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Serum Alanine Aminotransferase (serum + alanine_aminotransferase)
Terms modified by Serum Alanine Aminotransferase Selected AbstractsRelapse of hepatitis C in a pegylated-interferon-,-2b plus ribavirin-treated sustained virological responderHEPATOLOGY RESEARCH, Issue 6 2010Hideki Fujii A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-,-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR. [source] Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague,Dawley ratsHEPATOLOGY RESEARCH, Issue 9 2009Yanjun Mu Aim:, We studied the mechanisms of estrogen/androgen involvement in the induction of NASH by treating Sprague,Dawley (SD) rats fed with a normal or high fat (HF) diet by depriving them of endogenous estrogens/androgens. Methods:, Male adult SD rats (n = 10/group) on normal or HF diets were treated for 75 days either with tamoxifen (Tam) or flutamide (Flu) or Tam + Flu in order to induce NASH. We analyzed histopathologically the liver samples from the treated groups for NASH, checked the serum biochemical and lipid profile markers and finally analyzed the signal pathways underlying the molecular mechanisms for the induction process of NASH. Results:, Deprivation of endogenous estrogens and/or androgens (Tam or Flu or Tam + Flu) without the HF diet did not induce NASH. Tam or Tam + Flu induced NASH, compared to milder lesions without fibrosis in HF diet and Flu-treated liver. Serum alanine aminotransferase or lipid profile markers further proved the Tam, Flu or Tam + Flu effects on the induction of NASH in conjunction with a HF diet. Tam treatment predominantly downregulated the ER, and FAS and upregulated UCP2 and TNF-,. Conclusions:, Deprivation of endogenous estrogen/androgens in conjunction with a HF diet may induce NASH where the downregulated ER, and FAS, and upregulated UCP2 and TNF-, could be involved in their molecular pathomechanism pathways. These results could suggest the potential negative roles of estrogenic/androgenic depriving compounds in the induction of NASH, along with obesity. [source] Isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in the experimental model of rats,JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001Young-Hwa Chung Abstract Background and Aims: Serum alanine aminotransferase (ALT) and aspartate aminotransferase may not detect centrilobular hepatic necrosis (CLN) of a mild degree because these enzymes are known to be located predominantly in the periportal area. The aim of this study was to evaluate the usefulness of plasma isocitrate dehydrogenase (ICDH), which is located predominantly in the centrilobular zone, as a marker of CLN. Methods: In 56 adult male rats, centrilobular (n = 21) and periportal hepatic necrosis (PPN; n = 21) were induced experimentally by the intraperitoneal injection of bromobenzene and allylalcohol, respectively. Seven rats were used as solvent controls in both groups. Isocitrate dehydrogenase and ALT activities were measured in the plasma of rats with mild to moderate hepatic necrosis (17 CLN and 19 PPN). Isocitrate dehydrogenase and ALT were compared according to the sampling time (12, 24 and 48 h) and the location of hepatic necrosis. Ratios of ICDH/ALT were also calculated and compared between CLN and PPN groups at any time points. Results: Plasma ICDH activities were higher in rats with CLN than in those with PPN. In contrast, plasma ALT levels were higher in rats with PPN than in those with CLN at 12 h and were similar in both groups after 12 h. The ICDH/ALT ratios were much higher in rats with CLN compared to those with PPN (P < 0.001). The ratios were above 1.0 in 13 of 17 rats (77%) with CLN in contrast to none of the 19 rats with PPN. Conclusions: Our data suggested that the plasma ICDH/ALT ratio might be useful to differentiate between mild to moderate degrees of CLN from PPN, at least in the experimental model of rats. [source] Increased Lipopolysaccharide Sensitivity in Alcoholic Fatty Livers Is Independent of Leptin Deficiency and Toll-Like Receptor 4 (TLR4) or TLR2 mRNA ExpressionALCOHOLISM, Issue 6 2005Laszlo Romics Jr Background: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-,B and pro-inflammatory pathways that are activated in AFL and NAFL. Methods: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-,, and interleukin (IL)-6 levels; hepatic NF-,B activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. Results: Increased LPS sensitivity in AFL and NAFL was characterized by elevated serum TNF-, and IL-6 induction. However, there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob livers at baseline and after acute or chronic alcohol treatment. LPS increased TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS increased serum ALT and TNF-, levels in lean but not in ob/ob mice compared with pair-fed controls. Hepatic NF-,B activation was increased in both ob/ob and lean mice after chronic alcohol feeding compared with pair-fed controls. Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective protein, were higher in ob/ob compared with lean mice after chronic alcohol feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in ob/ob compared with lean mice. Conclusion: These results imply that the increased sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective mechanisms. [source] Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levelsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009V. W.