laboratory animals led to numerous studies in human volunteers; by the end of World War II, it was known that the diseases were caused by different filterable agents, and the terms "hepatitis A" and "B" were introduced in 1947 (though some long-incubation cases then designated B must in retrospect have been hepatitis C). The development of a number of liver function tests during the 1950s led to the recognition of anicteric infections and the existence of chronic carriers, but little more could be done until an infectious agent had been identified. Once Blumberg and colleagues had found a specific viral marker, the vast amount of accumulated epidemiologic and clinical data, together with huge numbers of stored serum samples, enabled rapid progress in understanding hepatitis B, and revealed the existence of a vast population of chronically infected people in Asia, Oceania and Africa. In this article, we place the identification of the Australia antigen within the historical context of research on viral hepatitis. Following a chronological review from 1865 to 1965, we summarize how the discovery led to improved safety of blood transfusion, the development of a highly effective vaccine and the eventual identification of the hepatitis C, D and E viruses. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B." Copyright © 2016 Elsevier B.V. All rights reserved.

Self-reported history of vaccination and disease and immunity against hepatitis A, hepatitis B, tetanus, diphtheria and varicella among Spanish military recruits.

PubMed

Arteaga, Alejandro; Desviat, Pilar Vallejo; Jaqueti, Jeronimo; Santos, Juana; de Miguel, Angel Gil; Garcia, Rodrigo Jiménez

2010-02-01

This study aims to evaluate the immune status against hepatitis A, hepatitis B, tetanus, diphtheria and varicella in military recruits and the validity of self-reporting of their disease and vaccination history. A total of 226 participants were studied (mean age, 20.2 years; SD 1.7). 10.4% presented antibodies to hepatitis A, 78.3% to hepatitis B, 94.2% to tetanus, 77.4% to diphtheria and 81.9% to varicella. The relationship between self-reporting of vaccination history and seroprotection showed a high Positive Predictive Value for tetanus (98.8%) and a high Negative Predictive Value for hepatitis A (91%). Hepatitis A vaccination and serology testing for varicella and Hepatitis B on joining the Spanish armed forces are recommended.

Spirulina Protects against Hepatic Inflammation in Aging: An Effect Related to the Modulation of the Gut Microbiota?

PubMed Central

Neyrinck, Audrey M.; Taminiau, Bernard; Walgrave, Hannah; Daube, Georges; Cani, Patrice D.; Bindels, Laure B.; Delzenne, Nathalie M.

2017-01-01

Aging predisposes to hepatic dysfunction and inflammation that can contribute to the development of non-alcoholic fatty liver disease. Spirulina, a cyanobacterium used as a food additive or food supplement, has been shown to impact immune function. We have tested the potential hepatoprotective effect of a Spirulina in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota. Old mice have been fed a standard diet supplemented with or without 5% Spirulina for six weeks. Among several changes of gut microbiota composition, an increase in Roseburia and Lactobacillus proportions occurs upon Spirulina treatment. Interestingly, parameters related to the innate immunity are upregulated in the small intestine of Spirulina-treated mice. Furthermore, the supplementation with Spirulina reduces several hepatic inflammatory and oxidative stress markers that are upregulated in old mice versus young mice. We conclude that the oral administration of a Spirulina is able to modulate the gut microbiota and to activate the immune system in the gut, a mechanism that may be involved in the improvement of the hepatic inflammation in aged mice. Those data open the way to new therapeutic tools in the management of immune alterations in aging, based on gut microbe-host interactions. PMID:28632181

Novel Interventional Management of Hepatic Hydatid Cyst with Nanosecond Pulses on Experimental Mouse Model.

PubMed

Chen, Xinhua; Zhang, Ruiqing; Aji, Tuerganaili; Shao, Yingmei; Chen, Yonggang; Wen, Hao

2017-07-03

The nanosecond pulsed electric field (nsPEF) is investigated as an alternative plan for benign hepatic hydatid cyst. Altogether 72 C57B6 mice were included. Normal group (n = 12) had no parasite injection and the other 60 mice were used to induce hydatid cyst in liver by injecting protoscolices in portal vein. The liver hydatid cysts were exposed to nsPEF with different doses and then follow up. The standard surgery was performed as positive control. The hydatid cyst growth was monitored by ultrasound; the morphology was checked by gross anatomy and pathology was tested by H&E stain. In nsPEF-treated groups no hepatic failure nor bleeding were observed. As a comparison, in the surgery group, high post-treatment complications occurred (50%). Significant parasite growth inhibition was seen in high nsPEF dose group as compared with control group (P < 0.05). Pathological analysis confirmed destruction of hydatid cyst with sharp demarcation defined by the electrodes. Laboratory analysis showed nsPEF stimulated a time-dependent infection and recoverable liver function. The traumatic reactions defined by white blood count was significant lower than surgery groups (P < 0.05).Preliminary studies demonstrate nsPEF ablation can be applied on hepatic hydatid by inhibiting parasite growth, destructing the cyst and stimulating infections.

Cavernous Transformation of Portal Vein Secondary to Portal Vein Thrombosis: A Case Report

PubMed Central

Ramos, Radhames; Park, Yoojin; Shazad, Ghulamullah; A.Garcia, Christine; Cohen, Ronny

2012-01-01

There are few reported cases of cavernous transformation of the portal vein (CTPV) in adults. We present a case of a 58 year-old male who was found to have this complication due to portal vein thrombosis (PVT). A 58-year old African American male with chronic alcohol and tobacco use presented with a 25-day history of weakness, generalized malaise, nausea and vomiting associated with progressively worsening anorexia and weight loss. The patient was admitted for severe anemia in conjunction with abnormal liver function tests and electrolyte abnormalities, and to rule out end stage liver disease or hepatic malignancy. The work-up for anemia showed no significant colon abnormalities, cholecystitis, liver cirrhosis, or liver abnormalities but could not rule out malignancy. An esophageogastroduodenoscopy (EGD) was suspicious for a mass compressing the stomach and small bowel. After further work-up, the hepatic mass has been diagnosed as a cavernous transformation of the portal vein (CTPV), a very rare complication of portal vein thrombosis (PVT). Cavernous Transformation of the Portal Vein (CTPV) is a rare and incurable complication of portal vein thrombosis (PVT) that should be considered as one of the differential diagnoses of a hepatic mass. Keywords Cavernous transformation of the portal vein; Portal vein thrombosis; Portal hypertension; Hyperbilirubinemia; Hepatic mass PMID:22383935

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

PubMed

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

2017-01-28

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

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

Care delivery and outcomes among US veterans with hepatitis B: A national cohort study.

PubMed

Serper, Marina; Choi, Gina; Forde, Kimberly A; Kaplan, David E

2016-06-01

Previous studies have identified gaps in hepatitis B care. The objectives of this study were to evaluate the delivery of care among a national cohort of US veterans with chronic hepatitis B infection and examine risk factors for adverse clinical outcomes. We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse from 1999 to 2013 to evaluate (1) care delivery and (2) clinical outcomes such as hepatocellular carcinoma, hepatic decompensation, and mortality among US veterans with hepatitis B. Incidence rates with 95% confidence intervals were calculated and Cox regression models were used to evaluate clinical outcomes. We identified 21,419 veterans with a positive hepatitis B surface antigen, and 97% of patients had alanine aminotransferase and 44% had hepatitis B virus DNA testing; hepatitis B e antigen and hepatitis B e antibody were tested <50% of the time. Patients receiving specialty care had a higher prevalence of recommended laboratory testing. Patients with elevated alanine aminotransferase in specialty care were more likely to receive antiviral therapy (50% versus 24% for specialty care versus no specialty care, P < 0.001). Among patients with cirrhosis, 69% received one-time liver imaging. The proportion of follow-up time adherent to annual imaging was 0.39 (standard deviation = 0.42), and the proportion was 0.28 (standard deviation = 0.33) for biannual imaging; both proportions were higher in the specialty care group (all P < 0.05). Antiviral therapy (hazard ratio = 0.85, 95% confidence interval 0.76-0.95, P = 0.005) and liver imaging (hazard ratio = 0.84, 95% confidence interval 0.76-0.91, P < 0.001) were independently associated with decreased mortality in adjusted analyses. We observed a low prevalence of recommended laboratory testing, antiviral therapy initiation, and liver imaging among a national cohort of veterans with hepatitis B infection; antiviral therapy and liver imaging were independently associated with decreased mortality. (Hepatology 2016;63:1774-1782). © 2015 by the American Association for the Study of Liver Diseases.

Safety of coitally administered tenofovir 1% gel, a vaginal microbicide, in chronic hepatitis B virus carriers: Results from the CAPRISA 004 trial

PubMed Central

BAXTER, Cheryl; YENDE-ZUMA, Nonhlanhla; TSHABALALA, Phindile; KARIM, Quarraisha ABDOOL; KARIM, Salim S ABDOOL

2013-01-01

Tenofovir disoproxil fumarate, a licensed oral treatment for both HIV and Hepatitis B virus (HBV) infections, has been associated with severe rebound hepatic flares when treatment is interrupted. A gel formulation of tenofovir is currently being assessed as a microbicide against HIV. If licensed, it is possible that tenofovir gel could be used either intentionally or unintentionally by HBV carriers. The purpose of this study was to establish the safety of tenofovir gel use in this patient group participating in the CAPRISA 004 tenofovir gel trial. HBV infection status was assessed at enrolment and study exit. Liver function testing was performed at enrolment, study months 3, 12, 24, study exit, and two months after exiting the study. At enrolment, 34 women were identified as being HBV carriers and 22 women acquired HBV infections during follow-up; 14 and 8 in the tenofovir and placebo gel arms respectively (p=0.21). Intermittent tenofovir gel use did not cause an increase in hepatic flares or impact on viral load suppression in women with HBV infection. There were 2 hepatic flares in each gel arm during follow-up and none two months after cessation of gel at study exit. The mean HBV DNA levels were similar at enrolment and exit in both study arms. Tenofovir gel, when used intermittently, was safe to use in women with HBV infection. PMID:23832086

[Effect of acute biliary pancreatitis on liver metabolism of phenazone].

PubMed

Hartleb, M; Nowak, A; Nowakowska-Duława, E; Mańczyk, I; Becker, A; Kacperek, T

1990-03-01

In 22 patients with acute pancreatitis caused by biliary calculi and 9 healthy controls the rate of hepatic elimination of phenazone was measured. The aim of the study was evaluation of the oxidative-detoxicating action of the liver in this disease in relation to its severity. In pancreatitis patients the half-time (T2) of phenazone was significantly (p less than 0.01 longer than in healthy subjects (23.6 +/- 10.5 vs 13.2 +/- 7.2 hrs). The T2 of phenazone was not correlated with the concentrations of transaminases, bilirubin and prothrombin, but was correlated positively with the concentration of hepatic lactic dehydrogenase (p less than 0.001). In the initial stage of pancreatitis the T2 of phenazone was without prognostic significance and showed no agreement with Ranson's clinical-laboratory classification of the severity of the disease. The degree of impairment of the hepatic metabolism of phenazone measured with the percent difference between T2 of phenazone in both tests was significantly (p less than 0.05) greater in the group of patients with complications than in those without pancreatitis complications (70.7 +/- 64.4% vs 21.4 +/- 16.2%). Biliary pancreatitis impairs the oxidative-reductive function of the liver proportionally to the degree of hepatic lactic dehydrogenase in the serum. Evaluation of the rate of hepatic elimination of phenazone in the initial stage of this pancreatitis was without prognostic importance for the severity of the disease.

Amelioration of L-thyroxine-induced hyperthyroidism by coumarin (1,2-benzopyrone) in female rats.

PubMed

Panda, Sunanda; Kar, Anand

2007-11-01

1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.

21 CFR 660.2 - General requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen... transmitting hepatitis. (4) If the product is dried, the final container label shall indicate “Reconstitution..., including hepatitis, in handling the product and any ancillary reagents and materials accompanying the...

21 CFR 660.2 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen... transmitting hepatitis. (4) If the product is dried, the final container label shall indicate “Reconstitution..., including hepatitis, in handling the product and any ancillary reagents and materials accompanying the...

21 CFR 660.2 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen... transmitting hepatitis. (4) If the product is dried, the final container label shall indicate “Reconstitution..., including hepatitis, in handling the product and any ancillary reagents and materials accompanying the...

21 CFR 660.2 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen... transmitting hepatitis. (4) If the product is dried, the final container label shall indicate “Reconstitution..., including hepatitis, in handling the product and any ancillary reagents and materials accompanying the...

21 CFR 660.2 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen... transmitting hepatitis. (4) If the product is dried, the final container label shall indicate “Reconstitution..., including hepatitis, in handling the product and any ancillary reagents and materials accompanying the...

Management of infants born to women infected with hepatitis B in the military healthcare system.

PubMed

Sainato, Rebecca J; Simmons, Elizabeth G; Muench, Dawn F; Burnett, Mark W; Braun, LoRanée

2013-08-28

Hepatitis B virus (HBV) is endemic worldwide. Given significant rates of infectivity, all infants born to Hepatitis B surface antigen positive mothers need to receive treatment at birth, immunization and post-vaccination serologic testing. However, not all infants complete these requirements. We performed a retrospective review of the management of infants born to Hepatitis B infected mothers at two large military hospitals in the United States that use a global electronic medical record to track patient results. We then compared these results to those recently published by the National Perinatal Hepatitis B Prevention Program (PHBPP), which does not include hospitals in the United States Military Healthcare System. Our results show that although all infants were managed appropriately at birth and immunization rates were very high, post vaccination follow-up testing rates were much lower than those seen in centers participating in the PHBPP. The rates of post vaccination serological testing were significantly higher for infants born to Hepatitis B e antigen positive mothers and those referred to a pediatric infectious disease specialist. Despite use of a global electronic medical record in the United States Military Healthcare System, management of HBV-exposed infants does not always follow recommended guidelines. These infants could benefit from a more systematic method of follow-up, similar to the PHBPP, to ensure HBV serologic testing is obtained after the vaccination series is complete.

Treatment With Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

PubMed Central

Cóndor, José M.; Rodrigues, Camila E.; de Sousa Moreira, Roberto; Canale, Daniele; Volpini, Rildo A.; Shimizu, Maria H.M.; Camara, Niels O.S.; Noronha, Irene de L.

2016-01-01

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 106 WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. Significance Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. PMID:27280799

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

PubMed

Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

2018-05-01

Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Study on hepatitis B virus (HBV) infection and hepatitis B virus carrier state in children at two Mobil Oil Indonesia locations in Indonesia.

PubMed

Lubis, C P; Judin, A

1990-01-01

Between May and July 1985, a cross-sectional study on hepatitis B virus (HBV) infection and hepatitis B virus carrier state was conducted in children at two locations of Mobil Oil Indonesia i.e. Jakarta and Medan. Two main groups of Mobil Oil Indonesia population namely "employees" and "dependents" were also included in this study. From each subject, 10 ml of venous blood was taken and the sera separated and kept in a freezer at the temperature of -20 degrees C before sending them to the laboratories and tested with reagents produced by the Abbott Laboratory for HBsAg, anti-HBs and anti-HBc by radioimmunoassay (AUSRIA II-125, AVSAB and CORAB respectively). The test of blood samples from Jakarta population was done by the "the PRODIA LABORATORY" in Jakarta, while the test of blood samples from Medan was conducted by "the PATH LABORATORY" in Singapore which is nearer from Medan than Jakarta. The result of HBV markers test from 197 children were as follows: Incubation period of carrier state (HBsAg+) 1%; acute hepatitis B or persistent carrier state (HBsAg + and anti-HBc +) 0.5%; recovery/immune (anti-HBs + and anti-HBc +) 3.5%; immunization without infection or recovery with loss of detectable anti-HBc (anti-HBs +) 2% and acute hepatitis B (Window period) or recovery with loss of detectable antiHBs (anti-HBc +) 5%. The conclusion is that hepatitis B virus infection in a low percentage was found in children of Mobil Oil Indonesia population.

Metabolic Effects of Chronic Cannabis Smoking

PubMed Central

Muniyappa, Ranganath; Sable, Sara; Ouwerkerk, Ronald; Mari, Andrea; Gharib, Ahmed M.; Walter, Mary; Courville, Amber; Hall, Gail; Chen, Kong Y.; Volkow, Nora D.; Kunos, George; Huestis, Marilyn A.; Skarulis, Monica C.

2013-01-01

OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT). RESULTS Self-reported cannabis use was: 9.5 (2–38) years; joints/day: 6 (3–30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups. CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance. PMID:23530011

Artificial and bioartificial liver support: A review of perfusion treatment for hepatic failure patients

PubMed Central

Naruse, Katsutoshi; Tang, Wei; Makuuchi, Masatoshi

2007-01-01

Liver transplantation and blood purification therapy, including plasmapheresis, hemodiafiltration, and bioartificial liver support, are the available treatments for patients with severe hepatic failure. Bioartificial liver support, in which living liver tissue is used to support hepatic function, has been anticipated as an effective treatment for hepatic failure. The two mainstream systems developed for bioartificial liver support are extracorporeal whole liver perfusion (ECLP) and bioreactor systems. Comparing various types of bioartificial liver in view of function, safety, and operability, we concluded that the best efficacy can be provided by the ECLP system. Moreover, in our subsequent experiments comparing ECLP and apheresis therapy, ECLP offers more ammonia metabolism than HD and HF. In addition, ECLP can compensate amino acid imbalance and can secret bile. A controversial point with ECLP is the procedure is labor intensive, resulting in high costs. However, ECLP has the potential to reduce elevated serum ammonia levels of hepatic coma patients in a short duration. When these problems are solved, bioartificial liver support, especially ECLP, can be adopted as an option in ordinary clinical therapy to treat patients with hepatic failure. PMID:17461442

Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor?

PubMed

Hinds, Terry D; Adeosun, Samuel O; Alamodi, Abdulhadi A; Stec, David E

2016-10-01

Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels. We have recently described a novel function of bilirubin as a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), which we show specifically binds to the nuclear receptor. Bilirubin may function as a selective PPAR modulator (SPPARM) to control lipid accumulation and blood glucose. However, it is not known to what degree bilirubin activation of PPARα is responsible for the protection afforded to reduce hepatic steatosis. We hypothesize that bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism through a PPARα-dependent mechanism which reduces hepatic lipid accumulation and protects against hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions.

PubMed Central

Merali, Z; Singhal, R L

1976-01-01

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc. PMID:183849

Factors associated with knowledge, attitude and practice related to hepatitis B and C among international students of Universiti Putra Malaysia.

PubMed

Ahmad, Abdulrahman; Munn Sann, Lye; Abdul Rahman, Hejar

2016-07-21

Knowledge of hepatitis B and C has been reported to be low among respondents in different studies. We conducted a cross-sectional study among international students of Universiti Putra Malaysia (UPM) to ascertain their levels of knowledge, attitude and practices regarding hepatitis B and C and its associated factors. Six hundred and sixty two (662) international students participated in this study. A cluster sampling method was employed and data was generated using self-administered questionnaire, which was validated and its reliability checked. Normality test was conducted followed by descriptive statistics, spearman's correlation and Chi-square tests to explore associations between variables in the study. The response rate was 71.49 %. Of these, 50.3 % of the respondents had better knowledge of hepatitis B; 52.7 % had better knowledge of hepatitis C; 54.8 % had positive attitude towards hepatitis B and C and 77.6 % had safer practices towards hepatitis B and C. Positive correlations were found between knowledge of hepatitis B and knowledge of hepatitis C; knowledge hepatitis B and attitude; knowledge hepatitis C and attitude; knowledge hepatitis B and practice; knowledge hepatitis C and practice; and attitude and practice regarding hepatitis B and C. Similarly, some socio-demographic variables and history of hepatitis were found to be associated with knowledge, attitude and practice related to hepatitis B and C. The levels of knowledge and attitude towards hepatitis B and C were low among respondents but majority of them exhibited safe practices. The study level, faculty, age, nationality, marital status and gender of the respondents were significantly associated with their levels of knowledge, attitude and practices towards the disease. These findings imply that there is need for hepatitis health promotion among the international students of UPM and possibly other international students across the globe. It will serve to improve their levels of knowledge, attitude and practices in short term and get them protected against the disease in the long run.

Hepatitis Infection in the Treatment of Opioid Dependence and Abuse

PubMed Central

Kresina, Thomas F; Sylvestre, Diana; Seeff, Leonard; Litwin, Alain H; Hoffman, Kenneth; Lubran, Robert; Clark, H Westley

2008-01-01

Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful pharmacotherapy for opioid addiction stabilizes patients and improves patient compliance to care and treatment regimens as well as promotes good patient outcomes. Implementation and integration of effective hepatitis prevention programs, care programs, and treatment regimens in concert with the pharmacological therapy of opioid addiction can reduce the public health burdens of hepatitis and injection drug use. PMID:25977607

Seroprevalence of antibodies and antigens against hepatitis A-E viruses in refugees and asylum seekers in Germany in 2015.

PubMed

Jablonka, Alexandra; Solbach, Philipp; Wöbse, Michael; Manns, Michael P; Schmidt, Reinhold E; Wedemeyer, Heiner; Cornberg, Markus; Behrens, Georg M N; Hardtke, Svenja

2017-08-01

Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies. A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively. Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3). The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

PubMed

Ciocca, Mirta; Moreira-Silva, Sandra Fagundes; Alegría, Sylvia; Galoppo, Maria Cristina; Ruttiman, Ricardo; Porta, Gilda; Da Silvera, Themis Reverbel; Rubio, Pilar; Macias, Mercedes; Cervantes, Yolanda; Avila-Aguero, Maria Luisa; Clemens, Sue Anne Costa; Clemens, Ralf; Weil, John

2007-08-01

This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). HAV was the main etiologic agent of ALF in the population studied.

