Natural course of HGV infection in haemophiliacs

The natural course of hepatitis G virus (HGV) infection was clarified in 70 haemophiliacs by testing for HGV RNA and antibodies against HGV envelope protein (anti-E2). None of 12 patients treated with only virus-inactivated coagulation factors were infected with HGV. Of 58 patients who received non-inactivated products, 28 (48%) were positive for HGV RNA and/or anti-E2. Of 16 patients with anti-E2, 14 were negative for the viral RNA, and had recovered from HGV infections. HCV antibodies were detected in 59 patients, and eight patients were successively negative for HCV RNA. Thus, the recovery rate of HGV infection (14/28, 50%) was higher than that of HCV (8/59, 14%) ( P  < 0.001). Longitudinal study revealed that anti-E2 developed either during viraemia or some years after seronegativity for HGV RNA. Hence the antibody response itself seemed not to play a major role in the clearance of HGV, though anti-E2 was associated with the clearance of HGV RNA. In conclusion, HGV and HCV are prevalent in patients treated with unsterilized coagulation factor concentrates. However, in contrast to HCV, spontaneous recovery is frequently observed in HGV infections.     

PREVALENCE AND CLINICAL SIGNIFICANCE OF HEPATITIS G VIRUS INFECTION IN ADULT BETA-THALASSAEMIA MAJOR PATIENTS

The risk of polytransfused patients for hepatitis C virus (HCV) infection is likely to extend to another recently identified member of the Flaviviridae, hepatitis G virus (HGV). We investigated the prevalence of HGV in 40 adult Italian patients with transfusion-dependent thalassaemia and evaluated the clinical significance of HGV infection. HGV-RNA was detected in 9/40 patients (22.5%). HGV infection was significantly associated with HCV viraemia ( P  =0.0012), with all patients positive for HGV being also viraemic for HCV. Overall, the clinical picture of patients with HCV/HGV co-infection was not different from that of patients with isolated HCV. However, patients co-infected with both viruses had lower values of alanine-transferase ( P  =0035) and a lower titre of HCV viraemia ( P  =0042) in the absence of other evident factors which could influence the clinical expression of HCV infection. In conclusion, HGV is highly prevalent among Italian polytransfused patients. No evidence of a clinically significant pathogenic role for HGV in liver disease could be found in these patients. In a subset of cases a possible interference of HGV with HCV infection was observed.     

Hepatitis G virus RNA and its relation to hepatitis C infection in adult haemophilic patients

The prevalence of hepatitis C virus (HCV) infection and hepatitis G virus (HGV) RNA were studied in 50 adult haemophilic patients who had received commercial clotting factors prior to 1980. HGV RNA was detectable in 6/50 patients (12%); 49/50 (98%) had antibody to HCV and 40/49 (82%) of these were viraemic with detectable HCV RNA; 5/6 patients with detectable HGV RNA had co-existing HCV infection and viraemia. The HGV PCR products from all six patients were directly sequenced and all were shown to be similar to that of HGV but more diverse from that of GB virus C. One patient who had persistent abnormal liver function tests had detectable HGV RNA but no evidence of hepatitis B or C. The presence of HGV RNA in the absence of hepatitis B and C infection indicates that this virus is capable of independent transmission. Independent response to interferon was demonstrated in one patient with co-infection who lost HGV but not HCV after interferon therapy.     

BRIEF COMMUNICATION: Efficacy of ribavirin plus interferon α on viraemia of GB virus-C/hepatitis G virus: Comparison with interferon α alone

We investigated the efficacy of ribavirin plus interferon (IFN) α on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon α alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFNα and three received oral ribavirin plus IFNα. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFNα alone and ribavirin plus IFNα at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFNα and ribavirin plus IFNα may not induce a higher sustained response.     

A high frequency of GBV-C/HGV coinfection in hepatitis C patients in Germany

AIM:To detect infection rate of GBV-C/HGV in hepatitis C patients, to determine the methods of higher sensitivity and the primers of higher efficiency for GBV-C/HGV RNA detection and to study the dominant subtype and mutation of GBV-C/HGV.METHODS:Quantitative RT-PCR for detection pf HCV RNA concentration in serum samples, RT-nested PCR with two sets of primers for detection of GBV-C RNA, RT-PCR ELISA with two sets of primers for detection of HGV RNA, nucleotide sequence and putative amino acid sequence analysis.RESULTS:The positive rates of GBV-C RNA at the 5'-NCR and NS3 region in 211 serums amples from the patients with HCV infection were 31.8% and 22.8% respectively. The positive rates of HGV RNA at the 5'-NCR and NS5 region in the same samples were 47.9% and 31.8% respectively. The total positive rate of GBV-C/HGV RNA was as high as 55.5%. HCV copy numbers in the patients without GBV-C/HGV coinfection were statistically higher than that in the patients with GBV-C/HGV coinfection (P<0.01).Frequent mutation of nucleotide residue was present in the amplification products. Frameshift mutation was found in two samples with GBV-C NS3 region nucleotide sequences. All nucleotide sequences from amplification products showed higher homology to HGV genome than to GBV-C genome even though part of the sequences were amplified with GBV-C primers.CONCLUSION:A high frequency of GBV-C/HGV coinfection existed in the hepatitis C patients. RT-PCR ELISA was more sensitive than RT-nested PCR for detection of GBV-C/HGV RNA. The primers derived from the 5'-NCR was more efficient than those derived from the NS3 and NS5 regions. A reverse relationship was found to exist between HCV RNA concentration and GBV-C/HGV infection frequency. HGV was the dominant subtype of the virus in the local area. The major mutations of GBV-C/HGV genomes were random mutation of nucleotide residue.     

