Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C.

This study aimed to develop a model for predicting anemia using the inosine triphosphatase (ITPA) genotype and to evaluate its relationship with treatment outcome. Patients with genotype 1b chronic hepatitis C (n = 446) treated with peg-interferon alpha and ribavirin (RBV) for 48 weeks were genotyped for the ITPA (rs1127354) and IL28B (rs8099917) genes. Data mining analysis generated a predictive model for anemia (hemoglobin (Hb) concentration <10 g/dl); the CC genotype of ITPA, baseline Hb <14.

Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey.

The role of hepatitis B virus (HBV) genetics in the clinical manifestations of infection is being increasingly recognized. Genotype D is one of eight currently recognized major HBV genotypes. The virus is ubiquitous worldwide, but shows different features in different regions.

Human blood dendritic cell antigen 3 (BDCA3)(+) dendritic cells are a potent producer of interferon-λ in response to hepatitis C virus.

Unlabelled: The polymorphisms in the interleukin (IL)-28B (interferon-lambda [IFN]-λ3) gene are strongly associated with the efficacy of hepatitis C virus (HCV) clearance. Dendritic cells (DCs) sense HCV and produce IFNs, thereby playing some cooperative roles with HCV-infected hepatocytes in the induction of interferon-stimulated genes (ISGs). Blood dendritic cell antigen 3 (BDCA3)(+) DCs were discovered as a producer of IFN-λ upon Toll-like receptor 3 (TLR3) stimulation.

[Present state and the future direction of HBV vaccine].

Hepatitis B virus (HBV) prevention program in Japan is considered one of the most successful and effective public anti-counter programs to HBV infection. However, almost all of population under twenty-five years is extremely susceptibility for HBV infection. HBV genotype A, which was not in Japan and has been from western countries, is increasing in chronic hepatitis B patients in Japan as a consequence of acute hepatitis B spreading in the younger generation through promiscuous sexual transmitted infection and the characteristics of HBV genotype A is a prolonged high HBVDNA viremia compared with other HBV genotypes.

Hepatitis C virus kinetics by administration of pegylated interferon-α in human and chimeric mice carrying human hepatocytes with variants of the IL28B gene.

Objective: Recent studies have demonstrated that genetic polymorphisms near the IL28B gene are associated with the clinical outcome of pegylated interferon α (peg-IFN-α) plus ribavirin therapy for patients with chronic hepatitis C virus (HCV). However, it is unclear whether genetic variations near the IL28B gene influence hepatic interferon (IFN)-stimulated gene (ISG) induction or cellular immune responses, lead to the viral reduction during IFN treatment.

Design: Changes in HCV-RNA levels before therapy, at day 1 and weeks 1, 2, 4, 8 and 12 after administering peg-IFN-α plus ribavirin were measured in 54 patients infected with HCV genotype 1.

Soluble MICA and a MICA variation as possible prognostic biomarkers for HBV-induced hepatocellular carcinoma.

MHC class I polypeptide-related chain A (MICA) molecule is induced in response to viral infection and various types of stress. We recently reported that a single nucleotide polymorphism (SNP) rs2596542 located in the MICA promoter region was significantly associated with the risk for hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) and also with serum levels of soluble MICA (sMICA). In this study, we focused on the possible involvement of MICA in liver carcinogenesis related to hepatitis B virus (HBV) infection and examined correlation between the MICA polymorphism and the serum sMICA levels in HBV-induced HCC patients.

Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.

Estimation of two real-time RT-PCR assays for quantitation of hepatitis C virus RNA during PEG-IFN plus ribavirin therapy by HCV genotypes and IL28B genotype.

Hepatitis C virus (HCV) RNA values measured with two real-time PCR methods (Cobas Ampliprep/Cobas TaqMan, CAP/CTM, and the Abbott real-time PCR test, ART) vary among patients with genotype 1. We investigated HCV RNA values measured by two real-time PCR assays during pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy. We evaluated 185 cases of chronic hepatitis C patients, among which 97 patients received the PEG-IFN/RBV therapy.

Novel cell culture-adapted genotype 2a hepatitis C virus infectious clone.

Although the recently developed infectious hepatitis C virus system that uses the JFH-1 clone enables the study of whole HCV viral life cycles, limited particular HCV strains have been available with the system. In this study, we isolated another genotype 2a HCV cDNA, the JFH-2 strain, from a patient with fulminant hepatitis. JFH-2 subgenomic replicons were constructed.

Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta) = 1.

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

Background: A recent genome-wide association study (GWAS) using chronic HBV (hepatitis B virus) carriers with and without hepatocellular carcinoma (HCC) in five independent Chinese populations found that one SNP (rs17401966) in KIF1B was associated with susceptibility to HCC. In the present study, a total of 580 HBV-derived HCC cases and 1351 individuals with chronic hepatitis B (CHB) or asymptomatic carrier (ASC) were used for replication studies in order to evaluate the reported association with HBV-derived HCC in other East Asian populations.

Results: We did not detect any associations between rs17401966 and HCC in the Japanese cohorts (replication 1: OR = 1.

Development of a prediction model for 10-year risk of hepatocellular carcinoma in middle-aged Japanese: the Japan Public Health Center-based Prospective Study Cohort II.

Objective: The purpose of the present study was to develop a risk estimation model for the 10-year risk of hepatocellular carcinoma (HCC) that could be easily used in a general population to aid in the prevention of HCC.

