Molecular characteristic-based epidemiology of hepatitis B, C, and E viruses and GB virus C/hepatitis G virus in Myanmar

We carried out a molecular characteristic-based epidemiological survey of various hepatitis viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and GB virus C (GBV-C)/hepatitis G virus (HGV), in Myanmar. The study population of 403 subjects consisted of 213 healthy individuals residing in the city of Yangon, Myanmar, and the surrounding suburbs and 190 liver disease patients (155 virus-related liver disease patients and 35 nonviral disease patients). The infection rates of the viruses among the 213 healthy subjects were as follows: 8% for HBV (16 patients), 2% for HCV (4 patients), and 8% for GBV-C/HGV (17 patients). In contrast, for 155 patients with acute hepatitis, chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma, the infection rates were 30% for HBV (46 patients), 27% for HCV (41 patients), and 11% for GBV-C/HGV (17 patients). In the nonviral liver disease group of 35 patients with alcoholic liver disease, fatty liver, liver abscess, and biliary disease, the infection rates were 6% for HBV (2 patients), 20% for HCV (7 patients), and 26% for GBV-C/HGV (9 patients). The most common viral genotypes were type C of HBV (77%), type 3b of HCV (67%), and type 2 of GBV-C/HGV (67%). Moreover, testing for HEV among 371 subjects resulted in the detection of anti-HEV immunoglobulin G (IgG) in 117 patients (32%). The age prevalence of anti-HEV IgG was 3% for patients younger than 20 years and 30% or more for patients 20 years of age or older. Furthermore, a high prevalence of anti-HEV IgG (24%) was also found in swine living together with humans in Yangon. These results suggest that these hepatitis virus infections are widespread in Myanmar and have led to a high incidence of acute and chronic liver disease patients in the region.     

GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5′-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive. J. Med. Virol. 54:75–79, 1998. © 1998 Wiley-Liss, Inc.     

Hepatitis G virus (HGV): current perspectives

Five viruses are usually associated with hepatitis in humans: A-E. In addition to these viruses as aetiological agents of hepatitis, there remain a number of patients with hepatitis in whom no virus could be identified. It was therefore postulated that there may be other agents which may be causing hepatitis. Recently, two viruses have been associated with hepatitis: hepatitis G virus (HGV), and transfusion transmissible virus (TTV). Hepatitis G virus (HGV) is a single stranded RNA virus which represents a newly discovered virus belonging to the flavivirus family. HGV is distinct from hepatitis C virus (HCV) and the newly discovered GBV-A and GBV-B agents, while GBV-C represents an isolate of HGV. The structure of the HGV genome resembles that of HCV. HGV replicates in peripheral blood cells, while replication in liver cells has not been observed till date. Diagnosis of HGV infection is mainly by use of polymerase chain reaction (PCR), as serological techniques are still being developed. Epidemiological data indicate that the virus is prevalent throughout the world, including India and is transmitted via blood/blood products, sexually and vertically from infected mothers to children. The relationship between infection with the virus and presence of liver pathology is controversial and has not been proven beyond doubt, as majority of patients with HGV have no detectable evidence of disease.     

Determination of hepatitis G virus markers in various risk groups

Study of prevalence of hepatitis G virus (HGV) markers in different risk groups showed the presence of HGV RNA in 3.2% blood donors, 24.2% patients with hepatitis C (HCV), and 28% patients with hemophilia. HGV antibodies were detected in 11.3% donors, 16.0% patients with HCV, 13.4% patients with hemophilia, and 8.5% HIV-infected subjects. Anti-E1 HGV were more often detected in the absence of HGV RNA. Antibodies to HGV E2 protein were significantly more often detected in adult HCV patients but not in adolescent patients aged 8-15 years.     

Low prevalence of antibody to hepatitis C virus in north east England

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in North East England in blood donors, local multiply transfused patients, local high risk individuals, and chronic liver disease patients. Anti-HCV was detected by enzyme-linked immunosorbent assay (ELISA) in 2/1120 (0.18%) blood donors; 1/84 chronic renal failure patients on haemodialysis who had received 1,992 units of blood (seroconversion rate of 0.05% per unit transfused), 1/207 cardiac patients 6 months post cardiac surgery transfused with 1,403 units of blood (1 anti-HCV pre-operatively, seroconversion rate 0.07%), 40/50 haemophilia A patients treated with commercial factor VIII, and 38/100 intravenous drug users. In addition anti-HCV was detected by ELISA in 5/35 cryptogenic chronic liver disease patients, 5/5 confirmed by recombinant immunoblot assay (RIBA) (14%); 3/30 patients with autoimmune chronic active hepatitis, 2/3 by RIBA (7%); 2/50 primary biliary cirrhosis patients, 1/2 by RIBA (2%); 0/30 alcoholic cirrhosis patients; and 2/9 patients with hepatocellular carcinoma, 1/2 by RIBA (11%). HCV is uncommon in North East England; it may be implicated in the aetiology of a minority of cases of cryptogenic liver disease and less than 5% of autoimmune chronic active hepatitis and primary biliary cirrhosis.     

