Letters to the Editor

GBV-C in the aetiology of fulminant hepatitis

Le GBV-C ou virus « dit » de l’hépatite G, découvert en 1995, a été proposé comme candidat responsable d’hépatites non A-E. Il s’agit d’un virus très répandu, dont la prévalence chez les donneurs de sang dans les pays développés se situe entre 1 à 5 %. Sept années d’études ont permis d’exclure son rôle direct en tant qu’agent étiologique significatif d’hépatites. Son site de réplication in vivo n’est pas définitivement identifié et aucune corrélation directe entre l’infection virale seule et l’induction de maladies hépatiques ou extra-hépatiques n’a pu être mise en évidence. Cependant, lors de co-infections avec d’autres virus, un rôle modulateur de l’infection GBV-C, susceptible d’aggraver les lésions hépatiques, ou au contraire, de ralentir la progression de l’infection VIH-1 vers le sida, semble se confirmer. À ce jour, aucun pays n’a pris la décision de mettre en œuvre un dépistage de l’infection à virus GBV-C chez les donneurs de sang. Des études complémentaires restent indispensables avant de pouvoir définitivement affirmer l’absence d’influence de l’infection à GBV-C sur la santé humaine dans le contexte d’autres infections virales.

Cette revue fait état de l’ensemble des données de la littérature sur une implication éventuelle du GBV-C dans des pathologies associées ou non à d’autres infections.

GB virus-C alias “hepatitis” virus G was discovered in 1995 as a putative causative virus of non A-E hepatitis. It is a very common virus found in 1 to 5% of eligible blood donors in developed countries. Numerous studies over seven years led to the exclusion of its role as a significant etiological agent of hepatitis. Its in vivo replication site is still unknown. Its direct involvement in the induction of significant hepatic or extra-hepatic diseases could not be demonstrated. However, coinfections with other viruses may contribute to changes in the evolution of both liver disease (negatively) and HIV/AIDS (favourably). Today, no country has decided to screen GBV-C in blood donors. However, more studies are necessary before the absence of influence of GBV-C infection on human health in the context of other viral infections could be confirmed definitely. This article is a review of the literature on a possible involvement of GBV-C in pathologies whether associated or not to other infections.

We describe a rare case of a pediatric patient with active GB virus C (GBV-C)/hepatitis G virus (HGV) infection who died of fulminant hepatic failure within less than a month after the onset of jaundice. The child tested negative for all other known hepatitis viruses and had no history of blood transfusions. This observation suggests that although GBV-C/HGV is usually not pathogenic to the liver, it may be associated with certain idiopathic forms of fulminant hepatitis. Whether this association is etiological or circumstantial remains to be seen.

Se cree que el poder citopático del virus de la hepatitis G (VHG) es escaso; noobstante, su efecto sobre el hígado es menos conocido en los casos de coinfección con el VHC.Los objetivos de este trabajo fueron estudiar la prevalencia de la coinfección en pacientes conhepatitis crónica C (HCC) y analizar los aspectos clínicos, epidemiológicos e histológicos y larespuesta al interferón (IFN).

Se incluyeron 180 pacientes con HCC y se determinó el ARN-VHG.

La prevalencia de la coinfección fue del 12,2% (n = 22). No se observaron diferenciasestadísticamente significativas entre el grupo no coinfectado y coinfectado al estudiar laedad, el sexo, los mecanismos de transmisión y la ingesta de alcohol. Tampoco había diferenciasen la bioquímica hepática, los autoanticuerpos no organoespecíficos, la lesión histológicay el índice de Knodell. La respuesta bioquímica (RB) y virológica (RV) del VHC a los 6 mesespost-IFN fue similar en los dos grupos (VHG negativo: RB = 29%, RV = 12%; VHG positivo: RB= 22%, RV = 18%). El ARN-VHG se determinó también a los 6 meses postratamiento en elgrupo de coinfectados (primer ciclo de IFN: n = 22; segundo ciclo de IFN: n = 9): 12 (55%)negativizaron el ARN-VHG y 5 (23%) el ARN-VHC (p = 0,021). Al comparar la RB con la RV eneste grupo, había 12 que negativizaron el ARN-VHG pero sólo 2 tenían RB (diferencias no significativas).Por el contrario, la RB sí se relacionó con la negativización del ARN-VHC (p =0,023).

