Prevalence of hepatitis G virus RNA in a monocentric population of French haemophiliacs

Hepatitis G virus (HGV) and hepatitis GB virus (GBV-C) have been reported as possible causes of non-A–E transfusional hepatitis. To assess the prevalence of hepatitis G virus infection in haemophiliacs we retrospectively investigated the presence of viral RNA in 92 patients with and without HCV infection. HGV/GBV-C RNA was reverse transcribed and amplified with primers from the 5' non-coding region of the genome. RNA was detected in 16/92 patients (17.4%). Restriction enzyme analysis revealed that the 16 patients belonged to the HGV-like genotype. Serology with E2-specific antibodies demonstrated that HGV viraemia underestimates previous infection by HGV. 33 patients were positive for HGV; all but two have cleared HGV RNA. 47/92 patients had a marker of prior infection by HGV.
No difference between HGV RNA positive and negative patients was observed concerning age, diagnosis, HIV and HCV status. Previous HBV infection correlated with the frequency of HGV infection. There was no difference in alanine aminotransferase levels between HGV positive and negative patients. All 18 patients exposed to only virally inactivated plasma-derived concentrates were negative for both HGV RNA and anti E2 antibodies.
Prior exposure to untreated concentrates correlated with HGV viraemia ( P =0.03), HGV seropositivity ( P =0.0002), and markers of HGV infection ( P <0.0001).
In haemophiliacs with a past exposure to non-inactivated concentrates, persistence of HCV RNA (53/74 patients) was more frequent than HGV RNA persistence (16/74 patients) although HGV viraemia is more frequent than HCV viraemia in blood donors. This may be related to a greater ability of individuals to clear HGV infection and suggests that hepatitis G virus infection in multi-transfused patients has a better outcome than infection with other blood-borne viruses.     

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.     

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.     

Low viraemia at enrollment in children with chronic hepatitis C favours spontaneous viral clearance

Summary.  The significance of hepatitis C viral (HCV)-RNA levels in long-term clinical outcomes of children with chronic HCV infection is not well understood. We conducted a long-term follow-up study of 42 children with chronic HCV infection that included clinical evaluation, biochemical tests, HCV genotyping and repeated quantitative HCV-RNA detection. Patients were divided into low and high viraemia groups according to RNA levels at enrollment (below/above 4.5 × 10⁴ IU/mL), and clinical, biochemical and virological factors were evaluated. Overall, 14.3% (6/42) of patients developed spontaneous viral clearance during a median 10.1 years of follow-up. HCV-RNA levels at enrollment and mean RNA levels during follow-up for each patient were significantly correlated ( R  = 0.9018, 95% CI: 0.6637–0.9038, P ≤  0.001). HCV-RNA level fluctuation was within two log units in 76% of patients. Cumulative viraemia probability during follow-up could be predicted by viraemia levels at enrollment ( P  =   0.0092). Chronic HCV-infected children, with an RNA level below 4.5 × 10⁴ IU/mL at enrollment, have a higher spontaneous viral clearance rate.     

Hepatitis G virus infection in patients with bleeding disorders

Eighty-two patients with bleeding disorders registered with our centre were screened for infection with hepatitis G virus (HGV). 80 patients were positive for hepatitis C (HCV) antibodies, 66 of whom (83%) were HCV PCR positive. 11 patients (13%) were HGV RNA-positive, a similar prevalence rate to that of other studies of patients with bleeding disorders who received factor concentrates prior to the introduction of viral inactivation procedures. There was no significant difference in histological activity index (HAI) between the 10 HGV RNA-positive and the 31 HGV RNA-negative patients who underwent liver biopsy for assessment of HCV infection (median HAI scores 5.5, range 2–10 and four, range 0–10 respectively, P  = 0.07). One patient in each group had established cirrhosis. In patients who underwent HCV quantitation there was no significant difference in HCV viral titre between HGV RNA-positive and negative patients (median HCV titre in HGV RNA-positive patients 2.10 × 10⁵ DNA copies /ml ( n  = 8) range 4.17 × 10² to 4.17 × 10⁶, median HCV titre in HGV RNA-negative patients 3.33 × 10⁵ ( n  = 31) range 1.00 × 10³ to 6.67 × 10⁶, P  = 0.68). In this study there was no evidence that individuals co-infected with HGV and HCV have more severe liver disease than those infected with HCV alone.     

Hepatitis C virus genotypes in chronic hepatitis C of children

SUMMARY. Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 3 3 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype Ib was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype la (16.6%), genotype 2 (11.1%). and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.     

Lower Hepatitis G Virus Infection Prevalence Compared to Hepatitis B and C Virus Infection Prevalences

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P < 0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P < 0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.     

Hepatitis G virus infection in Japanese haemophiliacs

The recently identified hepatitis G virus (HGV) (also known as GB virus-C) has been considered as a blood-transmissible agent. As many haemophiliacs have risk factors for infectious agents, to clarify the frequency of HGV infection is important. HGV-RNA was investigated in 77 Japanese haemophiliacs who had been treated with nonvirus-inactivated concentrates derived from pooled plasma. Detection of HGV-RNA was performed with a nested RT-PCR that recognizes the 5'-NCR of the HGV genome. HGV-RNA was detected in 19 (24.7%), including four (21.0%) infected with HGV alone, 12 (63.2%) co-infected with HCV and three (15.8%) who were HBV carriers. The patients infected with HGV alone showed a normal ALT level of 18.7 ± 4.1 IU L⁻¹. Most (36/37, 97.3%) of the patients with abnormal ALT levels had HCV-RNA. Patients infected with HCV alone or co-infected with HCV and HGV showed higher ALT levels of 108.8 ± 90.2 IU L⁻¹ ( n = 39) and 67.6 ± 62.6 IU L⁻¹ ( n = 11), respectively. However, there was no significant difference ( P = 0.16) in ALT levels between HCV infection alone and HCV/HGV co-infection. On the other hand, four of the patients who could be followed over 10 years showed HGV-RNA persistently. In two who underwent liver biopsy, the histological evidence showed no definitive fibrotic and necro-inflammatory changes. These results indicate that HGV infection has frequently occurred in haemophiliacs. It is possible that HGV infection does not cause aggressive hepatitis with elevated ALT levels, and that co-infection with HGV may not aggravate hepatitis caused by HCV.     

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.     

Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P  < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P  < 0.001). Among patients with triple infection ( n  = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two ( P  < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P  < 0.0001). Among patients with dual infection ( n  = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P  = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.     

单纯HGV感染急性肝炎患者的临床与病理研究

目的 通过对一组急性ＨＧＶ感染患者的肝组织病理和临床资料分析，探讨庚型肝炎病毒感染的致病性，方法 采用免疫组织化学技术对５９例不明原因包性肝炎患者的肝组织，进行乙、丙和庚型肝炎病毒怕检测，部分病例经原位杂交证实。结果 ＨＧＶＮＳ５怕的检出率为（５７．６％〈３４／５９），其中２０直组织中ＨＢｓＡｇ和／或ＨＣＶＮＳ３Ａｇ同时阳性ＩＨＧＶ合并感染组），ＨＧＶ阳性信号主要位于肝细胞浆内。ＨＧＶ单纯感染病例