Recommended treatment for hepatitis C virus genotype 1 (HCV-1) patients is peginterferon plus ribavirin for 48 weeks. We assessed whether treatment duration of 24 weeks is as effective as standard treatment in HCV-1 patients with a rapid virological response (RVR; seronegative for hepatitis C virus [HCV] RNA at 4 weeks). Two hundred HCV-1 patients were randomized (1:1) to either 24 or 48 weeks of peginterferon-alpha-2a (180 g/week) and ribavirin (1000-1200 mg/day) with a 24-week follow-up. The primary endpoint was a sustained virological response (SVR; seronegative for HCV RNA at 24-week follow-up). Overall, the 48-week arm had a significantly higher SVR rate (79%) than the 24-week arm (59%, P ‫؍‬ 0.002). For 87 (43.5%) patients with an RVR, the 24-week arm had a lower SVR rate [88.9%; 95% confidence interval (CI): 80%-98%] than the 48-week arm (100%, P ‫؍‬ 0.056). For 52 patients with low baseline viremia (<400,000 IU/mL) and an RVR, the 24-week arm had rates (CI) of relapse and SVR of 3.6% (؊3%-11%) and 96.4% (89%-103%), respectively, which were comparable to those of the 48-week arm (0% and 100%) with difference (CI) of 3.6% (؊7.2%-6.6%) and ؊3.6% (؊14.3% to ؊0.6%), respectively. Multivariate analysis in all patients showed that RVR was the strongest independent factor associated with an SVR, followed by treatment duration, mean weight-based exposure of ribavirin, and baseline viral load. Conclusion: HCV-1 patients derive a significantly better SVR from 48 weeks versus 24 weeks of peginterferon/ribavirin even if they attain an RVR. Both 24 and 48 weeks of therapy can achieve high SVR rates (>96%) in HCV-1 patients with low viral loads and an RVR.

Background: The recommended treatment for patients infected with hepatitis C virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for 24 weeks. Aim: To assess whether a shorter 16-week treatment is as effective as a standard 24-week treatment. Methods: Patients with HCV2 infection were randomised in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment with peginterferon a-2a (180 mg/week) and weight-based ribavirin 1000-1200 mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end point, sustained virological response (SVR), as seronegative for HCV RNA at the 24-week follow-up. Results: The rate of RVR and SVR was 86% (43/50, 95% confidence interval (CI) 76% to 96%) and 94% (47/ 50, CI 87% to 100%), respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80% to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate analysis showed that RVR and age were independent factors associated with SVR. Both treatment arms were equally well tolerated. The incidence of alopecia was significantly higher in the 24-week group (49%) than in the 16-week group (20%, p = 0.001). Conclusion: 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000-1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks.

Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)

Gastrointestinal tract involvement with hepatocellular carcinoma was observed in 8 out of 396 patients (2%) during the course of the disease. Histological involvement was confirmed in 6 cases. All 8 patients were men. The most common clinical presentation was frank gastrointestinal bleeding, which became evident in all cases. Esophageal varices were not seen in any patient. The sites of involvement were the stomach (3), duodenum (4), and jejunum (1). The median time between the diagnosis of primary tumors and gastrointestinal tract involvement was 4.5 months (range: 0 to 12 months). Hematogenous spread was presumed to have occurred in two patients with diffuse-type hepatocellular carcinoma, one of whom had main portal vein thrombosis. Direct invasion by contiguous neoplasm was the major mode of gastrointestinal tract involvement. This complication is more likely to develop in patients with large, subcapsular, massive type hepatocellular carcinoma treated by transcatheter arterial embolization and/or intra-arterial chemotherapy. The median survival after the diagnosis of gastrointestinal involvement was 1 month (2 weeks-4 months).

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HBV infection did not increase the association with T2DM. A significant mutual link between T2DM and HCV viremia existed in this HBV/HCV endemic area. There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM.

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Changes in hepatic fibrosis after interferon-based therapy may be important in determining the long-term outcome of chronic hepatitis C (CHC). The use of liver biopsy for posttreatment assessment is not a viable option as a routine follow-up procedure. This study evaluated the predictive value of a simple noninvasive index, the aspartate aminotransferase (AST)-to-platelet ratio index assessed 6 months after end of treatment (APRI-M6). We evaluated APRI-M6, platelet-M6, AST-M6, and ␣-fetoprotein-M6 of 776 CHC patients with interferon-based therapy as well as the parameters at baseline of 562 untreated patients who were evaluated to predict the risk of hepatocellular carcinoma (HCC) and mortality, during a mean follow-up period of 4.75 (1.0-12.2) and 5.15 (1.0-16) years, respectively. Based on analysis of receiver operating characteristics (ROC) and using optimized cutoff point, the APRI-M6 and platelet-M6 had superior prediction models for long-term outcome with area under the curve of 0.870-0.875 and 0.824-0.847, respectively, and accuracy of 78%-81% and 76%-78%, respectively, for interferonbased-treated patients. The predictive values of all 4 parameters were poor in untreated patients. In subgroup analysis, the APRI-M6 provided a more consistent prediction ratio than platelet-M6 for sustained responders and cirrhosis-free subgroups; both parameters had similar prediction power for nonresponders and were unsatisfactory in patients with cirrhosis. According to Cox proportional hazards analysis, cirrhosis and APRI-M6 were the 2 most important factors for predicting HCC. In conclusion, APRI-M6 can accurately predict the long-term outcome of patients subjected to interferon-based treatment. Nevertheless, the data needs further validation, particularly since the predictive accuracy for patients with cirrhosis is low. (HEPATOLOGY 2006;44:1086-1097