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Other Liver Diseases (other + liver_diseases)
Selected AbstractsNaltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literatureADDICTION BIOLOGY, Issue 1 2004Colin Brewer Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction. These concerns may be reinforced by advice in the UK product information sheet to perform LFTs before and during treatment, by high infection rates with hepatitis C virus (HCV) among injecting heroin addicts and by the frequency of abnormal LFTs in alcohol abusers. We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease. During the past decade, NTX has been shown to be safe and effective in the treatment of pruritus associated with severe jaundice caused by severe and sometimes life-threatening cirrhosis and other liver diseases. Its safety, even in these extreme conditions, is particularly reassuring. We suggest that it may be more appropriate and economical to advise patients to report promptly any suspected side effects than to perform regular LFTs, which may be misleading. [source] Identification of plasma membrane autoantigens in autoimmune hepatitis type 1 using a proteomics tool,,HEPATOLOGY, Issue 3 2008Fatima Tahiri Autoimmune hepatitis (AIH) is a liver disease with circulating autoantibodies predominantly directed against widely held cellular components. Because AIH is a liver-specific disease, autoantibodies against plasma membrane antigens may be involved in its pathogenesis and have been reported; however, no definite identification has been described. We thus investigated the fine specificity of anti-hepatocyte plasma membrane autoantibodies in type 1 AIH (AIH-1) using a proteomic tool. A plasma membrane,enriched fraction was validated using enzymatic activity and western blot analysis experiments. Sera from AIH-1 patients (n = 65) and from 90 controls, that is, healthy blood donors (n = 40) and patients with systemic diseases (n = 20) or other liver diseases (n = 30), were studied by immunoblot performed with plasma membrane proteins resolved by either sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or 2-dimensional (2D) electrophoresis. Proteins contained in the immunoreactive spots were identified by sequences provided by ion-trap mass spectrometry. Hepatocytes probed with sera were also studied using confocal immunofluorescence and immunoelectron microscopy. The more prominent bands stained by patient sera were located at 38 kDa, 48, 50, 52 kDa, 62 kDa, 70 kDa, and a 95-kDa double band. Six proteins with known potential plasma membrane expression were identified: liver arginase (38 kDa), cytokeratins (CK) 8 and 18 (48-52 kDa), heat shock proteins (HSP) of 60, 70, 90 kDa, and valosin-containing protein (VCP) of 92 kDa. The presence of anti-membrane antibodies was confirmed by immunofluorescence and immunoelectron microscopy. Conclusion: Overall, our data demonstrate that liver arginase, CK 8/18, HSP 60, HSP 70, HSP 90, and VCP represent potential candidate targets on liver membrane for autoantibodies in AIH-1. (HEPATOLOGY 2008;47:937,948.) [source] Coffee drinking and hepatocellular carcinoma risk: A meta-analysis,HEPATOLOGY, Issue 2 2007Francesca Bravi Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case,control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for case,control studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case,control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. Conclusion: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion. (HEPATOLOGY 2007.) [source] Defective regulation of cholangiocyte Cl,/HCO,3 and Na+/H+ exchanger activities in primary biliary cirrhosisHEPATOLOGY, Issue 6 2002Saida Melero Primary biliary cirrhosis (PBC) is a disorder of unknown origin with autoimmune features. Recently, impaired biliary secretion of bicarbonate has been shown in patients with PBC. Here we have investigated whether bile duct epithelial cells isolated from PBC patients exhibit defects in transepithelial bicarbonate transport by analyzing the activities of 2 ion exchangers, Cl,/HCO,3 anion exchanger 2 (AE2) and Na+/H+ exchanger (NHE) in isolated cholangiocytes. AE2 and NHE activities were studied in basal conditions and after stimulation with cyclic adenosine monophosphate (cAMP) and extracellular adenosine triphosphate (ATP), respectively. Cholangiocytes were grown from needle liver biopsies from 12 PBC patients, 8 normal controls, and 9 patients with other liver diseases. Also, intrahepatic cholangiocytes were cultured after immunomagnetic isolation from normal liver tissue (n = 6), and from recipients undergoing liver transplantation for end-stage PBC (n = 9) and other forms of liver disease (n = 8). In needle-biopsy cholangiocytes, basal AE2 activity was significantly decreased in PBC as compared with normal livers and disease controls. In addition, we observed that though cAMP increased AE2 activity in cholangiocytes from both normal and non-PBC livers, this effect was absent in PBC cholangiocytes. Similarly, though in cholangiocytes from normal