Characterization of human pegivirus infection in liver transplantation recipients.

Approximately 2% of healthy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. Here, we examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and patients with hepatectomy and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 patients with hepatectomy who received care at the Kyusyu University Hospital between May 1997 and September 2017. Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and 2 patients (1.1%) had HPgV viremia, respectively. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion because HPgV RNA was detected from the blood bag transfused to the recipient during LT. We reviewed the available literature on the prevalence HPgV infections in other organ-transplanted patients and whether they impacted clinical outcomes. They also had the higher prevalence of HPgV infection, while it appears to be of low or no consequences. In addition, HPgV infection induced the upregulation of interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells. LT recipients had higher HPgV viremia compared to patients with hepatectomy. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients.

Infection of human pegivirus 2 (HPgV-2) is associated with hepatitis C virus but not hepatitis B virus infection in people who inject drugs.

We evaluated the association between human pegivirus-2 (HPgV-2) infection and hepatitis C virus (HCV)/hepatitis B virus (HBV) co-infection in 745 plasma samples collected from HCV-positive but human immunodeficiency virus type one (HIV-1)-negative people who inject drugs in Hunan, China. The prevalence of anti-HPgV-2 was 4.43  % (33/745) and, within this, the HCV 6a genotype showed significantly higher prevalence as compared with the HCV non-6a genotypes, 6.29  % (18/286) vs. 1.69  % (4/236), respectively (P=0.009). HPgV-2 RNA was detected in 2.15  % (16/745), and was not significantly different between the HCV 6a and non-6a genotypes, 2.45  % (7/286) vs. 2.54  % (6/236), respectively (P =0.945). HBV single infection did not increase the risk of HPgV-2 infection. Compared with HCV single infection, HCV/HBV co-infection increased the risk of HPgV-2 infection by about three-fold: odds ratio (OR)=3.24 [95  % confidence interval (CI) 1.34-7.82, P=0.014] according to anti-HPgV-2 positivity or OR=3.51 (95  % CI 1.15-10.74, P=0.051) according to HPgV-2 viraemia. HPgV-2 infection did not increase the levels of liver-specific enzymes. Our study provides new findings regarding the association between HPgV-2 and HCV genotypes as well as HCV/HBV co-infection.

AIDS alters the commensal plasma virome.

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.

Chronic hepatitis associated with GB virus B persistence in a tamarin after intrahepatic inoculation of synthetic viral RNA.

Progress in understanding the pathogenesis of hepatitis C virus (HCV) has been slowed by the absence of tractable small animal models. Whereas GB virus B (GBV-B, an unclassified flavivirus) shares a phylogenetic relationship and several biologic attributes with HCV, including hepatotropism, it is not known to cause persistent infection, a hallmark of HCV. Here, we document persistent GBV-B infection in one of two healthy tamarins (Saguinus oedipus) inoculated intrahepatically with infectious synthetic RNA. High-titer viremia (108 to 109 genome equivalents per ml) and transiently elevated serum alanine transaminase activities were present from weeks 4 to 12 postinoculation in both animals. However, whereas GBV-B was eliminated from one animal by 20 weeks, the second animal remained viremic (103 to 107 genome equivalents per ml) for >2 years, with alanine transaminase levels becoming elevated again before spontaneous resolution of the infection. A liver biopsy taken late in the course of infection demonstrated hepatitis with periportal mononuclear infiltrates, hepatocellular microvesicular changes, cytoplasmic lipid droplets, and disordered mitochondrial ultrastructure, findings remarkably similar to chronic hepatitis C. GBV-B-infected hepatocytes contained numerous small vesicular membranous structures resembling those associated with expression of HCV nonstructural proteins, and sequencing of GBV-B RNA demonstrated a rate of molecular evolution comparable to that of HCV. We conclude that GBV-B is capable of establishing persistent infections in healthy tamarins, a feature that substantially enhances its value as a model for HCV. Mitochondrial structural changes and altered lipid metabolism leading to steatosis are conserved features of the pathogenesis of chronic hepatitis caused by these genetically distinct flaviviruses.

[HG-viral infection in adults]. / HG-virusnaia infektsiia u vzroslykh.

AIM: To characterize the clinical and laboratory manifestations in patients with HG viral infection frequently concurrent with chronic HCV infection and the potentialities of their treatment. MATERIALS AND METHODS: 109 patients with suspected chronic hepatic disease were examined. The markers of HGV, HCV, HBV, and TTV infections were determined. The possible factors of infection, biochemical parameters, and the efficiency of antiviral therapy were assessed. RESULTS: Hepatitis G virus RNK was detected in 32 cases, a combined variant of hepatitis G + C viruses RNA was found in 77 patients with chronic viral hepatitis (CVH). Among the presumed routes of contamination in the mixed variant of CVH, there were most common intravenous injection of narcotic drugs; in monoinfection (HGV), there were parenteral interventions in medical facilities and blood transfusion. Antiviral treatment of 13 patients with chronic HGV + HCV infection yielded a positive result in 5 patients after 3-month therapy. CONCLUSION: In patients with CVH, HG virus infection was more frequently observed in combination with CVHC, less frequently as monoinfection. In HG virus monoinfection, biochemical studies revealed the enhanced activity of transaminases and hyperbilirubinemia that was absent in the mixed variant of HGV + HCV. The financial capacities of patients should be taken into account while choosing therapy.

Prevalence of hepatitis G virus (HGV) infection in patients with chronic liver disease.

