Human immunodeficiency virus rather than hepatitis C virus infection is relevant to the development of an anti-cardiolipin antibody

We have investigated whether or not a relationship exists between anti-cardiolipin antibody (aCL) positivity and human immunodeficiency virus type 1 (HIV) and/or hepatitis C virus (HCV), and we have attempted to clarify which virus has close association with the development of aCL. We found that aCL positivity in HIV-infected patients was significantly higher than in HCV-infected patients. Furthermore, HIV/HCV dual-infected patients exhibited a higher aCL positivity than patients infected by HCV alone. From these results, we conclude that HIV rather than HCV plays an important role in the development of aCL.     

Long-term persistence of hepatitis C virus antibodies in a single source outbreak.

The occurrence of antibodies to hepatitis C virus (HCV) was investigated in 81 patients who developed hepatitis non-A, non-B (HNANB) after parenteral administration of contaminated immunoglobulin to prevent Rh sensitization. Sera from 74 of the 81 patients (89.9%) were anti-HCV positive at either 6-12 months or 9-10 years after administration of immunoglobulin. Sera were not available from any patients at either of the times: however, 52 of 56 sera (92.9%) were anti-HCV positive 6-12 months after use of immunoglobulin, and anti-HCV was present in 45 of 65 sera (69.2%) 9-10 years after immunoglobulin treatment. Of the latter, only two of 13 (15.4%) sera from patients who recovered from hepatitis were anti-HCV positive, whereas 43 of 52 patients (82.7%) with chronic disease were anti-HCV positive. The ELISA using a recombinant antigen was found a good detector as marker for a HCV infection because 90% of patients infected by a common source became anti-HCV positive. However, 10 years after infection most patients who did not develop chronic disease no longer had detectable antibodies.     

Prevalence of hepatitis C virus infection in the general population of northern Spain

OBJECTIVES: To estimate the prevalence of hepatitis C in a population of northern Spain and describe (i) the risk factors associated with infection and (ii) the distribution of genotypes. DESIGN: Randomized cross-sectional study. METHODS: A random sample of 1,170 people participated in the study. Sociodemographic data were obtained. Antibodies against hepatitis C virus (anti-HCV) and hepatitis C virus (HCV) genotypes were determined. RESULTS: Nineteen of 1,170 (1.6%) subjects were anti-HCV positive (95% CI 1.0-2.6%). In 12 cases (63%), viraemia was present, and the predominant genotype was 1 b (80%). Anti-HCV positive subjects were older than anti-HCV negative subjects (55.8 +/- 15.3 v. 44.8 +/- 20.9; P = 0.02). Two peaks of maximum frequency were found (in the fourth decade and in those over 60 years). Parenteral drug addiction predominates among those of the fourth decade, while transfusion and surgery predominate in people over 60 years. Three (16%) subjects knew they were carriers of HCV. Only three variables remained significant in the multivariate model (illegal drug use, P< 0.0001; previous hepatitis, P< 0.0001; and age, P< 0.02). CONCLUSIONS: Our study emphasizes the need to develop health policies that can cope with the foreseeable increases in the problems associated with HCV infection in the near future.     

湘南地区住院患者丙型肝炎病毒感染方式的特征分析

目的 了解湖南地区住院患者中HCV疑似感染方式分布的规律特征,为HCV感染的防治提供参考.方法 应用电子病历查询法对住院患者中诊断有丙型肝炎者进行回顾性分析.化学发光法检测抗HCV抗体,实时荧光定量PCR法检测HCV RNA定量.结果 肾内科患者主要经血液透析感染(80.0％),妇产科患者主要经手术感染(64.7％),感染科患者主要为输血感染(39.0％)和静脉吸毒感染(28.6％),其他科室患者也主要为输血感染(40.7％)和静脉吸毒感染(37.0％),不同科室住院患者的HCV疑似感染方式构成比存在明显差异(P＜0.01).年龄≤40岁患者主要经静脉吸毒感染( 38.2％),而年龄＞40岁患者主要经输血感染(49.3％),不同年龄患者HCV疑似感染方式构成比存在明显差异(P＜0.01).男性患者主要经静脉吸毒(35.0％)和输血感染( 32.5％),而女性患者主要经手术(32.7％)和输血( 26.9％)感染,不同性别患者HCV疑似感染方式构成比存在明显差异(P＜0.01).结论 HCV的感染方式已呈现明显的多样化,静脉吸毒将成为越来越重要的感染因素.     

