Hepatitis G Virus Isolates Research Articles

Sequencing and Phylogenetic Study of Partial NS3 Gene of Iranian GB Virus C/Hepatitis G Virus (HGV) Originated From Hemodialysis Patients in Tehran.

Background:Hepatitis viruses are one of the most important concerns in the patients on hemodialysis who are at high risk for blood-borne infections. GB virus C (GBV-C)/hepatitis G virus (HGV) is positive-stranded RNA virus with global distribution, which codes structural and nonstructural proteins (such as NS3).Objectives:Review on literature about Iranian HGV isolates showed that there was no report on sequencing and phylogenetic characteristics of NS3 gene and therefore, this study attempted to answers these challenges.Materials and Methods:Briefly, steps followed were as follows: preparation of nucleic acids from three Iranian hemodialysis HGV-positive samples and RNA extraction; reverse transcriptase-PCR (RT-PCR) for amplification of NS3 gene and gel electrophoresis; sequencing and analyzing sequencing data; NCBI Registering; blasting and alignment of sequences; and finally constructing the phylogenetic tree.Results:Nucleotide BLAST results emphasized that most similar sequences to Ir NS3 sequences were those from Europe (Spain, Germany, and the United Kingdom) and the United states and IR sequences were located with five leaves in a branch. In addition, homology of Ir sequences showed96.4% (between IR1 and IR2), 94.9% identity (between IR1 and IR3), and 96.5% identity (between IR2 and IR3).Furthermore, highly variation and significance differences in NS3 between GBC isolates from geographical regions and some little changes in IR sequences were seen. Finally, phylogenetic tree revealed that NS3 genotype of Iranian isolates was probably similar to European countries and USA.Conclusions:Overall, results of present study were consistent with the data reported earlier base on 5’ NTR in Iranian isolates and revealed genotype IR2 is major genotype in Iranian HGV-positive patient. It means there are higher similarities between Iranian and Europe-USA in HGV NS3 gene.

The entire nucleotide sequence of two hepatitis G virus isolates belonging to a novel genotype: isolation in Myanmar and Vietnam.

A novel genotype of hepatitis G virus (HGV) was recently identified in sera of subjects from countries in South-East Asia. These isolates were recovered from serum of Myanmarese (designated HGV-MY14) and Vietnamese (designated HGV-VT48) subjects, respectively. To characterize the viral genome in more detail, the full-length nucleotide sequence of the two different HGV isolates belonging to the novel genotype was cloned. Both HGV isolates were composed of 9228 nt and had a single open reading frame spanning 8529 nt and encoding 2843 aa residues. The isolates differed from previously reported HGV/GBV-C isolates types 1 to 3 by 13-15% (nucleotide sequence) and 4-6% (amino acid sequence). The putative core region of both isolates was not clearly identifiable as it consisted of only 16 aa residues. Based on phylogenetic analysis of full-length genome sequences and 5'-UTR sequences, HGV-MY14 and HGV-VT48 isolates can be classified as a novel genotype, designated type 4.

Analysis of hepatitis G virus infection markers in blood donors and patients with hepatitis.

The incidence and clinical significance of hepatitis G virus (HGV) is still not fully known. The aim of our study was to assess the frequency of HGV RNA and antibody to HGV E2 protein (anti-E2) in Polish blood donors and patients with hepatitis, and to compare the sequence of HGV clones with those reported by others. Two-hundred and nineteen blood donors and 83 patients with hepatitis were studied. HGV was detected in 3.2% and anti-E2 in 24.2% of blood donors and in 26.5% and 8.4% of patients with hepatitis, respectively. HGV was detected as a co-infection with HCV in four of 18 patients with chronic hepatitis, in four of 16 patients with acute hepatitis and in one of six patients with fulminant liver failure (FLF), and as a co-infection with HBV in one of six patients with FLF and in three of 10 patients with chronic hepatitis. In non-A-C hepatitis, eight of 23 patients with acute hepatitis and one of four patients with FLF were positive for HGV but all 10 patients with chronic cryptogenic hepatitis were negative. In the follow-up studies of patients with HGV alone, a correlation with viraemia and clinical symptoms was observed in two patients, but in three others HGV RNA was detected in spite of clinical resolution. Two HGV clones were sequenced, and the sequence of the HGV helicase region of the HGV isolates from donor and patient were homologous to those described by others. Hence, the frequency of HGV RNA in blood donors is similar to that obtained in other countries but the anti-E2 (marker of a past infection) frequency is higher. The incidence of HGV RNA and anti-E2 in hepatitis patients suggests that HGV plays a role in liver pathology, but careful analysis of individual cases does not confirm this.

