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Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A.

ABSTRACT: Acute hepatitis B virus (HBV) infection has been increasing through promiscuous sexual contacts, and HBV genotype A (HBV/A) is frequent in patients with acute hepatitis B (AHB) in Japan. To compare the geographic distribution of HBV genotypes in patients with chronic hepatitis B (CHB) in Japan between 2005 and 2006 and between 2000 and 2001, with special attention to changes in the proportion of HBV/A, a cohort study was performed to survey changes in genotypes of CHB patients at 16 hospitals throughout Japan. Furthermore, we investigated the clinical characteristics of each genotype and examined the genomic characteristics of HBV/A isolates by molecular evolutionary analyses. Of the 1,271 patients, 3.5%, 14.1%, and 82.3% were infected with HBV/A, -B, and -C, respectively. In comparison with our previous survey during 2000 and 2001, HBV/A was twice as frequent (3.5% versus 1.7%; P = 0.02). The mean age was lower in the patients with HBV/A than in those with HBV/B or -C. Based on phylogenetic analyses of 11 full-length genomes and 29 pre-S2/S region sequences from patients, HBV/A isolates were imported from Europe and the United States, as well as the Philippines and India. They clustered with HBV/A from AHB patients and have spread throughout Japan. HBV/A has been increasing in CHB patients in Japan as a consequence of AHB spreading in the younger generation through promiscuous sexual contacts, aided by a tendency of HBV/A to induce chronic hepatitis. The spread of HBV/A infection in Japan should be prevented by universal vaccination programs.

SUBMITTER: Matsuura K

PROVIDER: S-EPMC2681832 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A.

Matsuura Kentaro K Tanaka Yasuhito Y Hige Shuhei S Yamada Gotaro G Murawaki Yoshikazu Y Komatsu Masafumi M Kuramitsu Tomoyuki T Kawata Sumio S Tanaka Eiji E Izumi Namiki N Okuse Chiaki C Kakumu Shinichi S Okanoue Takeshi T Hino Keisuke K Hiasa Yoichi Y Sata Michio M Maeshiro Tatsuji T Sugauchi Fuminaka F Nojiri Shunsuke S Joh Takashi T Miyakawa Yuzo Y Mizokami Masashi M

Journal of clinical microbiology 20090318 5

Acute hepatitis B virus (HBV) infection has been increasing through promiscuous sexual contacts, and HBV genotype A (HBV/A) is frequent in patients with acute hepatitis B (AHB) in Japan. To compare the geographic distribution of HBV genotypes in patients with chronic hepatitis B (CHB) in Japan between 2005 and 2006 and between 2000 and 2001, with special attention to changes in the proportion of HBV/A, a cohort study was performed to survey changes in genotypes of CHB patients at 16 hospitals th ...[more]

PMID: 19297602

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Project description:BACKGROUND:IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon. OBJECTIVES:The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C. PATIENTS AND METHODS:In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS:The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46). CONCLUSIONS:It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

Project description:AimIn order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections).ResultsOverall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896.DiscussionHBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.

Project description:BackgroundThe highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).MethodsWe analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.Results355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005).ConclusionHCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.

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Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A.

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Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A.

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