Genetic variation near the IL28B gene and substitution of amino acid (aa) 70 and 91 in the core region of hepatitis C virus (HCV) genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the predictive factors of sustained virological response to a 12-week or 24-week regimen of triple therapy in 72 of 81 Japanese adults infected with HCV genotype 1. Overall, sustained virological response and end-of-treatment response were achieved by 61% and 89%, respectively. Especially, the sustained virological response was achieved by 45% and 67% in the 12-and 24-week regimens, respectively. Multivariate analysis identified rs8099917 near the IL28B gene (genotype TT) and substitution at aa 70 (Arg70) as significant determinants of sustained virological response. Prediction of response to therapy based on a combination of these factors had high sensitivity, specificity, and positive and negative predictive values. The efficacy of triple therapy was high in the patients with genotype TT, who accomplished sustained virological response (84%), irrespective of substitution of core aa 70. In the patients having genotype non-TT, those of Arg70 gained high sustained virological response (50%), and sustained virological response (12%) was the worst in patients who possessed both genotype non-TT and Gln70(His70). Conclusion: This study identified genetic variation near the IL28B gene and aa substitution of the core region as predictors of sustained virological response to a triple therapy of telaprevir/PEG-IFN/ribavirin in Japanese patients infected with HCV genotype 1b. (HEPATOLOGY 2010;52:421-429) H epatitis C virus (HCV) usually causes chronic infection that can result in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC).1,2 At present, treatments based on interferon (IFN), in combination with ribavirin, are the mainstay for combating HCV infection. In Japan, HCV genotype 1b (HCV-1b) in high viral loads (>100 KIU/ mL) accounts for more than 70% of HCV infections, making it difficult to treat patients with chronic hepatitis C.3 Such background calls for efficient treatments of Japanese patients with chronic HCV infection.Even with pegylated IFN (PEG-IFN) combined with ribavirin, a sustained virological response lasting over 24 weeks after the withdrawal of treatment is achieved in at most 50% of the patients infected with HCV-1b and high viral loads. 4,5 Recently, a new strategy was introduced in the treatment of chronic HCV infection by

Diabetes is present in patients with chronic hepatitis C virus infection. The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for type 2 diabetes after the termination of interferon therapy in Japanese patients positive for hepatitis C virus (HCV). A total of 2,842 HCV-positive patients treated with interferon (IFN) monotherapy or combination therapy with IFN and ribavirin were enrolled. The mean observation period was 6.4 years. An overnight (12-hour) fasting blood sample or a casual blood sample was taken for routine analyses during follow-up. The primary goal was the onset of type 2 diabetes. Evaluation was performed by using the Kaplan-Meier method and Cox proportional hazard analysis. Of 2,842 HCV patients, 143 patients developed type 2 diabetes. The cumulative development rate of type 2 diabetes was 3.6% at 5 years, 8.0% at 10 years, and 17.0% at 15 years. Multivariate Cox proportional hazard analysis revealed that type 2 diabetes development after the termination of IFN therapy occurred when histological staging was advanced (hazard ratio 3.30; 95% confidence interval [CI] 2.06-5.28; P < 0.001), sustained virological response was not achieved (hazard ratio 2.73; 95% CI 1.77-4.20; P < 0.001), the patient had pre-diabetes (hazard ratio 2.19; 95% CI 1.43-3.37; P < 0.001), and age was >50 years (hazard ratio 2.10; 95% CI 1.38-3.18; P < 0.001). H epatitis C virus (HCV) is one of the more common causes of chronic liver disease in world. Chronic hepatitis C is an insidiously progressive form of liver disease that relentlessly but silently progresses to cirrhosis in 20% to 50% of cases over a period of 10 to 30 years. [1][2][3] In addition, HCV is a major risk for hepatocellular carcinoma (HCC). 4-8 Moreover, chronic HCV infection has been associated with a variety of extrahepatic complications such as essential mixed cryoglobulinemia, porphyria cutanea tarda, membranoproliferative glomerulonephritis, autoimmune thyroiditis, sialadenitis, and cardiomyopathy. [9][10][11][12][13] Lately, data supporting a link between type 2 diabetes mellitus (T2DM) and chronic hepatitis C infection have been reported. 14,15 Although there is growing evidence to support the concept that HCV infection is a risk factor for developing T2DM, there have been a few interventional studies confirming this issue. This issue needs to be confirmed with a long-term follow-up of patients with high risk of developing diabetes. Thus, prospective studies including metabolic evaluations are clearly needed to clarify these issues.With this background in mind, the cohort study was initiated to investigate the cumulative incidence and risk factors of T2DM after prolonged follow-up in HCV-infected patients treated with interferon (IFN) monotherapy or combination therapy with IFN and ribavirin. The strengths of the current study are the large numbers of patients included and the long-term follow-up of patients. Patients and MethodsPatients. There were 5,890 patients diagnosed with chronic ...

Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (21.63 6 0.92 vs. 20.48 6 0.75 g/dL, P 5 0.001) and week 4 (23.5 6 1.1 vs. 22.2 6 0.96, P 5 0.001), as well as at the end of treatment (22.9 6 1.1 vs. 22.0 6 0.86, P 5 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 6 14% vs. 65 6 21% of the target dose, P 5 0.039), but the total RBV dose was no different between them (49 6 17% and 54 6 18% of the target, P 5 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P 5 0.724). Conclusion: ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes. (HEPATOLOGY 2011;53:415-421)

Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment.

HBcrAg is a predictor of the post-treatment recurrence of HCC during antiviral therapy. Serum HBcrAg and intrahepatic cccDNA suppression by NAs may be important to prevent HCC recurrence.