Clinical study on relationship between hepatocellular carcinoma and hepatitis C virus infection in patients with chronic liver disease]

The relationship between hepatocellular carcinoma (HCC) and hepatitis C virus (HCV) infection was investigated. Antibody to hepatitis C virus was detected in 88.8% and 87.0% of 240 patients with hepatocellular carcinoma and liver cirrhosis, respectively. A history of blood transfusion was shown in only 21.8% (21/96) of the HCV antibody positive HCC patients. Of 196 patients with chronic hepatitis type C and the HCV antibody positive liver cirrhosis, 10 developed HCC during the follow-up period of two years. A high prevalence of HCV antibody was also shown among 83 patients with alcoholic liver cirrhosis and HCC associated with alcoholic liver cirrhosis. HCV-RNA was detected in all patients with alcoholic HCC. These data support a causal association between hepatitis C virus and hepatocellular carcinoma.     

Prevalence of hepatitis G virus in Pakistani children with transfusion dependent beta- thalassemia major

We ought to obtain data on the prevalence of the newly discovered tranfusion transmittable hepatitis G virus in polytransfused b- thalassemia major children. Each individual had received multiple blood transfusions, from 12 to 36 per year. No documentation of prior hepatic infection was available. Serum samples were collected prospectively from the randomly selected subjects and were analyzed for HGV RNA by polymerase chain reaction using primer specific for two different regions of the HGV genome. Among the 100 individuals examined 21 were positive for HGV RNA. Four patients had evidence of dual infection, both HGV RNA and HCV RNA were isolated from their sera. While in one sample presence of both HGV RNA and HBV DNA was established. Only one child was positive for hepatitis E antibodies. The sera of 10 children were reactive for hepatitis B surface antigen whereas 35 individuals were positive for hepatitis C virus antibody. The ALT levels were variable in HGV infected children. Four out of 16 (25%) showed peak ALT levels of 218 IU/I, 8/16 (50%) children demonstrated slightly elevated ALT levels whereas 25% individuals showed normal ALT levels. Alkaline Phosphatase levels were elevated in 90% of the children and 20% patients of this series also had higher GGT levels. The observed AP levels were not statistically different among HGV, HGV/HCV or HGV/HBV groups. Even though the ALT levels were deranged in the children with HGV alone but none of the children had demonstrated symptoms of liver disease, their direct and total bilirubin levels were normal and no complain of jaundice was recorded. In conclusion, our findings suggested that like other blood borne hepatic viruses, HGV is also prevalent in the high risk group of multiple transfused patients in Pakistan but our results support the absence of any causal relationship between HGV and hepatitis.     

GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India.

BACKGROUND: GB virus C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) have been widely reported in patients with high parenteral risk such as haemodialysis and renal transplant recipients. The occurrence of these agents in association with hepatitis B virus (HBV) and hepatitis C virus (HCV), in Indian renal transplant recipients, is yet unreported. STUDY DESIGN: Molecular and serological markers of GBV-C/HGV and TTV were examined in addition to those for HBV, HCV and hepatitis D virus (HDV) in a selected group of seventy renal transplant recipients. HGV RNA detection was achieved using primers specific for the 5'NCR and NS5a regions of the genome. Anti-GBV-C/HGV antibody was detected using the mu plate anti-HG env kit (Roche, Germany). TTV DNA PCR was performed using primers specific for the coding region (method A) of the genome. In 50% of patients, TTV DNA was also tested for using primers specific for the non-coding region (method B). Host related factors such as age, alanine aminotransferase (ALT) levels, number of transfusions, haemodialysis sessions, and months following transplantation were also studied. RESULTS: Exposure rates to GBV-C/HGV, TTV (method A), HBV, HCV and HDV were 58.6, 32.9, 52.9, 54.3 and 2.9%, respectively. 'Active' infection as measured by viraemia and/or virus-specific antigenaemia for GBV-C/HGV, TTV, HBV and HCV was 52.9, 32.9, 15.7 and 52.9%, respectively. The majority of GBV-C/HGV and TTV infections were seen as co-infections with other hepatitis viruses. Single infection with GBV-C/HGV and TTV was seen in ten (14.2%) and eight (11.4%) patients, and was not associated with ALT elevation when compared to uninfected blood donors. Using univariate analysis, GBV-C/HGV RNA was significantly associated with > or =20 haemodialysis sessions. TTV DNA occurrence was not associated with any risk factors. CONCLUSIONS: There is a high occurrence of GBV-C/HGV and TTV in this select group of renal transplant recipients in India. These viruses mostly occurred in the context of co-infections with other hepatitis viruses. Long term effects of multiple hepatotropic viral infections need to be carefully documented in such transplant populations.     

