Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral hepatitis

Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were investigated in a case-control study conducted in 107 human immunodeficiency virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22 hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P = 0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4 counts, being HBsAg-positive was strongly associated with having negative serum HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may favour the elimination of HCV in HIV-infected patients, which may influence liver disease and therapeutic decisions.     

Low prevalence of hepatitis C virus infection in patients with auto-immune hepatitis type 1

Hepatitis C virus (HCV) antibodies were measured in 28 patients with auto-immune hepatitis type 1 using six different assay kits, three for C100–3 antibody and three for second generation HCV antibody, and two confirmatory tests to determine the prevalence of HCV infection in auto-immune hepatitis. These patients were confirmed to have human leucocyte antigen DR 4 or 2 which is susceptible to auto-immune hepatitis in Japanese. Of the 28 patients, four (14.3%) were positive for HCV antibody in all assays and reacted positively in at least one of the two confirmatory tests, indicating a true positive finding. Eight were positive for HCV antibody only by the Ortho ELISA kit and were negative in both confirmatory tests. The cut-off level for these results was low and became negative soon after the patients received corticosteroid treatment. Thus, these eight patients are presumed to be false-positive reactors. Hepatitis C virus RNA was detected in the serum of two of the four patients with HCV antibody and in none of 24 patients without HCV antibody. No significant difference was observed between the patients with and without HCV antibody in terms of clinical background, liver function tests and auto-antibodies. Our results showed that the prevalence of a past or present HCV infection in patients with auto-immune hepatitis in Japan is low; thus, auto-immune hepatitis is thought to be distinct from hepatitis type C. However, it is also suggested that HCV infection can potentially trigger auto-immune hepatitis.     

Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.     

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

BACKGROUND: Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. AIM: To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. PATIENTS: A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 40 subjects with hepatitis C virus-related chronic liver disease. METHODS: Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatitis G virus-RNA by polymerase chain reaction with primers from the 5' NC and NS5a regions. TT virus-DNA by nested polymerase chain reaction with primers from the ORF1 region. Results. Hepatitis G virus-RNA was detected in 4 out of 23 patients with cryptogenic chronic hepatitis and in 6 out of 40 with hepatitis C virus chronic hepatitis (17.4% vs 15% p=ns). At least one marker of hepatitis G virus infection (hepatitis G virus-RNA and/or anti-hepatitis G virus, mostly mutually exclusive) was present in 6 out of 23 patients with cryptogenic hepatitis and 16 out of 40 with hepatitis C virus liver disease (26. 1% vs 40% p=ns). T virus-DNA was present in serum in 3 subjects, 1 with cryptogenic and 2 with hepatitis C virus-related chronic liver disease. Demographic and clinical features, including stage and grade of liver histology, were comparable between hepatitis G virus-infected and uninfected subjects. Severe liver damage [chronic hepatitis with fibrosis or cirrhosis) were significantly more frequent in subjects with hepatitis C virus liver disease. CONCLUSIONS: In Southern Italy, hepatitis G virus infection is widespread among patients with chronic hepatitis, independently of parenteral risk factors. Its frequency in subjects with cryptogenic liver disease parallels that observed in hepatitis C virus chronic liver disease, thus ruling out an aetiologic role of hepatitis G virus. TT virus infection is uncommon in patients with cryptogenic or hepatitis C virus-related liver disease who do not have a history of parenteral exposure.     

HBV感染者HCV的重叠感染关系研究

目的 研究HBV感染患者中HCV的重叠感染状况及其相互关系。 方法 采用ELISA法对767例HBV感染患者同步检测HBV和HCV血清标志物,对可疑HCV感染但抗HCV阴性和/或抗-HCV阳性患者血清,采用PCR法检测HCV-RNA。 结果 HCV重叠感染率为4.82％,且在各类乙肝患者中存在非常显著差异(P<0.01);HBV/HCV感染组重症肝炎的发生率显著高于非HCV感染组(P<0.01);HBV/HCV感染组HBsAg阳性率显著低于单纯HBV感染组(P<0.05);HBV/HCV感染组HCV-RNA阳性率显著低于单纯HCV感染组(P<0.05)。 结论 HCV重叠感染与乙肝患者的发病、病情加重及重症肝炎的发生相关;HCV可抑制或中止HBsAg携带状态,但这种作用远不如对病情的加重作用重要;同时HBV对HCV的复制亦存在抑制作用。     