Epidemiology of hepatitis B, C, E, and G virus infections and molecular analysis of hepatitis G virus isolates in Bolivia.

Prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis G virus (HGV), and hepatitis E virus (HEV) was investigated among 574 healthy blood donors in Bolivia. HCV RNA and HGV RNA in the serum were identified by a nested reverse transcription-PCR using primers derived from the 5' untranslated region (5' UTR). We also tested for hepatitis B surface antigen (HBsAg) and for the antibody to HEV. The results revealed that HGV RNA was present in 84 of 574 (14.6%) tested blood donors, whereas HBsAg was detected in only 2 (0.3%) donors, and no individuals positive for HCV RNA were found. Anti-HEV immunoglobulin G (IgG) was detected in 93 (16.2%) individuals and anti-HEV IgM was found in 10 (1.7%) individuals among the same population. Phylogenetic analysis of 44 HGV isolates in the 5' UTR showed that 27 (61%) isolates were genotype 3 (Asian type) and the remaining 17 (39%) isolates were genotype 2 (United States and European type). Moreover, we obtained a full-length nucleotide sequence of the HGV genome (designated HGV-BL230) recovered from a Bolivian blood donor. The BL230 was composed of 9,227 nucleotides and had a single open reading frame, encoding 2,842 amino acid residues. Interestingly, the BL230 belonged to genotype 2 of HGV at the level of a full-length sequence, although this was classified as genotype 3 by a phylogenetic analysis based on the 5' UTR sequence. The BL230 differed from previously reported HGV/hepatitis GB virus type C isolates by 12 to 13% of the nucleotide sequence and 4% of the amino acid sequence. Our data indicate a high prevalence of HGV in native Bolivians, and the major genotype of HGV was type 3.

Prevalence of hepatitis G virus and characterization of viral genome in Ghana

The prevalence of hepatitis G virus (HGV) infection was investigated in 85 human immunodeficiency virus (HIV)-infected and 30 uninfected individuals' sera obtained from Ghanaians. HGV RNA in serum was identified by a nested reverse transcription polymerase chain reaction (RT-PCR) using primers derived from the 5′-noncoding region. We also tested for hepatitis C virus by nested RT-PCR and for hepatitis B surface antigen (HBsAg) by passive hemagglutination method. HGV RNA was detected in 17 of 85 (20%) HIV sero-positive and three of 30 (10%) sero-negative Ghanaians, respectively. The prevalence of HGV infection was much greater than hepatitis C (0.9%) and hepatitis B virus (7.8%) infections in the present study. Ninety four percent of HGV infected patients were seronegative for hepatitis B and C virus infections. The nine different Ghanaian isolates in the 5′-untranslated region of the HGV genome had one nucleotide deletion at the same position when compared with other HGV isolates. Phylogenetic analysis showed that all Ghanaian isolates belonged to type 1 (West Africa type) of the HGV genotypes. Moreover, we determined nearly full-length nucleotide sequence of the HGV genome (denoted HGV-GA128) recovered from a Ghanaian infected with HIV. The HGV-GA128 was composed of 9231 nucleotides and had a single open reading frame, encoding 2843 amino acid residues. This isolate differed from previously reported HGV/GBV-C isolates by 10–15% of the nucleotide sequence and 2–5% of the amino acid sequence. Our data indicate a high prevalence of HGV, especially genotype 1, in Ghana.

