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HCV RNA (hcv + rna)
Kinds of HCV RNA Terms modified by HCV RNA Selected AbstractsTreatment of chronic hepatitis C in patients with haemophilia: a review of the literatureHAEMOPHILIA, Issue 5 2006D. POSTHOUWER Summary., Chronic hepatitis C is a major cause of morbidity and mortality in haemophilia patients. In contrast to studies in the general population, the studies of antiviral therapy in haemophilia patients are limited and often include small numbers of patients. A review of the literature was performed to assess the efficacy of interferon (IFN)-based therapy for patients with haemophilia chronically infected with hepatitis C virus (HCV). Studies were identified by electronic searches (Medline, Embase) and hand searches in references of key articles. Data of the included studies were pooled, and responses to therapy were stratified according to treatment regimen, HIV co-infection status, and treatment history. The main outcome was a sustained virological response (SVR) defined as absence of HCV RNA both at the end of treatment and 24-week post-treatment. Thirty-five studies were identified that included 1151 patients. After pooling the data of included patients, the SVR in HIV-negative treatment naïve patients was 22% for IFN monotherapy, 43% for IFN and ribavirin, and 57% for pegylated IFN and ribavirin, respectively. Re-treatment with IFN and ribavirin of those who failed to respond to previous IFN monotherapy was successful in 33%. In HCV/HIV-coinfected patients, response to IFN monotherapy was 8% and to IFN combined with ribavirin 39%. Responses to IFN-based therapy in patients with haemophilia have been improved over time and are nowadays approximately 50,60%. However, data on haemophilic HCV/HIV-coinfected patients and in patients who failed to respond to previous therapy are limited and future studies in these specific patient population are necessary. [source] Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia,,§HEPATOLOGY, Issue 5 2010Mark H. Kuniholm Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1,2.6), B*5701 (PR=2.0; 95% CI = 1.0,3.1), B*5703 (PR = 1.7; 95% CI = 1.0,2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0,3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2,0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2,11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010.) [source] Outcomes of a patient-to-patient outbreak of genotype 3a hepatitis C,HEPATOLOGY, Issue 2 2009Mark E. Mailliard Between March 2000 and July 2001, at least 99 persons acquired a hepatitis C virus genotype 3a (HCV-3a) infection in an oncology clinic. This nosocomial HCV outbreak provided an opportunity to examine the subsequent clinical course in a well-defined cohort. This was a retrospective/prospective observational study of the short-term significant health outcomes of a large, single-source, patient-to-patient HCV-3a outbreak. Outbreak patients or their legal representatives consenting to study were enrolled between September 2002 and December 2007. We measured history and physical examinations, medical records, HCV serology, HCV RNA and genotype, liver enzymes, histology, response to antiviral therapy, and liver-related morbidity and mortality. Sixty-four of the 99 known HCV-3a outbreak patients participated. During a 6-year period, six patients developed life-threatening complications from liver disease, three died, one received a liver transplant, and two were stable after esophageal variceal banding or diuretic therapy of ascites. Thirty-three patients underwent antiviral therapy, with 28 achieving a sustained viral remission. One patient acquired HCV-3a infection sexually from an outbreak patient and was successfully treated. Eleven study patients died of malignancy, including two that had achieved a sustained viral remission after antiviral therapy. Conclusion: Our patient cohort had a nosocomial source and an oncologic or hematologic comorbidity. Compared with previous HCV outcome studies, a patient-to-patient HCV outbreak in an oncology clinic exhibited significant morbidity and mortality. Attention is needed to the public health risk of nosocomial HCV transmission, emphasizing infection control, early diagnosis, and therapy. (HEPATOLOGY 2009.) [source] Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1,infected patients,,HEPATOLOGY, Issue 2 2009Thomas Berg Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection. Individually tailored reduction in treatment duration in HCV type 1,infected patients represents one possible strategy. Four hundred thirty-three patients were randomly assigned to receive either 1.5 ,g/kg peginterferon alfa-2b weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an individually tailored treatment duration (18-48 weeks; n = 208, group B). In the latter group, treatment duration was calculated using the time required to induce HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL) multiplied by the factor 6. All bDNA negative samples were retested with the more sensitive transcription-mediated amplification (TMA) assay (sensitivity limit, 5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7% versus 14.2% [P< 0.0005]). Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment. Taking the simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative TMA test within the first 4 weeks as predictors for treatment response, SVR rates were comparable between both treatment schedules with an SVR probability of >80% obtained in patients treated for only 18 or 24 weeks. Conclusion: The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia. (HEPATOLOGY 2009.) [source] Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection,HEPATOLOGY, Issue 2 2009Alessandra Mangia In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 ,g/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm3 [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. Conclusion: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI. (HEPATOLOGY 2008.) [source] Cell culture,produced hepatitis C virus does not infect peripheral blood mononuclear cells,HEPATOLOGY, Issue 6 2008Svetlana Marukian Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed in association with other tissues and cells including B and T lymphocytes, monocytes, and dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates HCV entry, replication and virus production in vitro to re-examine the issue of HCV infection of blood cell subsets. The HCV replicase inhibitor 2,C-methyl adenosine was used to distinguish HCV RNA replication from RNA persistence. Whereas cell culture,grown HCV replicated in Huh-7.5 hepatoma cells, no HCV replication was detected in B or T lymphocytes, monocytes, macrophages, or dendritic cells from healthy donors. No blood cell subset tested expressed significant levels of Claudin-1, a tight junction protein needed for HCV infection of Huh-7.5 cells. A B cell line expressing high levels of Claudin-1, CD81, and scavenger receptor BI remained resistant to HCV pseudoparticle infection. We bypassed the block in HCV entry by transfecting HCV RNA into blood cell subsets. Transfected RNA was not detectably translated and induced high levels of interferon-,. Supernatants from HCV RNA,transfected macrophages inhibited HCV replication in Huh-7.5 cells. Conclusion: We conclude that multiple blocks prevent blood cells from supporting HCV infection. (HEPATOLOGY 2008;48:1843-1850.) [source] A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3,,HEPATOLOGY, Issue 6 2008Peter Ferenci We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa-2a 180 ,g/week in treatment-naive patients infected with hepatitis C virus (HCV) genotype 2 or 3. A total of 97 of 141 patients randomized to group A (68.8%, 95% confidence interval [CI] 60.5%-76.3%) and 90 of 141 patients randomized to group B (63.8; 95% CI 55.3%-71.7%) achieved a sustained virological response, defined as undetectable serum HCV RNA at the end of untreated follow-up (week 48). Among patients infected with genotype 3, the rate of sustained virological response was 67.5% (95% CI 58.4%-75.6%) in group A and 63.9% (95% CI 54.7%-72.4%) in group B, and among patients infected with genotype 2, the rate of sustained virological response was 77.8% (95% CI 54.2%-93.6%) in group A and 55.6% (95% CI 38.4%-83.7%) in group B. Relapse rates in the 2 treatment groups were similar (17% in group A and 20% in group B). The incidence of adverse events, laboratory abnormalities, and dose reductions was similar in the 2 treatment groups. Conclusion: The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3. (HEPATOLOGY 2008.) [source] Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response,HEPATOLOGY, Issue 1 2008Olav Dalgard A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA,positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon ,-2b (1.5 ,g/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, ,0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (HEPATOLOGY 2007.) [source] Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis,,§HEPATOLOGY, Issue 6 2006Vincenzo Mazzaferro Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA,positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc],negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc,positive) groups, then randomized to