Vietnamese community screening for hepatitis B virus and hepatitis C virus

Summary. Asian Americans represent an important cohort at high risk for viral hepatitis. To determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection and HBV vaccination in a Vietnamese community, a total of 322 Vietnamese subjects from a local doctor’s office and annual Vietnamese Health Fair were included in this study. Demographic and clinical data were collected. 2.2% of the screened cohort tested positive for anti‐HCV and 9.3% tested positive for HBsAg. Unlike HBV‐positive subjects, HCV‐positive subjects had significantly higher liver enzymes (P = 0.0045 and P = 0.0332, respectively). The HBV‐positive group was more likely to report jaundice (P = 0.0138) and a family history of HBV (P = 0.0115) compared to HBV‐negative subjects. Forty‐eight patients (15.5%) reported a family history of liver disease (HBV, HCV, HCC, cirrhosis, other). Of this 48, 68.8% reported no personal history of HBV vaccination and 77.1% reported no family history of vaccination for HBV. Among the 183 subjects without a family history of liver disease, 156 (85.2%) reported no personal history of vaccination and 168 (91.8%) reported no family history of vaccination. HBV vaccination rates in those reporting a family history of liver disease were significantly higher (P = 0.020). There was a high prevalence of HBV infection in this community screening. Nevertheless, the rate for HBV vaccination was low. The low prevalence of abnormal liver enzymes in HBV‐positive subjects emphasizes the need for screening to be triggered by risk factors and not by abnormal liver enzymes.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

血液透析患者HCV感染的危险因素

目的 研究血液透析患者HCV感染的相关因素。 方法 血清采自血透前、血透后2-60月的10例肾衰患者,用ELISA检测抗HCV,用PCR法检测HCV,RNA和HCV基因型。 结果 10例患者透析前无HCV感染。透析后2-60月,3例抗HCV阳性(30％),2例HCV RNA阳性(20％),其基因型均为HCVⅡ型。10例患者中7例有输血史,其中4例(57％)HCV感染,所有抗HCV阳性和HCV RNA阳性患者均有输血史。而无输血史的3例患者未见HCV感染。两组有非常显著性差异(P<0.001)。HBV感染与HCV感染无相关性。 结论 反复输血是血透患者感染HCV的高危因素,长期血液透析是参考因素。     

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia

Introduction

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood.

Methods

Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid‐lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use were assessed by multivariate logistic regression.

Results

A total of 1587 HIV‐monoinfected, 190 HIV/HBV‐coinfected and 255 HIV/HCV‐coinfected patients were evaluated. Most were male (85–92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44–56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120–370) cells/μL in HIV‐monoinfected participants, 195 (110–330) cells/μL in HIV/HBV‐coinfected participants and 268 (140–409) cells/μL in HIV/HCV‐coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001).

Conclusions

HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART‐related hyperlipidaemia.     

Expression and characterization of the hepatitis G virus helicase

The hepatitis G virus (HGV) is a new member of the Flaviviridae family and has a genomic organization similar to that of hepatitis C virus (HCV). Protein sequence motifs are present suggesting that HGV encodes a serine proteinase, an RNA-dependent RNA polymerase and a helicase. We have cloned and expressed the putative helicase of HGV and have shown that it contains a poly (U)-stimulated NTPase activity and is able to function as a DNA helicase. Preliminary characterization of the HGV helicase activity reveals similarities with other members of the Flaviviridae, but especially with HCV, raising the possibility that HGV could be used as a surrogate virus for the development of therapies against HCV.     

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV)

Abstract: We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.     

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...