Student health policy of a German medical school--results of a cross sectional study concerning students' immunity to vaccine-preventable diseases.

PubMed

Schmid, Klaus; Wallaschofski, Hanka; Drexler, Hans

2004-12-01

Medical students come into contact with infectious materials early in their medical education. Aim of this study was to assess medical students' immunity to vaccine-preventable diseases and to ensure immunity against hepatitis B. An occupational health medical was offered to all medical students with special emphasis on preclinical students. The examination included a check of the certificates of vaccination and serological tests concerning hepatitis B virus, hepatitis C virus and, on request, HIV. A lecture on occupational risks and general precautions was given to the students. In 7 of 804 tested students serological markers of a previous hepatitis B infection were discovered, fortunately none of the students was infectious. No case of infection with the hepatitis C virus (n=804) or HIV (n=700 tested voluntary) was identified. For 52 percent of the students vaccination against hepatitis B was necessary to guarantee protective immunity. Documented protection against other vaccine-preventable diseases as tetanus (71%), diphtheria (67%), poliomyelitis (56%), pertussis (2%), measles (32%), mumps (24%) and rubella (25%) was also insufficient. As a result a vaccination against hepatitis B in childhood without documented response doesn't guarantee a sufficient protection. An occupational health medical at the beginning of preclinical training seems to be an adequate method of making medical students aware of occupational risks, immunization policies and the importance of occupational medicine.

Liver maximum capacity (LiMAx) test as a helpful prognostic tool in acute liver failure with sepsis: a case report.

PubMed

Buechter, Matthias; Gerken, Guido; Hoyer, Dieter P; Bertram, Stefanie; Theysohn, Jens M; Thodou, Viktoria; Kahraman, Alisan

2018-06-20

Acute liver failure (ALF) is a life-threatening entity particularly when infectious complications worsen the clinical course. Urgent liver transplantation (LT) is frequently the only curative treatment. However, in some cases, recovery is observed under conservative treatment. Therefore, prognostic tools for estimating course of the disease are of great clinical interest. Since laboratory parameters sometimes lack sensitivity and specificity, enzymatic liver function measured by liver maximum capacity (LiMAx) test may offer novel and valuable additional information in this setting. We here report the case of a formerly healthy 20-year old male caucasian patient who was admitted to our clinic for ALF of unknown origin in December 2017. Laboratory parameters confirmed the diagnosis with an initial MELD score of 28 points. Likewise, enzymatic liver function was significantly impaired with a value of 147 [> 315] μg/h/kg. Clinical and biochemical analyses for viral-, autoimmune-, or drug-induced hepatitis were negative. Liver synthesis parameters further deteriorated reaching a MELD score of 40 points whilst clinical course was complicated by septic pneumonia leading to severe hepatic encephalopathy grade III-IV, finally resulting in mechanical ventilation of the patient. Interestingly, although clinical course and laboratory data suggested poor outcome, serial LiMAx test revealed improvement of the enzymatic liver function at this time point increasing to 169 μg/h/kg. Clinical condition and laboratory data slowly improved likewise, however with significant time delay of 11 days. Finally, the patient could be dismissed from our clinic after 37 days. Estimating prognosis in patients with ALF is challenging by use of the established scores. In our case, improvement of enzymatic liver function measured by the LiMAx test was the first parameter predicting beneficial outcome in a patient with ALF complicated by sepsis.

Seroprevalence survey of varicella, measles, rubella, and hepatitis A and B viruses in a multinational healthcare workforce in Saudi Arabia.

PubMed

Almuneef, M A; Memish, Z A; Balkhy, H H; Otaibi, B; Helmi, M

2006-11-01

To determine the prevalence of the vaccine-preventable diseases caused by varicella, measles, rubella, and hepatitis A and B viruses in a multinational healthcare workforce. Prospective cohort study. A 750-bed tertiary care center located in Riyadh, Saudi Arabia. In compliance with hospital policy, newly recruited healthcare workers (HCWs) were enrolled in the study from September 2001 to March 2005. Serum samples were collected from all HCWs during the initial hiring process and tested for IgG antibodies against each of the 5 viral agents. Nonimmune HCWs were subsequently vaccinated at the earliest opportunity. A total of 4,006 newly hired (international and local) employees were included in the study. All underwent serologic testing for IgG antibodies against varicella, measles, rubella, hepatitis A, and hepatitis B viruses. Of the total, 63% were female and 37% were male. Middle Eastern employees comprised 47% of the total, followed by employees from the Far East (35%), the West (10%), and Africa (8%). Forty-two percent were nurses, 27% were in administration, 18% were medical technicians, and 13% were physicians. Among the 4,006 newly hired HCWs, 14% had negative IgG antibody test results for varicella virus, 13% for measles virus, 10% for rubella virus, 33% for hepatitis A virus, and 43% for hepatitis B virus. More women than men were susceptible to hepatitis A (40% vs. 24%; P<.001), whereas more men were susceptible to hepatitis B (55% vs. 35%; P<.001). Varicella susceptibility was more common among HCWs from the Far East (19%), whereas susceptibility to measles, rubella, hepatitis A, and hepatitis B was highest among HCWs from the Middle East. Both relative youth and male sex were associated with lack of antibodies against hepatitis B virus and rubella virus. In contrast, female sex and younger age were associated with lack of antibodies against hepatitis A virus (P<.001). Seroprevalence surveys of vaccine-preventable diseases among HCWs, although labor intensive, are invaluable in caring for a multinational workforce.

21 CFR 660.41 - Processing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.41 Processing. (a... that will reduce the risk of transmitting type B viral hepatitis. (b) Ancillary reagents and materials... its dating period. (d) Date of manufacture. The date of manufacture of Hepatitis B Surface Antigen...

21 CFR 660.41 - Processing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.41 Processing. (a... that will reduce the risk of transmitting type B viral hepatitis. (b) Ancillary reagents and materials... its dating period. (d) Date of manufacture. The date of manufacture of Hepatitis B Surface Antigen...

21 CFR 660.41 - Processing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.41 Processing. (a... that will reduce the risk of transmitting type B viral hepatitis. (b) Ancillary reagents and materials... its dating period. (d) Date of manufacture. The date of manufacture of Hepatitis B Surface Antigen...

21 CFR 660.41 - Processing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.41 Processing. (a... that will reduce the risk of transmitting type B viral hepatitis. (b) Ancillary reagents and materials... its dating period. (d) Date of manufacture. The date of manufacture of Hepatitis B Surface Antigen...

21 CFR 660.41 - Processing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.41 Processing. (a... that will reduce the risk of transmitting type B viral hepatitis. (b) Ancillary reagents and materials... its dating period. (d) Date of manufacture. The date of manufacture of Hepatitis B Surface Antigen...

Specific Inhibition of the Redox Activity of Ape1/Ref-1 by E3330 Blocks Tnf-Α-Induced Activation of Il-8 Production in Liver Cancer Cell Lines

PubMed Central

Vascotto, Carlo; Leonardi, Antonio; Kelley, Mark R.; Tiribelli, Claudio; Tell, Gianluca

2013-01-01

APE1/Ref-1 is a main regulator of cellular response to oxidative stress via DNA-repair function and co-activating activity on the NF-κB transcription factor. APE1 is central in controlling the oxidative stress-based inflammatory processes through modulation of cytokines expression and its overexpression is responsible for the onset of chemoresistance in different tumors including hepatic cancer. We examined the functional role of APE1 overexpression during hepatic cell damage related to fatty acid accumulation and the role of the redox function of APE1 in the inflammatory process. HepG2 cells were stably transfected with functional and non-functional APE1 encoding plasmids and the protective effect of APE1 overexpression toward genotoxic compounds or FAs accumulation, was tested. JHH6 cells were stimulated with TNF-α in the presence or absence of E3330, an APE1 redox inhibitor. IL-8 promoter activity was assessed by a luciferase reporter assay, gene expression by Real-Time PCR and cytokines (IL-6, IL-8, IL-12) levels measured by ELISA. APE1 over-expression did not prevent cytotoxicity induced by lipid accumulation. E3330 treatment prevented the functional activation of NF-κB via the alteration of APE1 subcellular trafficking and reduced IL-6 and IL-8 expression induced by TNF-α and FAs accumulation through blockage of the redox-mediated activation of NF-κB. APE1 overexpression observed in hepatic cancer cells may reflect an adaptive response to cell damage and may be responsible for further cell resistance to chemotherapy and for the onset of inflammatory response. The efficacy of the inhibition of APE1 redox activity in blocking TNF-α and FAs induced inflammatory response opens new perspectives for treatment of inflammatory-based liver diseases. PMID:23967134

Epidemiology of hepatitis B infection in Liberian infants.

PubMed

Prince, A M; White, T; Pollock, N; Riddle, J; Brotman, B; Richardson, L

1981-05-01

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers.

Epidemiology of hepatitis B infection in Liberian infants.

PubMed Central

Prince, A M; White, T; Pollock, N; Riddle, J; Brotman, B; Richardson, L

1981-01-01

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers. PMID:7251143

Using Bovine Viral Diarrhea Virus (BVDV) As Surrogate for Human Hepatitis C Virus

EPA Pesticide Factsheets

This test is designed to validate virucidal effectiveness claims for a product to be registered as a virucide. It determines the potential of the test agent to disinfect hard surfaces contaminated with human Hepatitis C virus (HCV).

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-06-16

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

Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α.

PubMed

Adil, Mohammad; Kandhare, Amit D; Visnagri, Asjad; Bodhankar, Subhash L

2015-01-01

Chronic exposure of a naturally occurring metal arsenic leads to renal and hepatic diseases. Naringin, a flavanone glycoside, possesses anti-inflammatory and anti-oxidant potential. The aim of this investigation was to evaluate the protective effect of naringin against arsenic-induced renal and hepatic toxicity in rats. Renal and hepatic toxicity was induced in rats by sodium arsenite (5 mg/kg, p.o.). Rats were treated orally with either vehicle or naringin (20, 40, and 80 mg/kg) or Coenzyme Q10 (10 mg/kg) for 28 days. Various biochemical, histological, and molecular biomarkers were assessed in kidney and liver. Treatment with naringin (40 and 80 mg/kg) significantly and dose-dependently restored (p < 0.01 and p < 0.001) altered levels of kidney (serum creatinine, urine creatinine, BUN, uric acid, and creatinine clearance) and liver function test (AST and ALT) induced by sodium arsenite. Elevated levels of oxido-nitrosative stress in renal and hepatic tissue was significantly and dose-dependently decreased (p < 0.01 and p < 0.001) by naringin (40 and 80 mg/kg) treatment. It significantly and dose-dependently down-regulated (p < 0.01 and p < 0.001) renal KIM-1, Caspase-3, TGF-β, and TNF-α mRNA expression. Histopathological alteration induced in kidney and liver by sodium arsenite was reduced by naringin (40 and 80 mg/kg) treatment. In conclusion, naringin treatment ameliorates arsenic-induced renal and hepatic damage in rats due its antioxidant and anti-inflammatory properties via down-regulation of elevated oxido-nitrosative stress, KIM-1, Caspase-3, TGF-β, and TNF-α levels.