Methods: Our prediction model was derived from data obtained on 17,654 Japanese aged 40 to 69 years who participated in health checkups (follow-up: 1993-2006). Cox proportional hazards regression was applied to obtain coefficients for each predictor.

Novel evidence of HBV recombination in family cluster infections in western China.

Two hepatitis B virus (HBV) C/D recombinants were isolated from western China. No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence. In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants.

Development of specific and quantitative real-time detection PCR and immunoassays for λ3-interferon.

Aim:   Single nucleotide polymorphisms (SNP) around interferon (IFN)-λ3 have been associated with the response to pegylated IFN-α treatment for chronic hepatitis C. Specific quantification methods for IFN-λ3 are required to facilitate clinical and basic study.

Methods:   Gene-specific primers and probes for IFN-λ1, 2 and 3 were designed for real-time detection PCR (RTD-PCR).

Increase in platelet count based on inosine triphosphatase genotype during interferon beta plus ribavirin combination therapy.

Background And Aim: The inosine triphosphatase (ITPA) genotype is associated with ribavirin-induced anemia and pegylated interferon α (PEG IFN-α)-induced platelet reduction during PEG IFN-α plus ribavirin combination therapy. Natural IFN-β plus ribavirin therapy is associated with increases in platelet counts during treatment. We investigated decreases in platelet counts according to ITPA genotype during natural IFN-β/ribavirin therapy to determine if patients with low platelet counts were eligible for this combination therapy.

Development of new IL28B genotyping method using Invader Plus assay.

IL28B polymorphism is associated with the response to pegylated interferon-α with ribavirin (PEG-IFN-α/RBV) treatment in chronic hepatitis C patients. As a genotyping assay for IL28B single nucleotide polymorphisms (SNPs) in clinical practice, the Invader Plus assay was developed. The accuracy, intra-assay, inter-assay precision, and the limit of detection of the Invader Plus assay were evaluated.

Factors responsible for the discrepancy between IL28B polymorphism prediction and the viral response to peginterferon plus ribavirin therapy in Japanese chronic hepatitis C patients.

Aim:   IL28B polymorphisms serve to predict response to pegylated interferon plus ribavirin therapy (PEG IFN/RBV) in Japanese patients with chronic hepatitis C (CHC) very reliably. However, the prediction by the IL28B polymorphism contradicted the virological response to PEG IFN/RBV in some patients. Here, we aimed to investigate the factors responsible for the discrepancy between the IL28B polymorphism prediction and virological responses.

LecT-Hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients.

Unlabelled: Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is critical for predicting disease progression and determining future antiviral therapy. LecT-Hepa, a new glyco-marker derived from fibrosis-related glyco-alteration of serum alpha 1-acid glycoprotein, was used to differentiate cirrhosis from chronic hepatitis in a single-center study. Herein, we aimed to validate this new glyco-marker for estimating liver fibrosis in a multicenter study.

Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma.

Background & Aims: Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Although consumption of fish and n-3 PUFA has been reported to protect against the development of some types of cancer, little is known about its association with hepatocellular carcinoma (HCC).

Methods: We investigated the association between fish and n-3 PUFA consumption and HCC incidence (n = 398) in a population-based prospective cohort study of 90,296 Japanese subjects (aged, 45-74 y).

Multiple intra-familial transmission patterns of hepatitis B virus genotype D in north-eastern Egypt.

The transmission rate of intra-familial hepatitis B virus (HBV) and mode of transmission were investigated in north eastern Egypt. HBV infection was investigated serologically and confirmed by molecular evolutionary analysis in family members (N = 230) of 55 chronic hepatitis B carriers (index cases). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prevalence was 12.

Replication and infectivity of a novel genotype 1b hepatitis C virus clone.

Hepatitis C virus infection is a major public health problem because of an estimated 170 million carriers worldwide. Genotype 1b is the major subtype of HCV in many countries and is resistant to interferon therapy. Study of the viral life cycle is important for understanding the mechanisms of interferon resistance of genotype 1b HCV strains.

Using decision tree learning to predict the responsiveness of hepatitis C patients to drug treatment.

The recommended treatment for patients with chronic hepatitis C, pegylated interferon α (PEG-IFN-α) plus rebavirin (RBV), does not provide a sustained virologic response in all patients, especially those with hepatitis C virus (HCV) genotype 1. It is therefore important to predict whether or not a new patient with HCV genotype 1 will be cured by the recommended treatment. We propose a prediction method for a new patient using a decision tree learning model based on SNPs evaluated in a genome-wide association study.

Discovery of critical host factor, IL-28B, associated with response to hepatitis C virus treatment.

Chronic hepatitis C affects 2.2-3.0% of the world population (130 million-170 million).

Production of infectious chimeric hepatitis C virus genotype 2b harboring minimal regions of JFH-1.

To establish a cell culture system for chimeric hepatitis C virus (HCV) genotype 2b, we prepared a chimeric construct harboring the 5' untranslated region (UTR) to the E2 region of the MA strain (genotype 2b) and the region of p7 to the 3' UTR of the JFH-1 strain (genotype 2a). This chimeric RNA (MA/JFH-1.1) replicated and produced infectious virus in Huh7.

An updated analysis of hepatitis C virus genotypes and subtypes based on the complete coding region.

Background: The hepatitis C virus (HCV) genomic database is expanding rapidly.

Aims: There is a need to provide an updated phylogenetic tree analysis based on the complete coding region of HCV.

Methods: All available HCV complete genome sequences in the HCV databases available through October 2010 were analyzed.