Efficacy and changes of the nonstructural 5A GENE by prolonged interferon therapy for patients with hepatitis C virus genotype 1b and a high level of serum HCV-RNA.
(25/3013)
OBJECT: The aim of this study was to examine the efficacy and the changes of amino acid sequences of the interferon sensitivity-determining region (ISDR) by prolonged interferon (IFN) treatment in patients who have serum hepatitis C virus (HCV)-genotype 1b and a high level of serum HCV-RNA. METHODS: Inclusion criteria were biopsy-proven chronic hepatitis, positive HCV-RNA, and an abnormal serum aminotransferase level. Twenty-five patients received 6 MU of natural IFN-alpha daily for 8 weeks, followed by three times weekly for 40 weeks (1,056 MU). One patient was withdrawn from the study due to IFN side effects. Therefore, the remaining 24 patients (group 1) were studied the efficacy of IFN administration and changes of ISDR. As a control, 22 patients (group 2) treated with natural IFN-alpha for 24 weeks for the same period were studied retrospectively. Patients were defined as complete responders (CR) if serum HCV-RNA levels were negative for 6 months after IFN therapy. RESULTS: According to this criterion, CR was 25% (6/24) in group 1 and 9.1% (2/22) in group 2. The normalization rates of alanine aminotransferease (ALT) for six months after termination of IFN was 41% (10/24) in group 1 and 18.2% (4/22) in group 2. Regarding the changes of ISDR in patients with no CR, the change rates of ISDR were 16.7% (3/18) in group 1 and 10% (2/20) in group 2. CONCLUSION: We concluded that prolonged IFN therapy was effective for patients with HCV-genotype 1b and a high level of serum HCV-RNA. (+info)
Hepatitis C virus genotype does not affect patient survival among renal transplant candidates. The New England Organ Bank Hepatitis C Study Group.
(26/3013)
BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk for infection with different hepatitis C virus (HCV) genotypes and multiple genotype infections. However, to date, the effect of the type and number of infecting HCV genotypes on survival among ESRD patients has not been carefully examined, and this was the objective of this study. METHODS: Sera from patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 were tested for anti-HCV using a third-generation enzyme-linked immunosorbent assay. All anti-HCV-positive serum samples were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction (PCR) with primers derived from the highly conserved 5'UTR region of the HCV genome. HCV genotypes were determined by restriction fragment length polymorphism of the 5'UTR PCR product. The duration of follow-up was calculated from the date of the first available serum specimen until death, loss to follow-up, or December 31, 1995, whichever occurred earlier. Two separate multivariate models were constructed: one to examine the impact of HCV genotype on mortality and the other to examine the impact of the single versus mixed infection on mortality. In both models, the independent variables were HCV genotype and transplantation. The HCV genotype was treated as a time-independent (baseline) variable. Transplantation was treated as a time-dependent variable in which the status changed after transplantation. RESULTS: HCV RNA was detected by PCR in 224 patients (81%) in whom sera were available. Complete clinical data on baseline covariates, subsequent transplantation, and mortality were available in 180 patients (80%), and these patients constituted the final study cohort. HCV genotypes 1a and 1b were the two most common genotypes encountered and were found in 60 and 24% of the patients, respectively. One hundred and sixty-two (90%) patients were infected with a single HCV single genotype, 16 patients (9%) with two genotypes, and two patients (1%) with three genotypes. Among the 180 patients in the final study cohort, 86 (48%) underwent transplantation, and 66 (37%) patients died during follow-up. Compared with patients infected with HCV genotype 1a, the relative risk (RR) of death from all causes was not significantly increased among patients infected with genotype 1b (RR = 1.02, 95% CI, 0.55 to 1.89) or other genotypes (RR = 1.08, 95% CI, 0.50 to 2.30). Likewise, compared with patients with a single infection, the RR of death among patients with mixed infection (RR = 1.18, 95% CI, 0.52 to 2.66) was not significantly increased. CONCLUSIONS: The results of this study suggest that the type and number of HCV genotypes may not have a significant impact on survival among ESRD patients. (+info)
Effect of retreatment with interferon alone or interferon plus ribavirin on hepatitis C virus quasispecies diversification in nonresponder patients with chronic hepatitis C.