-S. Summary Background, Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear. Aim, To evaluate the metabolic and histological features of NAFLD patients with different ALT levels. Methods, A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared. Results, Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis. Discussion, Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level. [source] Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance,DIABETIC MEDICINE, Issue 10 2008M. Toshihiro Abstract Aims, We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods, The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan,Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social,psychological factors. Results, Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1,6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions, In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT. [source] Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection,HEPATOLOGY, Issue 2 2009Alessandra Mangia In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 ,g/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm3 [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. Conclusion: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI. (HEPATOLOGY 2008.) [source] Treatment recommendations for chronic hepatitis B: An evaluation of current guidelines based on a natural history study in the United States,HEPATOLOGY, Issue 4 2008Myron John Tong Current guidelines for treatment of chronic hepatitis B include hepatitis B e antigen (HBeAg) status, levels of hepatitis B virus (HBV) DNA, and serum alanine aminotransferase (ALT) values in the setting of either chronic hepatitis or cirrhosis. Based on findings from a prospective study of hepatitis B surface antigen (HBsAg)-positive patients, we determined whether these guidelines included patients who developed hepatocellular carcinoma (HCC) and who died of non-HCC liver-related complications. The criteria for treatment from four published guidelines were matched to a cohort of 369 HBsAg-positive patients enrolled in the study. During a mean follow-up of 84 months, 30 patients developed HCC and 37 died of non-HCC liver-related deaths. Using criteria for antiviral therapy as stated by the four guidelines, only 20%-60% of the patients who developed HCC, and 27%-70% of patients who died of non-HCC liver-related deaths would have been identified for antiviral therapy according to current treatment recommendations. If baseline serum albumin levels of 3.5 mg/dL or less or platelet counts of 130,000 mm3 or less were added to criteria from the four treatment guidelines, then 89%-100% of patients who died of non-HCC liver-related complications, and 96%-100% of patients who developed HCC would have been identified for antiviral therapy. In addition, if basal core promoter T1762/A1764 mutants and precore A1896 mutants also were included, then 100% of patients who developed HCC would have been identified for treatment. Conclusion: This retrospective analysis showed that the current treatment guidelines for chronic hepatitis B excluded patients who developed serious liver-related complications. (HEPATOLOGY 2008.) [source] The nuclear bile acid receptor FXR as a novel therapeutic target in cholestatic liver diseases: Hype or hope?HEPATOLOGY, Issue 1 2004Michael Trauner M.D. Farnesoid X receptor (FXR) is a bile acid,activated transcription factor that is a member of the nuclear hormone receptor superfamily. FXR-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease. [source] Role of V, 14 NKT cells in the development of impaired liver regeneration in vivoHEPATOLOGY, Issue 5 2003Hiroyasu Ito Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by ,-galactosylceramide (,-GalCer) on murine liver regeneration using V, 14 NKT knockout (J, 281,/,) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in J, 281+/+ but not in J, 281,/, mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) , and tumor necrosis factor , (TNF-,) messenger RNA (mRNA) after stimulation with both factors in J, 281+/+ mice. Either anti-IFN-, or TNF-, antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-, injection similarly caused injury in hepatectomized livers of both J, 281+/+ and J, 281,/, mice; indeed, adoptively transferred TNF-,+/+ NKT cells enhanced liver injury after hepatectomy in TNF-, knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-, synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration. [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotectionHEPATOLOGY, Issue 2 2003Xiu-Da Shen Ischemia/reperfusion (I/R) injury remains an important problem in clinical organ transplantation. There is growing evidence that T lymphocytes, and activated CD4+ T cells in particular, play a key role in hepatic I/R injury. This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury. Using a partial lobar warm ischemia model, groups of wild-type (WT), T cell,deficient, Stat4-/Stat6-deficient knockout (KO) mice were assessed for the extent/severity of I/R injury. Ninety minutes of warm ischemia followed by 6 hours of reperfusion induced a fulminant liver failure in WT and Stat6 KO mice, as assessed by hepatocellular damage (serum alanine aminotransferase [sALT] levels), neutrophil accumulation (myeloperoxidase [MPO] activity) and histology (Suzuki scores). In contrast, T cell deficiency (nu/nu mice) or disruption of Stat4 signaling (Stat4 KO mice) reduced I/R insult. Unlike adoptive transfer of WT or Stat6-deficient T cells, infusion of Stat4-deficient T cells failed to restore hepatic I/R injury and prevented tumor necrosis factor , (TNF-,) production in nu/nu mice. Diminished TNF-,/Th1-type cytokine messenger RNA (mRNA)/protein elaborations patterns, along with overexpression of heme oxygenase-1 (HO-1),accompanied hepatic cytoprotection in Stat4 KO recipients. In contrast, HO-1 depression restored hepatic injury in otherwise I/R resistant Stat4 KOs. In conclusion, Stat4 signaling is required for, whereas Stat4 disruption protects against, warm hepatic I/R injury in mice. The cytoprotection rendered by Stat4 disruption remains HO-1,dependent. [source] Low-dose TNF-, protects against hepatic ischemia-reperfusion injury in mice: Implications for preconditioningHEPATOLOGY, Issue 1 2003Narci Teoh Tumor necrosis factor , (TNF-,) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor ,B (NF-,B) and cell cycle entry. We examined the pattern of TNF-, release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In naïve mice, hepatic and plasma levels of TNF-, rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-, levels, but, during a second prolonged ischemic interval peak, TNF-, values were lower than in naïve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 ,g or 5 ,g/kg body weight TNF-, 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-, pretreatment activated NF-,B DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-, injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-, levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury. [source] Course and outcome of hepatitis CHEPATOLOGY, Issue 5B 200231 Center Dr., Jay H. Hoofnagle Bldg. 3, Room 9A2 The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. [source] The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis CHEPATOLOGY, Issue 2 2000Stuart C. Gordon M.D. We sought to determine whether pretreatment serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis C virus (HCV) correlate with demographic features and other disease characteristics and whether these values influence response to therapy. A total of 1,744 patients with HCV received either interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT determinations at entry visit of ,1.3 × the upper limit of normal (ULN). By analysis of variance both pretreatment histologic activity index (HAI) scores (P < .0001) and fibrosis scores (P = .003) were significantly lower among patients with baseline ALT levels ,1.3 × ULN. Individuals with lower pretreatment ALT values were younger and weighed less than the ALT >1.3 × ULN cohort. Baseline ALT was not related to gender, race, baseline viral level, or HCV genotype. Using logistic regression analysis, the only demographic feature associated with ALT ,1.3 × ULN was lower baseline weight and lower baseline HAI score. There was no difference in sustained response between patients with baseline ALT levels ,1.3 × ULN and those with >1.3 × ULN, in all treatment groups (26 of 105, 24.8% for ALT ,1.3 × ULN; 440 of 1,639, 26.8% for ALT >1.3 × ULN). We conclude that HCV patients with minimally raised ALT values (,1.3 × ULN) weigh less, and have lower histologic inflammatory scores than patients with more conventionally elevated ALT levels. Despite these differences, these patients have a similar sustained response to antiviral therapy. [source] Effect of nucleoside analog-interferon sequential therapy on patients with acute exacerbation of chronic hepatitis BHEPATOLOGY RESEARCH, Issue 5 2010Chiaki Okuse Aim:, Nucleoside analog (NA)-interferon (IFN) sequential therapy may enable the long-term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA-IFN sequential therapy for acute exacerbation of CHB. Methods:, A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN-, 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN-, alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). Results:, Four out of nine (44.4%) HBeAg-positive and all three HBeAg-negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core-related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. Conclusion:, NA-IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment. [source] Effect of interferon ,-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitisHEPATOLOGY RESEARCH, Issue 5 2009Mika Kurokawa Aim:, The objective of this study was to elucidate the long-term effects of interferon (IFN),-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Methods:, A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-,-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis. Results:, A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non-SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of , 40 IU/L after the combination therapy (P = 0.021). Conclusions:, These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development. [source] Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxicationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2005Inmaculada Bando Abstract Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:154,161, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20067 [source] Effect of Cadmium and Aluminum Intake on the Antioxidant Status and Lipid