HGV: the identification,biology and prevalence of an orphan virus

ABSTRACT— Hepatitis G virus (HGV) and GB virus C (GBV-C) (both hereinafter referred to as HGV) were independently identified in patients with hepatitis of unknown aetiology. HGV is a positive-sense RNA virus of the family Flaviviridae. The virus can establish both acute and chronic infection and appears to be sensitive to interferon. Horizontal transmission is mainly parenteral, although other routes such as vertical have been well documented. High risk groups include intravenous drug users (IVDUs), the multiply transfused, haemodialysis patients and haemophiliacs. Up to 90% of IVDUs are positive for either HGV-RNA or antibodies to HGV envelope-2 protein (anti-E2). HGV is frequently detected in patients with HBV and HCV infection. Its link to hepatitis has now become less certain. Only around 3–6% of non-A–E hepatitis cases are HGV viraemic, clearly showing that HGV is not the major cause of idiopathic hepatitis as originally hoped. Around 1–5% of volunteer blood donors in developed countries are HGV viraemic, but the prevalence is 10–20% in the general population in some developing countries. At present, it is not known whether HGV is associated with other diseases in humans, is a passenger virus, or only becomes virulent under certain conditions.     

GBV-C/HGV在血清学非甲～戊型急性肝炎发生中的作用

探讨GBV-C/HGV在血清学非甲～戊型急性肝炎发生中的作用及临床意义.采用免疫组化方法对56例血清学非甲～戊型急性肝炎患者肝组织标本进行GBV-C/HGV NS5抗原的检测,结合临床资料进行分析.血清学非甲～戊型急性肝炎肝组织中GBV-C/HGV NS5抗原检出率为53.6%,主要是以和HBV/HCV重叠感染的形式存在,重叠感染组的ALT升高和HBV/HCV感染组差异无显著意义.单纯GBV-C/HGV感染占16.1%,所引起的血清ALT升高明显低于HBV/HCV感染,而与病原不明病例差异无显著意义.GBV-C/HGV可能没有致病性或者有弱致病性,不是血清学非甲～戊型急性肝炎的主要致病因子.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

GBV-C/HGV and HCV infection in mixed cryoglobulinaemia

Recently, a new, suspected hepatotropic virus has been identified. Named GBV-C/HGV, this virus shares with the hepatitis C virus (HCV) routes of transmission and molecular organization. Indeed, a proportion of HCV-infected patients (10-25%) are also carriers of GBV-C/HGV. Since mixed cryoglobulinaemia (MC) is closely associated with HCV infection, the aim of this study was to determine the prevalence of GBV-C/HGV infection in MC patients, and to investigate whether the double infection influenced the clinical and/or laboratory aspects of the disease. 52 patients affected by MC were studied. 100 patients affected by HCV-positive chronic liver disease (CLD) without MC were used as control group. To determine the prevalence of GBV-C/HGV infection in general population, 150 blood donors were studied, as well as 80 patients affected by non-A-E CLD. Among the MC patients, only five (9.6%) were positive for both HCV and GBV-C/HGV infection. No difference was found between patients with and without double infection as regards main clinical and laboratory aspects. Among HCV-positive CLD cases, 27 were positive for double infection. Among blood donors, the prevalence of GBV-C/HGV infection was 8.0%, whereas in cases with cryptogenetic CLD the prevalence was 5.0%. In conclusion, these data show that GBV-C/HGV infection does not play any role in the pathogenesis of MC.     

HGV/GBV-C infection in patients with acute hepatitis of different etiology and in patients with chronic hepatitis C

To investigate the prevalence of hepatitis G virus (HGV/GBV-C) in patients with liver disease and to confirm its hypothesized ability to cause liver damage, we studied 130 subjects; 61 had chronic hepatitis C virus infection and 69 had acute hepatitis of either defined etiology (n = 57) or of unknown origin (n = 12). Positivity for HGV/GBV-C RNA was detected in 10 of the 61 subjects with chronic hepatitis C (16.3%) and in 11 of the 57 subjects with acute hepatitis of defined etiology (19%), whereas we failed to detect HGV/GBV-C viremia in subjects with hepatitis of non-established etiology. Patients exhibiting positivity for HGV/GBV-C RNA were found to be comparable to those exhibiting negativity for HGV/GBV-C RNA in terms of both liver function tests and Knodell's score (in liver biopsies); the affect of HGV/GBV-C infection on the biohumoral and histological activity in patients with chronic hepatitis C therefore appears to be minimal or absent. Similar clinical features were observed in patients with acute hepatitis of known etiology whether they were positive or negative for HGV/GBV-C RNA. However, long-term clinical studies are still required to clarify the actual impact of HGV/GBV-C co-infection. In our geographic, i.e., a region or north-east Italy, HGV/GBV-C infection appears to be strictly related to intravenous drug use, and this agent does not seem to be responsible for acute hepatitis of unknown etiology; other etiological agents are probably involved. Received Feb. 17, 1997; accepted June 27, 1997     

Infection of hepatitis A virus in Japanese haemophiliacs

OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have been reported from many countries. The aim of this study was to determine the prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs. METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV infection. We also compared the rate of HAV infection with that of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus (HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb. Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV, HCV, and HGV were not statistically different between HAVAb positive and HAVAb negative haemophiliacs. We suggest that the use of clotting factor concentrates is closely associated with HAV infection, but HAV infection does not have an effect on clinical course. CONCLUSIONS: Administration of clotting factor concentrates may increase risk of HAV infection in haemophiliacs.