GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India.

BACKGROUND: GB virus C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) have been widely reported in patients with high parenteral risk such as haemodialysis and renal transplant recipients. The occurrence of these agents in association with hepatitis B virus (HBV) and hepatitis C virus (HCV), in Indian renal transplant recipients, is yet unreported. STUDY DESIGN: Molecular and serological markers of GBV-C/HGV and TTV were examined in addition to those for HBV, HCV and hepatitis D virus (HDV) in a selected group of seventy renal transplant recipients. HGV RNA detection was achieved using primers specific for the 5'NCR and NS5a regions of the genome. Anti-GBV-C/HGV antibody was detected using the mu plate anti-HG env kit (Roche, Germany). TTV DNA PCR was performed using primers specific for the coding region (method A) of the genome. In 50% of patients, TTV DNA was also tested for using primers specific for the non-coding region (method B). Host related factors such as age, alanine aminotransferase (ALT) levels, number of transfusions, haemodialysis sessions, and months following transplantation were also studied. RESULTS: Exposure rates to GBV-C/HGV, TTV (method A), HBV, HCV and HDV were 58.6, 32.9, 52.9, 54.3 and 2.9%, respectively. 'Active' infection as measured by viraemia and/or virus-specific antigenaemia for GBV-C/HGV, TTV, HBV and HCV was 52.9, 32.9, 15.7 and 52.9%, respectively. The majority of GBV-C/HGV and TTV infections were seen as co-infections with other hepatitis viruses. Single infection with GBV-C/HGV and TTV was seen in ten (14.2%) and eight (11.4%) patients, and was not associated with ALT elevation when compared to uninfected blood donors. Using univariate analysis, GBV-C/HGV RNA was significantly associated with > or =20 haemodialysis sessions. TTV DNA occurrence was not associated with any risk factors. CONCLUSIONS: There is a high occurrence of GBV-C/HGV and TTV in this select group of renal transplant recipients in India. These viruses mostly occurred in the context of co-infections with other hepatitis viruses. Long term effects of multiple hepatotropic viral infections need to be carefully documented in such transplant populations.     

Prevalence of hepatitis B, hepatitis C, GB virus C/hepatitis G and TT viruses in predialysis and hemodialysis patients

Patients with chronic renal failure on hemodialysis have a high risk of infections with viruses such as hepatitis B (HBV), hepatitis C (HCV), GB virus C/hepatitis G (GBV-C/HGV) and TT (TTV) viruses. The prevalence of HBV, HCV, GBV-C/HGV and TTV in patients with chronic renal failure who are on conservative management before entering into a hemodialysis program (predialysis) in comparison with hemodialyzed patients was studied to elucidate whether the high prevalence of these viruses is influenced by that observed in the predialysis stage. The presence of hepatitis B virus surface antigen (HBsAg), HCV RNA, GBV-C/HGV RNA and TTV DNA was analyzed in sera from 80 patients with chronic renal failure (35 on predialysis and 45 on hemodialysis). HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.8%), six (17.1%), eight (22.5%) and 16 (45.7%) of the 35 patients on predialysis. Two (5.7%) of these patients were coinfected with HCV and GBV-C/HGV, whereas six (17.1%) had GBV-C/HGV and TTV coinfection. In the 45 hemodialyzed patients, HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.2%), two (4.4%), seven (15.5%) and 26 (57.7%). One (2.2%) patient had HBV and TTV coinfection, two (4.4%) HCV and TTV coinfection whereas four (8.8%) were coinfected with GBV-C/HGV and TTV. No differences regarding age, gender, previous surgery and number of transfusions were found between infected and uninfected patients within and between both groups. In conclusion, the prevalence of the viruses studied in predialysis may influence their prevalence in dialysis units.     