La prevalencia de coinfección por VHG en pacientes con hepatitis crónica C es elevada(12,8%). El VHG no aumenta la patogenicidad del VHC ni modifica la respuesta al IFN,aunque el VHG es más sensible al IFN que el VHC. La determinación del VHG no es necesariaen los pacientes con HCC.

It is thought that the cytopathic effect of HGV is not important. Nevertheless, thecytopathic effect on liver is less known in the cases of co-infection with HCV. The aim was tostudy the prevalence of co-infection in patients with chronic hepatitis C (CHC) and to analysethe clinical-epidemiological and histological data and the interferon (IFN) response.

We included 180 patients with CHC and the HGV-RNA was determined.

The prevalence of co-infection was 12.2% (n = 22). No statistical differences were observedbetween the non co-infected and co-infected groups with regard to the age, sex, mechanismof transmission and alcohol abuse. Also, there were no differences in the hepatic biochemical,no organspecific antibodies, histological lesions and Knodell index. The HCVbiochemical response (BR) and virological response (VR) after 6 months post-IFN were thesame in both groups (HGV negative: BR = 29%, VR = 12%; HGV positive: BR = 22%, VR =18%). HGV was determined after 6 months postreatment in the co-infected group (first cycle ofIFN, n = 22; second cycle of IFN, n = 9): 12 (55%) were HGV-RNA negative and 5 (23%)HCV-RNA negative, (p = 0.021). When we compared the BR vs VR in this group, there were 12HGV-RNA negative but only two had BR (NS). On the contrary, the BR was related to HCV-RNAnegative (p = 0.023).

The prevalence of HGV co-infection is important in our area (12.8%). The HGV doesnot increase the pathogenycity of HCV and does not change the IFN response, although the HGVis more IFN sensible than HCV. The determination of HGV is not necessary in patients with HCV.

Background/Aims: Recently, GB virus C (GBV-C) has been identified as another virus potentially causing viral hepatitis. However, its hepatotropism and pattern of infection in humans is still unknown. To elucidate the presence and replication of GBV-C in the human liver, we investigated tissue samples of six explanted livers from five GBV-C mono- or GBV-C/HCV co-infected patients for GBV-C RNA plus- and minus-strand RNA.

Methods: These tissues were examined using nested RT-PCR followed by Southern blot hybridization as well as fluorescence in situ hybridization on liver cryosections. To further substantiate susceptibility of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C monoinfected serum was performed.

Results: By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 liver specimens (4/5 patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA could be detected in 4 of 6 liver specimens (4/5 patients). One liver sample was negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in situ hybridization. Virus infection appeared to be restricted to hepatocytes and detection of minus-strand RNA showed viral replication in a few highly infected liver cells. In vitro infection of HepG2 or HuH7 cells confirmed these findings by a release of virions into supernatant.

Conclusion: In conclusion, our results establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin in vivo and in vitro.

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.

Although the clinical relevance of GB virus C (GBV-C) is still elusive, this virus has been found with high prevalence in several groups of patients with liver disease. As was shown for hepatitis C virus (HCV), minus-strand RNA is supposed to function as a replicative intermediate. We have established a reliable and sensitive detection system for GBV-C minus-strand RNA based on nested RT-PCR (reverse transcription-polymerase chain reaction) with a tagged primer system. Sensitivity and specificity was extensively tested using in-vitro transcribed GBV-C sequences and genomic viral RNA. Specificity of the amplified fragments was proven by Southern blot hybridization. Using this detection system, we found the presence of GBV-C minus-strand RNA in 6/41 (14.6%) sera of GBV-C infected or GBV-C/HCV coinfected patients. No correlation with virological parameters such as amount of GBV-C plus-strand RNA, genotype or titer of HCV could be detected.