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Background and Aim: IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort., Methods: This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed., Results: IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype., Conclusions: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aim: Pegylated interferon-α (PEG-IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non-controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG-IFN-α2A in CHB patients in a clinical setting., Methods: Chronic hepatitis B patients treated with PEG-IFN-α2A (180µg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA <351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion., Results: Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post-treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50-75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs., Conclusion: In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aims: As the merits of screening at-risk populations for hepatocellular carcinoma (HCC) remain unclear, we compared the clinico-pathologic features and survival of patients with cirrhosis and HCC detected by screening (Group A) to that in non-screened cases (Group B)., Methods: We studied cirrhotics who developed HCC between 1994 and 2002. During this period, cirrhotics managed by the Gastroenterology Unit were regularly screened at 6-12 monthly intervals while those managed by other hospital units were not. Demographic data, tumor details, treatment received and survival were recorded and compared according to screening status., Results: There were 96 cases identified; 41 by screening (group A) and 55 by non-screening methods (Group B). HCC in Group A were smaller (P < 0.01), more likely unilobar (P < 0.01), at an early stage (P < 0.0005) and before vascular invasion (P < 0.005) than Group B cases. The frequency of hepatic surgery and/or local ablation was higher in Group A than Group B (P = 0.001). Overall median survival of Group A was 882 days versus 99 days in Group B (P < 0.0001). One- and 3-year probabilities of survival in Group A were 89% and 38%, versus 33% and 19% in Group B (P < 0.001). Independent predictors of survival included screening, Child-Pugh score, creatinine, tumor stage and absence of alcohol as the etiology., Conclusions: Screening for HCC in cirrhosis identifies tumors at an earlier stage, results in a higher chance of receiving curative treatment and possibly improves patient survival. The absence of alcoholic liver disease impacts favorably on survival., ((c) 2005 Blackwell Publishing Asia Pty Ltd.)

Background and Aim: Hyaluronic acid (HA) is a glycosaminoglycan synthesized by hepatic stellate cells that has been shown to correlate with liver fibrosis in chronic hepatitis C (HCV) patients. However, its use in monitoring fibrosis over time has not been established. The aim of the present study was to assess the serial relationships between HA and liver fibrosis before and after treatment., Methods: Seventy-six previously untreated chronic HCV patients received interferon-based therapy over 48 weeks. Serum HA levels were measured and liver biopsies were obtained at baseline, and 24 weeks post-treatment. Histological fibrosis was assessed by using the Knodell and METAVIR scoring systems., Results: Knodell fibrosis was evaluated in 76 patients; METAVIR fibrosis in 72 patients. Following treatment, patients were grouped into those with increased fibrosis (Knodell = 17; METAVIR = 16), no change (Knodell = 50; METAVIR = 45), or decreased fibrosis (Knodell = 9; METAVIR = 11), relative to baseline. Moderate correlations between HA and fibrosis scores were found before treatment (Knodell R = 0.45; METAVIR R = 0.40) and post-treatment (Knodell R = 0.45; METAVIR R = 0.61). However, changes in HA correlated poorly with changes in fibrosis scores over the study period (Knodell R = 0.11; METAVIR R = 0.06). There was poor qualitative agreement between the direction of HA change and the direction of change in fibrosis scores (Knodell kappa = 0.04; METAVIR kappa = 0.08). The sustained virological response group (n = 18) had a significantly decreased mean HA compared with non-responders (-27.9 vs 21.7 micro g/L; P = 0.009), but pretreatment HA did not predict a response., Conclusions: Serum HA showed a modest association with hepatic fibrosis, and remains a useful non-invasive marker. However, serum HA alone has limited value in predicting histological changes over a treatment period.

Background: Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C infection is associated with advanced liver disease, including cirrhosis. The cellular mechanisms underlying this process, which appear to occur over decades, are unknown. Increased hepatocyte apoptosis has been observed in association with hepatitis C infection. The aim of this study was to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in hepatitis C-infected patients., Methods: Liver tissue from 20 hepatitis C-infected patients with variable alcohol consumption, and 10 normal control subjects was examined for hepatocyte apoptosis, proliferation and bcl-2 expression., Results: Hepatocyte apoptosis was significantly greater in hepatitis C-infected patients than in controls. In hepatitis C-infected patients, significantly more hepatocyte apoptosis was seen in those consuming at least 30 g per day of alcohol compared with those drinking less than 10 g daily. Bcl-2, an inhibitor of apoptosis, was not detected in liver tissue from patients with the highest ethanol intake and rate of hepatocyte apoptosis. In contrast, patients drinking lesser amounts of ethanol had lower rates of hepatocyte apoptosis and more frequent bcl-2 expression., Conclusions: This study confirms that both hepatitis C infection and ethanol consumption induce hepatocyte apoptosis in humans. Ethanol-induced hepatocyte apoptosis has previously been shown only in animal models of alcohol-related liver injury. The precise role of apoptosis in the pathogenesis of hepatitis C-related liver injury remains unclear, but its induction may be related to downregulation of bcl-2 expression associated with ethanol consumption.

Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.