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

PubMed Central

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes.

PubMed

Bril, Fernando; Kadiyala, Sushma; Portillo Sanchez, Paola; Sunny, Nishanth E; Biernacki, Diane; Maximos, Maryann; Kalavalapalli, Srilaxmi; Lomonaco, Romina; Suman, Amitabh; Cusi, Kenneth

2016-01-01

The underlying mechanisms responsible for the development and progression of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) are unclear. Since the thyroid hormone regulates mitochondrial function in the liver, we designed this study in order to establish the association between plasma free T4 levels and hepatic triglyceride accumulation and histological severity of liver disease in patients with T2DM and NAFLD. This is a cross-sectional study including a total of 232 patients with T2DM. All patients underwent a liver MR spectroscopy ((1)H-MRS) to quantify hepatic triglyceride content, and an oral glucose tolerance test to estimate insulin resistance. A liver biopsy was performed in patients with a diagnosis of NAFLD. Patients were divided into 5 groups according to plasma free T4 quintiles. We observed that decreasing free T4 levels were associated with an increasing prevalence of NAFLD (from 55% if free T4≥1.18 ng/dL to 80% if free T4<0.80 ng/dL, p=0.016), and higher hepatic triglyceride accumulation by (1)H-MRS (p<0.001). However, lower plasma free T4 levels were not significantly associated with more insulin resistance or more severe liver histology (ie, inflammation, ballooning, or fibrosis). Decreasing levels of plasma free T4 are associated with a higher prevalence of NAFLD and increasing levels of hepatic triglyceride content in patients with T2DM. These results suggest that thyroid hormone may play a role in the regulation of hepatic steatosis and support the notion that hypothyroidism may be associated with NAFLD. No NCT number required. Copyright © 2016 American Federation for Medical Research.

Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

PubMed

Sandoval-Sus, Jose D; Mogollon-Duffo, Francis; Patel, Ankita; Visweshwar, Nathan; Laber, Damian A; Kim, Richard; Jagal, Michael V

2017-01-01

We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.

Computational Modeling in Liver Surgery

PubMed Central

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

2017-01-01

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

Diagnostic value of fibronectin discriminant score for predicting liver fibrosis stages in chronic hepatitis C virus patients.

PubMed

Attallah, Abdelfattah M; Abdallah, Sanaa O; Attallah, Ahmed A; Omran, Mohamed M; Farid, Khaled; Nasif, Wesam A; Shiha, Gamal E; Abdel-Aziz, Abdel-Aziz F; Rasafy, Nancy; Shaker, Yehia M

2013-01-01

Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment. To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions. Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA. A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference. FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

Furostanolic saponins from Trigonella foenum-graecum alleviate diet-induced glucose intolerance and hepatic fat accumulation.

PubMed

Hua, Yinan; Ren, Sidney Y; Guo, Rui; Rogers, Olivia; Nair, Rama P; Bagchi, Debasis; Swaroop, Anand; Nair, Sreejayan

2015-10-01

The objective of this study was to evaluate the effect of fenugreek furostanolic saponins (Fenfuro(TM) ) either alone or in combination with chlorogenic acid (GCB-70(TM) ) on insulin resistance in mice. Male C57BL/6J mice were subjected to a normal or high-fat diet (HFD) and were randomly assigned to receive Fenfuro(TM) , GCB-70(TM) , or their combination for 24 wk. Metabolic parameters, glucose tolerance, serum triglycerides, cardiac function, and hepatic insulin signaling were evaluated using indirect open-circuit calorimetry, intraperitoneal glucose tolerance test, oil red O staining, echocardiography, and Western blotting, respectively. Intraperitoneal glucose tolerance test revealed glucose intolerance in the mice receiving HFD, which was attenuated by Fenfuro(TM) . Serum triglyceride that was elevated following an HFD was reconciled by both Fenfuro(TM) and the combination. HFD compromised myocardial contractile function, which was unaffected by the treatment. Insulin-stimulated phosphorylation of Protein kinase B (AKT) in the liver was attenuated in mice receiving HFD, which was partially rescued by GCB-70(TM) . Neither treatment altered metabolic parameters or energy expenditure. Collectively, our data suggest that fenugreek furostanolic saponins and green coffee bean extract may have potential benefits in treating insulin resistance and related conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetically controllable 3D microtissues based on magnetic microcryogels.

PubMed

Liu, Wei; Li, Yaqian; Feng, Siyu; Ning, Jia; Wang, Jingyu; Gou, Maling; Chen, Huijun; Xu, Feng; Du, Yanan

2014-08-07

Microtissues on the scale of several hundred microns are a promising cell culture configuration resembling the functional tissue units in vivo. In contrast to conventional cell culture, handling of microtissues poses new challenges such as medium exchange, purification and maintenance of the microtissue integrity. Here, we developed magnetic microcryogels to assist microtissue formation with enhanced controllability and robustness. The magnetic microcryogels were fabricated on-chip by cryogelation and micro-molding which could endure extensive external forces such as fluidic shear stress during pipetting and syringe injection. The magnetically controllable microtissues were applied to constitute a novel separable 3D co-culture system realizing functional enhancement of the hepatic microtissues co-cultured with the stromal microtissues and easy purification of the hepatic microtissues for downstream drug testing. The magnetically controllable microtissues with pre-defined shapes were also applied as building blocks to accelerate the tissue assembly process under magnetic force for bottom-up tissue engineering. Finally, the magnetic microcryogels could be injected in vivo as cell delivery vehicles and tracked by MRI. The injectable magnetic microtissues maintained viability at the injection site indicating good retention and potential applications for cell therapy. The magnetic microcryogels are expected to significantly promote the microtissues as a promising cellular configuration for cell-based applications such as in drug testing, tissue engineering and regenerative therapy.

Evaluation of MELD score and Maddrey discriminant function for mortality prediction in patients with alcoholic hepatitis.

PubMed

Monsanto, Pedro; Almeida, Nuno; Lrias, Clotilde; Pina, Jos Eduardo; Sofia, Carlos

2013-01-01

Maddrey discriminant function (DF) is the traditional model for evaluating the severity and prognosis in alcoholic hepatitis (AH). However, MELD has also been used for this purpose. We aimed to determine the predictive parameters and compare the ability of Maddrey DF and MELD to predict short-term mortality in patients with AH. Retrospective study of 45 patients admitted in our department with AH between 2000 and 2010. Demographic, clinical and laboratory parameters were collected. MELD and Maddrey DF were calculated on admission. Short-term mortality was assessed at 30 and 90 days. Student t-test, χ2 test, univariate analysis, logistic regression and receiver operating characteristic curves were performed. Thirty-day and 90-day mortality was 27% and 42%, respectively. In multivariate analysis, Maddrey DF was the only independent predictor of mortality for these two periods. Receiver operating characteristic curves for Maddrey DF revealed an excellent discriminatory ability to predict 30-day and 90-day mortality for a Maddrey DF greater than 65 and 60, respectively. Discriminatory ability to predict 30-day and 90-day mortality for MELD was low. AH remains associated with a high short-term mortality. Maddrey DF is a more valuable model than MELD to predict short-term mortality in patients with AH.

Sadness and mild cognitive impairment as predictors for interferon-alpha-induced depression in patients with hepatitis C.

PubMed

Sarkar, Susanne; Sarkar, Rahul; Berg, Thomas; Schaefer, Martin

2015-01-01

Antiviral therapy with interferon-alpha (IFN-α) for hepatitis C virus (HCV) infection is associated with increased risk for depression. To identify clinical predictors for IFN-α-induced depression during antiviral therapy for HCV infection. Depression (defined with the Montgomery-Åsberg Depression Rating Scale (MADRS)) was evaluated before and during antiviral treatment in 91 people with chronic HCV infection without a history of psychiatric disorders. Cognitive function was evaluated using the Trail Making Test A/B (TMT A/B). (Trial registration at ClinicalTrials.gov: NCT00136318.) Depression during antiviral therapy was significantly associated with a baseline MADRS score of 3 or higher (P = 0.006). In total, 89% (n = 16) of patients who had a baseline score >0 for the single item sadness developed depression. Poor baseline performance in the TMT A (P = 0.027) and TMT B (P = 0.033) was predictive for severe depression. Pre-treatment screening for subthreshold depressive and cognitive symptoms will help to identify those at risk for IFN-α-associated depression among patients with chronic hepatitis C. Royal College of Psychiatrists.

Attitudes and Awareness Regarding Hepatitis B and Hepatitis C Amongst Health-care Workers of a Tertiary Hospital in India.

PubMed

Setia, S; Gambhir, Rs; Kapoor, V; Jindal, G; Garg, S; Setia, S

2013-10-01

Hepatitis is an inflammatory disease of the liver. In sever cases, it may lead to permanent liver damage including liver cirrhosis or hepato-cellular carcinoma and may ultimately lead to death. Health-care workers (HCWs), due to their regular contact with patients are at a high-risk of acquiring this disease. The aim of this study was to assess the knowledge and attitude toward hepatitis B and C infection among the health-care interns and correlate the level of awareness to the attitude they behold toward the disease. A closed ended questionnaire consisting of questions to evaluate the knowledge regarding hepatitis B and C infection and attitude of the (HCWs/interns) was duly filled by 255 participants including, 100 dental, 100 medical, and 55 nursing interns. Statistical analysis was carried out using the Chi-square test, ANOVA test, post-hoc test and Pearson's correlation. Although most of the interns were aware of the existence of hepatitis B and C infection, the level of awareness regarding the modes of transmission and vaccination was found to be dissatisfactory. Awareness level regarding the infection among nursing interns was statistically significantly lower than the dental and medical interns. A direct positive correlation as found between awareness score and behavior score, which reveals that interns with better awareness level had better attitudes toward the infection and prevention of its transmission. There is an urgent need to increase the level and quality of training among HCWs to prevent the spread of hepatitis B virus and hepatitis C virus.

Characteristics of an outpatient chronic hepatitis B virus infection cohort

PubMed Central

de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

2015-01-01

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

Susceptibility to T cell-mediated liver injury is enhanced in asialoglycoprotein receptor-deficient mice.