Hepatitis G virus infection in Chinese patients with chronic hepatitis B, C or non-A-E: clinical and molecular aspects

In the present study we investigated the epidemiology, clinical significance and molecular characteristics of hepatitis G virus (HGV) infection in Chinese patients with chronic hepatitis B, C or non-A-E. Based on the detection of HGV RNA by reverse transcription polymerase chain reaction, 17 of 70 patients (24%) with chronic post-transfusion hepatitis C were coinfected with HGV. In contrast, none of 21 patients with non-A-E hepatitis had detectable HGV RNA. Among nine patients with severe chronic hepatitis caused by HBV/HCV coinfection, two were HGV RNA positive without affecting the outcome. Sustained biochemical response to interferon-alpha was similar in patients with HCV infection only (22/51, 43%) and in patients with HCV/HGV coinfection (7/17, 41%). Among ten Chinese HGV isolates, the nucleotide sequence homology in the 5′-UTR was 91–100% as compared to 84–95% between the Chinese HGV isolates and those from other countries. No core gene was found in the Chinese HGV isolates examined. In conclusion, about 20% of Chinese patients with chronic hepatitis C are coinfected with HGV. Coinfection did not affect the natural course of chronic hepatitis C or the response to antiviral therapy. Sequence analyses revealed a high degree of homology among Chinese HGV isolates. HGV infection does not appear to play a major clinical role in Chinese patients with chronic hepatitis B, C or non-A-E.

Hepatitis G virus in multitransfused thalassaemics from India.

Hepatitis G virus (HGV)/GB virus-C (GBV-C) has been identified as a blood-borne agent with disputed pathogenicity. This virus belongs to the flaviviridae with a distant relationship to hepatitis C virus (HCV). Genetically divergent HGV isolates have been reported from different parts of the world. This study describes the prevalence of HGV in multitransfused thalassaemic children in India and genomic sequence variations in 11 HGV isolates from the same geographical location. Hepatitis G virus RNA was detected in 39.7% multitransfused thalassaemic children. The seroprevalence of hepatitis B virus (HBV) and HCV was 23.8% and 17.1%, respectively, and 11.4% had dual infection. The nucleotide sequence of a 166 bp HGV genomic segment from the putative capsid-envelope region (nucleotide; nt 578-743) from 11 Indian isolates was compared to the sequences available in the nucleotide databases. The isolates from India were 81.3-94.5% homologous to the isolates from other parts of the world. On phylogenetic analysis, it was observed that HGV isolates from India may belong to two genetically divergent types.

Viremia, genetic heterogeneity, and immunity to hepatitis G/GB-C virus in multiply transfused patients with thalassemia.

Thalassemia patients are at high risk for posttransfusion hepatitis. Hepatitis G virus (HGV) has been suspected of being responsible for acute and chronic hepatitis. The prevalence of HGV infection, its possible association to liver disease, the genetic heterogeneity among the various HGV isolates, and immunity to HGV were studied in 36 thalassemia patients with reverse transcriptase-polymerase chain reaction assay and sequence analysis. HGV RNA was detected in seven patients (19.4%), only two of whom had evidence of hepatitis C virus infection as well. Sequence analysis of the NS3 gene from isolates of the five patients infected with HGV alone revealed 84.7 to 90.9 percent homology at the nucleotide level. Prolonged HGV viremia was not associated with significant liver enzyme elevation. All five patients were chronically infected with the same viral strain. E2 antibodies were detected in 57 percent of the HGV-nonviremic patients and in only 1 of 7 viremic patients. HGV is associated with persistent viremia but not with significant biochemical evidence of liver damage. There is some genetic heterogeneity among HGV isolates from thalassemia patients in Israel.