IFN-, (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09,0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment. (HEPATOLOGY 2006;44:1543,1554.) [source] Hepatitis C virus load and survival among injection drug users in the United States,HEPATOLOGY, Issue 6 2005Michie Hisada Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RHadj= 2.26 per log10 IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RHadj= 2.57 per log10 IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RHadj= 1.14 and 1.29 per log10 IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RHadj= 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RHadj= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection. (HEPATOLOGY 2005.) [source] Intrafamilial transmission of hepatitis C in Egypt,HEPATOLOGY, Issue 3 2005Mostafa K. Mohamed The incidence of hepatitis C (HCV) infection and associated risk factors were prospectively assessed in a cohort of 6,734 Egyptians from 2 rural villages who were negative for antibodies to HCV (anti-HCV). Initial and follow-up sera were tested for anti-HCV by enzyme immunoassay (EIA), and possible incident cases were confirmed by using the microparticle enzyme immunoassay (MEIA) and tested for HCV RNA. All follow-up serum samples converting from negative to positive without detectable HCV-RNA were further tested by recombinant immunoblot assay. Over an average of 1.6 years, asymptomatic anti-HCV seroconversion occurred in 33 people (3.1/1,000 person-years [PY]), including 28 (6.8/1,000 PY) in the Nile Delta village (AES), where prevalence was 24% and 5 (0.8/1,000 PY) in the Upper Egypt village (baseline prevalence of 9%). The strongest predictor of incident HCV was having an anti-HCV,positive family member. Among those that did, incidence was 5.8/1,000 PY, compared (P < .001) with 1.0/1,000 PY; 27 of 33 incident cases had an anti-HCV,positive family member. Parenteral exposures increased the risk of HCV but were not statistically significant; 67% of seroconverters were younger than 20 years of age, and the highest incidence rate (14.1/1,000 PY) was in children younger than 10 who were living in AES households with an anti-HCV,positive parent. In conclusion, young children would especially benefit from measures reducing exposures or preventing infection with HCV. (HEPATOLOGY 2005.) [source] High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C,HEPATOLOGY, Issue 2 2005Karin Lindahl Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (,24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation. (HEPATOLOGY 2005;41:275,279.) [source] Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: A pilot studyHEPATOLOGY, Issue 6 2004Olav Dalgard The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 ,g/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis. (HEPATOLOGY 2004;40: 1260,1265.) [source] Long-term follow-up after successful interferon therapy of acute hepatitis CHEPATOLOGY, Issue 1 2004Johannes Wiegand Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-,-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-,) ELISPOT analysis detected HCV-specific CD4+ T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8+ T-cell responses were found in 4 of 5 HLA -A2,positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-,-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8+ (but not CD4+) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment. (HEPATOLOGY 2004;40:98,107.) [source] Course and outcome of hepatitis CHEPATOLOGY, Issue 5B 200231 Center Dr., Jay H. Hoofnagle Bldg. 3, Room 9A2 The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. [source] Maternal-infant transmission of hepatitis C virus infectionHEPATOLOGY, Issue 5B 2002Eve A. Roberts 555 University Ave. Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. The prevalence of antibody to HCV (anti-HCV) in pregnant women is 0.1% to 2.4%, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia is 60% to 70%. Transmission of HCV occurs only when serum HCV RNA is detectable and may be related to higher levels (above 106 copies per mL). The rate of mother-to-infant transmission is 4% to 7% per pregnancy in women with HCV viremia. Co-infection with human immunodeficiency virus (HIV) increases the rate of transmission 4 to 5 fold. The actual time and mode of transmission are not known. Elective Cesarean section is not recommended for women with chronic HCV infection alone. The role of treatment to prevent transmission is limited by the fetal toxicity of currently available medications for hepatitis C. Breast feeding poses no important risk of HCV transmission if nipples are not traumatized and maternal hepatitis C is quiescent. Pregnant women at high risk for HCV infection should be screened for anti-HCV, and HCV RNA testing should be performed if anti-HCV is positive. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months and again at 18 to 24 months, along with serum anti-HCV. The natural history of mother-to-infant hepatitis C remains uncertain, especially the course in the first year of life when some infants appear to have spontaneous resolution. [source] Maternal-infant transmission of hepatitis C virus infectionHEPATOLOGY, Issue S1 2002Eve A. Roberts M.D., FRCPC Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. The prevalence of antibody to HCV (anti-HCV) in pregnant women is 0.1% to 2.4%, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia is 60% to 70%. Transmission of HCV occurs only when serum HCV RNA is detectable and may be related to higher levels (above 106 copies per mL). The rate of mother-to-infant transmission is 4% to 7% per pregnancy in women with HCV viremia. Co-infection with human immunodeficiency virus (HIV) increases the rate of transmission 4 to 5 fold. The actual time and mode of transmission are not known. Elective Cesarean section is not recommended for women with chronic HCV infection alone. The role of treatment to prevent transmission is limited by the fetal toxicity of currently available medications for hepatitis C. Breast feeding poses no important risk of HCV transmission if nipples are not traumatized and maternal hepatitis C is quiescent. Pregnant women at high risk for HCV infection should be screened for anti-HCV, and HCV RNA testing should be performed if anti-HCV is positive. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months and again at 18 to 24 months, along with serum anti-HCV. The natural history of mother-to-infant hepatitis C remains uncertain, especially the course in the first year of life when some infants appear to have spontaneous resolution. (HEPATOLOGY 2002;36:S106,S113). [source] Intrahepatic hepatitis C viral RNA status of serum polymerase chain reaction,negative individuals with histological changes on liver biopsyHEPATOLOGY, Issue 6 2001Sharon Barrett For individuals testing anti-HCV positive but negative for HCV RNA in serum, diagnosis remains unclear. Debate exists over whether these individuals have resolved infection or have similar clinical, histological, and virological profiles as serum PCR,positive individuals. The aim of this study was to assess the significance of histological changes in the liver of 33 serum PCR,negative women by investigation of clinical, histological, and intrahepatic HCV RNA status. For comparison, clinical and histological data from 100 serum PCR,positive women is presented. Viral RNA status was determined in snap-frozen liver biopsies using a sensitive nested PCR with an internal control. Although serum PCR,positive and ,negative individuals shared similar age at diagnosis, source, and duration of infection, they differed from a clinical, histological, and virological perspective. Mean serum ALT levels were significantly lower in serum PCR,negative women (27.4 IU/L ± 18 vs. 58.7 IU/L ± 40 P < .001). Similarly, although inflammation (82%) and mild fibrosis (15%) were observed in PCR,negative biopsies, the mean HAI/fibrosis scores were significantly lower than in serum PCR,positive biopsies (1.9 ± 1.5/0.15 ± 0.4 vs. 4.2 ± 1.4/1.1 ± 1.3, respectively). Finally, HCV RNA was not detectable in serum PCR,negative liver biopsies but was detectable in all serum PCR,positive control biopsies. In conclusion, serum PCR,negative individuals may have mild histological abnormalities more suggestive of nonspecific reactive changes, steatosis or nonalcoholic steatohepatitis rather than chronic HCV, even when significant antibody responses are present in serum. Negative serum PCR status appears to reflect cleared past-exposure in liver. [source] Relapse of hepatitis C in a pegylated-interferon-,-2b plus ribavirin-treated sustained virological responderHEPATOLOGY RESEARCH, Issue 6 2010Hideki Fujii A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-,-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR. [source] Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis C virus infection for the fiscal year 2008 in JapanHEPATOLOGY RESEARCH, Issue 1 2010Hiromitsu Kumada In the 2008 guidelines for the treatment of patients with chronic hepatitis C, pegylated interferon (Peg-IFN) combined with ribavirin for 48 weeks are indicated for treatment-naive patients infected with hepatitis C virus (HCV) of genotype 1. Treatment is continued for an additional 24 weeks (72 weeks total) in the patients who have remained positive for HCV RNA detectable by the real-time polymerase