The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).

In patients with chronic HCV-1b infection, there is a substantial correlation between responses to interferon and mutations in the NS5A gene.

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24). This study is registered with http://ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia. Conclusion: Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083–2091)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death not only in Japan but also worldwide. Clinical practice guidelines for HCC were first published in 2001 by the European Society of Study of the Liver (EASL) followed by the American Association for the Study of Liver Disease (AASLD) published in 2005 and updated in 2010. However, these guidelines have proven to be somewhat unsuitable for Japanese patients. In 2005, supported by the Japanese Ministry of Health, Labour and Welfare, evidence-based clinical practice guidelines for HCC were compiled in Japan. In 2009, a revised version of evidence-based guidelines was published. Based on both ‘evidence-based’ guidelines and the consensus of an expert panel on HCC, the Japan Society of Hepatology (JSH) published the Consensus-Based Clinical Practice Manual in 2007 and updated in 2010. In this article, the 2010 updated version of this manual, especially issues on prevention, surveillance, pathology, diagnosis, staging, and treatment algorithm are summarized.

The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness.