Correlation of Primary Hepatocellular Carcinoma with HBV Genotypes, Subgenotypes and Gene Mutations in Gansu Province

Objective To investigate the occurrence of basal core promoter(BCP) and pre-C mutations in patients with hepatitis B virus(HBV) infection in Gansu Province, China, and to analyze the correlation of HBV mutation and HBV genotype with primary hepatocellular carcinoma(HCC). Methods PCR-RFLP was applied to detect HBV subgenotypes, and the presence of the pre-C and BCP mutations in 62 patients with HCC, 70 patients with hepatitis B induced liver cirrhosis(LC) and 90 patients with chronic hepatitis B(CHB). Results In HCC patients, genotype C was the major genotype(70.97%). The pre-C mutation was found in 59.68%, 31.43% and 16.67% patients with HCC, LC and CHB, respectively. The frequency of BCP mutations was significantly different between patients with HCC, LC and CHB(74.19%, 51.43% and 37.78%, respectively; χ2=30.727, 19.540, respectively, P < 0.01). Patients in HCC group had a higher incidence of pre-C as well as BCP mutations compared to the other groups. The prevalence of pre-C and BCP mutations was significantly higher in patients with genotype C1(44.32% and 69.32%, respectively) compared to patients with other subgenotypes(P < 0.05). Conclusions The incidence of pre-C and BCP mutations increases with disease progression. Pre-C and BCP mutations frequently occur in patients with genotype C1. HBV genotype C, pre-C mutations and BCP mutations are closely related to the occurrence of HCC.

Enigmatic origin of hepatitis B virus:An ancient travelling companion or a recent encounter?

Hepatitis B virus(HBV)is the leading cause of liver disease and infects an estimated 240 million people worldwide.It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication.The ten genotypes(A-J)that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution.Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe(mainly represented by subgenotypes D1-3 and A2);genotypes B and C are restricted to eastern Asia and Oceania;genotype E to central and western Africa;and genotypes H and F(classified into 4 subgenotypes)to Latin America and Alaska.This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes,particularly those concerning the origin and dispersion histories of genotypes A,D,E and F and their subgenotypes.The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain.It is hypothesised that HBV evolutionary rates are time dependent,and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.

Prevalence and genotype distribution of hepatitis B virus among migrant workers in Lombok Island, Indonesia

Objective:To examine the potential risk of hepatitis B virus(HBV)spread in Indonesia by migrant workers,based on the molecular characteristics of HBV strains.Methods:Sera collected from migrant workers traveling to their destination countries(pre-migrant workers)and those returning to Indonesia(post-migrant workers)were screened for HBsAg by ELISA,followed by HBV DNA detection by PCR and(sub)genotype/subtype determination according to surface region and whole genome sequencing.Results:Of 87 pre-migrant workers,15(17.24%)were HBsAgpositive,whereas 15(12.10%)of 124 post-migrant workers were HBs Ag seropositive.HBV genotype analysis based on the S region showed that HBV-B3/adw2 was predominant(96.15%,25/26)whereas 3.85%(1/26)of isolates were HBV-C3/adrq+.Whole genome sequencing of selected strains and phylogenetic tree analysis identified subgenotype B7 in three samples previously categorized as subgenotype B3 based on S region analysis,supporting a recent argument that subgenotypes B5/B7/B8/B9 could be considered as a quasi-subgenotype of B3.Conclusions:A high prevalence of HBsAg carriers was detected among migrant workers from Lombok Island,with no significant difference in prevalence between before and after returning to Indonesia.All strains were classified into genotypes common in Indonesia,and the results suggested that migrant workers are not a risk factor for HBV transmission into Indonesia.

Viral Hepatitis B: Seroprevalence and Genetic Diversity in Blood Donors North of Congo

Introduction: Viral hepatitis B is the most formidable and confusing of all viral hepatitis, given its cirrhogenic and carcinogenic potential. The objective of the study is to characterize the molecular profile of hepatitis virus B in northern Congo. Materials and Methods: This was a descriptive and cross-sectional study that was carried out between January and September 2014, that is 9 months, in the establishments of the National Center for Blood Transfusion (CNTS) of the 4 departments of the north of the Congo. Epidemiological, serological and molecular variables (HBsAg, HBV DNA, genotypes and subtypes) were studied. The HBs antigen was searched by rapid test and confirmed by ELISA. For all positive donors, conventional and specific gene extraction and amplification techniques were performed for the identification of genotypes and subtypes from the serum. Results: A total of 892 donors were included. The average age was 35.36 ± 12.36 years with extremes ranging from 18 to 65 years old. The sex ratio (M/F) was 3.3. The prevalence of HBV was 8.6%. The viral DNA of HBV was amplified in 83.1%. Four genotypes were found: E (40.6%), A (3.1%), B (3.1%) and C (1.6%). Two cases of co-infection were identified: E/A (15.6%) and B/C (1.6%). Subgenotypes A1, B2 and C1 were highlighted. Conclusion: The prevalence of HBV is high, HBV infection remains a major public health problem for blood donors in Congo. Genotypes E, A, B, C as well as subtypes A1, B2, C1 have been identified in northern Congo.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Molecular epidemiology of hepatitis B virus in Asia

Although safe and effective vaccines against hepatitis B virus(HBV) have been available for three decades, HBV infection remains the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma(HCC) worldwide, especially in Asian countries. HBV has been classified into at least 9 genotypes according to the molecular evolutionary analysis of the genomic DNA sequence and shown to have a distinct geographical distribution. Novel HBV genotypes/subgenotypes have been reported, especially from Southeast Asian countries. The clinical characteristics and therapeutic effectiveness of interferon(IFN) and nucleos(t)ide analogues vary among different HBV genotypes. Mutations at T1653 C in subgenotype C2 from Japan and South Korea, C/A1753 T and C1858 T in subgenotype C1 from Vietnam, and C1638 T and T1753 V in subgenotype B3 from Indonesia were reported to be associated with advanced liver diseases including HCC. Genotype distribution in Japan has been changed by an increasing ratio of subgenotype A2 in chronic hepatitis B. While a large number of epidemiological and clinical studies have been reported from Asian countries, most of the studies were conducted in developed countries such as Taiwan, China, South Korea and Japan. In this review, the most recent publications on the geographical distribution of genetic variants of HBV and related issues such as disease progression and therapy in Asia are updated and summarized.