GB virus C/hepatitis G virus infection in autoimmune liver diseases

Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.     

Clinical significance of hepatitis GB virus C infection in alcoholic liver disease

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and gamma-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.     

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China

The latest meeting of the AAMC's Forum on the Future of Academic Medicine, on April 29, 1998, opened with a talk by Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute, who reviewed the significant progress that the Human Genome Project (HGP) has made and speculated on how genetic discoveries and technologies would transform health-related research and ultimately the practice of medicine. The HGP's findings will offer clear improvements in diagnosis and prevention, and eventually in treatments, and the relationship between the academic medical center and the pharmaceutical industry will change--but remain good--as that industry applies the findings of the HGP. He stressed the need for the public and health care providers to develop a greater understanding of genetic issues, and urged changes in medical education to accomplish this. Forum members and Dr. Collins discussed the ethics and economics in patient care resulting from genetic research; forum members also asked whether academic medical centers could profit from genetic research findings. The second speaker was John Eisenberg, MD, administrator of the Agency for Health Care Policy and Research, which fosters health care research and disseminates to clinicians and others the findings of such research. Among other topics, Dr. Eisenberg described the new emphasis on health care outcomes and quality and described how his agency promotes research in these areas. Forum members asked who would pay for the information systems needed to communicate the findings of health services research and also noted that there is an expanding definition of health that places new pressures on already stressed academic medical centers, their missions, and their curricula, which must change. Michael Whitcomb, MD, of the AAMC, noted that the view that medical schools can't change their curricula has been proved wrong, and that 24 medical schools are working with the AAMC's Medical Schools Objectives Project on curricular reform. The forum closed with discussion of a few broader issues affecting academic medical centers.     

Prevalence, incidence, and clinical characteristics of hepatitis G virus/GB virus C infection in Scottish blood donors

The prevalence, incidence, clinical features, and natural history of hepatitis G virus (HGV) or GB virus C (GBV-C) were investigated in a non-remunerated blood donor population to determine its clinical significance and its impact on blood safety. Of 1020 regular blood donors, 23 (2.25%) were positive for plasma HGV/GBV-C RNA. Alanine aminotransferase levels were lower than in uninfected donors (median, 20 IU/mL; 32 IU/mL in controls; P=.015). Clinical examination produced no other evidence for hepatitis or for shared nonhepatic diseases. Fifteen of 17 donors excreted HGV/GBV-C in saliva (mean level, 8x103 copies of RNA/mL). Testing of previous donations indicated an incidence of 170-200 new infections with HGV/GBV-C per 100,000 donor-years. The absence of further clinicopathologic data and the limitations of current polymerase chain reaction-based methods for screening suggests that it is neither necessary nor practical to commence screening.     

Sexual transmission of GB virus C/hepatitis G virus

Tooth transposition is a positional interchange of two adjacent teeth. The most commonly transposed tooth is the permanent canine with either the first premolar or lateral incisor. The records of 54 subjects with transposed canines, both maxillary and mandibular, were collected. Pretreatment study models of these subjects were matched with a similar number of models from unaffected individuals. Bucco-lingual and mesio-distal tooth widths, arch depth and arch width were measured on each model. Thirty-four subjects (63 per cent) were female. Thirty-seven (68.5 per cent) of the cases involved the maxillary arch and thirty-three (89.2 per cent) of these upper arch transpositions were of the canine and first premolar. In cases involving the lower arch the canine was invariably transposed with the lateral incisor. Peg-shaped lateral incisors, supernumerary and/or congenitally absent teeth occurred in 19 subjects. There were some small, but significant differences in the dimensions of some teeth, however there were no statistically significant differences in arch depths, arch widths and most tooth dimensions in subjects with and without transposed canines. These factors do not appear to be related to the development of canine transposition.     

