Correlation of interferon treatment response with GBV-C/HGV genomic RNA and anti-envelope 2 protein antibody

The clinical significance of GB virus C/hepatitis G virus (GBV-C/HGV) co-infection was studied retrospectively in 100 consecutive patients with hepatitis C virus (HCV) infection. All 100 patients had been treated with interferon-alpha (IFN-alpha). Co-infection with GBV-C/HGV and HCV was detected in 10 of the 100 patients (10%) and anti-envelope 2 region (anti-E2) antibody was detected in 25 patients. None of the patients with GBV-C/HGV RNA had anti-E2 antibody. Co-infected patients were younger (P < .005) and their serum transaminase levels were lower than HCV-only infected patients (P< .01). In 7 of the 10 co-infected patients, HCV RNA was eradicated from serum after IFN-alpha treatment and normal alanine transaminase (ALT) levels continued in 6 of these 7 patients. In one patient who was negative for HCV RNA but positive for GBV-C/HGV RNA, the ALT level relapsed transiently. The rate of clearance of HCV and normalization of the ALT level was significantly higher in co-infected patients than in HCV-only infected patients (P < .05). GBV-C/HGV RNA disappeared from 6 of the 10 co-infected patients (60%) upon cessation of IFN-alpha treatment. However, continuous clearance of GBV-C/HGV was observed in only two patients and anti-E2 antibody could not be detected in the serum of these patients. These results indicate that co-infected patients tend to be younger and more sensitive to IFN-alpha treatment. However, long-term clearance of GBV-C/HGV after IFN-alpha treatment may be difficult. Moreover, anti-E2 antibody may act to neutralize GBV-C/ HGV.     

Multicenter trial on mother-to-infant transmission of GBV-C virus

Evidence indicates that the GBV-C or hepatitis G virus can cause persistent infection in humans, but little is known on the importance of vertical transmission. To assess the risk of mother-to-infant transmission and the clinical outcome of infected babies, we investigated 175 anti-HCV positive mothers and followed-up their children for 3–33 months. GBV-C RNA was detected by RT-PCR and anti-E2 antibody was assayed by EIA. Thirty-four (19.4%) women were GBV-C RNA positive and transmission occurred to 21 (61.8%) babies; 20 (95.2%) acquired GBV-C alone, and one (4.8%) GBV-C and HCV. Maternal factors such as intravenous drug use, HIV coinfection, HCV-RNA positivity, and type of feeding were not correlated with GBV-C transmission. GBV-C RNA remained persistently positive in all infected babies but one baby who seroconverted to anti-E2. Seven (35%) babies with GBV-C alone developed marginally elevated ALT; the baby with HCV and GBV-C co-infection had the highest ALT peak value (664 IU/l). Seven of the 141 (5%) babies born to the GBV-C RNA negative mothers acquired HCV and six (85.7%) had abnormal ALT. The mean ALT peak value was significantly higher (P < 0.05) for babies with HCV than for those with GBV- C. None of the children with GBV-C or with HCV became icteric. GBV-C is frequently present in anti-HCV positive women. The infection is transmitted efficiently from mother to baby and rate of transmission is much higher than that for HCV. GBV-C can cause persistent infection in babies but usually without clear evidence of liver disease. J. Med. Virol. 54: 107–112, 1998. © 1998 Wiley-Liss,Inc.     

Profiles of GBV-C/hepatitis G virus markers in patients coinfected with hepatitis C virus.

GBV-C/Hepatitis G virus (GBV-C/HGV) is a newly discovered viral agent, found widely among healthy blood donors and among individuals at risk of parenterally transmitted infections. GBV-C/HGV is found frequently in coinfection with HCV. A population of 109 HCV positive patients was examined for the presence of GBV-C/HGV RNA and antibodies to E2. Of the 109 patients, 23 (21%) had serum GBV-C/HGV RNA in serum, 39 (36%) had only antibodies to E2 and 8 (7%) were positive for both markers, with an overall prevalence of 64%. Different serologic and virological patterns were observed in GBV-C/HGV exposed patients according to their infection status. Active infection was characterized by positive RT/PCR signal with primers for both the 5'UTR and NS5 genomic regions, viremia levels above 10(4) copies/mL by real time quantitative RT/PCR and absence of detectable anti-E2. In the transition phase between active infection and recovery, GBV-C/HGV RNA was only detectable by RT/PCR using primers from the 5' untranslated region and viremia levels were below 10(4) copies/ml by quantitative PCR, with or without simultaneous presence of anti-E2 antibodies. Resolved infection was characterized by absence of detectable viremia and, in most patients, by the presence of anti-E2.     

Elevata prevalenza ma bassa incidenza della infezione da HGV in pazienti con epatite cronica C

Objectives To determine 1. The prevalence and incidence of HGV infection in patients with chronic hepatitis C and 2. Its influence on the clinical outcome of chronic hepatitis C. Patients and methods Sixty-five patients with non-parenteral chronic hepatitis C virus infection were investigated for HGV infection using the polymerase chain reaction for HGV-RNA and by detecting serum antibodies against the E2 protein of HGV (anti-E2 antibodies). Results HGV-RNA in serum was found in 12 patients (18.4%) and anti-E2 antibodies in 4 (6.1%). No difference in age, sex, liver histology, basal ALT or ?GT was found between HGV positive and negative cases. Thirty-four patients (6 with HGV-RNA) were followed-up for 4 years; 4 of the 6 lost HGV-RNA, one of whom seroconverted to anti-E2. None of the 28 HGV-RNA negative cases presented HGV infection during the follow-up period. The presence of HGV infection did not influence either basal HCV viremia or the response of HCV to IFN therapy. Conclusions The study demonstrated that HGV had an intense circulation through non-classic parenteral routes, but its impact on HCV replication and liver disease is negligible.     

GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5′-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive. J. Med. Virol. 54:75–79, 1998. © 1998 Wiley-Liss, Inc.     

Evolution of hepatitis C virus (HCV) infection acquired at birth

Objectives Our aim was to analyze the evolution of HCV infection in children infected at birth. Methods Between September 1994 and December 1998 we analyzed in a prospective study 8 children born of anti-HCV and HCV RNA positive women. Each baby was controlled at birth, every 3 months during the first year of life, and then every 6 months searching for anti-HCV antibodies (ELISA 3, RIBA 2-3), HCV RNA (RT PCR), ALT and viral genotype. Results Viral RNA was detectable in the first 3 months of life in all babies (100%) and remained positive during the follow-up. Viral genotypes were the same for mothers and their children. In 6 babies (75%) ALT remained pathologic during follow-up. Conclusions HCV infection in children usually has an asymptomatic outcome; the infection has chronic features in the majority of cases.     

Prevalence of hepatitis G virus in Pakistani children with transfusion dependent beta- thalassemia major

We ought to obtain data on the prevalence of the newly discovered tranfusion transmittable hepatitis G virus in polytransfused b- thalassemia major children. Each individual had received multiple blood transfusions, from 12 to 36 per year. No documentation of prior hepatic infection was available. Serum samples were collected prospectively from the randomly selected subjects and were analyzed for HGV RNA by polymerase chain reaction using primer specific for two different regions of the HGV genome. Among the 100 individuals examined 21 were positive for HGV RNA. Four patients had evidence of dual infection, both HGV RNA and HCV RNA were isolated from their sera. While in one sample presence of both HGV RNA and HBV DNA was established. Only one child was positive for hepatitis E antibodies. The sera of 10 children were reactive for hepatitis B surface antigen whereas 35 individuals were positive for hepatitis C virus antibody. The ALT levels were variable in HGV infected children. Four out of 16 (25%) showed peak ALT levels of 218 IU/I, 8/16 (50%) children demonstrated slightly elevated ALT levels whereas 25% individuals showed normal ALT levels. Alkaline Phosphatase levels were elevated in 90% of the children and 20% patients of this series also had higher GGT levels. The observed AP levels were not statistically different among HGV, HGV/HCV or HGV/HBV groups. Even though the ALT levels were deranged in the children with HGV alone but none of the children had demonstrated symptoms of liver disease, their direct and total bilirubin levels were normal and no complain of jaundice was recorded. In conclusion, our findings suggested that like other blood borne hepatic viruses, HGV is also prevalent in the high risk group of multiple transfused patients in Pakistan but our results support the absence of any causal relationship between HGV and hepatitis.     

35型庚型肝炎临床及酶学变化观察

For the purpose of making sure the clinical significance of hepatitis G virus, RT-nested PCR was applied to detect HGV RNA in 165 hepatitis patients, which included 24 acute hepatitis, 78 chronic hepatitis, 18 hepatitic cirrhosis, 4 hepatocellularcarcinom and 41 HBV and HCV carriers. The results showed that the infection of HGV existed in all kinds of hepatitis patients. Among the acute hepatitis 12.5% (3/24) was HGV RNA positive. 19 (24.4%) cases were HGV RNA positive in chronic hepatitis, among which 4 cases were simply HGV RNA positive (5.13%). The serum ALT level in 3 cases of simple acute HGV patients was between 488 +/- 65 U/L, the value of AST between 452 +/- 71 U/L, the TBiL at about 77.1 +/- 14.3 mumol/L. All these showed that only HGV infection could lead to acute hepatitis. The rising enzyme dropped to normal about a month later in acute hepatitis while HGV RNA would remain. The problem whether HGV infection is caused by simple acute and chronic hepatitis infection is under investigation.     

Hepatitis G virus co-infection may affect the elimination of hepatitis C virus RNA from the peripheral blood of hemodialysis patients

Hemodialysis patients are at risk for hepatitis C virus (HCV) and hepatitis G virus (HGV) infection. The aim of this study was to investigate the possible influence of HGV co-infection on HCV RNA elimination from the peripheral blood of hemodialysis patients. The study involved 144 persons, all with HCV antibodies and HCV RNA. Among 144 patients 24 (16.7%) were positive for HGV RNA. After 2.5 years of observation 80 patients (55.6%) were still HCV RNA-positive. In the latter group 18 patients were co-infected with HGV and 62 were HGV RNA-negative. During 2.5 years of the follow-up study 64 patients eliminated HCV RNA from the serum. In this group only 6 patients were HGV co-infected. None of the HGV-positive patients eliminated HGV RNA from the serum. The higher incidence of HGV co-infection in the group of patients who remained HCV RNA-positive (18/80, 22.5%), in comparison to the group of HCV antibodies-positive patients who lost HCV in the blood (6/64, 9.4%, P < 0.0001) suggests, that the co-infection with HGV may delay the spontaneous elimination of HCV RNA from the blood.     

GBV-C/hepatitis G virus in acute nonA-E hepatitis and in acute hepatitis of defined aetiology in Italy

The role of GBV-C/HGV in the aetiology of acute non A-E hepatitis and its impact on the course of acute hepatitis of defined aetiology were investigated by detecting viral RNA by RT-PCR and antibody to the E2 protein of GB virus C (anti-E2) by EIA. Ninety-eight patients with acute nonA-E hepatitis, 35 patients with acute hepatitis A, 63 with acute hepatitis B, 29 with acute hepatitis C and 270 controls were enrolled in this study. The prevalence of GBV-C/HGV RNA was similar among patients with acute nonA-E hepatitis (3.1%), with acute hepatitis A (2.9%), and controls (3.7%), but significantly higher (P < 0.05) among those with hepatitis B or C (19.0% and 48.3%, respectively). Similar figures were obtained considering the total rate of GBV-C/HGV exposure (viral RNA or anti-E2 positivity). The majority (24/30 or 80%) of GBV-C/HGV RNA positive patients reported a parenteral source of exposure whereas the remaining 20% denied having known risk factors. The liver function test values and the rate of chronic hepatitis B and C were similar in patients co-infected and in those not co-infected with GBV-C/HGV. This study excludes a significant role of GBV-C/HGV infection in the aetiology of acute nonA-E hepatitis in Italy. Concomitant GBV-C/HGV and HBV or HCV infection does not worsen the clinical course of illness among patients with acute hepatitis.     

单纯GBV-C/HGV感染人体血清学和病理学追踪研究

目的 从临床和病理学方面探讨庚型肝炎病毒（GBV－C／HGV）的致病性。方法 收集24例单纯血清GBV－C／HGV RNA阳性人体的穿刺活检肝组织及血清标本,其中8例作间隔2年以上的二次肝穿,进行血清和肝组织GBV－C／HGV RNA、血清抗E2抗体及ALT水平、肝组织NS3和NS5抗原检测,并作肝组织光、电镜观察。结果 24例血清GBV－C／HGV RNA阳性者首次肝穿前3d内平均ALT水平为60．17IU／ml(42-87IU/ml),抗E2抗体阳性率4．17％,首次肝组织GBV－C／HGV RNA阳性率为75．00％,NS3和（或SN5抗原阳性率为54．17％。GBV－C／HGV RNA及NS3和NS5抗原主要于肝细胞质内检出,阳性细胞呈散在分布,少数浸润的单个核细胞内有病毒RNA检出。肝细胞呈极轻度急、慢性炎症病变者占79．17％。与2年前比较,2年后24例观测对象血清GBV－C／HGV RNA自然转阴率66．67％（P＜0．001）,血清ALT复常率75．00％（P＜0．001）,E2抗体阳性率为41．67％（P＜0．001）,8例二次穿刺肝组织除2例有灶状肝细胞水样变性外,余均复常。结论 庚型肝炎病毒可引起极轻度自限性肝炎,提示其致肝损伤作用微弱且具有自限性;血清E2抗体是GBV－C／HGV感染恢复性标志,是否存在其他恢复性血清标志物尚待研究。     

Immunoreactivity to putative B-cell epitopes of hepatitis G virus polyprotein in viremic and nonviremic subjects.

The hepatitis G virus (HGV) polyprotein was scanned by computer-aided prediction of antigenicity to search for B-cell epitopes. Four polypeptide sequences, V37D (amino acids [aa] 1685 to 1721), V36S (aa 2102 to 2137), P37R (aa 2156 to 2192), and C40P (aa 2280 to 2319), were identified and synthesized for use in immunoassays. Antibodies to these peptides were searched for in a panel of 239 serum samples, which were also tested for anti-E2 antibodies and HGV RNA. Furthermore, the course of HGV markers was studied prospectively in four patients who had been transfused with HGV RNA-positive blood. There was a negative association between immunoreactivity to V37D and P37R and presence of HGV RNA (2 of 53 and 1 of 53, respectively; P < 0.05); none of the subjects with dual antibody positivity was HGV RNA positive. Anti-V37D and anti-P37R antibodies compared favorably with anti-E2 antibodies as markers of recovery from HGV infection. These results might be useful for the development of new, more sensitive diagnostic assays.     

Prospective follow-up of patients with GBV-C/HGV infection: specific mutational patterns, clinical outcome, and genetic diversity

An association between a specific mutational pattern within the nonstructural (NS)3 region of GB virus-C/hepatitis G virus (GBV-C/HGV) genome and fulminant hepatic failure has been suggested recently. The mutational pattern consists of 3-6 nucleotide mutations of which one is leading to an amino acid exchange. In the present study, patients with GBV-C/HGV mono-infection (n = 24) or GBV-C/HGV and HCV co-infection (n = 20) were investigated prospectively. In 6/44 patients (14%) the mutational pattern within GBV-C/HGV NS3 previously associated with fulminant hepatic failure was identified by direct sequence analysis of the NS3 region. All 44 patients were asymptomatic clinically and had normal liver functions at initial presentation and after a median follow-up of 2.2 years. In 22/24 patients with GBV-C/HGV mono-infection and all patients with GBV-C/HGV and HCV co-infection GBV-C/HGV RNA remained detectable at the end of the study period, whereas two patients infected with GBV-C/HGV alone became negative for GBV-C/HGV RNA and developed GBV-C/HGV anti-E2 antibodies indicating recovery from GBV-C/HGV infection. Aminotransferase levels remained elevated or became normal independent of the persistence of serum GBV-C/HGV RNA. The median rate of nucleotide substitutions in GBV-C/HGV mono-infected and HCV co-infected patients was 3.4 x 10(-3) and 3.2 x 10(-3) per site per year, respectively. In conclusion, the prevalence of the mutational pattern within NS3 region of GBV-C/HGV associated previously with fulminant hepatic failure is about 14% and not associated specifically with severe liver disease. Over a median follow-up of 2.2 years less than 5% of patients cleared spontaneously GBV-C/HGV and no correlation between viraemia and elevated liver enzymes was observed.     

Serum level of soluble forms of membranous antigens of immune system cells in carriers of virus hepatitis G markers

The levels of soluble CD38 (sCD38), CD50 (sCD50), and CD95 (sCD95) antigens and HLA class I (sHLA-I) were determined in the serum samples from persons infected with hepatitis G virus (HGV). HGV monoinfection was accompanied by a rise in the serum content of sCD38, sCD50, and sCD95 antigens. The serum presence of HGV RNA and anti-E2 HGV antibodies was characterized by the normal content of sCD38 and sCD95 while the level of sCD50 was elevated and the serum content of sHLA-I was decreased. If the serum contained only anti-E2 HGV antibodies, the level of sCD50 remained increased 4-fold. It is suggested that the higher adhesion-inhibiting level of sCD50 is a reason of a weak immune response to HGV and hence of a long HGV persistence in the body.     

Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors

One hundred twenty-six mother-infant couples were studied and 105 exposed babies were monitored for at least 12 months to define the risk of mother-to-infant HCV transmission. Infection occurred in 5 out of 76 infants (6.6%) born to 69 viraemic mothers and in none of 29 born to 26 non-viraemic mothers. Only one child was HCV RNA positive one month after birth, while the remaining children became positive at the 3rd to 4th month. HCV genotypes of the babies matched those of their mothers. No difference was found between women who transmitted the virus and those who did not with regard to age, history of drug abuse, HIV infection, ALT abnormal values, HCV genotype, type of delivery, and breast-feeding. Four out of 5 infected infants were born to mothers with IgM anti-HCV (P = 0.04). The mean viral titre in transmitting women (10(7.2)) was higher than in non-transmitting (10(6.5)), and the proportion of mothers with viral load > or = 10(7) was statistically higher in transmitting than non-transmitting women (P = 0.03). These data show that HCV perinatal infection is a rare event and suggest that IgM positivity and high viral load (> or = 10(7)) in the mother are independent variables correlated with HCV transmission (O.R. = 14.5; 95% CI: 1.3-160.7 and O.R. = 16.3; 95% CI: 1.5-179.9, respectively).     

酶联免疫吸附法检测庚型肝炎病毒抗体

目的 探讨抗庚型肝炎病毒（ＨＧＶ）ＩｇＧ与各种病毒感染,丙氨到转氨酶（ＡＬＴ）及ＨＧＶ ＲＮＡ的相关性。方法 用酶联免疫吸附试验（ＥＬＩＳＡ）法检测了３１５例各种肝炎病毒（Ａ￣Ｅ）感染乾和１１７例健康献血员血清的抗－ＨＧＶ ＩｇＧ,并测定其ＡＬＴ,对抗－ＨＧＶ ＩｇＧ阳性的标本用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）法检测ＨＧＶ ＲＮＡ。结果 献血员抗－ＨＧＶ ＩｇＧ的阳性率为３．４２％（４／１１７     

Immunoreactivity to Putative B-Cell Epitopes of Hepatitis G Virus Polyprotein in Viremic and Nonviremic Subjects

The hepatitis G virus (HGV) polyprotein was scanned by computer-aided prediction of antigenicity to search for B-cell epitopes. Four polypeptide sequences, V37D (amino acids [aa] 1685 to 1721), V36S (aa 2102 to 2137), P37R (aa 2156 to 2192), and C40P (aa 2280 to 2319), were identified and synthesized for use in immunoassays. Antibodies to these peptides were searched for in a panel of 239 serum samples, which were also tested for anti-E2 antibodies and HGV RNA. Furthermore, the course of HGV markers was studied prospectively in four patients who had been transfused with HGV RNA-positive blood. There was a negative association between immunoreactivity to V37D and P37R and presence of HGV RNA (2 of 53 and 1 of 53, respectively; P < 0.05); none of the subjects with dual antibody positivity was HGV RNA positive. Anti-V37D and anti-P37R antibodies compared favorably with anti-E2 antibodies as markers of recovery from HGV infection. These results might be useful for the development of new, more sensitive diagnostic assays.