(27/3013)
Alpha interferon (IFN-alpha) treatment is effective on a long-term basis in only 15 to 25% of patients with chronic hepatitis C. The results of recent trials indicate that response rates can be significantly increased when IFN-alpha is given in combination with ribavirin. However, a large number of patients do not respond even to combination therapy. Nonresponsiveness to IFN is characterized by evolution of the hepatitis C virus (HCV) quasispecies. Little is known about the changes occurring within the HCV genomes when nonresponder patients are retreated with IFN or with IFN plus ribavirin. In the present study we have examined the genetic divergence of HCV quasispecies during unsuccessful retreatment with IFN or IFN plus ribavirin. Fifteen nonresponder patients with HCV-1 (4 patients with HCV-1a and 11 patients with HCV-1b) infection were studied while being retreated for 2 months (phase 1) with IFN-alpha (6 MU given three times a week), followed by IFN plus ribavirin or IFN alone for an additional 6 months (phase 2). HCV quasispecies diversification in the E2 hypervariable region-1 (HVR1) and in the putative NS5A IFN sensitivity determining region (ISDR) were analyzed for phase 1 and phase 2 by using the heteroduplex tracking assay and clonal frequency analysis techniques. A major finding of this study was the relatively rapid evolution of the HCV quasispecies observed in both treatment groups during the early phase 1 compared to the late phase 2 of treatment. The rate of quasispecies diversification in HVR1 was significantly higher during phase 1 versus phase 2 both in patients who received IFN plus ribavirin (P = 0.017) and in patients who received IFN alone (P = 0. 05). A trend toward higher rates of quasispecies evolution in the ISDR was also observed during phase 1 in both groups, although the results did not reach statistical significance. However, the NS5A quasispecies appeared to be rather homogeneous and stable in most nonresponder patients, suggesting the presence of a single well-fit major variant, resistant to antiviral treatment, in agreement with published data which have identified an IFN sensitivity determinant region within the NS5A. During the entire 8 months of retreatment, there was no difference in the rate of fixation of mutation between patients who received combination therapy and patients who were treated with IFN alone, suggesting that ribavirin had no major effects on the evolution of the HCV quasispecies after the initial 2 months of IFN therapy. (+info)
Prevalence and characterization of hepatitis C virus in hemodialysis patients.
(28/3013)
OBJECT: Chronic hepatitis C virus (HCV) infection is common in hemodialysis (HD) patients. In the present study, the prevalence and properties of HCV in HD patients were analyzed. METHODS AND RESULTS: Of 125 HD patients, 34 (27%) were positive for antibody to HCV, and HCV-RNA was detected in 23 (68%) of the 34 patients using reverse transcription polymerase chain reaction. The HCV-RNA sequence analysis did not identify the alterations specific to HD patients with HCV, although one patient had a variant virus containing the deletion of the core gene sequence. When serial changes in the levels of HCV-RNA were evaluated in 15 patients by a branched DNA assay, the values decreased immediately after HD procedure, but returned to the baseline values 2 days after the procedure. CONCLUSION: These results indicate that HCV in HD patients is replication-competent, although a transient reduction in the levels of HCV-RNA occurs during HD. (+info)
Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens.
(29/3013)
BACKGROUND: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients. METHODS: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months. RESULTS: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis. CONCLUSIONS: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis. (+info)
Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort.
(30/3013)
BACKGROUND: Several retrospective and prospective studies report an increased prevalence of non-organ-specific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) related chronic liver disease (CLD). Some of the data so far available are controversial and the true prevalence of NOSAs in the general population is still not known. AIM: To explore the prevalence of NOSAs, their relation to different HCV genotypes, and the presence and severity of CLD in the general population of Northern Italy. PATIENTS: All 226 anti-HCV positive and 87 hepatitis B surface antigen (HBsAg) positive patients of the Dionysos cohort study were analysed and compared with sex and age matched cases (226) negative for both anti-HCV antibody and HBsAg selected from the same cohort. METHODS: Sera tested for the presence of NOSAs (anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomes type 1 antibody (LKM1)) were screened by indirect immunofluorescence at a 1:40 serum dilution. HCV RNA and HCV genotypes were also determined by nested polymerase chain reaction (PCR) of the 5' non-coding region and by PCR amplification of the core region with type specific primers. RESULTS: The overall prevalence of NOSA reactivity was significantly higher in anti-HCV positive subjects than in both normal and pathological controls (25% v 6% and 7% respectively, p<0.05). ANA, SMA, and LKM1 occurred in 16, 10, and 1. 3% of cases respectively. No specific association between NOSAs and a specific HCV genotype was found. NOSAs were found more often associated with more than one genotype (35.7%) and with untypable genotypes (34.6%), although the association was not statistically significant. NOSAs were associated with HCV RNA and CLD but not with the presence of cirrhosis and/or hepatocellular carcinoma. On univariate analysis, NOSA reactivity was independently associated with abnormal alanine aminotransferase (p<0.01) and gamma-glutamyltranspeptidase levels (p<0.05). The risk for the presence of NOSAs was 5.1 times higher in anti-HCV subjects than in controls. CONCLUSIONS: In the general population the prevalence of NOSAs is higher in anti-HCV positive subjects than in normal or disease controls. Moreover NOSAs are associated with CLD and with a more active disease in terms of alanine aminotransferase activity. (+info)
The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.
(31/3013)
BACKGROUND: Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. METHODS: We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. RESULTS: The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. CONCLUSIONS: In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection. (+info)
Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection.
(32/3013)
Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk. (+info)