Hepatitis G infection and therapeutic response to interferon in HCV-related chronic liver disease.

Circulating HGV-RNA was determined in 117 patients with HCV-related chronic liver disease and in 200 healthy blood donors. The patients, aged 50.8+/-13.8 years, were classified as chronic hepatitis (CH; n = 82), liver cirrhosis (n = 25) and hepatocellular carcinoma (HCC; n = 10). HGV-RNA was detected in 5 (4.3%) patients, all with CH and in 10 (5%) of blood donors. The majority of all groups (52% to 70%) were infected with HCV genotype II/1b, including 4/5 patients with HGV co-infection. Of 5 patients with HGV co-infection, 4 were positive for anti-HBs and anti-HBc and none exhibited jaundice. A 24-week course of interferon treatment with 12-month follow-up was achieved in 27 patients with chronic active hepatitis, including 3 with HGV co-infection. Of these, 55.6% responded to the therapy, but only 6/27 (22.2%) patients were sustained responders. The majority of sustained responders were HCV genotype III/2a (4/6) while genotype II/1b was found in the majority of patients with relapse (7/9) and non-responders (9/12). At the 48- month follow up, 2/6 sustained responders (one with HGV co-infection) became HCV RNA positive. These results show that the prevalence of HGV infection in HCV-related chronic liver disease is low, as in the general population, and is found in younger patients with chronic hepatitis. HGV coinfection does not interfere with clinical severity, disease progression or response to interferon in patients with HCV-related chronic liver disease. The favorable factors ofinterferon treatment for HCV infection are young age, low HCV-RNA levels and HCV genotype III/2a.     

A new hepatitis C virus-like flavivirus in patients with cryptogenic liver disease associated with elevated GGT and alkaline phosphatase serum levels

Summary. The intriguing co-infection of two flaviviruses (GBV-A and GBV-B) in tamarins and the recent discovery of another flavivirus (GBV-C/HGV) in humans raises the question of the relations between hepatitis C virus (HCV) and GBV-C/HGV. To address this issue the sera of 285 patients with liver disease (102 patients with cryptogenic and 183 with known forms of chronic liver disease) and 19 patients without liver disease were tested for HGV-RNA. GBV-C/HGV-RNA was detected by RT-PCR using primers encompassing 5'NC and NS5 regions and hybridization with specific biotinilated and radiolabelled probes. GBV-C/HGV RNA was found in 11 of 20 (55%) acute hepatitis C patients, in 13 of 117 (11.1%) patients with chronic hepatitis C, in 11 of 27 patients with a liver transplant (40.7%), one of 19 (5.3%) patients with chronic HBV infection, 15 out of 102 (14.7%) patients with cryptogenic liver disease and two out of 19 patients with inflammatory bowel disease. In cryptogenic patients, elevated serum gammaglutamyl transpeptidase (GGT, higher than twice the normal values) and alkaline phosphatase (ALP, above normal values) levels were significantly associated with GBV-C/HGV-RNA infection ( P <0.001). In conclusion GBV-C/HGV appears to be transmitted in humans by blood exposure and to be associated with liver disease in HCV co-infected patients and in a minority of patients with cryptogenic disease. The virus is only occasionally pathogenic for the liver and when liver damage is present; the association with the combined elevation of GGT and APH serum levels might represent a specific feature of the liver tropism of the agent.     

Hepatitis G virus infection in patients with hepatitis C virus infection undergoing liver transplantation

BACKGROUND & AIMS: Hepatitis G virus (HGV) is transmissible by blood transfusion, but its role in chronic liver disease is unknown. The aim of this study was to determine the prevalence of HGV infection in patients infected with hepatitis C virus (HCV) undergoing transplantation and evaluate the effects of HGV coinfection on the course of posttransplantation HCV infection. METHODS: One hundred twenty-four patients infected with HCV undergoing liver transplantation were studied. Serum samples were tested for HCV and HGV RNA; HCV RNA was quantitated by branched DNA assay, and HCV genotype was determined. RESULTS: The prevalence of pretransplantation and posttransplantation HGV infection was 24% and 28%, respectively. Pre-transplantation HGV infection was positively correlated with posttransplantation HGV infection (P < 0.001). Pretransplantation clinical features were not different in patients infected with HCV with and without HGV infection. Posttransplantation HCV RNA levels were not significantly different in patients with and without HGV coinfection, but HCV genotype 1b was more frequent in patients with HGV coinfection. There were no differences in the histological severity of posttransplantation liver disease, graft, and patient survival between patients with and without HGV infection. CONCLUSIONS: Although HGV coinfection is frequent in patients with end- stage HCV disease undergoing liver transplantation, there is no association between the presence of HGV coinfection and the severity of liver disease post-transplantation, graft, or patient survival. (Gastroenterology 1996 Dec;111(6):1569-75)     

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation

Background/Aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation.Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC^TM assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection.Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p = 0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3–63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection.Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.     