Hepatitis G virus (HGV) may cause acute and chronic infection in humans but its role in liver injury and chronic hepatitis is unclear. In this study, the prevalence of HGV was investigated in patients with chronic liver diseases in an endemic area of hepatitis B and C virus. Sixty patients with chronic liver diseases, 11 with hepatitis B virus, 44 with hepatitis C virus and 5 patients with hepatitis of unknown etiology and 60 healthy blood donors as the control were included in the study. HGV RNA was investigated by the reverse transcription polymerase chain reaction. HGV RNA was detected in none of the patients with chronic liver diseases (0%) and only one patient (1.6%) in the control group. There was no difference between the groups. This observation indicated that the prevalence of HGV is very low in patients with chronic liver diseases and healthy people in our geographical area. The role of this novel virus in the pathogenesis of chronic liver injury seems insignificant.

Prevalence of and risk factors for hepatitis G (HGV) infection in haemodialysis patients: a multicentre study.

BACKGROUND: Hepatitis G virus (HGV) or GB-virus type C (GBV-C) is, like hepatitis C, a blood-borne virus and a member of the family of flaviviridae. HGV is distributed globally and is present in the volunteer blood donor population. Thus, for epidemiological reasons, HGV is of interest in haemodialysis patients, who are at risk of parenterally transmitted infections. The aim of the present investigation was to assess the prevalence of HGV by antibody testing and HGV-RNA determination by PCR. METHODS: The study was performed in haemodialysis units of the Patienten-Heim-Versorgung, an organization of haemodialysis units throughout Germany. A total of 2796 out of 3042 patients (92%) from 43 haemodialysis units were enrolled prospectively in the trial. Liver function tests were performed and epidemiologic data were obtained to evaluate risk factors for HGV in haemodialysis patients. RESULTS: Antibodies against HGV were detected in 485 patients (17.5%). Viraemia was seen in 380 out of 1935 patients tested (19.6%). Fifty-eight patients (3.0%) were positive for both antibodies and HGV-RNA. Using a standard questionnaire in 1717 out of the 2786 patients, it was found that more than five blood transfusions increased the risk of HGV infection significantly (P<0.05). There was no association found between HGV infection and the length of time on haemodialysis. CONCLUSION: HGV is common in German haemodialysis patients but, in contrast to other parenterally transmitted viruses, there is no further risk for new infections during haemodialysis, except for patients who have received several blood transfusions.

GB virus C/hepatitis G virus exposure in Italian pediatric and young adult thalassemic patients.

BACKGROUND: The aim was to estimate the prevalence and the persistence of GB virus C/hepatitis G virus (GBV-C/HGV) exposure markers in a group at high risk for transfusion-transmitted agents. PATIENTS AND METHODS: Serum samples from 37 thalassemic patients were screened for GBV-C/HGV RNA by reverse transcription PCR (RT-PCR) and for antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). RESULTS AND DISCUSSION: GBV-C/HGV RNA and anti-E2 were detected in 13 (35%) and 12 (32%) sera, respectively. Contemporary presence of both markers was found in one patient. GBV-C/HGV exposure was found in 24 patients (64.8%). Mean levels of liver enzymes were similar in both exposed and unexposed GBV-C/HGV groups. 33 out of 35 patients showed no change in GBV-C/HGV RNA and anti-E2 status in sera taken 6 months apart. The rate of persistent infection was 92.3% and the anti-E2 seroconversion rate was 23% for sera taken at least 6 months apart. The temporal overlap between anti-E2 seroconversion and loss of detectable GBV-C/HGV RNA may last more than 6 months.

Persistent hepatitis G virus (HGV) infection in chronic hemodialysis patients and non-B, non-C chronic hepatitis.

Three groups of patients have been studied longitudinally for 24 months to analyze the role of hepatitis G virus (HGV) in hepatic disease. Group 1 consisted of 50 patients with non-B, non-C chronic hepatitis, group 2 consisted of 44 hemodialyzed patients, and group 3 consisted of 50 healthy blood donors. The presence of HGV RNA was detected by both reverse transcription-polymerase chain reaction (RT-PCR) and capillary zone electrophoresis (CZE). At the baseline visit the HGV RNA was detected in seven out of 50 patients with non-B, non-C chronic hepatitis, in two out of 44 hemodialyzed patients, and in three out of 50 healthy blood donors. HGV-infected hemodialyzed patients and HGV viremic blood donors had serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within normal limits. During the follow-up period the two HGV-positive hemodialyzed patients and the three infected healthy blood donors did not show any sign of hepatic disease. There were no significant differences between HGV-positive patients in the three groups at the beginning and at the end of the follow-up. No considerable deterioration of general health conditions was observed on the basis of clinical and laboratory data in HGV-positive chronic hepatitis patients. Finally, HGV does not seem to be responsible for hepatic disease.

[A study on the pathogenicity of acute hepatitis G infection].

OBJECTIVE: To study the infection due to hepatitis G virus (HGV) in liver tissues of patients with acute hepatitis and to investigate its pathogenicity. METHODS: HGV NS5 antigen was detected by using immunohistochemical method in the liver biopsy tissues of patients with acute hepatitis but serologically negative to hepatitis virus antigens from A to E. The clinical and pathological data were also analysed. RESULTS: 37 samples were tested, HGV NS5 antigen was detected in 14 (37.8%). 4 of the 14 were positive for HGV NS5 antigen alone (acute hepatitis G group) and 10 other cases were also positive for HBsAg, hepatitis C virus (HCV) NS3 antigen or EB virus antigen (superinfection group). 7 cases were HBsAg positive alone (acute hepatitis B group) and the remaining 16 cases were negative for all the antigens mentioned above (non-A - G hepatitis group). There was no difference among the 4 groups in the detecting rate of Fas antigen, histological activity index (HAI), serum alanine transferase (ALT) and total bilirubin (TBil). CONCLUSION: It is suggested that HGV appears to play some role in the pathogenesis of acute viral hepatitis and the degree of liver injury in acute hepatitis G may be as severe as that of hepatitis caused by other types of viruses.