Geographical characterization of hepatitis G virus genome: Evidence for HGV genotypes based on phylogenetic analysis

Recently, the genome from a novel virus, termed hepatitis G virus (HGV) and GB virus C (GBV-C), has been discovered in the serum of patients. To investigate the heterogeneity of this viral genome, we sequenced 188 nucleotides at the 5′untranslated region (5′UTR) of HGV genome in 48 individuals from 11 different countries, including the USA, Asia (Japan, Korea, Nepal, Myanmar, Cambodia, Vietnam and Thailand), Spain, Egypt and Ghana and compared the results with these isolates. The data showed that there was a consensus genome sequence among the HGV isolates from each country and that it could be classified into at least three different groups or genotypes. Construction of phylogenetic trees, bootstrap analysis and calculation of mean distances between possible genotypes in the 5′UTR of HGV isolates also showed three major genotypes, which were defined as West Africa (type 1), US/Europe (type 2) and Asia types (type 3). Type 2 was found in various geographic areas, including USA, Europe, Egypt and Asia, while type 1 was found predominantly in West Africa. Type 3 was found mainly in Asia. Furthermore, type 3 could be clearly differentiated into a regional group, compared with the other two types, by bootstrap analysis. The HGV sequence of 5′UTR obtained from one Japanese patient showed no mutation over 12 years. These results suggest that HGV have genotypes corresponding to genetic heterogeneity and is correlated with geographic distribution.

Hepatitis G and C viruses respond to interferon-alpha with different virologic kinetics.

The aim of this work was to specify the time course of response to interferon (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected individuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to select seven coinfected patients. Spontaneous recovery from HGV infection was excluded through the detection of antibodies to the envelope-2 protein of HGV and HCV isolates were genotyped. Within three months of treatment, we found that HGV RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable response was very low (1/7). In addition, considering the same individuals separately, it was shown that HGV and HCV responded to IFN with different kinetics in 5/7 patients. Taken together, these results underscore the importance of the virological basis of the resistance to IFN treatment.

Phylogenetic Analysis of Hepatitis GB Virus Type C/Hepatitis G Virus in Spanish Patients with Chronic Hepatitis B or C Virus Infection

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5′-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5′-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5′-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.

Identification of a single genotype of hepatitis G virus by comparison of one complete genome from a healthy carrier with eight from patients with hepatitis.

Different isolates of a putative hepatitis virus called hepatitis GB virus C or hepatitis G virus (HGV) have been cloned recently from patients with hepatitis. This virus has also been found commonly in healthy carriers. We have cloned and sequenced a complete HGV genome, designated HGVCN, from a healthy Chinese blood donor. HGVCN shares 85.8-90.0% nucleotide sequence identity and 95.4-97.5% amino acid identity with the eight available full-length HGV genomes. Furthermore, the majority (82.8%) of the nucleotide substitutions found in HGVCN were synonymous and a fairly uniform distribution of changes was found across the entire genome without identification of any hypervariable region. When compared with the African isolates GBVC and GBVC-EA, the HGVCN-encoded polyprotein contained a 31 amino acid N-terminal extension which was predicted to be a defective core-like sequence. The sequences of the HGV E1 and E2 proteins displayed unique motifs and were highly conserved. Phylogenetic analysis revealed that all nine complete HGV isolates were closely related and that HGVCN grouped with the other Chinese HGV isolate (HGVC964). Taken together, our findings suggest that there is one single genotype of HGV and that the HGV genome cloned from the healthy carrier is not significantly different from those derived from patient sera.

Sequence variation and phylogenetic analysis of envelope glycoprotein of hepatitis G virus.