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.     

Hepatitis viruses and chronic liver disease

We have investigated several groups of Thai patients diagnosed with chronic liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma, as well as cholangiocarcinoma, for the prevalence of infection with either one of the hepatitis viruses B, C, G and the novel hepatitis virus TT (TTV). The 168 patients tested comprised 120 men and 48 women with their median age ranging from 42.3 to 62.3 years. Screening for antibodies to HBV and HCV was performed by a commercially available serological test kit, for the presence of HBV and TTV DNA by PCR, and of HCV and HGV RNA by RT-PCR, respectively. There was a clear two-fold higher prevalence of HBV (49%) over HCV (27%) infection and a four-fold higher frequency compared to HGV (13%) and TTV (11%) infection, respectively, in those individuals with chronic hepatitis, cirrhosis, and hepatocellular carcinoma, whereas all but one patient with cholangiocarcinoma the etiology of which has been ascribed to parasitic infestation, were free of all viral markers. In Thailand chronic HBV, and to a lesser extent, chronic HCV infection represent the two most common causes of hepatitis potentially proceeding to chronic liver disease, whereas the clinical significance pertinent to HGV and TTV remains to be elucidated.     

慢性肝病患者肝组织中HGV抗原的表达及意义

目的探讨慢性肝病患者组织中庚型肝炎病毒（ＨＧＶ）表达与意义。方法应用免疫组织化学方法以鼠抗ＨＧＶＮＳ５甲克隆抗体检测１４２例慢性肝病患者肝组织中ＨＧＶ抗原，部分患者采用ＲＴ－ＰＣＲ方法检测其血清中ＨＣＶＲＮＡ。结果１４２例肝病患者中，２９例（２０．４％）组织中检出ＨＧＶ抗原，肝硬化组（４２．９％，１２／２８）较慢性肝炎（１５．９％８／１１）和肝癌（１４．３％，９／６３）组检出率高。阳性信号位于胞浆中，阳性细胞可成散在、簇状或弥漫性分布。阳性细胞周围可有炎性坏死；肝癌患者抗原阳性细胞主要位于癌旁肝组织，癌巢中仅偶见少数散在分布的阳必细胞；绝大多数组织抗原阳性者其血清ＨＧＶＲＮＡ为阳性。有４例患者组织中ＨＧＶ抗原阳性但其血清ＨＧＶＲＮＡ阴性。结论ＨＧＶ可在慢性肝病包括肝细胞肝癌患者肝组织中表达，ＨＧＶ感染在慢性肝炎病期进展及肝癌发生中具有一定意义。     

GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.     

Prevalence of hepatitis G virus in liver disease.

The prevalence of hepatitis G virus (HGV) in liver disease of non-A, -B, -C viral hepatitis, hepatitis B and hepatitis C was determined. Two of 44 patients (4.5%) with liver injury without any hepatitis A, B or C marker were positive for HGV. One of five cases of hepatocellular carcinoma was positive for HGV. One of three cases with fulminant hepatitis was positive for HGV. This case was negative at the onset of fulminant hepatitis and became positive after plasmapheresis. No patient with acute (n=8) or chronic (n=5) hepatitis or liver cirrhosis (n=8) was positive for HGV in non-A, -B, -C liver disease. One of 30 patients with various HBV-positive liver diseases and nine (17.3) of 52 patients with type C liver disease were positive for HGV. In patients with hepatitis C, four (28.6%) of 14 HGV-co-infected patients were complicated with diabetes mellitus compared with four (10.5%) of 38 single hepatitis C virus (HCV)-infected patients (not significant). In 12 HGV-positive patients, eight of 10 (80%) had a history of blood transfusion. In HCV-positive patients, co-infection with HGV was not a risk factor in patients with diabetes mellitus as a complication. HGV appeared to cause non-A, -B, -C hepatitis rarely, and its main route of infection was blood transfusion.