PubMed

McVicker, Benita L; Thiele, Geoffrey M; Casey, Carol A; Osna, Natalia A; Tuma, Dean J

2013-05-01

T cell activation and associated pro-inflammatory cytokine production is a pathological feature of inflammatory liver disease. It is also known that liver injury is associated with marked impairments in the function of many hepatic proteins including a hepatocyte-specific binding protein, the asialoglycoprotein receptor (ASGPR). Recently, it has been suggested that hepatic ASGPRs may play an important role in the physiological regulation of T lymphocytes, leading to our hypothesis that ASGPR defects correlate with inflammatory-mediated events in liver diseases. Therefore, in this study we investigated whether changes in hepatocellular ASGPR expression were related to the dysregulation of intrahepatic T lymphocytes and correlate with the development of T-cell mediated hepatitis. Mice lacking functional ASGPRs (receptor-deficient, RD), and wild-type (WT) controls were intravenously injected with T-cell mitogens, Concanavalin A (Con A) or anti-CD3 antibody. As a result of T cell mitogen treatment, RD mice lacking hepatic ASGPRs displayed enhancements in liver pathology, transaminase activities, proinflammatory cytokine expression, and caspase activation compared to that observed in normal WT mice. Furthermore, FACS analysis demonstrated that T-cell mitogen administration resulted in a significant rise in the percentage of CD8+ lymphocytes present in the livers of RD animals versus WT mice. Since these two mouse strains differ only in whether they express the hepatic ASGPR, it can be concluded that proper ASGPR function exerts a protective effect against T cell mediated hepatitis and that impairments to this hepatic receptor could be related to the accumulation of cytotoxic T cells that are observed in inflammatory liver diseases. Published by Elsevier B.V.

Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

PubMed

Kołodziejski, Paweł A; Pruszyńska-Oszmałek, Ewa; Strowski, Mathias Z; Nowak, Krzysztof W

2017-06-01

Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

PubMed

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Changing patterns of hepatitis A and E sero-prevalences in children after the 1999 earthquakes in Duzce, Turkey.

PubMed

Kaya, Ayse Demet; Ozturk, C Elif; Yavuz, Taner; Ozaydin, Cigdem; Bahcebasi, Talat

2008-04-01

Hepatitis A and E are enteric viral diseases that are characteristically found in developing countries. Sero-epidemiological data about both infections showed higher prevalence rates soon after the 1999 earthquakes in Duzce, Turkey. The aim of the present study was to evaluate the data 4 years after the earthquakes. The study group included 589 children (72.3% boys) who were between the ages of 6 months and 17 years (mean age 11.5 years). The children were separated into three groups: Group 1 (ages 6 months to 5.9 years), Group 2 (ages 6.0-12.9 years) and Group 3 (ages 13.0-17.0 years). Serum anti-hepatitis A virus IgG and anti-hepatitis E virus IgG were determined using commercial enzyme-linked immunosorbent assay kits. The data were tested for statistical significance with the chi(2)-test. The sero-prevalence rates of hepatitis A and E were 63.8% and 0.3%, respectively. The sero-prevalence rates of both hepatitis A and E increased with age, and there was no significant difference between the genders. Hepatitis A infection was associated with socio-economic condition, crowded living environment, and education level of the family (P < 0.01). Hepatitis A infection is still common, whereas hepatitis E infection appears to be relatively rare in paediatric age groups in Duzce, Turkey.

Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes.

PubMed

Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu

2015-01-01

The ubiquitous shortage of primary human hepatocytes has urged the scientific community to search for alternative cell sources, such as immortalized hepatic cell lines. Over the years, several human hepatic cell lines have been produced, whether or not using a combination of viral oncogenes and human telomerase reverse transcriptase protein. Conditional approaches for hepatocyte immortalization have also been established and allow generation of growth-controlled cell lines. A variety of immortalized human hepatocytes have already proven useful as tools for liver-based in vitro testing and fundamental research purposes. The present chapter describes currently applied immortalization strategies and provides an overview of the actually available immortalized human hepatic cell lines and their in vitro applications.

21 CFR 660.3 - Reference panel.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.3 Reference panel. A Reference Hepatitis B Surface Antigen Panel shall be obtained from the Center... shall be used for determining the potency and specificity of Antibody to Hepatitis B Surface Antigen...

21 CFR 660.3 - Reference panel.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.3 Reference panel. A Reference Hepatitis B Surface Antigen Panel shall be obtained from the Center... shall be used for determining the potency and specificity of Antibody to Hepatitis B Surface Antigen...

21 CFR 660.3 - Reference panel.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.3 Reference panel. A Reference Hepatitis B Surface Antigen Panel shall be obtained from the Center for... used for determining the potency and specificity of Antibody to Hepatitis B Surface Antigen. [40 FR...

21 CFR 660.3 - Reference panel.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.3 Reference panel. A Reference Hepatitis B Surface Antigen Panel shall be obtained from the Center... shall be used for determining the potency and specificity of Antibody to Hepatitis B Surface Antigen...

21 CFR 660.3 - Reference panel.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Antibody to Hepatitis B Surface Antigen § 660.3 Reference panel. A Reference Hepatitis B Surface Antigen Panel shall be obtained from the Center... shall be used for determining the potency and specificity of Antibody to Hepatitis B Surface Antigen...

21 CFR 610.40 - Test requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... virus, type 1; (2) Human immunodeficiency virus, type 2; (3) Hepatitis B virus; (4) Hepatitis C virus.... Except as specified in paragraphs (c) and (d) of this section, you, an establishment that collects blood... of transmission of communicable disease. (c) Exceptions to testing for allogeneic transfusion or...

[Hematologic, biochemical, and immunological tests in clinical practice of rheumatoid arthritis].

PubMed

Yukawa, Naoichiro; Mimori, Tsuneyo

2013-07-01

In clinical practice of rheumatoid arthritis (RA), various kinds of laboratory tests are required for diagnosis, assessment of the disease activity, assessment of complications and risk factors before starting therapy, and assessment of adverse effects during the therapy. Anemia, thrombocytosis, and leukocytosis are common in active RA. During RA therapies, liver function tests (including ALT and AST) and renal function tests (including serum creatinine and urinalysis) should be performed. Anti-CCP antibody is an especially useful marker for diagnosis of RA, and the presence of the antibody has been included in ACR/EULAR 2010 RA classification criteria. Reactivation of hepatitis B virus (HBV) after immunosuppressive therapies is a potentially serious complication. HBc and/or HBs antibodies should be measured before starting the therapies even if HBs antigen is negative, and appropriate interventions including measurement of HBV-DNA and starting prophylaxis (entecavir is recommended) should be performed.

Hepatitis B knowledge, testing, and vaccination among Chinese and Vietnamese adults in Australia.

PubMed

Vu, Lan H; Gu, Zhihong; Walton, Jodie; Peet, Anthony; Dean, Judith; Dunne, Michael P; Debattista, Joseph

2012-03-01

Hepatitis B is a significant public health challenge within some subpopulations in Australia, including Chinese and Vietnamese migrants. There has been limited research on hepatitis B knowledge and actions in these communities. The authors conducted a self-administered survey among 442 Chinese and 433 Vietnamese in Brisbane. Generally, the knowledge is best described as "moderate." One in 2 could not identify the sexual transmission risk and less than one third knew that sharing foods or drinks did not spread the disease. The majority of Vietnamese (80%) and 60% of Chinese respondents indicated prior testing. Vaccination was reported in 60% of the Vietnamese and in 52% of the Chinese. Knowledge was better among Chinese people who had been tested and vaccinated compared with those who were nontested and nonvaccinated. Only 3.5% of the Chinese, but 11.6% of the Vietnamese, indicated having a positive test result hepatitis B virus. This study helps identify strategies for programs targeting both communities and practitioners.

Disclosure of Sexual Orientation and Uptake of HIV Testing and Hepatitis Vaccination for Rural Men Who Have Sex With Men.

PubMed

Metheny, Nicholas; Stephenson, Rob

2016-03-01

The decision and ability of primary care clinician to make recommendations for routine human immunodeficiency virus (HIV) testing and hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccines are shaped by knowledge of their patient's risk behaviors. For men who have sex with men, such knowledge requires disclosure of same-sex sexual behavior or sexual identity. Data were analyzed from a national survey of rural men who have sex with men (N = 319) to understand whether the disclosure of sexual identity to clinicians was associated with increased uptake of HIV testing and hepatitis vaccinations. We found that disclosure of sexual identity to clinicians was significantly associated (OR = 1.26; 95% CI, 1.08-1.47) with uptake of routine HIV testing and HAV/HBV vaccination. Our finding reinforces the need for safe, nonjudgmental settings for patients to discuss their sexual identities freely with their clinicians. © 2016 Annals of Family Medicine, Inc.

Impact of Vaccination History on Serological Testing in Pregnant Women.

PubMed

Desjardins, Michaël; Boucoiran, Isabelle; Paquet, Caroline; Laferrière, Céline; Gosselin-Brisson, Anne; Labbé, Annie-Claude; Martel-Laferrière, Valérie

2018-04-01

Serological testing guidelines for vaccine-preventable infectious diseases in pregnant women are heterogeneous. It is unclear how vaccination history influences health care workers' (HCWs) attitudes about testing. The aim of this study was to describe current practices in screening for rubella, hepatitis B, and varicella-zoster virus (VZV) in pregnant women in the province of Québec. In 2015, an electronic survey was distributed to HCWs who followed the case of at least one pregnant woman in the previous year and who could be contacted by email by their professional association. A total of 363 of 1084 (33%) participants were included in the analysis: general practitioners (57%), obstetrician-gynaecologists (20%), midwives (41%), and nurse practitioners (31%). For rubella, 48% of participants inquired about vaccination status, and of these, 98% offered serological testing for unvaccinated women versus 44% for vaccinated women. Similarly, of the 48% of participants who asked about hepatitis B vaccination status before offering testing, 96% ordered testing for hepatitis B surface antigen, 28% ordered testing for hepatitis B surface antibody, and 1% ordered no serological testing to unvaccinated women versus 72%, 46%, and 8%, respectively, for vaccinated women. Among the 81% of respondents who discussed VZV during prenatal care, 13% ordered serological testing if patients had a history of VZV infection, 87% if the VZV history was uncertain, and 19% if patients had a positive history of vaccination. Asking about vaccination status influences HCWs' attitudes about serological testing for rubella, hepatitis B, and VZV. In the context of increasing vaccination coverage in women of child-bearing age, it is important to clarify the impact of vaccination status in serological screening guidelines in pregnant women. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa.

PubMed Central

Schoub, B. D.; Matai, U.; Singh, B.; Blackburn, N. K.; Levin, J. B.

2002-01-01

OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children. PMID:12075363

[Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners].

PubMed

Bouma, M; van Geldrop, W J; Numans, M E; Wiersma, Tj; Goudswaard, A N

2008-12-06

The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.