Serum hepatitis G virus RNA in patients with chronic viral hepatitis

OBJECTIVES: The hepatitis G virus (HGV) is a newly described flavivirus that affects a high proportion of patients with chronic viral hepatitis: our objective was to determine what role HGV might play in the course of disease. METHODS: We evaluated stored serum samples from 108 patients with chronic hepatitis B and 99 patients with chronic hepatitis C who participated in trials of alpha-interferon or ribavirin for the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by branched DNA and for the presence of HGV RNA by polymerase chain reaction (PCR), using primers from the NS5 region of the genome. RESULTS: Initially, 20 (19%) patients with hepatitis B and 11 (11%) with hepatitis C had HGV RNA in their serum. Patients with and without HGV infection were similar with regard to clinical features, laboratory tests, and hepatic histology. HGV RNA levels fell during interferon therapy and became undetectable in those receiving the highest doses; however, HGV RNA levels returned to pretreatment values when therapy was stopped. With ribavirin therapy, HGV RNA levels did not change. Two- to 12-yr follow-up serum samples were available from 17 initially HGV RNA-positive patients, of whom only 10 (59%) were still positive. CONCLUSIONS: HGV infection is common among patients with chronic hepatitis B and C but has little effect on the short-term course of disease or response to therapy. HGV RNA levels are suppressed but not eradicated by alpha-interferon and are unaffected by ribavirin treatment. Spontaneous loss of HGV RNA occurs over time in a proportion of patients.     

Hepatitis G virus co-infection in liver transplantation recipients with chronic hepatitis C and nonviral chronic liver disease

Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally transmitted and has been found frequently in patients with chronic hepatitis C infection. To determine the impact of hepatitis G virus co-infection on morbidity and mortality following liver transplantation, we measured HGV RNA by polymerase chain reaction in pre and posttransplantation sera from a cohort of patients transplanted for chronic hepatitis C and a control group of patients transplanted for nonviral causes who were negative for hepatitis C virus (HCV) RNA in serum. The overall prevalence rate of HGV RNA in transplanted patients with chronic hepatitis C was 20.7%. HGV infection was present before transplantation in 13% while it appeared to have been acquired at the time of transplantation in 7.4%. Mean serum alanine aminotransferase activity, hepatic histological activity, and patient and graft survival were similar between HGV-positive and HGV-negative patients. The prevalence rate of HGV RNA in transplanted controls was 64% (P < .01) with a significantly higher rate of acquisition of HGV infection following transplantation (53%, P < .001) when compared with patients with chronic hepatitis C. Mean serum alanine aminotransferase activity was significantly lower in the control patients with HGV infection alone following transplantation than in patients co-infected with hepatitis C (37 +/- 9 vs. 70 +/- 33 U/L, P < .01). Thus, HGV is frequently found in transplantation patients co-infected with hepatitis C although it appears to have minimal clinical impact. In patients transplanted for nonviral causes of end-stage liver disease, a high rate of hepatitis G acquisition at the time of transplantation may occur but does not appear to predispose to chronic hepatitis.     

Efficacy of ribavirin plus interferon alpha on viraemia of GB virus-C/hepatitis G virus: comparison with interferon alpha alone

We investigated the efficacy of ribavirin plus interferon (IFN) alpha on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon alpha alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFN alpha and three received oral ribavirin plus IFN alpha. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFN alpha alone and ribavirin plus IFN alpha at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFN alpha and ribavirin plus IFN alpha may not induce a higher sustained response.     

Natural history and molecular biology of hepatitis G virus/GB virus C

BACKGROUND: The hepatitis G virus (HGV) or GB virus C (GBV-C) is a new member of the Flaviviridae family. The virus is transmitted by transfusion of blood, infusion of some blood products, and by parenteral exposure to blood during intravenous drug use (IVDU) and haemodialysis. Transmission from mother to infant and by sexual contact has also been documented. Although the virus has been found in patients with acute and chronic hepatitis, evidence of disease association has not been forthcoming. The majority of patients carry the virus in the absence of liver enzyme abnormalities. OBJECTIVES: To review what is currently known about HGV/GBV-C in order to evaluate its similarity with other members of the Flaviviridae and the association of the virus with disease. RESULTS: The genomic organisation of the virus is typical for Flaviviridae, with long 5' and 3' untranslated regions (UTR). However, a clearly identifiable nucleocapsid encoding region is lacking. Polyprotein synthesis is mediated through an internal ribosome entry site (IRES) contained within the 5' UTR. Phylogenetic tree analysis of sequences derived from this region has demonstrated the existence of at least three genotypes. Apart from serum, HGV-RNA has been detected in lymphocytes also, but the quasispecies present in the two compartments appear to be different. The envelope glycoprotein E2 lacks a hypervariable region and is potentially the target of a neutralising antibody response. CONCLUSION: Molecular analysis of HGV reveals close similarity of the virus with HCV. However, an association of the virus with liver disease remains unresolved and no association of the virus with hepatocellular carcinoma has been reported.     

GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients?