A transfusion-transmissible agent provisionally designated hepatitis G virus (HGV) was recently identified. In this study, we examined the variability of the HGV genome by analysing sequences in the putative envelope region from 72 isolates obtained from diverse geographical sources. The 1561 nucleotide sequence of the E1/E2/NS2a region of HGV was determined from 12 isolates, and compared with three published sequences. The most variability was observed in 400 nucleotides at the N terminus of E2. We next analysed this 400 nucleotide envelope variable region (EV) from an additional 60 HGV isolates. This sequence varied considerably among the 75 isolates, with overall identity ranging from 79.3% to 99.5% at the nucleotide level, and from 83.5% to 100% at the amino acid level. However, hypervariable regions were not identified. Phylogenetic analyses indicated that the 75 HGV isolates belong to a single genotype. A single-tier distribution of evolutionary distances was observed among the 15 E1/E2/NS2a sequences and the 75 EV sequences. In contrast, 11 isolates of HCV were analysed and showed a three-tiered distribution, representing genotypes, subtypes, and isolates. The 75 isolates of HGV fell into four clusters on the phylogenetic tree. Tight geographical clustering was observed among the HGV isolates from Japan and Korea.

Hepatitis G virus infection in patients with chronic non-A–E hepatitis

To elucidate the role of hepatitis G virus (HGV) infection in chronic non-A-E hepatitis and sequence the partial NS5 genome of HGV isolated from the serum of a Chinese patient with chronic non-A-E hepatitis Serum samples of patients with chronic non-A-E hepatitis were collected and total nucleic acids were extracted and subjected to reverse transcriptase-nested-polymerase chain reaction (RT-nested-PCR) using primers from the putative NS5 region of HGV genome. Then, 994bp cDNA was prepared from the positive serum, purified with electrophoresis of polyacrylamide gels, and directly sequenced using the dideoxy-mediated chain-termination method. HGV-RNA was detected in 1 of the 35 patients with chronic non-A-E hepatitis. Compared with the 2 HGV isolates (PNF2161 and R10291) obtained from American patients, the HGV NS5 gene of this Beijing isolate (HG-G) showed homology of 88.0% and 89.2% respectively. On the other hand, in comparison with the West African isolate (GBV-C), the Beijing isolate showed homology of 93.5%. The patient showed persistent increase of alanine transaminase, but normal levels were achieved after interferon therapy with persistent positive HGV RNA. HGV is one of the causes of chronic non-A-E hepatitis, but it may not be a very important cause. The nucleotide sequence of partial NS5 gene of HG-G was found to be highly homologous to the West Africa isolate.

Mutation Rate of GB Virus C/Hepatitis G Virus over the Entire Genome and in Subgenomic Regions

A patient on maintenance hemodialysis was infected with a recently discovered putative non-A to -E hepatitis virus designated GB virus C (GBV-C) or hepatitis G virus (HGV) by transfusion. The viral isolate was recovered from the patient soon after she turned positive for GBV-C/HGV RNA in serum (GSI85) and 8.4 years thereafter (GSI93), and the entire nucleotide sequences were determined. They both had a genomic length of 9391 nucleotides with a defective C gene made of only 42 nucleotides. Between GSI85 and GSI93, 31 (0.33%) nucleotides were different, which changed 5 (0.18%) of the encoded 2842 amino acids. Thus, GBV-C/HGV was estimated to have a mutation rate of 3.9 × 10−4base substitutions per site per year. Nucleotide conversions were distributed over subgenomic regions, except in the 5′ untranslated region of 552 nucleotides and a defective short C gene, which were conserved in sequence. The change in the putative envelope genes (E1 and E2) was no different from that in the entire genome with only 6 (0.35%) nucleotide substitutions among the 1730, just 1 of which induced an amino acid conversion. Taken along with the comparison of the two isolates with the reported five GBV-C or HGV isolates, these results indicate that GBV-C/HGV would not have hypervariable regions and would use a strategy for viral persistence that is different from immune escape.