Hepatic encephalopathy in a liver transplant recipient with stable liver function.

PubMed

Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

2013-04-01

Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis

PubMed Central

Anand, Sudarshan; Wang, Pu; Yoshimura, Kiyoshi; Choi, In-Hak; Hilliard, Anja; Chen, Youhai H.; Wang, Chyung-Ru; Schulick, Richard; Flies, Andrew S.; Flies, Dallas B.; Zhu, Gefeng; Xu, Yanhui; Pardoll, Drew M.; Chen, Lieping; Tamada, Koji

2006-01-01

LIGHT is an important costimulatory molecule for T cell immunity. Recent studies have further implicated its role in innate immunity and inflammatory diseases, but its cellular and molecular mechanisms remain elusive. We report here that LIGHT is upregulated and functions as a proinflammatory cytokine in 2 independent experimental hepatitis models, induced by concanavalin A and Listeria monocytogenes. Molecular mutagenesis studies suggest that soluble LIGHT protein produced by cleavage from the cell membrane plays an important role in this effect through the interaction with the lymphotoxin-β receptor (LTβR) but not herpes virus entry mediator. NK1.1+ T cells contribute to the production, but not the cleavage or effector functions, of soluble LIGHT. Importantly, treatment with a mAb that specifically interferes with the LIGHT-LTβR interaction protects mice from lethal hepatitis. Our studies thus identify a what we believe to be a novel function of soluble LIGHT in vivo and offer a potential target for therapeutic interventions in hepatic inflammatory diseases. PMID:16557300

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression.

PubMed

Bellanti, Francesco; Villani, Rosanna; Tamborra, Rosanna; Blonda, Maria; Iannelli, Giuseppina; di Bello, Giorgia; Facciorusso, Antonio; Poli, Giuseppe; Iuliano, Luigi; Avolio, Carlo; Vendemiale, Gianluigi; Serviddio, Gaetano

2018-05-01

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury. Copyright © 2017. Published by Elsevier B.V.

Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report.

PubMed

Yamada, Naoya; Sanada, Yukihiro; Katano, Takumi; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Miki, Atsushi; Sasanuma, Hideki; Urahashi, Taizen; Sakuma, Yasunaru; Mizuta, Koichi

2016-11-28

This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

Hepatitis C Virus: Patients' Risk Factors and Knowledge in an Urban Clinic Providing Wound Care.

PubMed

Pieper, Barbara; Sickon, Katharine

2018-03-01

Affecting about 3.2 million people in the United States, hepatitis C virus (HCV) is the primary cause of chronic liver disease and a global health challenge. Hepatitis C virus can affect the functioning of the liver, the health of the person, and thus wound healing. This quality project explores risk factors of HCV; self-reported screening, occurrence, and treatment; and knowledge of HCV in patients seeking wound care in an urban clinic. Demographic risk factors, HCV history, and responses to a 22-item true-false-don't know HCV Knowledge Test were obtained from 58 patients. Risk factors included age (mean, 61.07 years), male sex (n = 41), non-Hispanic black race/ethnicity (n = 51), and history of injection drugs (n = 38). Thirty-nine (67.2%) stated they had been screened for HCV; 31 were told they were infected. Only 14 went to a clinic for HCV care and 11 reported they were treated. The mean number of correct answers on the HCV Knowledge Test was 14.4 (standard deviation, 5.7). This urban clinic had patients with multiple HCV risk factors; they often lacked HCV screening and/or referral for treatment. Their HCV knowledge was generally low. As a major public health problem that could impact wound healing, wound care practitioners should ask patients about their HCV status, encourage HCV screening and care, and provide HCV information.

Pseudoaneurysm following laparoscopic cholecystectomy.

PubMed

Madanur, Mansoor Ahmed; Battula, Narendra; Sethi, Harsheet; Deshpande, Rahul; Heaton, Nigel; Rela, Mohamed

2007-06-01

Laparoscopic cholecystectomy (LC) is the operation of choice for removal of the gallbladder. Unrecognized bile duct injuries present with biliary peritonitis and systemic sepsis. Bile has been shown to cause damage to the vascular wall and therefore delay the healing of injured arteries leading to pseudoaneurysm formation. Failure to deal with bile leak and secondary infection may result in pseudoaneurysm formation. This study was to report the incidence and outcomes of pseudoaneurysm in patients with bile leak following LC referred to our hospital. A retrospective analysis of our prospectively maintained liver database using key words pseudoaneurysm, bile leak and bile duct injury following laparoscopic cholecystectomy from January 2000 to December 2005 was performed. A total of 86 cases were referred with bile duct injury and bile leak following LC and of these, 4 patients (4.5%) developed hepatic artery pseudoaneurysm (HAP) presenting with haemobilia in 3 and massive intra-abdominal bleed in 1. Selective visceral angiography confirmed pseudoaneurysm of the right hepatic artery in 2 cases, cystic artery stump in one and an intact but ectatic hepatic artery with surgical clips closely applied to the right hepatic artery at the origin of the cystic artery in the fourth case. Effective hemostasis was achieved in 3 patients with coil embolization and the fourth patient required emergency laparotomy for severe bleeding and hemodynamic instability due to a ruptured right hepatic artery. Of the 3 patients treated with coil embolization, 2 developed late strictures of the common hepatic duct (CHD) requiring hepatico-jejunostomy and one developed a stricture of left hepatic duct. All the 4 patients are alive at a median follow up of 17 months (range 1 to 65) with normal liver function tests. HAP is a rare and potentially life-threatening complication of LC. Biloma and subsequent infection are reported to be associated with pseudoaneurysm formation. Late duct stricture is common either due to unrecognized injury at LC or secondary to ischemia after embolization.

Center not liable for defamation from false-positive hepatitis test.

PubMed

1997-04-18

The Nebraska Court of Appeals ruled that [name removed] does not have a cause of action against the Lincoln Plasma Center in Lincoln, NE. The center blacklisted him as a carrier of hepatitis B virus; subsequent tests proved [name removed] was uninfected. [Name removed], a paid plasma donator, was placed on an ineligible list after he tested positive for the hepatitis B surface antigen. [Name removed] sued, alleging that Lincoln defamed him by publishing false information to blood banks about his eligibility to donate. The Court of Appeals upheld a trial court's directed verdict because there was no evidence that the plasma center acted in malice.

Variations of ultrasonic anatomy of the hepatic veins within the human liver.

PubMed

Lamanna, I; Bilić, A; Ljubicić, N; Bakula, B

1990-01-01

The aim of this study was to investigate various physiological variations of the hepatic veins within the liver of the 60 healthy subjects. All participants required physical examinations, different laboratory tests and upper abdominal ultrasonogram--all completely normal. Demonstration of the hepatic veins have been performed on sector real-time systems. The results clearly demonstrated that the physiological variations of the hepatic veins are very common. Ultrasonography obviously represents a diagnostic method of choice in the evaluation of anatomy of the hepatic venous system.

Granular Cell Tumor of the Common Hepatic Duct as an Unusual Cause of Jaundice in a Hepatitis C Patient.

PubMed

Chopade, Tripti R; Smith, Colin L; Maley, Warren R; Siddiqui, Ali A; Sass, David A

2016-01-01

A 33-year-old woman with a history of intravenous cocaine abuse presented with fatigue, nausea, and jaundice. Serologic testing revealed a positive hepatitis C virus (HCV) antibody and HCV RNA. Ultrasound and magnetic resonance imaging/magnetic resonance cholangiopancreatography showed a partially obstructing lesion in the common hepatic duct, which was confirmed by endoscopic retrograde cholangiopancreatography. Surgical excision revealed a granular cell tumor of the common hepatic duct, with immunohistochemical staining of tumor cells positive for S-100.

Sorafenib Action in Hepatitis B Virus X-Activated Oncogenic Androgen Pathway in Liver through SHP-1.

PubMed

Wang, Sheng-Han; Yeh, Shiou-Hwei; Shiau, Chung-Wai; Chen, Kuen-Feng; Lin, Wei-Hsiang; Tsai, Ting-Fen; Teng, Yuan-Chi; Chen, Ding-Shinn; Chen, Pei-Jer

2015-10-01

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) shows a higher incidence in men, mainly because of hepatitis B X (HBx)-mediated enhancement of androgen receptor (AR) activity. We aimed to examine this pathway in hepatocarcinogenesis and to identify drug(s) specifically blocking this carcinogenic event in the liver. HBx transgenic mice that spontaneously develop HCC (n = 28-34 per group) were used, either by knockout of hepatic AR or by castration. Efficacy of several HCC-targeted drugs in suppressing HBx-induced AR activity was evaluated, and cellular factors mediating suppression were investigated in cultured cells. Tissue specificity of the candidate drug was validated using mouse tissues. Data were analyzed with Chi-square and Student's t tests. All statistical tests were two-sided. The androgen pathway was shown to be important in early stage hepatocarcinogenesis of HBx transgenic mice. The tumor incidence was decreased from 80% to 32% by AR knockout (P < .001) and from 90% to 25% by early castration (P < .001). Sorafenib markedly inhibited the HBx-enhanced AR activity through activating the SHP-1 phosphatase, which antagonized the activation of Akt/GSK3β and c-Src by HBx. Moreover, SHP-1 protein level was much higher in the liver than in testis, which enabled sorafenib to inhibit aberrant AR activity in the HBx-expressing liver, while not affecting the physiological AR function in normal liver or testis. The androgen pathway may be a druggable target for the chemoprevention of HBV-related HCC, and sorafenib might be used as a tissue- and disease-specific regimen for the chemoprevention of HBV-related HCC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Isolation and expansion of human pluripotent stem cell-derived hepatic progenitor cells by growth factor defined serum-free culture conditions.

PubMed

Fukuda, Takayuki; Takayama, Kazuo; Hirata, Mitsuhi; Liu, Yu-Jung; Yanagihara, Kana; Suga, Mika; Mizuguchi, Hiroyuki; Furue, Miho K

2017-03-15

Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable. In order to solve this problem, expansion culture for hPSC-derived hepatic progenitor cells, including hepatic stem cells and hepatoblasts which can self-renewal and differentiate into hepatocytes should be valuable as a source of hepatocytes. However, the mechanisms of the expansion of hPSC-derived hepatic progenitor cells are not yet fully understood. In this study, to isolate hPSC-derived hepatic progenitor cells, we tried to develop serum-free growth factor defined culture conditions using defined components. Our culture conditions were able to isolate and grow hPSC-derived hepatic progenitor cells which could differentiate into hepatocyte-like cells through hepatoblast-like cells. We have confirmed that the hepatocyte-like cells prepared by our methods were able to increase gene expression of cytochrome P450 enzymes upon encountering rifampicin, phenobarbital, or omeprazole. The isolation and expansion of hPSC-derived hepatic progenitor cells in defined culture conditions should have advantages in terms of detecting accurate effects of exogenous factors on hepatic lineage differentiation, understanding mechanisms underlying self-renewal ability of hepatic progenitor cells, and stably supplying functional hepatic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

PubMed

Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

2016-06-01

Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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 that are under investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

[Prevention of virus hepatitis A to E].

