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 infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

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.     

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 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.     

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.     

Hepatitis TT virus infection in high-risk groups

Aim of the present study was to evaluate the effect of acute hyperglycemia on peripheral nerve conduction measurements. Five healthy male volunteers aged 36-42 years underwent nerve conduction studies during hyperglycemia (blood glucose approximately 12 mmol/l) induced by intravenous infusion of glucose and maintained for 120 minutes. Peroneal motor and sural sensory nerve conduction velocities and amplitudes were measured from the right leg at 15 min intervals starting at 15 min before and continuing 30 min after glucose infusion. Data were analysed using paired t-test comparing measurements at each time point after the start of the infusion to the second control measurement immediately prior to the infusion. All nerve conduction velocities and amplitudes were similar before, during and after induced hyperglycemia. The results suggest that it is unnecessary to standardise blood glucose concentration during measurement of peripheral nerve functions.     

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 B virus infection in dental surgical practice

Sixty-one dental surgeons at King's College Hospital were interviewed to establish the incidence of attacks of viral hepatitis and to relate this to environmental risk factors. Six (10%) had a history of hepatitis, in one case due to infection with the hepatitis B virus. Screening blood for HBsAg by radioimmunoassay showed no carriers of the antigen, but transient antigenaemia was observed in one dentist. Antibody to HBsAg, tested by radioimmunoassay, was detected in four dentists (7%), only one of whom had had clinical hepatitis. Dental surgeons may be more at risk from infection with the hepatitis B virus than the general population, although this should be minimised in hospital practice, where the most infected patients will already have been identified and appropriate precautions can be taken. The risk of transmission from an antigen-positive dentist to his patients is probably much smaller, and there is no evidence to restrict his clinical activities.     

Hepatitis GB virus C infection in Japanese hemophiliacs with persistent hepatitis C virus infection

We investigated the prevalence of infection of GBV-C, which has been cloned recently and is considered a parenterally transmissible virus. Ninety-one Japanese hemophiliacs who were persistently infected with HCV were evaluated. The presence of GBV-C RNA was measured by nested RT-PCR. We analyzed the prevalence and the association with subtypes of coinfected HCV. 20.9% of hemophiliacs were infected with GBV-C. The distribution of HCV subtypes of patients who are coinfected with GBV-C was similar to that of patients who are coinfected with HIV, and the prevalence of GBV-C infection of patients with HCV subtype la was significantly higher than that of patients without HCV subtype la. High prevalence of GBV-C infection was observed in Japanese hemophiliacs, and most were thought to be imported isolates from foreign origins, as well as HIV infection in these patients.     

Hepatitis C in the patient with human immunodeficiency virus infection

1. The structure activity relationships for the insulin secretagogues N-benzoyl-D-phenylalanine (NBDP) and related compounds were examined at the sulphonylurea receptor level by use of cultured HIT-T15 and mouse pancreatic beta-cells. The affinities of these compounds for the sulphonylurea receptor were compared with their potencies for K(ATP)-channel inhibition. In addition, the effects of cytosolic nucleotides on K(ATP)-channel inhibition by NBDP were investigated. 2. NBDP displayed a dissociation constant for binding to the sulphonylurea receptor (K(D) value) of 11 microM and half-maximally effective concentrations of K(ATP)-channel inhibition (EC50 values) between 2 and 4 microM (in the absence of cytosolic nucleotides or presence of 0.1 mM GDP or 1 mM ADP). 3. In the absence of cytosolic nucleotides or presence of GDP (0.1 mM) maximally effective concentrations of NBDP (0.1-1 mM) reduced K(ATP)-channel activity to 47% and 44% of control, respectively. In the presence of ADP (1 mM), K(ATP)-channel activity was completely suppressed by 0.1 mM NBDP. 4. The L-isomer of N-benzoyl-phenylalanine displayed a 20 fold lower affinity and an 80 fold lower potency than the D-isomer. 5. Introduction of a p-nitro substituent in the D-phenylalanine moiety of NBDP did not decrease lipophilicity but lowered affinity and potency by more than 30 fold. 6. Introduction of a p-amino substituent in the D-phenylalanine moiety of NBDP (N-benzoyl-p-amino-D-phenylalanine, NBADP) reduced lipophilicity and lowered affinity and potency by about 10 fold. This loss of affinity and potency was compensated for by formation of the phenylpropionic acid derivative of NBADP. A similar difference in affinity was observed for the sulphonylurea carbutamide and its phenylpropionic acid derivative. 7. Replacing the benzene ring in the D-phenylalanine moiety of NBDP by a cyclohexyl ring increased lipophilicity, and the K(D) and EC50 values were slightly lower than for NBDP. Exchange of both benzene rings in NBDP by cyclohexyl rings further increased lipophilicity without altering affinity and potency. 8. This study shows that N-acylphenylalanines interact with the sulphonylurea receptor of pancreatic beta-cells in a stereospecific manner. Their potency depends on lipophilic but not aromatic properties of their benzene rings. As observed for sulphonylureas, interaction of N-acylphenylalanines with the sulphonylurea receptor does not induce complete inhibition of K(ATP)-channel activity in the absence of inhibitory cytosolic nucleotides.