chain reaction at 12 weeks after the start of treatment, but who turn negative for HCV RNA during 13,36 weeks on treatment. Re-treatment is aimed to either eradicate HCV or normalize transaminase levels for preventing the development of hepatocellular carcinoma (HCC). For patients with compensated cirrhosis, the clearance of HCV RNA is aimed toward improving histological damages and decreasing the development of HCC. The recommended therapeutic regimen is the initial daily dose of 6 million international units (MIU) IFN continued for 2,8 weeks that is extended to longer than 48 weeks, if possible. IFN dose is reduced to 3 MIU daily in patients who fail to clear HCV RNA by 12 weeks for preventing the development of HCC. Splenectomy or embolization of the splenic artery is recommended to patients with platelet counts of less than 50 × 103/mm3 prior to the commencement of IFN treatment. When the prevention of HCC is at issue, not only IFN, but also liver supportive therapy such as stronger neo-minophagen C, ursodeoxycholic acid, phlebotomy, branched chain amino acids (BCAA), either alone or in combination, are given. In patients with decompensated cirrhosis, by contrast, reversal to compensation is attempted. [source] Rapid loss of hepatitis C virus genotype 1b from serum in patients receiving a triple treatment with telaprevir (MP-424), pegylated interferon and ribavirin for 12 weeksHEPATOLOGY RESEARCH, Issue 11 2009Fumitaka Suzuki Aim:, To evaluate the efficacy and safety of the triple treatment with telaprevir (MP-424), pegylated interferon (PEG-IFN) and ribavirin during 12 weeks on-treatment. Methods:, The triple treatment was given to 20 patients with chronic hepatitis C who had been infected with hepatitis C virus (HCV)-1b in high viral load (median: 6.8 log IU/mL [range: 5.5,7.2]), with a median age of 54 years (range: 36,65 years). They were followed for early dynamics of HCV RNA in serum during 12 weeks and side-effects. Results:, HCV RNA levels decreased by 4.8 logs by 7 days and 5.5 logs by 14 days. HCV RNA disappeared in 50% (10/20) at 2 weeks, 79% (15/19) at 4 weeks, 88% (14/16) at 6 weeks, 94% (15/16) at 8 weeks and 100% (13/13) at 12 weeks. HCV RNA disappeared equally frequently in 10 treatment-naive patients, six non-responders to IFN monotherapy and four non-responders to PEG-IFN and ribavirin. It was no different in the patients with and without amino acid substitutions reducing the response to IFN. The treatment was withdrawn in seven (35%) patients, mostly due to reduced hemoglobin of less than 8.5 g/dL, of whom six (86%) remained clear of HCV RNA at 12 weeks. Conclusion:, HCV RNA was lost from serum rapidly and universally in patients infected with HCV-1b in high viral loads by the triple treatment. Because an early loss of HCV RNA correlates with high rates of sustained virological response (SVR), it would increase SVR substantially, and merit the patients who have not responded to previous therapies. [source] Predicting the response to 48-week combination therapy with peginterferon ,-2b plus ribavirin from the estimated HCV RNA load index after negative serum change in genotype 1b hepatitis C patientsHEPATOLOGY RESEARCH, Issue 6 2009Keiji Tsuji Aim:, We estimated viral dynamics after serum hepatitis C virus (HCV) RNA became negative and assessed the relation between the estimated viral load at the end of treatment (EVE) index and the response to the combination therapy with peginterferon ,-2b plus ribavirin. Methods:, Patients with chronic HCV, genotype 1b, and a high viral load were treated with this combination therapy for 48 weeks, and serum HCV RNA was measured frequently during the treatment period. In the patients showing an end-of-treatment response (ETR), the viral load profile from the start of treatment until serum HCV RNA became negative was expressed by an approximate curve. Then the EVE index was calculated by using the expression obtained from the curve, and differences between the sustained virologic response (SVR) and relapse groups were investigated. Results: The SVR rate increased as the EVE index became lower, and the EVE index was significantly lower in the SVR group than in the relapse group. The SVR rate was higher for those in whom the EVE index was below the cut-off point. Conclusion:, Prediction of SVR and relapse from the EVE index is more useful than prediction from viral dynamics at the time when HCV RNA becomes negative or when HCV RNA shows a decrease of 2-log or more. [source] Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus and non-diabetic on haemodialysisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2006S. Ocak Summary Type 2 diabetes