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.

Origin and evolution of the unique hepatitis C virus circulating recombinant form 2k/1b.

Since its initial identification in St. Petersburg, Russia, the recombinant hepatitis C virus (HCV) 2k/1b has been isolated from several countries throughout Eurasia. The 2k/1b strain is the only recombinant HCV to have spread widely, raising questions about the epidemiological background in which it first appeared.

A study of genotypes, mutants and nucleotide sequence of hepatitis B virus in Pakistan: HBV genotypes in pakistan.

Background: Hepatitis B virus (HBV) genotypes and mutations are gaining importance in determining the clinical course of chronic liver disease.

Objectives: To determine and compare the distribution of HBV genotypes and genomic variations in Pakistan to other parts of the world.

Patients And Methods: We conducted a prospective study at Aga Khan University Hospital from December 2006 to December 2008.

Genetic variation of the IL-28B promoter affecting gene expression.

The current standard of care for the treatment of chronic hepatitis C is pegylated interferon-α (PEG-IFNα) and ribavirin (RBV). The treatment achieves a sustained viral clearance in only approximately 50% of patients. Recent whole genome association studies revealed that single nucleotide polymorphisms (SNPs) around IL-28B have been associated with response to the standard therapy and could predict treatment responses at approximately 80%.

Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral response to peginterferon and ribavirin.

Aim:   The aim of this study was to investigate the relationship among the expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs in the IL28B locus, and the outcome of interferon therapy.

Methods:   Prior to interferon treatment, we immunostained 67 liver specimens from chronic hepatitis C (CHC) patients who were receiving peginterferon alpha-2b/ribavirin therapy for suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3, IL28 polymorphisms and other clinical factors between the patients and compared their eventual outcomes.

Results:   Significant differences between the low SOCS3 group and high SOCS3 group were found in age, as well as in the platelet, transaminase, gamma-glutamyl transpeptidase levels.

[Genome-wide association study on and the clinical application to chronic hepatitis C].

Based on the data and technology generated in previous international projects, such as the Human Genome Project and the HapMap, for the building of the common patterns of genetic variation in humans, a genome-wide association study (GWAS) to HCV infection was conducted to reveal genetic effects against treatment response or the induction of side effects. Single nucleotide polymorphisms (SNPs) associated with response to pegylated-interferon (PEG-IFN) and ribavirin (RBV) therapy were determined around IL-28B in chromosome 19, and the strong association was also observed in spontaneous viral clearance regardless of population. These data imply that an important interaction between HCV infection and IL-28B is critical for viral persistence or clearance.

Prevalence of amino acid mutation in hepatitis C virus core region among Japanese volunteer blood donors.

It is not known whether there is a trend of increasing or decreasing incidence of new hepatitis C virus (HCV) infections in Japan. From the treatment point of view, it is important to verify HCV genotypes and the prevalence of treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all blood samples obtained from blood donation have been screened using serological methods and the minipool nucleic acid amplification testing.

Easy-to-use phylogenetic analysis system for hepatitis B virus infection.

Aim:   The molecular phylogenetic analysis has been broadly applied to clinical and virological study. However, the appropriate settings and application of calculation parameters are difficult for non-specialists of molecular genetics. In the present study, the phylogenetic analysis tool was developed for the easy determination of genotypes and transmission route.

Relationship between polymorphisms of the inosine triphosphatase gene and anaemia or outcome after treatment with pegylated interferon and ribavirin.

Background: A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in combination with other factors.

Methods: Genotype 1b chronic hepatitis C patients (n=132) treated with pegylated interferon (PEG-IFN)-α and RBV for 48 weeks were genotyped for ITPA rs1127354 and examined for anaemia and treatment outcome.