Prognosis of chronic hepatitis C with regard to the aim of treatment

Epidemiology of hepatitis C virus(HCV) infection and clinical prognosis of chronic hepatitis C were presented here to reveal the object of treatment of Chronic Hepatitis C. Hepatitis C Virus is transmitted by blood and blood products. After acute HCV infection, about 70% developed persistent HCV infection, and the diagnosis is by finding viral RNA in the serum of patients with anti-HCV antibody. Persistent HCV infection causes chronic hepatitis, in which the natural clearance of HCV is almost impossible and there is almost no natural cure for chronic hepatitis caused by HCV. Chronic hepatitis C tends to develop gradually and to progress to liver cirrhosis, and is involved in the pathogenesis of hepatocellular carcinoma. In Japanese patients with chronic hepatitis C, 45% developed liver cirrhosis pass through a phase of chronic active hepatitis over a 15-year course after initial HCV infection, and 25% developed hepatocellular carcinoma over a 20-year course after the initial HCV infection. In addition the remaining patients may start to develop rapidly to chronic active hepatitis and to liver cirrhosis after 20 to 30 years duration of inactive phase. Thus, this type of chronic hepatitis reveals a poor long-term prognosis. For etiological treatment of chronic hepatitis C, eradication of persistent HCV infection is needed. If this is impossible, then preventing the development of liver cirrhosis and hepatocellular carcinoma is important.     

庚型肝炎病毒致病性的初步研究

目的 探讨庚型肝炎病毒（ＨＧＶ）的致病性。方法 应用ＲＴ－ｎＰＣＲ检测３６８例肝炎患者血清ＨＧＶ ＲＮＡ和血清酶的变化,并对其中１例单独庚型肝炎肝硬化病例进行肝脏活组织是检测。结果 在７１例急性黄疸型肝炎中检出单纯性ＨＧＶ ＲＮＡ阳性７例,１５５例慢性肝炎中检出单纯性ＨＧＶ ＲＮＡ阳性２２例,５１例肝硬化中检出单纯ＨＧＶ ＲＮＡ阳性３例。其中１例肝穿组织免疫组化证实为ＨＧＶ ＮＳ ５Ａｇ阳性。结论 争性黄疸型肝炎及乙、丙型肝炎病毒携带者,其慢性肝炎、肝硬化和肝癌中均可检出ＨＧＶ ＲＮＡ,ＨＧＶ感染可为单独感中与乙／丙型肝炎病毒混合或重叠感染,肝脏病理和免疫组化检查证实庚型肝炎病毒是一种嗜肝病毒,其定位主要存在于细胞浆内,可引起慢性病毒性肝炎甚至肝硬化。庚型肝炎病毒很可能具有致病性。     

Elevata prevalenza ma bassa incidenza della infezione da HGV in pazienti con epatite cronica C

Objectives To determine 1. The prevalence and incidence of HGV infection in patients with chronic hepatitis C and 2. Its influence on the clinical outcome of chronic hepatitis C. Patients and methods Sixty-five patients with non-parenteral chronic hepatitis C virus infection were investigated for HGV infection using the polymerase chain reaction for HGV-RNA and by detecting serum antibodies against the E2 protein of HGV (anti-E2 antibodies). Results HGV-RNA in serum was found in 12 patients (18.4%) and anti-E2 antibodies in 4 (6.1%). No difference in age, sex, liver histology, basal ALT or ?GT was found between HGV positive and negative cases. Thirty-four patients (6 with HGV-RNA) were followed-up for 4 years; 4 of the 6 lost HGV-RNA, one of whom seroconverted to anti-E2. None of the 28 HGV-RNA negative cases presented HGV infection during the follow-up period. The presence of HGV infection did not influence either basal HCV viremia or the response of HCV to IFN therapy. Conclusions The study demonstrated that HGV had an intense circulation through non-classic parenteral routes, but its impact on HCV replication and liver disease is negligible.     

Unidentified virus-like particles are detected in plasmas with elevated ALT levels: are they significant of etiological agent(s) of non-B,non-C hepatitis?