mellitus (DM) has emerged as the commonest cause of end-stage renal disease. Haemodialysis (HD) treatment constitutes a high-risk environment for the transmission of hepatitis C virus (HCV). The aim of this study was to establish a potential relationship between type 2 DM and HCV infection in HD patients. Of the 267 HD patients, 67 (25.1%) had type 2 DM and 200 (74.9%) were with diverse aetiology for end-stage renal disease. The serum markers of HCV infection were tested by a second-generation enzyme-linked immunosorbent assay test for antibodies and by qualitative reverse-transcription polymerase chain reaction technique for viral RNA. The overall prevalence of anti-HCV antibodies and HCV RNA was found to be 12.7% (34/267) and 10.1% (27/267), respectively. Patients with type 2 DM were found to have a higher HCV prevalence compared with non-diabetic patients [20.8% (14/67) vs. 10% (20/200)] (p < 0.05). The mean period on dialysis of anti-HCV-positive patients with type 2 DM was shorter than that observed for anti-HCV-positive non-diabetic patients (43.9 ± 9.8 months vs. 59.7 ± 28.4 months) (p < 0.05). This study has shown that although the period on dialysis of diabetic patients are shorter than non-diabetic patients, the prevalence of HCV in HD patients with type 2 DM is higher than that detected in non-diabetic HD patients. [source] Erythema dyschromicum perstans and hepatitis C virus infectionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2001George J. Kontochristopoulos MD A 48-year-old woman with a 10-month history of widespread, hyperpigmented, slightly pruritic macules, with a red border, involving the trunk and the proximal limbs (Fig. 1) was referred to our outpatient department. The oral mucosa, palms, soles, scalp, and nails were normal. Figure 1. Multiple hyperpigmented macules with an active border on the trunk Laboratory tests showed elevated liver enzymes [alanine aminotransferase (ALT), 68 IU/L (normal value, <,40 IU/L); aspartate aminotransferase (AST), 41 IU/L (normal value, <,40 IU/L)], the presence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA (Amplicor Roche). In addition, cryoglobulinemia type III (IgM,,,, IgG,,,) was detected with a high cryocrit value, and there was detectable C-reactive protein, rheumatoid factor, and a low titer of antinuclear antibodies (1 : 80). A percutaneous liver biopsy showed changes compatible with mild chronic hepatitis (grade, 6; stage, 0). The possible source of infection was unknown, as the patient had no history of parenteral transmission (e.g. blood transfusions, intravenous illicit drug use). A skin biopsy specimen from the active border of a lesion showed hyperkeratosis, parakeratosis, and hydropic degeneration of the basal cell layer, with the formation of colloid bodies in the epidermis. A moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules was observed in the upper dermis (Fig. 2). Immunostaining of paraffin-embedded tissue sections with the TORDJT-22 IgG1 mouse monoclonal antibody to HCV (Biogenex, Son Ramon, USA), which is specific for the nonstructural region of HCV (NS3-NSH, C100 antigen) using the avidin,biotin,peroxidase complex (ABC) as well as the alkaline phosphatase antialkaline phosphatase (APAAP) methods, failed to detect HCV in the lesion of erythema dyschromicum perstans (EDP) (Nakopoulou L, Manolaki N, Lazaris A et al. Tissue immunodetection of C100 hepatitis C virus antigen in major thalassemic patients. Hepato-Gastroenterol 1999; 46: 2515,2520). Direct immunofluorescence showed IgG, IgM, IgA, and fibrinogen deposits on colloid bodies. EDP was diagnosed on the basis of these clinical and laboratory findings. Figure 2. Hydropic degeneration of the basal cell layer with colloid bodies in the epidermis. Moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules in the upper dermis (hematoxylin and eosin, ×,200) The patient was treated with interferon-,2b (Intron-A, Schering Plough Athens, Greece), 3 MU thrice weekly subcutaneously for 12 months, with additional topical steroid application. There was no response to this treatment with new lesions appearing in previously unaffected areas of the trunk and extremities. HCV RNA remained persistently positive. Thus, a modified regimen with interferon-,2b, 6 MU thrice weekly for 6 months, was tried. At the end of the treatment course, the eruption of EDP had greatly improved. Liver enzymes were normal (ALT, 22 IU/L; AST, 24 IU/L) and HCV RNA had become negative. Four months later, however, cutaneous lesions reappeared and hepatitis C relapsed. At this time point, combination therapy of interferon-,2b, 3 MU thrice weekly, with ribavirin, 1000 mg daily, was given. Six