Peroxidation in Rat TissuesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2001Shohda A. El-Maraghy Abstract This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:207,214, 2001 [source] Pre- and post-treatment predictors of the early achievement of HBeAg loss in lamivudine-resistant patients receiving adefovir therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2007Jeong Won Jang Abstract Background and Aim:, This study investigated the clinical variables that predict hepatitis B e antigen (HBeAg) loss in lamivudine-resistant patients receiving adefovir therapy. Methods:, Fifty-six consecutive HBeAg-positive patients treated with adefovir for at least 12 months were enrolled in this study. All had serum alanine aminotransferase (ALT) levels over twice the upper limit of normal (ULN) as a result of lamivudine resistance. Predictors of HBeAg loss after switching from lamivudine to adefovir were examined. Results:, During the follow-up period, 18 (32.1%) of 56 patients showed a loss of HBeAg. The estimated rates of HBeAg loss at 6, 12, and 18 months were 11.5%, 26.8%, and 42.9%, respectively. Univariate analysis revealed that pretreatment ALT levels >10 × ULN (P = 0.029), a viral load at 3 months of therapy (P = 0.017), and viral decline by >3 log10 from baseline at 3 months (P < 0.001) were significantly associated with the loss of HBeAg within 12 months of therapy. With multivariate analysis using the stepwise logistic regression model, pretreatment ALT > 10 × ULN (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.09,19.44; P = 0.044) and viral suppression >3 log10 at 3 months (OR, 10.39; 95% CI, 1.86,58.07; P = 0.008) were identified as the two independent predictors of HBeAg loss. Conclusions:, Pretreatment ALT levels and the initial pattern of post-treatment viral decline are the strongest predictors of the early achievement of HBeAg loss following treatment with adefovir in lamivudine-resistant patients. These results may provide useful information for the optimal timing of adefovir rescue as well as for better monitoring after treatment. [source] Four years of lamivudine treatment in Chinese patients with chronic hepatitis BJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2004TING-TSUNG CHANG Abstract Background and Aims:, This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD-variant hepatitis B virus (HBV). Methods:, Fifty-eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four-year data are reported here. Results:, The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2,5 × upper limit of normal) pre-treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV-DNA compared with baseline, despite the emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug-related adverse events in the fourth year of the study. Conclusions:, Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine. [source] Circulating soluble cytochrome c in liver disease as a marker of apoptosisJOURNAL OF INTERNAL MEDICINE, Issue 2 2003Z. Ben-Ari Abstract. Ben-Ari Z, Schmilovotz-Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur-Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168,175. Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. Design. Laboratory research study with comparison group. Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. Subjects. A total of 108 patients with liver disease and 30 healthy controls. Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings. Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL,1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL,1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL,1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL,1) than the portal vein (mean 169.2 ± 143.3 ng mL,1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL,1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL,1) than treated patients (77.9 ± 35.8 ng mL,1; P = 0.001). Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis. [source] Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients,JOURNAL OF MEDICAL VIROLOGY, Issue 9 2010L.Y. Lin Abstract Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40,IU/L and a serum HBV DNA >10,000,copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r,=,0.41, P,=,0.018) and log total intrahepatic HBV DNA (r,=,0.71, P,<,0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P,=,0.15) or log total intrahepatic HBV DNA (P,=,0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P,=,0.03 and 5.46 vs. 4.64, P,<,0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B. J. Med. Virol. 82:1494,1500, 2010. © 2010 Wiley-Liss, Inc. [source] The protective action of scutellarin against immunological liver injury induced by concanavalin A and its effect on pro-inflammatory cytokines in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2007Zheng Huai Tan Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor ,B (NF-,B), tumor necrosis factor , (TNF-,), interferon , (IFN-,), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg,1 via the tail vein. Scutellarin 50 or 100 mg kg,1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2,/NO3, and TNF - , were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-, kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-,, IFN-,, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and I,B proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg,1 significantly decreased