PubMed

Cornberg, M; Manns, M P

2011-03-01

Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.

Covert hepatic encephalopathy leads to distinct alterations in the emotional state, independently of MELD-Score.

PubMed

Greinert, Robin; Ripoll, Cristina; Zipprich, Alexander

2018-05-01

 Covert hepatic encephalopathy impairs many aspects of quality of life, although its impact on the emotional state has not been evaluated. This study aims to evaluate the impact of covert hepatic encephalopathy on the emotional state and which factors are associated with changes in the emotional state in patients with cirrhosis.  This single-center study included all patients with cirrhosis who underwent the portosystemic encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional state assessment with the Eigenschaftswörterliste 60-S in 2011. Covert hepatic encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests were used according to variable distribution.  One hundred seventeen patients with cirrhosis were included (median age: 59 [interquartile range: 48 - 67], 32 % female, 74 % alcohol-associated). Seventy patients had covert hepatic encephalopathy (60 %) with a higher MELD (16 [interquartile range: 13 - 21], p = 0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without encephalopathy. Patients with covert encephalopathy felt reduced mental activity (p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p = 0.021). The scores in the negative domains such as general lethargy (p = 0.031) and anxiousness/depressiveness (p = 0.033) were higher in patients with covert hepatic encephalopathy. There was no correlation between MELD and the emotional state. Patients with 2 pathological tests (critical flicker frequency and PSE) showed the most distinct alterations in the emotional state in the group of patients with covert hepatic encephalopathy.  Patients with covert hepatic encephalopathy have an alteration of the emotional state, which is more marked in patients with 2 pathological tests. Interestingly, MELD had no impact on the emotional state. © Georg Thieme Verlag KG Stuttgart · New York.

Substantial decline in hepatitis B virus infections following vaccine introduction in Tajikistan.

PubMed

Khetsuriani, Nino; Tishkova, Faina; Jabirov, Shamsidin; Wannemuehler, Kathleen; Kamili, Saleem; Pirova, Zulfiya; Mosina, Liudmila; Gavrilin, Eugene; Ursu, Pavel; Drobeniuc, Jan

2015-07-31

Tajikistan, considered highly endemic area for hepatitis B virus (HBV) in a pre-vaccine era, introduced hepatitis B vaccine in 2002 and reported ≥80% coverage with three doses of hepatitis B vaccine (HepB3) since 2004. However, the impact of vaccine introduction has not been assessed. We tested residual serum specimens from a 2010 national serosurvey for vaccine-preventable diseases in Tajikistan and assessed the prevalence of HBV infection across groups defined based on the birth cohorts' routine infant hepatitis B vaccination program implementation and HepB3 coverage achieved (≥80% versus <80%). Serosurvey participants were selected through stratified multi-stage cluster sampling among residents of all regions of Tajikistan aged 1-24 years. All specimens were tested for antibodies against HBV core antigen (anti-HBc) and those found positive were tested for HBV surface antigen (HBsAg). Seroprevalence and 95% confidence intervals were calculated and compared across subgroups using Satterthwaite-adjusted chi-square tests, accounting for the survey design and sampling weights. A total of 2188 samples were tested. Prevalence of HBV infection markers was lowest among cohorts with ≥80% HepB3 coverage (ages, 1-6 years): 2.1% (95% confidence interval, 1.1-4.3%) for anti-HBc, 0.4% (0.1-1.3%) for HBsAg, followed by 7.2% (4.1-12.4%) for anti-HBc and 2.1% (0.7-6.1%) for HBsAg among cohorts with <80% HepB3 coverage (ages, 7-8 years), by 12.0% (8.7-16.3%) for anti-HBc and 3.5% (2.2-5.6%) for HBsAg among children's cohorts not targeted for vaccination (ages, 9-14 years), and 28.9% (24.5-33.8%) for anti-HBc and 6.8% (4.5-10.1%) for HBsAg among unvaccinated adult cohorts (ages, 15-24 years). Differences across groups were significant (p<0.001, chi-square) for both markers. The present study demonstrates substantial impact of hepatitis B vaccine introduction on reducing HBV infections in Tajikistan. To achieve further progress in hepatitis B control, Tajikistan should maintain high routine coverage with hepatitis B vaccine, including birth dose. Published by Elsevier Ltd.

Brief report on the United States Food and Drug Administration Blood Products Advisory Committee recommendations for management of donors and units testing positive for hepatitis B virus DNA.

PubMed

Lucey, C

2006-11-01

This article briefly recounts the 21st July 2005, Blood Products Advisory Committee (BPAC) meeting concerning recommendations for management of donors and units testing positive for hepatitis B virus (HBV) DNA. The author attended the meeting. The United States Food and Drug Administration (FDA) web site was used for meeting materials, and handouts were collected at the meeting to provide narrative information. Two European experts assisted with HBV subject matter. The proceedings of the advisory committee, the issue briefing materials, and testing algorithms are presented. BPAC voted concurrence with the FDA algorithm for Management of Donors and Units Testing Positive for Hepatitis B Virus DNA.

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

PubMed Central

Chang, Hua-Ming; Liao, Yi-Wen; Chiang, Chih-Hung; Chen, Yi-Jen; Lai, Ying-Hsiu; Chang, Yuh-Lih; Chen, Hen-Li; Jeng, Shaw-Yeu; Hsieh, Jung-Hung; Peng, Chi-Hsien; Li, Hsin-Yang; Chien, Yueh; Chen, Szu-Yu; Chen, Liang-Kung; Huo, Teh-Ia

2012-01-01

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. PMID:22489170

Hepatic stellate cells in liver development, regeneration, and cancer

PubMed Central

Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

2013-01-01

Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

Interrelationship of hepatitis C virus genotypes with patient characteristics in Bahrain

PubMed Central

Abdulla, Maheeba A; Murad, Eman A; Aljenaidi, Hend A; Aljowder, Duha R; Aljeeran, Omar IK; Farid, Eman; Al Qamish, Jehad R

2017-01-01

Aim Hepatitis C virus (HCV) shows genotype-based variation in prevalence across geographical regions. This study was conducted to understand the clinical interrelationship of HCV genotypes with patient characteristics. Methods Medical records of 122 patients positive for HCV RNA test collected during 2013 and 2014 were included for analysis. Only adults were included in the study. HCV RNA extraction and genotyping was done as part of the routine diagnostic requirements. The association of continuous and categorical variables with genotypes was analyzed through analysis of variance and chi-square tests, respectively. Results Of the 122 patients selected, 103 were Bahrainis, 18 non-Bahrainis, and 1 was unregistered. Genotype 1 was the predominant (53%) one, followed by types 3 (23%) and 4 (20%). Classical symptoms, clinical signs, liver function test, and ultrasonographic results were recorded. Cirrhosis and ascites showed significant variation across genotypes. Although alanine transaminase, total bilirubin, and albumin levels were increased, gamma-glutamyltransferase and alkaline phosphatase levels were normal. About 12% of the subjects were alcohol users, 4% were positive for HIV infection and 2.4% were positive for hepatitis B virus infection. The circulating HCV RNA load was at medium-level in the study cohort and showed significant association with the HCV genotypes and subtypes. Patients with genotype 1a had 6 times more load than patients with type 4 (P<0.05). Conclusion This study reconfirmed the incidence and distribution of different genotypes in Bahrain population, and delineated the relationship of HCV RNA viral load with the severity of liver disease in our cohort. PMID:28280398

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Disability. A substantial disruption of a person's ability to conduct normal life functions. Life-threatening... severity) if the labeling only referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral...

Lovastatin decreases mortality and improves liver functions in fulminant hepatic failure from 90% partial hepatectomy in rats.

PubMed

Cai, S R; Motoyama, K; Shen, K J; Kennedy, S C; Flye, M W; Ponder, K P

2000-01-01

Liver insufficiency occurs when the liver cannot perform critical functions such as ammonia metabolism, gluconeogenesis, or production of coagulation factors The hypothesis of this study was that decreased function of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits cholesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver functions, and lovastatin might prevent these changes Rats received 90% partial hepatectomy (90% PH), and either lovastatin or vehicle alone daily. Survival and liver functions were assessed. Lovastatin increased survival to 58% (vs. 6% in controls that received 90% PH without drug), decreased the peak ammonia level to 427 microM (vs. 846 microM in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s in controls), and decreased the peak activated partial thromboplastin time to 29 s (vs. 39 s in controls). The full survival and metabolic benefits were observed when lovastatin was started at 30 min after 90% PH, but lovastatin was less efficacious when started at later times. Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.

Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.

PubMed

Castillo, Inmaculada; Pardo, Margarita; Bartolomé, Javier; Ortiz-Movilla, Nuria; Rodríguez-Iñigo, Elena; de Lucas, Susana; Salas, Clara; Jiménez-Heffernan, Jose A; Pérez-Mota, Arturo; Graus, Javier; López-Alcorocho, Juan Manuel; Carreño, Vicente

2004-01-01

There are patients in whom the etiology of long-standing abnormal results of liver-function tests is unknown (ALF-EU) after exclusion of all known causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA in liver-biopsy specimens from 100 patients who were negative for anti-HCV antibodies and for serum HCV RNA and who had ALF-EU. HCV RNA status was tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ hybridization, in liver and peripheral-blood mononuclear cells (PBMCs). HCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of these 57 patients with occult HCV infection. Nucleotide-sequence analysis confirmed the specificity of detection of HCV RNA and that patients were infected with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40 (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with occult HCV infection were more likely to have necroinflammatory activity (P=.017) and fibrosis (P=.022) than were patients without intrahepatic HCV RNA. Patients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA.

Characteristics of hepatic stem/progenitor cells in the fetal and adult liver.

PubMed

Koike, Hiroyuki; Taniguchi, Hideki

2012-11-01

The liver is an essential organ that maintains vital activity through its numerous important functions. It has a unique capability of fully regenerating after injury. Regulating a balance between self-renewal and differentiation of hepatic stem cells that are resources for functional mature liver cells is required for maintenance of tissue homeostasis. This review describes the characteristics of hepatic stem/progenitor cells and the regulatory mechanism of their self-renewal and differentiation capacity. In liver organogenesis, undifferentiated hepatic stem/progenitor cells expand their pool by repeated self-renewal in the early stage of liver development and then differentiate into two different types of cell lineage, namely hepatocytes and cholangiocytes. Liver development is regulated by expression of stem cell transcription factors in a complex multistep process. Recent studies suggest that stem cells are maintained by integrative regulation of gene expression patterns related to self-renewal and differentiation by epigenetic mechanisms such as histone modification and DNA methylation. Analysis of the proper regulatory mechanism of hepatic stem/progenitor cells is important for regenerative medicine that utilizes hepatic stem cells and for preventing liver cancer through clarification of the carcinogenetic mechanism involved in stem cell system failure.