Failure of hepatitis C therapy in HIV-coinfected drug users is not due to a shift in hepatitis C virus genotype

Because most patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are injection drug users (IDUs) who might have been exposed to multiple HCV genotypes while sharing needles, coinfection with distinct HCV genotypes could be frequent in them. Blood samples from 203 coinfected IDUs who did not respond to at least 24 weeks of interferon (IFN)-based therapies were analyzed. At baseline, 131 patients had HCV genotype 1, 4 had HCV genotype 2, 52 had HCV genotype 3, and 16 had HCV genotype 4. Changes in HCV genotype were not found in any patient when samples obtained before and after HCV therapy were compared. HCV therapy did not appear to select for IFN-resistant HCV genotypes that might have been present at baseline. Coinfection with distinct HCV genotypes is unlikely in former IDUs coinfected with HIV and does not explain the lower efficacy of HCV therapy in this population.     

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region. METHODS: We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration. RESULTS: Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis. CONCLUSIONS: We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.     

Fatty acid synthase is up-regulated during hepatitis C virus infection and regulates hepatitis C virus entry and production

Hepatitis C virus (HCV) is a major human pathogen that causes serious illness, including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Using a mass spectrometry-based proteomics approach, we have identified 175 proteins from a cell culture supernatant fraction containing the HCV genotype 2a (JFH1) virus, among which fatty acid synthase (FASN), the multifunctional enzyme catalyzing the de novo synthesis of fatty acids, was confirmed to be highly enriched. Subsequent studies showed that FASN expression increased in the human hepatoma cell line, Huh7, or its derivative, upon HCV infection. Blocking FASN activity by C75, a pharmacological FASN inhibitor, led to decreased HCV production. Reduction of FASN by RNA interference suppressed viral replication in both replicon and infection systems. Remarkably, FASN appeared to be selectively required for the expression of claudin-1, a tight junction protein that was recently identified as an entry coreceptor for HCV, but not for the expression of another HCV coreceptor, CD81. The decrease in Claudin-1 expression resulting from FASN inhibition was accompanied by a decrease in transepithelial electric resistance of Huh7 cells, implying a reduction in the relative tightness of the cell monolayer. Consequently, the entry of human immunodeficiency virus-HCV pseudotypes was significantly inhibited in C75-treated Huh7 cells. CONCLUSION: As far as we know, this is the first line of evidence that demonstrates that HCV infection directly induces FASN expression, and thus suggests a possible mechanism by which HCV infection alters the cellular lipid profile and causes diseases such as steatosis.     

The impact of hepatitis C antibody screening of source plasma donors on hepatitis C virus RNA in factor VIII concentrates

Summary. We have used the polymerase chain reaction technique for the detection of hepatitis C RNA in nine different plasma-derived factor VllI concentrates and in two factor IX concentrates. Four concentrates were investigated both prior to and after the introduction of donor screening for hepatitis C antibodies. A negative reaction was consistently found in the ultra-pure factor VIII concentrates Octonativ-M (Pharmacia) and Hemofil M (Baxter), both prepared by affinity purification with factor VI1I:C monoclonal antibodies and virus inacti- vated hy solvent/detergent procedures, as well as in both the low-purity factor IX concentrates. I f produced from unscreened plasma, the other factor VIII concentrates manifested positive reactions irrespective of preparation procedure and type of virus inactivation or the temperature at which it was performed. We conclude that the preparation procedure of clotting factor concentrates, rather than type of virus inactivation, determines the degree of contamination by hepatitis C virus RNA, and that screening of source plasma seems effective in removing hepatitis C RNA from the final product as determined with a sensitive PCR method. I t is important to stress that the presence of viral RNA does not necessarily imply clinical infectivity.     