and disease control livers extracellular ATP induced a marked enhancement of NHE activity, cholangiocytes from PBC patients failed to respond to purinergic stimulation. In conclusion, our findings provide functional evidence that PBC cholangiocytes exhibit a widespread failure in the regulation of carriers involved in transepithelial H+/HCO,3 transport, thus, providing a molecular basis for the impaired bicarbonate secretion in this cholestatic syndrome. [source] Mouse models in non-alcoholic fatty liver disease and steatohepatitis researchINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2006Quentin M. Anstee Summary Non-alcoholic fatty liver disease (NAFLD) represents a histological spectrum of liver disease associated with obesity, diabetes and insulin resistance that extends from isolated steatosis to steatohepatitis and cirrhosis. As well as being a potential cause of progressive liver disease in its own right, steatosis has been shown to be an important cofactor in the pathogenesis of many other liver diseases. Animal models of NAFLD may be divided into two broad categories: those caused by genetic mutation and those with an acquired phenotype produced by dietary or pharmacological manipulation. The literature contains numerous different mouse models that exhibit histological evidence of hepatic steatosis or, more variably, steatohepatitis; however, few replicate the entire human phenotype. The genetic leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse and the dietary methionine/choline-deficient model are used in the majority of published research. More recently, targeted gene disruption and the use of supra-nutritional diets to induce NAFLD have gained greater prominence as researchers have attempted to bridge the phenotype gap between the available models and the human disease. Using the physiological processes that underlie the pathogenesis and progression of NAFLD as a framework, we review the literature describing currently available mouse models of NAFLD, highlight the strengths and weaknesses of established models and describe the key findings that have furthered the understanding of disease pathogenesis. [source] Mutation of keratin 8 in patients with liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006Maximilian Schöniger-Hekele Abstract Background:, Epithelial tissues of the gastrointestinal tract and the liver express predominantly cytokeratin 8 and cytokeratin 18. In vitro experiments and animal studies have demonstrated a protective influence of keratin 8 and keratin 18 against toxic damage of hepatocytes. A specific mutation of keratin 8 (G61C) was found to be a genetic risk factor for the development of cryptogenic liver cirrhosis. The purpose of the present paper was therefore to determine the prevalence of cytokeratin 8 (G61C) and cytokeratin 18 mutations (Y53H) in patients with liver disease. Methods:, Overall 152 patients (male, n = 93, 61%; female, n = 59, 39%) were included in the present study. The 152 patients consisted of 107 patients with liver disease (70.4%; male, n = 71, 66.4%; female, n = 36, 33.6%) and 45 control patients (29.6%; male, n = 22, 48,9%; female, n = 23, 51,1%) without liver disease. Of the patients with liver disease 46 had alcoholic liver disease; 25, chronic hepatitis C; 15, cryptogenic liver disease; and 21, other liver diseases of various etiologies. Cytokeratin 8 and 18 genotypes were specified by polymerase chain reaction (PCR) amplification and direct sequence analysis was used to detect the previously described mutations in cytokeratin 8 (G61C) and in cytokeratin 18 (Y53H). Results:, Four out of 152 patients (male n = 2, female n = 2) with a mutation (G61C) in cytokeratin 8 were found. The etiology was alcoholic liver disease (n = 1), cryptogenic liver disease (n = 1) and idiopathic liver disease with minimal changes in liver biopsy (n = 1). Also, one out 45 disease control patients with an adenoma of the colon but without liver disease was found to carry the mutation G61C of cytokeratin 8. Therefore, the mutation G61C in cytokeratin 8 was found in 2.8% of patients with liver disease and in 2.2% of control patients without liver disease. Two of 15 patients (13.3%) with cryptogenic liver disease had the mutation G61C in cytokeratin 8 (P = 0.069 vs patients with non-cryptogenic liver disease). In the 152 patients studied, no mutation in cytokeratin 18 was found. Discussion:, The mutation G61C in the cytokeratin 8 gene was found in one patient with alcoholic liver disease and in two patients with liver disease of unknown etiology. Also, one patient without liver disease had the cytokeratin 8 G61C mutation. In summary, the cytokeratin 8 mutation G61C, which has been found to be associated with cryptogenic liver cirrhosis, was also found in the present patient population. However, the clinical relevance is yet to be determined in further investigations. [source] Liver-infiltrating CD56 positive T lymphocytes in hepatitis C virus infectionLIVER INTERNATIONAL, Issue 5 2000Kenji Yonekura Abstract:Aim: Hepatitis C virus (HCV) is