21 CFR 610.40 - Test requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

...; (3) Hepatitis B virus; (4) Hepatitis C virus; (5) Human T-lymphotropic virus, type I; and (6) Human T... requirements. (a) Human blood and blood components. Except as specified in paragraphs (c) and (d) of this... adequately and appropriately the risk of transmission of communicable disease. (c) Exceptions to testing for...

21 CFR 610.40 - Test requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; (3) Hepatitis B virus; (4) Hepatitis C virus; (5) Human T-lymphotropic virus, type I; and (6) Human T... requirements. (a) Human blood and blood components. Except as specified in paragraphs (c) and (d) of this... adequately and appropriately the risk of transmission of communicable disease. (c) Exceptions to testing for...

Minimal hepatic encephalopathy in patients with cirrhosis by measuring liver stiffness and hepatic venous pressure gradient.

PubMed

Sharma, Praveen; Kumar, Ashish

2012-01-01

Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis. Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls). 150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE. TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis.

Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health.

PubMed

Kleefeld, Felix; Heller, Sophie; Ingiliz, Patrick; Jessen, Heiko; Petersen, Anders; Kopp, Ute; Kraft, Antje; Hahn, Katrin

2018-05-21

The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.

Prevalence of Hepatitis B surface antigen among biomedical students of African descent in Usmanu Danfodiyo University, Sokoto, Nigeria.

PubMed

Okwesili, A N; Onuigwe, F U; Ibrahim, K; Buhari, H; Ibrahim, A; Jafaru, H; Erhabor, O; Onuigwe, F U; Isaac, Z; Ahmed, M H; Mainasara, M Y; Adias, T C; Yeldu, M H; Uko, E K; Udoma, F

2015-12-23

Hepatitis B (HB) is a serious global public health problem that put health professionals particularly at risk. The aim of this study was to investigate the prevalence of Hepatitis B surface antigen (HBsAg) among Biomedical Students of African descent attending Usmanu Danfodiyo University Sokoto in North-Western Nigeria. The Onsite HBsAg (CTK Biotech, USA) was used to detect the presence of hepatitis B surface antigen. We tested 186 consecutively-recruited students consisting of 147 males and 39 females aged 18-35 years (mean age 26 ± 2.0 years). Of the 186 students tested, 25 (13.4%) were positive for HBsAg. The prevalence of HBsAg was significantly higher among students in the 21-25 years age group. Hepatitis B vaccination uptake among students was 7%. Majority of subjects were single 173(93.1%) compared to married 13 (6.9%). Ethnic distribution of the subjects indicated that 104(55.9%) were Hausa compared to Yoruba 32 (17.2%), other ethnic groups 21(11.3%), Fulani 20(10.8%) and Igbo 9(4.8%). This study indicates a high prevalence of hepatitis B virus infection among Biomedical students in Sokoto, North Western, Nigeria. Finding from this study is enough justification for the implementation of a policy to routinely test students entering into the biomedical professions for Hepatitis B virus infection. There is the need to provide hepatitis B vaccination universally to all those who are found negative prior to commencement of their biomedical training. There is also need to educate students entering biomedical professions and healthcare workers on the modes of transmission and prevention, importance of being compliant with protective vaccination as well as the need to observe universal precaution and infection control guidelines during their training and future professional practice.

Immortalized human hepatic cell lines for in vitro testing and research purposes

PubMed Central

Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu

2015-01-01

Summary The ubiquitous shortage of primary human hepatocytes has urged the scientific community to search for alternative cell sources, such as immortalized hepatic cell lines. Over the years, several human hepatic cell lines have been produced, whether or not using a combination of viral oncogenes and human telomerase reverse transcriptase protein. Conditional approaches for hepatocyte immortalization have also been established and allow generation of growth-controlled cell lines. A variety of immortalized human hepatocytes have already proven useful as tools for liver-based in vitro testing and fundamental research purposes. The present chapter describes currently applied immortalization strategies and provides an overview of the actually available immortalized human hepatic cell lines and their in vitro applications. PMID:26272134

Hematoma induced by thorium dioxide

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

Mann, N.S.; Chaudhry, A.; Thaler, S.

1976-04-01

A 74-year-old man complained of anorexia and weight loss. Twenty-six years earlier he had received an injection of Thorotrast. A needle biopsy of the liver showed thorium dioxide granules and periportal fibrosis. On laparotomy, a hepatoma of the left lobe of the liver was discovered. Hepatic malignancy should be suspected in any patient with abnormal results of liver function tests, particularly an elevated level of alkaline phosphatase, who previously has had an injection of Thorotrast.

Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Hepatic Toxicity tests.

DTIC Science & Technology

1980-10-01

Thomas Ralph Wands Awadh Singh kor Lydia Thomas October 1980 Supported by US Army Medical Research and Development Command Fort Detrick, Frederick...Contracting Officer’s Technical Representative: D Mary C. Henry, Ph.D. US Army Medical Bloengineering Research and Development Laboratory I..., Fort...OFFICE NAME AND ADDRESS 12. REPORT DATE U.S. Army Medical Research and Development October 1980 Command 13. NUMBER OF PAGES Fort Detrick, Frederick

NTCP opens the door for hepatitis B virus infection.

PubMed

Yan, Huan; Liu, Yang; Sui, Jianhua; Li, Wenhui

2015-09-01

A liver bile acids transporter, sodium taurocholate cotransporting polypeptide (NTCP, encoded by SLC10A1) was recently identified as a functional receptor for hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). NTCP-complemented human hepatoma HepG2 cells (HepG2-NTCP) were shown to support infection of HBV and HDV in vitro, providing a much-needed and convenient cell culture system for the viruses. Identification of NTCP as a functional receptor for HBV has significantly advanced our understanding of the viral life cycle and opened new opportunities for developing anti-HBV interventions. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B". Copyright © 2015 Elsevier B.V. All rights reserved.

Idiopathic noncirrhotic portal hypertension: current perspectives

PubMed Central

Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d’Amati, Giulia

2016-01-01

The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID:27555800

Idiopathic noncirrhotic portal hypertension: current perspectives.

PubMed

Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d'Amati, Giulia

2016-01-01

The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis.

Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs.

PubMed

Lausten, S B; Grøfte, T; Andreasen, F; Vilstrup, H; Jensen, S L

1999-04-01

We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference. Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1-3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed. Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0. 001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor alpha, and interleukin 8 among groups intra- and postoperatively. The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself.

Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

PubMed

Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

2013-11-01

To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon.

PubMed

Dionne-Odom, Jodie; Mbah, Rahel; Rembert, Nicole J; Tancho, Samuel; Halle-Ekane, Gregory E; Enah, Comfort; Welty, Thomas K; Tih, Pius M; Tita, Alan T N

2016-01-01

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resource-limited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1-9.6%), HIV 6% (3.0-10.2%), and syphilis 1.7% (1.3-3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6-5.4) and HIV (aOR 3.5, CI 1.9-6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0-8.8%), HIV 2.2% (1.4-2.8%), syphilis 4% (3.3-4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5-2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine.

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats.

PubMed

Zhao, Shuangshuang; Li, Naren; Zhen, Yongzhan; Ge, Maoxu; Li, Yi; Yu, Bin; He, Hongwei; Shao, Rong-Guang

2015-12-01

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-05-01

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

Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Magen, I; Poutahidis, T; Vorobiav, L; Zolotarev, O; Ilan, Y; Mechoulam, R; Berry, EM

2009-01-01

Background and purpose: Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy. Experimental approach: Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB1, CB2 and TRPV1 receptor agonist); HU308 (CB2 receptor agonist), SR141716A (CB1 receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB2 receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively. Results: Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin. Conclusions: Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value. PMID:19764982

Aronia melanocarpa (chokeberry) polyphenol-rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice.

PubMed

Kim, Bohkyung; Ku, Chai Siah; Pham, Tho X; Park, Youngki; Martin, Derek A; Xie, Liyang; Taheri, Rod; Lee, Jiyoung; Bolling, Bradley W

2013-05-01

We hypothesized that a polyphenol-rich chokeberry extract (CBE) would modulate hepatic lipid metabolism and improve antioxidant function in apolipoprotein E knockout (apoE(-/-)) mice. ApoE(-/-) mice were fed diets containing 15% fat with 0.2% cholesterol alone or supplemented with 0.005% or 0.05% CBE for 4 weeks. CBE polyphenol content was determined by the total phenols, 4-dimethylaminocinnamaldehyde, and ultra high-performance liquid chromatography-mass spectrometry methods. The 0.05% CBE diet provided mice with mean daily doses of 1.2 mg gallic acid equivalents of total phenols, 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins (as catechin-equivalents), and 0.02 mg flavonols. The 0.05% CBE group had 12% less plasma total cholesterol concentrations than the control. Despite the hypocholesterolemic effect of CBE, hepatic mRNA levels of low-density lipoprotein receptor, hydroxyl-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase in CBE-fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipid content or the hepatic expression of genes involved in lipogenesis and fatty acid β-oxidation such as fatty acid synthase, carnitine palmitoyltransferase 1 and acyl-CoA oxidase. Plasma paraoxonase and catalase activities were significantly increased in mice fed 0.05% CBE. Both CBE diets increased hepatic glutathione peroxidase (GPx) activity but the 0.05% CBE group had 24% less proximal intestine GPx activity relative to controls. Thus, dietary CBE lowered total cholesterol and improved plasma and hepatic antioxidant function at nutritionally-relevant doses in apoE(-/-) mice. Furthermore, the CBE cholesterol-lowering mechanism in apoE(-/-) mice was independent of hepatic expression of genes involved in cholesterol metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey.

PubMed

Dumortier, Jérôme; Cottin, Judith; Lavie, Caroline; Guillaud, Olivier; Hervieu, Valérie; Chambon-Augoyard, Christine; Scoazec, Jean-Yves; Vukusic, Sandra; Vial, Thierry

2017-09-01

Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug. In addition, 3 of these 5 patients underwent unintended single or multiple positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to 10 (highly probable). MP-induced liver injury is probably very rare, since only less than 30 cases have been reported in the literature. Nevertheless, our cases strongly illustrates that many cases could have been unrecognized; final diagnosis in 3 of 5 of our patients was made after the second or third episode of acute hepatitis. In conclusion, these cases we report here strongly illustrates that high-dose MP-induced liver injury can occur in patients treated for MS or auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can help to distinguish it from autoimmune hepatitis. Performing liver function tests routinely both before and after MP administration would be beneficial, as the timely recognition of this complication and early drug withdrawal may prevent progression of severe necrosis hepatic injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.