Lung disease is a rare complication of inflammatory bowel disease (IBD). Herein is a series of seven IBD patients who developed new, persistent and unexplained symptoms of respiratory disease, particularly chronic productive cough. Using a CT scan of the chest, a diagnosis of bronchiectasis was made in five patients, while the diagnosis of chronic bronchitis was made in two patients. Factors, other than IBD, that could account for pulmonary disease in these patients were absent. Several important clinical patterns for IBD-associated large airway disease were uncovered and are reviewed in light of earlier case reports in the medical literature. A discussion regarding the possible pathogenesis of IBD-associated airway disease follows.     

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis

We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.     

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.     

Histopathology of the liver in children with chronic hepatitis C viral infection

Although the epidemiology, natural history, and pathological aspects of chronic hepatitis C are well-defined in the adult population, little is known about the characteristics of chronic hepatitis C infection in children. Reports on the histological features and progression of hepatitis C in children are scarce, and consist primarily of multicenter studies in Japanese and European children. Given the geographic variations in viral genotype and the association of pathology with genotype, whether the Japanese and European studies can be extended to the North American populations is unclear. We report the histopathology of the liver in 40 children with chronic hepatitis C infection treated in a single North American institution. The children included 19 males and 21 females ranging in age from 2.0 to 18.6 years at the time of liver biopsy (mean +/- SD: 11.4 +/- 4.3 years). Our findings indicate that the characteristic histopathological lesions of chronic hepatitis C infection, including sinusoidal lymphocytosis, steatosis, portal lymphoid aggregates/follicles, and bile duct epithelial damage, occur with approximately the same frequencies in children as have been reported in adults. Necroinflammatory activity was generally mild. Portal fibrosis was present in 78% of the specimens, including fibrous portal expansion (26%), bridging fibrosis (22%), bridging fibrosis with architectural distortion (22%), and cirrhosis (8%). Centrilobular pericellular fibrosis, which has not been previously reported in the context of chronic hepatitis C infection in adults or children, was also a prominent feature in our series, occurring with a similar frequency as steatosis or portal lymphoid aggregates/follicles. Our data suggest that in spite of mild histological necroinflammatory activity in general, the stage of fibrosis in children can be severe in spite of relatively short duration of infection.     

Molecular evolutionary analysis of GB viruses and hepatitis G virus

Cysteine proteases have been identified in parasitic protozoa including the causative agent of Chagas' disease Trypanosoma cruzi. T. cruzi lysates subjected to substrate-containing SDS-polyacrylamide gel electrophoresis exhibit major bands of proteolytic activity in the 45-55 kDa molecular mass range (cruzipain activity). Paradoxically, addition of kininogen (a cystatin-like protease inhibitor) to the lysates before electrophoresis results in the appearance of additional bands of proteolytic activity in the 160-190 kDa molecular mass range. This inhibitor-activated protease activity depends upon the reaction conditions and exhibits novel properties. For example, a 24-48 hour preincubation at low temperature (-20 degrees C optimum) greatly enhances the proteolytic activity. The results suggest that a metastable complex forms between kininogen and a cryptic 30 kDa cysteine protease from T. cruzi and that this complex participates in the activation of proteolytic activity.     

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.     

Does hepatitis G virus cause significant clinical liver disease?

Regarding the newly discovered hepatitis G virus (HGV), little is known about its relation to the cause and clinical significance of acute and chronic liver disease and hepatocellular carcinoma. Lacking a reliable serum immunoassay, the only method available for detecting the viral RNA in patients consists of the rather costly and time consuming RT-PCR. HGV has a worldwide distribution with up to 5% voluntary and 12.9% commercial blood donors infected, yet it appears to be asymptomatic. Moreover, HGV is frequently found as a coinfection with HCV or, to a lesser extent, HBV with symptoms tending to follow the patterns known for HCV or HBV infection, respectively. Being a blood-borne virus, it is most prevalent among members of high risk groups, such as IVDUs, patients on hemodialysis, recipients of blood and blood products and patients infected with HCV, HBV, or HIV, HGV can be parenterally, vertically, or sexually transmitted and after prolonged exposure, the virus may be eliminated by the patient's immune response. As yet, no unambiguous evidence exists regarding HGV's role in causing acute or chronic liver disease and, apart from a few isolated reports to the contrary, the infections appear rather mild. Therefore, more studies are required before a decision can be made whether to routinely screen blood donors for the presence of HGV RNA.