Infection with an unenveloped DNA Virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand

An unenveloped single-stranded DNA virus (TTV) has been reported in association with posttransfusion and acute and chronic hepatitis of unknown etiology. DNA of TTV was tested for by polymerase chain reaction with heminested primers in 127 patients with chronic liver disease and 105 healthy blood donors in Thailand. TTV DNA was detected in 23 (59%) of the 39 patients without hepatitis B surface antigen or RNA of hepatitis C virus, at a frequency significantly higher than the detection in 21 (36%) of the 59 patients with HBsAg (P < 0.05) or in 38 (36%) of the 105 blood donors (P < 0.05). Among patients with chronic liver disease, TTV DNA occurred in those with liver cirrhosis and hepatocellular carcinoma more frequently than in those with chronic hepatitis (35 of 65 or 54% vs. 20 of 62 or 32%, P < 0.05). There were no differences in age, sex, or markers of infection with hepatitis B, C and GBV-C/HGV viruses, indicating a mode of transmission of TTV different from those of the other hepatitis viruses. Phylogenetic analysis indicated three different genotypes of TTV with six distinct subtypes in Thailand. Based on these results, TTV would have a role in the development of chronic liver disease of unknown etiology in Thailand. J. Med. Virol. 56:234–238, 1998. © 1998 Wiley-Liss, Inc.     

Detection of TT virus sequences in children with liver disease of unknown etiology

DNA sequences of TT virus (TTV) in 55 serum samples taken from 20 children with liver disease of unknown etiology (16 with acute liver disease, 2 with fulminant hepatitis, and 2 with chronic liver disease) and from 35 healthy children as controls were examined by using the hemi-nested polymerase chain reaction (PCR). The PCR was carried out using the established primers (NG059, NG061, NG063) to amplify TTV DNA sequences. The sequences were detected in 6 of the 20 patients (30.0%) with liver disease and in 5 of the 35 healthy children (14.2%) by direct gel analysis. There was no significant difference between the prevalence of liver disease patients and controls. However, both patients with fulminant hepatitis and both patients with chronic hepatitis had TTV DNA sequences. Four of the six TTV isolates from liver disease patients were genotype 1a, whereas only one of the five TTV isolates from controls was genotype 1a. Although the study population was small, it is possible that genotype 1a of TTV might be more pathogenic than other genotypes in children.     

Prevalence of TT Virus and GBV-C Infections among Patients with Liver Diseases and the General Population in Shanghai,China

To determine the prevalence of TT virus (TTV) and GB virus C/hepatitis G virus (GBV-C) infections among patients with liver disease and the general population in Shanghai, China, we studied 90 patients with liver diseases (acute hepatitis, 28; chronic hepatitis, 27; liver cirrhosis, 20; hepatocellular carcinoma, 15) and 90 age, sex matched healthy blood donors as controls. There were no significant differences in the clinical and demographic characteristics between the two groups, except for liver function test values. There was a statistical difference between the patient group and the control group with regard to the prevalence of TTV DNA (23.5% in patient group, 11.1% in control group, P<0.05), although no differences in clinical features could be found between TTV DNA-positive and negative subjects. Also, no differences in TTV DNA prevalence among various categories of liver diseases were noted (P = NS). The prevalence of HBsAg was significantly different between the patient group (36.7%) and the control group (3.3%) (P<0.01), whereas the prevalence of anti-HCV and GBV-C RNA were not significantly different between the two groups. The nucleotide sequences were determined in the TTV DNA-positive samples and evaluated using phylogenetic analysis which suggested that they could be divided into two main genotypes designated as genotype 1 and 2. There were five samples clustered into 3 hitherto unknown subtypes of genotype 2. We concluded that (1) although TTV infection is widespread among both groups and there is a statistical difference of TTV infection between them, no hepatic damaging evidence and correlation with certain liver disease could be found in this study, suggest that TTV may not be major cause of liver disease, (2) GBV-C infection is frequent, but the virus is not the cause of liver diseases, and (3) new subtypes of TTV may exist in Shanghai, China.     

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.     

Infection with GB virus C in leprous patients in Japan

The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV-C) was determined by the polymerase chain reaction with primers deduced from a helicase-like region in 229 leprous patients in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV-C and HCV. The nine patients infected with GBV-C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase-like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV-C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV-C, and that the infection with GBV-C alone would not induce hepatic injuries as severe as HCV infection. © 1996 Wiley-Liss, Inc.     