New infection with heterotypic hepatitis C virus in a patient with long-term hepatitis C virus eradication

BACKGROUND: Experimental hepatitis C virus infection in chimpanzees has shown that natural hepatitis C virus infection does not induce protective immunity and reinfection can occur in seroconverted animals. AIM: To study the clinical, virological and histological outcome of a new infection sustained by a different hepatitis C virus strain after a primary infection with eradication of the original virus. PATIENTS AND METHODS: A young Italian man with chronic hepatitis C virus type 4 hepatitis was treated with Interferon therapy and achieved a sustained biochemical and virological response. After long follow-up, an asymptomatic flare-up of alanine transaminase occurred. This alanine transaminase increase was associated with serum hepatitis C virus RNA positivity and a low viral load, and the infecting hepatitis C virus genotype was type 3. The clinical and virological course of this new infection is described. RESULTS AND CONCLUSIONS: This report shows that there is no protective immunity against hepatitis C virus type 3 after infection by hepatitis C virus type 4 strain.     

Risk factors for acquisition of hepatitis C virus infection in blood donors: results of a case-control study

BACKGROUND & AIMS: Few studies have explored risk factors predicting hepatitis C virus (HCV) infection in blood donors; their results are contradictory. The aim of this study was to evaluate the association between HCV infection and various risk factors in Canadian volunteer blood donors. METHODS: Four transfusion centers were involved in this case-control study. A total of 267 confirmed anti-HCV-positive blood donors were interviewed along with 1068 seronegative blood donors matched for sex, age, donation site, and date. Information was collected using a structured telephone interview. The main outcome measures were odds ratios (ORs) and 95% confidence intervals (CIs) for various risk factors from univariate and multivariate analyses using conditional logistic regression. RESULTS: By univariate analysis, 23 variables were associated with anti-HCV positivity. In the final multivariate analysis, only 5 factors remained independently predictive of HCV infection: previous intravenous drug use (OR, 127.5; 95% CI, 26.0-625.0), having lived in a prison or juvenile detention center (56.1; 11.4-275.7), previous blood transfusion (10.5; 4.7-23.2), sexual contact with an intravenous drug user (6.9; 3.1-15.2), and tattooing (5.7; 2.5-13). CONCLUSIONS: Most blood donors acquire infection by percutaneous exposure to contaminated blood. A role for sexual transmission is suggested by this study.     

Occult hepatitis C virus infection： A new form of hepatitis C

INTRODUCTION The etiology of liver disease is unknown in approximately 10% of patients with abnormal results on liver function tests. Some authors have reported that occult hepatitis B virus could be the cause of a proportion of these cryptogenic chronic …     

Investigating the source of hepatitis C virus infection among individuals whose route of infection is undefined: a study of ten cases

Hepatitis C virus (HCV) transmission is predominantly parenteral via infected blood products or shared injecting equipment. Many infected individuals, however, deny these risk factors. This study set out to determine whether an in-depth interview would determine the likely source of infection for those whose route of infection was undefined. Between May 1999 and July 1999, risk factor information was sought, through in-depth interview, from 10 patients whose source of hepatitis C infection was undefined. The clinical notes of the patients were scrutinized to complement the information provided through the questionnaire. Despite undertaking an in-depth interview, it was not possible to establish the likely route of infection for 9 of the 10 individuals studied as they reported several risk events. There is little benefit to interviewing routinely those HCV-infected people who have no history of injecting drugs or having received a contaminated blood/blood product transfusion, to ascertain their likely source or time of infection; at best, such effort might only increase one's confidence that infection was acquired through means other than these 2 routes.