GB virus C (GBV-C) and hepatitis G virus (HGV) have been proposed as new viruses etiologically implicated in non-B, non-C hepatitis, but the morphology of these particular virus particles is still unknown, and most cases of non-A to E hepatitis do not relate to their infections. We tried to visualize virus-like particles (VLPs) in plasma samples from hepatitis B surface antigen- and antibody to hepatitis C virus (HCV)-negative blood donors with elevated alanine aminotransferase (ALT), and examined the association of the virus-like particles and the genomes of parenterally transmissible GBV-C/HGV. Twenty-three plasma samples, 13 with elevated ALT levels and 10 with normal ALT values, from blood donors without infections of hepatitis B virus (HBV) and HCV, were subjected to a 20%–60% sucrose density gradient centrifugation, and virus-like particles were observed by electron microscopy. GBV-C/HGV RNAs in the plasmas were tested. Virus-like particles were found in the fractions with densities of 1.15–1.16 g/ml from 12 of 13 (92.3%) plasmas with elevated ALT levels and 1 of 10 (10%) normal controls. The ultrastructural morphology of visualized VLPs was pleomorphic in size and appearance; the majority of the VLPs were 50- to 80-nm spherical particles with a 35- to 45-nm inner core and 9- to 12-nm-long surface spikelike projections. Rodlike VLPs 50–70 nm in diameter with a length of 110–160 nm were also observed in the same samples. The incidence of detection of the circulating VLPs was significantly (P < 0.001) related to elevated ALT levels, but GBV-C/HGV RNAs were detected in none of the plasmas containing the virus-like particles. Spherical VLPs are detected in HBV- and HCV-negative plasmas significantly correlated with the elevation of ALT, suggesting that they are implicated in non-B, non-C hepatitis.     

HGV／GBV—C与HCV混合感染者HGV／GBV—C复制中间体的研究

目的 关于ＨＧＶ／ＢＧＶ－Ｃ组织亲和性的研究尚无结论性资料。我们研究了ＨＧＶ／ＧＢＶ－Ｃ与ＨＣＶ混合感染者ＰＢＭＣ和肝脏中ＨＧＶ／ＧＢＶ－Ｃ复制中间体（负链ＲＮＡ）的存在状况。方法 应用逆转录－巢式ＰＣＲ技术,检测了３２例肝炎患者ＨＧＶ／ＧＢＶ－Ｃ和ＨＶＣ正、负链ＲＮＡ。结果 有２６例ＨＧＶ／ＧＢＶ－Ｃ与ＨＣＶ混合感染者ＰＢＭＣ和肝脏中均未检测到ＨＧＶ／ＧＢＶ－Ｃ负链ＲＮＡ;而在９份ＰＢＭＣ和１５     

Genetic heterogeneity and molecular epidemiology of GB virus C/hepatitis G virus in China

OBJECTIVE: The inter- and intrapatient genetic variation of GB virus C (GBV-C)/hepatitis G virus (HGV) was investigated to characterize the molecular epidemiologic profile of GBV-C/ HGV infection in China, an area endemic for viral hepatitis. The intrapatient variation of hepatitis C virus (HCV) from the same patients was compared to that of GBV-C/HGV. STUDY DESIGN/METHODS: GB virus C/HGV RNA was amplified by polymerase chain reaction in 88 patients with hepatitis C, hepatitis B or presumed non-A-E hepatitis from three cities in China. Five clones of the GBV-C/HGV NS3 region were sequenced from each GBV-C/HGV RNA-positive patient. The corresponding region of HCV was also sequenced from patients co-infected with HCV. Representative sequences of the GBV-C/HGV NS3 region from each patient and those of isolates from other continents were subjected to phylogenetic analyses. RESULTS: GB virus C/HGV was detected in 22 (25.25%) of 88 patients: 9 (21.4%) of 42 patients with presumed non-A-E hepatitis, 10 (27.7%) of 36 patients with hepatitis C, 3 (30.0%) in 10 patients with hepatitis B and C, and in none of 60 volunteer blood donors. The extent of nucleotide variation was less between Chinese isolates (2.4-17%; median, 10.4%) than between Chinese isolates and seven isolates from outside China (10.5-19.5%; median, 15.3%). Intrapatient sequence variation ranged from 0 to 1.75%, with a mean of 0.57 +/- 0.51%. Phylogenetic analysis grouped most Chinese isolates into four geographically specific clusters with a divergence of 10% to 16% from each other. The ratio of nonsynonymous to synonymous substitutions of GBV-C/HGV (Ka/Ks 0.019) was much lower than for HCV (0.071) in the same patients. CONCLUSION: Chinese isolates of GBV-C/HGV are genetically distinct. There are local strains as well as shared strains between different locales. The extent of amino acid sequence conservation suggests strong selection against nonsynonymous substitutions in the GBV-C/HGV genome.