Seroepidemiology of TT virus, GBC-C/HGV, and hepatitis viruses B, C, and E among women in a rural area of Tanzania

The seroprevalence and determinants of hepatitis B, C, and E virus infection, and of GBV-C/hepatitis G virus and TT virus infection were investigated among women from a rural area of northeastern Tanzania. High seroprevalence rates were found for TTV (74%), HBV (74%), and GBV-C/HGV (35%), whereas 7% of the women had evidence of HCV and HEV infection. The majority of TTV DNA sequences in the study population belonged to the genotypes 1 or 2. One sequence seems to represent a new subtype of genotype 4. The GBV-C/HGV sequences either belonged to the genomic Group 1b or to the recently described Group 4. In multivariate analysis, the detection of TTV DNA was associated significantly with a larger number of children in the household and with older age. A history of injections of contraceptive hormones was an independent risk factor for HCV infection. The findings on TTV are consistent with fecal-oral transmission, and recurrent infections may occur in adults.     

GBV-C/HGV infection in chronic hepatitis C patients: Its effect on clinical features and interferon therapy

A novel virus (GBV-C/HGV) may be associated with some liver diseases including fulminant hepatitis and acute and chronic hepatitis. On the other hand, many investigations showed that this infection does not contribute to liver disease. GBV-C/HGV has been found to occur in association with infection with other hepatitis viruses. We investigated the effect of GBV-C/HGV infection on the clinical features and interferon treatment in patients with chronic hepatitis C. A total of 262 hepatitis C virus (HCV) RNA positive patients with chronic hepatitis were examined in this study. The detection of serum GBV-C/HGV RNA was done by RT-PCR using specific primers from the NS5 regions. Interferon-alpha was given at a dose of 6 MU/day for 16 or 24 weeks. A responder was defined as a patient with ALT normalization and HCV RNA disappearance after treatment. GBV-C/HGV RNA was detected in 28 (11%) patients. No significant difference was detected in clinical features (age, sex, liver-related biochemical tests, and histological examination) between the 28 GBV-C/HGV-positive patients and the GBV-C/HGV-negative patients. Using interferon therapy for hepatitis C, the responder rates of GBV-C/HGV-positive and -negative patients were 14% and 20%, respectively. Of the 28 patients with GBV-C/HGV RNA, GBV-C/HGV RNA was tested after interferon therapy in 16 and of these GBV-C/HGV RNA was not detected in nine patients after therapy. These findings suggest that GBV-C/HGV infection dose not affect the clinical features in patients with HCV and the efficacy of interferon therapy for chronic hepatitis C. J. Med. Virol. 55:98–102, 1998. © 1998 Wiley-Liss, Inc.     

Amplification of GB virus-C/hepatitis G virus RNA with primers from different regions of the viral genome

GB virus-C/hepatitis G virus (GBV-C/HGV) is a newly identified RNA virus. The aim of the study was to compare three primer pairs from the 5′ untranslated region (5′UTR), envelope region 2 (E 2) and nonstructural region 3 (NS 3) of GBV-C/HGV genome for their ability to detect GBV-C/HGV RNA by polymerase chain reaction (PCR) assays. By using PCR with primers from different regions of the viral genome, serum GBV-C/HGV RNA was assayed in 200 at-risk individuals. The sensitivity of this assay was assessed by a titration experiment, and nucleotide sequences of the amplified products were determined directly. Of 200 serum samples, 43 (21.5%) were positive for GBV-C/HGV RNA with at least one of the primer pairs. The positive rates by 5′UTR, NS 3, and E 2 primers were 100%, 98%, and 84%, respectively, and the sensitivity of PCR assays using 5′UTR primers was 10 to 100 times more likely to detect GBV-C/HGV RNA than that of NS 3 and E 2 primers. The average homology of amplified targets to the prototype HGV genome was 89%, 80%, and 85% and the similarity between each amplified target was up to 100%, 90%, and 92% in the 5′UTR, E 2, and NS 3 regions, respectively. Therefore, the 5′UTR of GBV-C/HGV genome is highly conserved and primers deduced from this region can provide a sensitive and specific PCR assay for GBV-C/HGV RNA. J. Med. Virol. 51:284–289, 1997. © 1997 Wiley-Liss, Inc.     