the serum ALT, AST, NO2,/NO3,and TNF-, levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg,1 down-regulated expression of TNF-, and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of I,B, in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-,B-TNF-,-iNOS transduction pathway. [source] Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2004Jing Gao The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCI4)-induced acute liver damage and D-galactosamine (D-GaIN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7- and 2.0-fold) induced by CCI4 were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100 mg kg,1 TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9- and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GaIN were blocked by pre-treatment with 0.05, 0.1, 0.5 gL,1 TCCE. In addition, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited by 50,500 ,m ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500 ,m, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals. [source] Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2006Min Pan Abstract:, Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin,eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions. [source] The protective effects of garlic oil on acute ethanol-induced oxidative stress in the liver of miceJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 13 2008Tao Zeng Abstract BACKGROUND: Alcoholic liver disease is so serious that no effective therapies have been developed up to now. This study was conducted to elucidate the effects of garlic oil (GO) on acute ethanol-induced liver injury. Male Kun-Ming mice were orally administered GO (50, 100 or 200 mg kg,1) for 30 days and then ethanol (4.8 g kg,1). At 16 h after ethanol treatment the mice were sacrificed. Subsequent serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) levels, hepatic malondialdehyde (MDA) and glutathione (GSH) levels and antioxidant enzyme activities were measured. Histopathological examination of mouse liver sections was performed by Sudan III staining. RESULTS: GO pretreatment significantly inhibited acute ethanol-induced increase in ALT, AST, TG and MDA and decrease in GSH in a dose-dependent manner. In the three GO groups the level of GSH increased by 10.3%, 15.8% (P < 0.05) and 25.5% (P < 0.01) respectively compared with that in the ethanol group. The activities of superoxide dismutase, catalase and glutathione reductase were increased markedly in the 200 mg kg,1 GO group (P < 0.01). Histopathological examination showed fewer fat droplets in liver sections of GO-pretreated mice. CONCLUSION: GO may have protective effects against acute ethanol-induced liver injury through restoration of the GSH level and enhancement of the activities of antioxidant enzymes. Copyright © 2008 Society of Chemical Industry [source] Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B,JOURNAL OF VIRAL HEPATITIS, Issue 1 2010R. G. Gish Summary., This retrospective analysis was conducted to describe the characteristics of nucleoside-naïve hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B, who achieved hepatitis B surface antigen (HBsAg) loss during entecavir or lamivudine therapy. HBeAg-positive adults with chronic hepatitis B, elevated serum alanine aminotransferase, and compensated liver disease were randomized to double-blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day. HBsAg and hepatitis B virus (HBV) DNA were measured at regular intervals during and off-treatment follow-up. Through a maximum duration of 96 weeks on-treatment and 24 weeks off-treatment, HBsAg loss was confirmed in 18/354 (5.1%) patients treated with entecavir and 10/355 (2.8%) patients treated with lamivudine. Among the 28 patients with confirmed HBsAg loss, 27 (96%) achieved HBV DNA <300 copies/mL, and 27 (96%) achieved confirmed HBeAg loss. All entecavir recipients with HBsAg loss had HBV DNA <300 copies/mL. Caucasian patients, and those infected with HBV genotype A or D, were significantly more likely to lose HBsAg. This retrospective analysis of data from a randomized, global phase three trial shows that confirmed loss of HBsAg occurred in 5% of nucleoside-naïve HBeAg-positive patients treated with entecavir, and that HBsAg loss is associated with sustained off-treatment suppression of HBV DNA. [source] Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009R. LOOMBA Summary Background, Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. Aim, To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. Methods, Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. Results, Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. Conclusion, Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss. [source] Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinomaJOURNAL OF VIRAL HEPATITIS, Issue 3 2007F.-C. Tsai Summary., Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (,40 years of age) and old (>40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 ± 24.1 vs 58.4 ± 65.4 IU/L, P = 0.006) and HBV DNA levels (log10 titre: 4.20 ± 1.33 vs 4.80 ± 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log10 titre: 4.79 ± 1.34 vs 3.27 ± 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075,2.333] rather than in young patients (OR 0.848, 95% CI 0.645,1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC. [source] | ||||||||||||||||||||||||||||||||||