Hepatitis G Virus Replication in Human Cultured Cells Displaying Susceptibility to Hepatitis C Virus Infection

We recently developed a hepatitis C virus (HCV) replication system using two cultured human cell lines: MT-2C, a human T-cell leukemia virus type I-infected cloned T cell line, and PH5CH, a non-neoplastic human hepatocyte line. In the course of the study, we found evidence that replication of hepatitis G virus (HGV), which has recently been identified, was supported in both MT-2C and PH5CH cells. When these cells were inoculated with serum 1B-3 containing both HCV and HGV obtained from a blood donor, the 5′-noncoding (5′-NC) regions of HCV RNA and HGV RNA were detected by RT-nested PCR in both cell lines more than 30 days postinoculation, and the 3′-noncoding region of HGV RNA was also detected in the both cell lines more than 30 days postinoculation. Sequence analysis of the 5′-NC region of HGV RNA revealed the quasispecies nature of HGV, although the 5′-NC region was highly conserved among HGV isolates. This HGV-infected culture system will be useful for various biological and virological studies of HGV.

New variant groups identified from HGV isolates.

We have determined the primary sequence of the 5' noncoding region (5' NCR) and putative helicase regions (NS-3) of hepatitis G virus (HGV) and GB virus C (GBV-C) that were isolated in Japan from suspected cases of nonA-nonB and/or nonA-nonB-nonC viral hepatitis by using RT-PCR, and we compared the newly isolated sequences with three established isolates. The addition of a "G" residue was found at the 5' terminus of all 8 Japanese isolates. These isolates were more clearly distinguished from the prototype viruses by comparison with the 5' NCR sequence than by comparison with the NS-3 region. Our results suggested that at least three distinct genomic variants of HGV exist. Genotyping of HGV by using RT-PCR based on the sequence of the 5' NCR seems highly feasible.

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Genetic heterogeneity of hepatitis G virus isolates from different parts of the world.

Comparative sequence analysis of a 354 nt fragment of the NS5 region of hepatitis G virus (HGV) isolates was performed to assess two levels of HGV genomic variability: (1) heterogeneity of HGV within an infected individual, and (2) heterogeneity of different HGV isolates. Comparison of nucleotide sequences of DNA clones from two virus isolates demonstrated that in each infected individual HGV is represented by a population of virions with closely related but heterogeneous genomes (quasi-species). Phylogenetic analysis of nucleotide sequences of 42 isolates collected from 14 countries revealed less significant genome variability of HGV as compared to hepatitis C virus. Sequences of all HGV isolates fell into one group of distribution of evolutionary distances. On a phylogenetic tree all HGV sequences segregated into numerous branches. All sequences of isolates from Africa, South and South-East Asia, however, were clustered together and were separated from those of other isolates collected in Europe, North America and Central Asia.

GBV-C/HGV: a new human hepatitis-related virus

Two novel potentially hepatotropic flavi-like viruses were recently identified in patients with acute or chronic hepatitis and were provisionally called GBV-C and hepatitis G virus (HGV). The sequence identity analysis of these two viruses clearly indicated that GBV-C and HGV are two isolates of the same virus. In addition, the phylogenic analysis of the aligned viral polyprotein sequences showed that the GBV-C and HGV isolates are closely related to two Flaviviruses (GBV-A and GBV-B) that cause hepatitis in tamarins, and are distantly related to hepatitis C virus (HCV). Taken together, these results demonstrate that GBV-C/HGV belongs to the Flaviviridae family. GBV-C/HGV genomic RNA is detectable in both acute and chronic non-A, nonE hepatitis as well as in a minor proportion of patients with fulminant hepatic failure, hepatocellular carcinoma and in blood donors with or without abnormal alanine aminotransferase. However, the majority of patients with prospectively followed HGV infections have no evidence of liver damage. The high frequency of GBV-C/HGV infections in patients who are coinfected with HBV and/or HCV suggests that these viruses can share a common mode of transmission.