Hepatitis G virus infection in hemodialysis patients

The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.     

Hepatitis G virus in the general population and in patients on hemodialysis

To determine the routes of transmission of hepatitis G virus (HGV) and the relationship between HGV and hepatitis C virus (HCV) infections, we tested for HGV RNA by polymerase chain reaction and antibody to HCV (anti-HCV) in 494 hemodialysis patients, 638 inhabitants of two HCV endemic areas, and in 400 blood donors in Japan. HGV RNA was detected in 6.9% of hemodialysis patients, in 1.4% of inhabitants, and in 0.8% of donors, and anti-HCV was detected in 39.3%, 12.4%, and 1.8%, respectively. Of HGV RNA-positive hemodialysis patients, and HGV RNA-positive inhabitants, 64.7% and 11.1%, respectively, had been given blood transfusions. The prevalences of HGV RNA and anti-HCV significantly increased with the duration of hemodialysis. Of all HGV RNA positives, 74.4% were coinfected with HCV and subjects with HGV RNA alone had normal liver function. In conclusion, HGV is transmitted by blood transfusion and within the hemodialysis unit itself. HGV does not seem to injure hepatocytes.     

Hepatitis G virus infection in human immunodeficiency virus type 1-infected mothers and their children

Hepatitis G virus (HGV) RNA and anti-E2 glycoprotein antibody (E2Ab) seroprevalence was studied in 58 human immunodeficiency virus type 1 (HIV-1)-infected mothers (34 injecting drug users [IDUs] and 24 with risky sexual behavior [RSB]) and their children (median age, 5 days; range, 1-27). Twelve women (20.6%) were RNA- and 20 (34.4%) E2Ab-positive. Seroprevalence was similar in the IDU and RSB groups and high in RSB partners of IDU men. Five (41.6%) children of RNA-positive mothers were HGV-infected, at a median age of 5 days (range, 1-27), independent of maternal CD4 T lymphocyte numbers, mode of delivery, and HIV-1 transmission; no other child at risk became RNA-positive subsequently. No HGV-infected child (follow-up, 16 months; range, 12-52) showed increased liver enzyme levels; 3 children cleared RNA and E2Ab-seroconverted after 10-48 months. Thus, in HIV-1-infected women, HGV infection is common and also sexually transmitted, and clearance may be impaired. Mother-to-child transmission is frequent and occurs antenatally; children remain long infected without evident disease.     

Hepatitis G virus infection in American patients with cryptogenic cirrhosis: no evidence for liver replication

OBJECTIVE: This study was conducted (1) to determine in vitro placental villous cytotrophoblast secretion of prostacyclin, prostaglandin E2, and endothelin-1, (2) to examine the effect of serum from normal and preeclamptic women on secretion of these vasoactive substances, and (3) to determine whether responses to these sera by cytotrophoblasts from preeclamptic pregnancies are different from those of normal pregnancies. STUDY DESIGN: Cytotrophoblasts isolated from human placentas collected at cesarean section from normal and preeclamptic women were incubated for 20 hours in 20% (vol/vol) sera from preeclamptic or gestational age-matched normal pregnant women. Levels of prostacyclin (measured as 6-keto-prostaglandin F1alpha), prostaglandin E2, and endothelin-1 were measured in cytotrophoblast supernatants. RESULTS: In normal pregnancy sera preeclamptic cytotrophoblasts secreted significantly lower amounts of prostacyclin and prostaglandin E2 but higher amounts of endothelin-1 than did normal cytotrophoblasts. In preeclamptic sera the abnormality of prostacyclin secretion by preeclamptic cytotrophoblasts was partially corrected, but there was no effect on prostaglandin E2 or endothelin-1 secretion. Preeclamptic sera had no effect on secretion by normal cytotrophoblasts. CONCLUSIONS: The differences between normal and preeclamptic cytotrophoblasts in prostacyclin, PGE2, and endothelin-1 secretion and in response to preeclamptic serum suggest altered arachidonic acid metabolism in preeclampsia.     

Hepatitis G virus infection among liver graft recipients: anatomoclinical correlations

Hepatitis G virus (HGV) causes persistent infection in man, but its disease association is controversial. We studied the HGV disease association in 25 liver transplantation (LT) recipients without evidence of hepatitis B and C infection. HGV RNA was tested by semiquantitative RT-PCR in serial serum samples and its presence was correlated with the biochemical and histological evidence of liver damage. The overall prevalence of HGV infection in this population was 9/25 (36%), one patient being HGV RNA positive since before LT, while the other eight apparently acquired de novo infections after LT. In five cases, appearance of HGV was followed by biochemical and histological evidence of liver damage: the liver biopsy showed acute rejection in two cases, acute cholangitis in two, and acute hepatitis in one. At the end of follow-up, histological evidence of chronic hepatitis was found in one HGV-positive patient but also in three HGV-negative patients, whereas the only patient with acute hepatitis at the time HGV RNA was first detected in serum developed an intralobular gigantocellular granuloma. In conclusion, HGV infection after LT may be seldom associated with acute and chronic liver damage, but comparable histological features can be observed also among HGV-negative controls.     