a major cause of post-transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus-specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV-infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56+ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH-C). Material and Methods: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH-C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. Results: The CD56+ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly ,,-TCR. There was a correlation between the ratio of CH-C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. Conclusion: The correlation between CD56+ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver-infiltrating CD56+ T lymphocytes play an important pathologic role in hepatocellular injury in CH-C. [source] Recurrence of primary sclerosing cholangitis after liver transplantationLIVER TRANSPLANTATION, Issue 7 2002Ivo W. Graziadei MD Orthotopic liver transplantation (OLT) has become the only effective therapeutic option for patients with end-stage liver disease caused by primary sclerosing cholangitis (PSC). Excellent long-term outcome has been reported, with 5-year patient survival rates of approximately 80%. In the last few years, increasing evidence has emerged that PSC recurs after OLT. The diagnosis of PSC is based on well-defined cholangiographic features combined with biochemical and histological findings. However, none of these features is specific for PSC, particularly after OLT, because biliary strictures in the liver allograft can occur from a variety of causes other than recurrence. Therefore, PSC recurrence remains a controversial issue, especially because of a lack of a gold standard for diagnosis and well-established diagnostic criteria. Some reports provided cholangiographic evidence that post-OLT biliary strictures occurred more frequently in patients with PSC than in those who underwent OLT for other liver diseases (including patients with a Roux-en-Y biliary reconstruction). Because no other possible cause of biliary strictures could be invoked to explain the greater prevalence of these strictures, recurrent disease has been implicated. There also is histological evidence suggesting that PSC recurs after OLT. Histological findings suggestive of PSC were found more often in PSC allografts compared with a control group. Furthermore, histological features typical for PSC (fibro-obliterative lesions) were seen exclusively in liver biopsy specimens from patients with PSC. Recurrence of PSC was defined in a recent study from the Mayo Clinic by means of strict cholangiographic and histological criteria in a large cohort of patients with PSC in whom other causes of biliary strictures were excluded. PSC recurrence was found in 20% of patients. No risk factor for PSC recurrence could be found, and recurrent disease did not influence patient or graft survival after a mean follow-up of 4.5 years. In conclusion, several studies provided convincing evidence that PSC recurs after OLT, with an incidence of 5% to 20% and an interval to diagnosis of at least 1 year after OLT. To date, patient and graft survival do not appear to be negatively affected by disease recurrence in the intermediate term of follow-up. (Liver Transpl 2002;8:575-581.) [source] Reduced post-operative neutrophil activation in liver transplant recipients suffering from post-hepatitic cirrhosisCLINICAL TRANSPLANTATION, Issue 6 2009Björn Jüttner Abstract:, Background:, It has been supposed that liver transplant recipients with hepatitis C virus infection have a higher incidence of infectious complications after transplantation. This study was designed to investigate whether neutrophil function is immediately affected by liver transplantation. Methods:, Biochemical values, plasma levels of myeloperoxidase (MPO), hydrogen peroxide production of neutrophils and neutrophil,platelet complexes were analyzed in 32 patients who underwent liver transplantation and 20 healthy volunteers. Results:, MPO levels were significantly increased 24 h after reperfusion. In post-hepatitic patients levels were significantly lower three d up to one wk post-transplant than in patients due to other liver diseases. One wk post-operatively the respiratory burst activity following N -formyl-methionyl-leucylphenylalanine (fMLP) or (tumor necrosis factor-,) TNF-,/fMLP stimulation was depressed in post-hepatitic recipients. Respiratory burst stimulated with phorbol 12-myristate 13-acetate in these patients was increased one wk after transplantation. One d after transplantation the neutrophil,platelet complexes decreased significantly throughout the post-operative period. Conclusions:, The results of this study suggest a reduced post-operative neutrophil activation in liver transplant recipients suffering from post-hepatitic cirrhosis compared to cirrhosis due to other causes. We hypothesized that neutrophil dysfunction in those patients depends on the underlying disease with an increased susceptibility to bacterial or fungal infections. 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