TT virus infection in patients with chronic liver disease of unknown etiology

The role of a novel virus, designated as TT virus (TTV), as a cause of chronic liver disease has not been well defined. We investigated the prevalence of TTV among 69 patients with chronic liver disease of unknown etiology and 50 volunteer blood donors with normal transaminase levels. TTV DNA was amplified by polymerase chain reaction (PCR) by using two different sets of primers: one based on the sequence of the original N22 clone within the open reading frame 1 (set A) and the other derived from the untranslated region (set B). The prevalence of TTV detected by PCR primers set A only, set B only, and in total (by either set A or B) was 11 (31%), 31 (86%), and 31 (86%) of 36 patients with chronic hepatitis; 2 (40%), 4 (80%), and 4 (80%) of 5 with cirrhosis; 11 (39%), 17 (61%), and 22 (79%) of 28 with hepatocellular carcinoma; and 9 (18%), 39 (78%), and 40 (80%) of 50 volunteer blood donors, respectively. Of the interpretable 25 PCR products amplified with primers set A, 9 were classified as genotype 1a, 10 as genotype 1b, 4 as genotype 2, 1 as genotype 3, and 1 as genotype 4. Molecular evolutionary analysis did not suggest any particular strains of TTV that might be associated with chronic liver disease. The nucleotide sequences of the untranslated region on which PCR primers set B were designed were highly conserved, and the interpretable 22 PCR products amplified with primers set B were not clearly divisible into distinct genotypes. Our findings provided no evidence that TTV is a causative agent of chronic liver disease.     

Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients with the co-infection

Of 74 patients who were infected with hepatitis C virus (HCV) and received interferon, 12 (16%) were positive for RNA of GB virus C (GBV-C). RNA of GBV-C was determined in sera from the co-infected patients retrospectively, and the effect of interferon on GBV-C was compared with that on HCV in them. Titers of both GBV-C and HCV RNAs decreased during interferon in all of them. Two patients lost both GBV-C and HCV RNAs and remained clear until 6 months after treatment with interferon, while 2 lost RNA for GBV-C only and 2 for HCV RNA alone. Low pre-treatment RNA titers of GBV-C and HCV correlated with the efficacy of interferon in clearing. Alanine aminotransferase returned to normal only in the patients who lost HCV RNA, regardless of the persistence or loss GBV-C RNA. These results indicate that the response to interferon of GBV-C is comparable to but independent of that of HCV and that the persistence of GBV-C would not prevent the normalization of aminotransferases in response to interferon in patients with chronic hepatitis C. J. Med. Virol. 52:156–160, 1997. © 1997 Wiley-Liss, Inc.     

利多组套式引物的测庚型肝炎病毒RNA

利用庚型肝炎病毒ＮＳ３－５区序列合成了四组套式引物，建立了灵敏，特异的 型肝炎病毒ＲＮＡ双扩增聚合酶链反应检测方法，用此方法检测了１０份庚型肝炎病毒抗体阳性患者血清及１０份阴性的健康人血清。前者不同组引物的检出率为ＮＳ３（１）引物９份了是性，ＮＳ３（２）引物８份阳性，ＮＳ４引物４份阳性，ＮＳ５（１）引物５份阳性，ＮＳ５（２）引物９份阳性；后者各组引物匀为阴性。结果表明，庚型肝炎病毒不同区域引物用于     

利用多组套式引物检测庚型肝炎病毒RNA

利用庚型肝炎病毒（ＧＢＶ－Ｃ／ＨＧＶ）ＮＳ３～５区序列合成了四组套式引物，建立了灵敏、特异的庚型肝炎病毒ＲＮＡ双扩增聚合酶链反应（ＰＣＲ）检测方法。用此方法检测了１０份庚型肝炎病毒抗体阳性患者血清及１０份阴性的健康人血清。前者不同组引物的检出率为ＮＳ３（１）引物９份阳性，ＮＳ３（２）引物８份阳性，ＮＳ４引物４份阳性，ＮＳ５（１）引物５份阳性，ＮＳ５（２）引物９份阳性；后者各组引物检测均为阴性。结果表明，庚型肝炎病毒不同区域引物用于ＲＴ－ＰＣＲ检出率差异较大。ＮＳ３（１）及ＮＳ５（２）这两组引物检出率最高，更适合用于ＲＴ－ＰＣＲ检测庚型肝炎病毒ＲＮＡ。