Responsiveness to interferon alpha treatment in patients with chronic hepatitis C coinfected with hepatitis G virus

BACKGROUND/AIMS: Patients with chronic hepatitis C are often coinfected with the new identified Flaviviridae-like agent, termed hepatitis G virus (HGV). The aim of the study was to investigate the responsiveness of hepatitis G virus to interferon alpha and to evaluate whether a hepatitis G virus coinfection negatively influences the outcome of treatment in chronic hepatitis C. METHODS: One hundred and fifteen patients with histologically proven chronic hepatitis C were treated with interferon alpha and investigated for the presence of hepatitis G virus coinfection by nested polymerase chain reaction with primers from the helicase region of hepatitis G virus. All patients received at least 3 MU (range 3-6) interferon alpha thrice weekly for at least 6 months (mean 8, range 6-12). Polymerase chain reaction products of seven pre- and post-treatment hepatitis G virus positive patients were directly sequenced for identification of sequence variability during the follow-up. RESULTS: Eighteen (16%) patients were coinfected with hepatitis G virus. Although nine (50%) of these patients became HGV RNA negative during interferon alpha therapy, only three patients (17%) remained HGV RNA negative at the end of follow-up (mean 24 months). The rate of sustained response of chronic hepatitis C was not significantly different between patients with hepatitis C virus infection and HCV/HGV coinfection (19% vs 28%). Severity of liver disease as determined by alanine aminotransferase levels, histology and hepatitis C virus viremia was not significantly different in patients with hepatitis C virus or HCV/HGV coinfection. Sequence analysis of the helicase region revealed that our isolates all belonged to the hepatitis G virus and not to the GBV-C like genotype. No amino acid exchanges during the observation period of up to 48 months were observed, indicating that this region is highly conserved. CONCLUSIONS: The responsiveness of hepatitis G virus to interferon alpha in chronic HCV/HGV coinfected patients is similar to that observed in chronic hepatitis C. Hepatitis G virus coinfection seems not to interfere with the efficacy of interferon alpha treatment in patients with chronic hepatitis C.     

Hepatitis G virus infection before and after liver transplantation. Liver Transplantation Database

The hepatitis G virus is a newly discovered flavivirus that has been linked to acute and chronic hepatitis of unknown cause. We determined the prevalence of hepatitis G virus infection in 179 selected patients undergoing liver transplantation at three centers participating in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Pretransplantation and posttransplantation specimens were tested for hepatitis G virus RNA by polymerase chain reaction. Before transplantation, 9 of 38 (24%) patients with fulminant hepatic failure, 9 of 62 (15%) with cryptogenic cirrhosis, 3 of 35 (9%) with cholestatic liver disease, and 5 of 44 (11%) with chronic hepatitis C were positive for hepatitis G virus RNA (P = .27). Patients with and without viral RNA were similar in clinical features, liver test abnormalities, and survival after transplantation. Posttransplantation serum specimens were tested from 73 patients; 9 of 11 (82%) who were positive for viral RNA before transplantation remained positive, but 35 of 62 (56%) patients who were initially negative became positive after transplantation, a rate consistent with that predicted from the number of blood products administered. Only 5% of de novo HGV infections could be attributed to preexisting hepatitis G virus RNA in the donor. Comparison of patients with and without hepatitis G virus infection showed no difference in incidence of hepatitis after transplantation. Thus, hepatitis G virus infection was present in 15% of patients before and appeared de novo in half of patients after liver transplantation. Although hepatitis G virus infection was not associated with poor outcome, the frequency of this infection after transplantation calls for further long-term evaluation.     

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection

Behavioral relevance of norepinephrine is associated with neuronal processing underlying arousal, affect, attention, learning and memory, and is associated with beta-adrenergic modifications of neuronal activation in the hippocampal formation. This study utilized l-isoproterenol to initiate pathway-specific activation of afferents to hippocampal CA1 pyramidal cells. The consistent effects of l-isoproterenol on the initiation of action potentials to field CA1 pyramidal neurons to single-pulse stimulation was repeatedly associated with the activation of the Schaffer collateral pathway. In contrast, l-isoproterenol plus single-pulse stimulation never elicited action potential initiation of the perforant pathway to CA1. We interpret these results as indicating that beta-adrenergic modification underlies the augmentation of information processing via the Schaffer collateral pathway in the trisynaptic circuit vs the direct perforant pathway.     

Hepatitis C virus infection in the elderly. Epidemiology, prophylaxis and optimal treatment

Chronic infection with the hepatitis C virus (HCV) occurs throughout the world and appears to be the main cause of hepatocellular carcinoma. Studies have shown that, in areas of high endemicity, the prevalence of HCV infection is low in children but high in people aged > 60 years. Medical interventions were found to play an important role in the spread of HCV infection, because elderly patients became infected via contaminated blood transfusions or when contaminated syringes and needles were used. Maternal and sexual transmission do not appear to be the main routes of HCV infection. Interferon treatment eliminates HCV in 20 to 30% of patients with chronic HCV infection. The response to interferon therapy is usually complete in 70 to 80% of people with low levels of HCV RNA, HCV of genotype 2 and young women, but poor in elderly patients. Because liver disease can be severe in elderly patients, more effective therapies are clearly needed.