months later, liver enzymes were normal (ALT, 42 IU/L; AST, 39 IU/L), HCV RNA was negative, and the lesions of EDP had resolved. [source] Transcription-mediated amplification linked to line probe assay as a routine tool for HCV typing in clinical laboratories,JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2007R.S. Ross Abstract Typing of hepatitis C virus (HCV) isolates is currently a prerequisite for adequate tailoring of antiviral combination therapy. In many diagnostic laboratories, there seems to be a tendency toward convenient and time-saving procedures utilizing amplification products, which are already available from preceding qualitative or quantitative HCV ribonucleic acid (RNA) assays. In this context, we evaluated the performance characteristics of a combination of techniques, i.e., transcription-mediated amplification-line probe assay (TMA-LiPA), which links highly sensitive TMA of HCV RNA to the VERSANT HCV Genotype Assay (version 1). A total of 100 clinical samples were genotyped by TMA-LiPA. The obtained results were compared to those recorded by the original, nested reverse transcription (RT)-polymerase chain reaction (PCR)-based VERSANT assay, the core-related GEN-ETI-K DEIA, and phylogenetic analyses of partial sequences from the HCV core and NS5B regions. TMA-LiPA assigned the correct genotype to all 100 HCV isolates. For subtyping of genotype 1 and 2 isolates, TMA-LiPA only showed discriminatory powers of 82% and 53%, respectively. Thus, TMA-LiPA in our hands turned out as a convenient and time-saving routine procedure for HCV typing which currently provides sufficient information for clinical purposes. Like all 5,untranslated region (UTR)-based assays, the technique is limited, however, in its potentials to resolve the complexity of existing HCV subtypes. J. Clin. Lab. Anal. 21:340,347, 2007. © 2007 Wiley-Liss, Inc. [source] Efficacy of interferon-, treatment in Japanese children with chronic hepatitis CJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2003EISUKE NAKASHIMA Abstract Background: We investigated the efficacy of natural interferon (IFN)-, treatment in 34 Japanese children with chronic hepatitis C. Methods: Thirty-four children completed 6 months of therapy with natural IFN-, and were followed for 12 months or longer. We examined the serum hepatitis C virus (HCV) RNA titer and liver histology before, during, and after IFN treatment. Results: At 6 months after the cessation of IFN-, treatment, 16 patients (47%) had normal serum alanine aminotransferase concentration and no detectable serum HCV RNA. There were no major side-effects, excluding some influenza-like symptoms during the IFN-, treatment. Most genotype 2a patients had a complete response (80%). Moreover, patients who had a low HCV RNA titer (<102 copies/mL) after 1 month of IFN-, treatment became complete responders at 6 months after the cessation of treatment. Histological improvement was observed in almost all patients after IFN-, treatment. Conclusion: Interferon-, treatment is safe and effective for children with chronic hepatitis C and has no serious side-effects. A HCV RNA concentration of <102 copies/mL after 1 month of IFN-, treatment and genotype 2a may be useful predictors of long-term IFN efficacy. © 2003 Blackwell Publishing Asia Pty Ltd [source] Hepatitis C virus infection in a Japanese leprosy sanatorium for the past 67 yearsJOURNAL OF MEDICAL VIROLOGY, Issue 4 2010Kazuya Shiogama Abstract Oku-Komyo-En is one of the national leprosy sanatoria, located on a small island in Setouchi city, Okayama prefecture of Japan since 1938. Since autopsies were carried out routinely on almost all patients who had died in the sanatorium up to 1980, approximately 1,000 formalin-fixed autopsy tissue samples were available for analysis. When these samples were reviewed, the pathological data indicated a sharp rise in the death rate caused by cirrhosis of the liver and hepatocellular carcinoma (HCC) since 1960 and 1970, respectively. Hepatitis C virus (HCV) infection is a common cause of HCC in Japan. The presence of HCV RNA was demonstrated in paraffin sections prepared from the autopsied liver tissue fixed in formalin for a prolonged period of time, by employing nested RT-PCR using type-specific primers. The data showed that HCV RNA was detectable in samples of the liver archived as early as 1940, representing the liver tissues kept in formalin for up to 67 years. HCV genotypes 1b and 2a were found by RT-PCR at 85.7% and 14.3%, respectively, in patients with leprosy. J. Med. Virol. 82:556,561, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular detection of hepatitis B, hepatitis C, and torque teno viruses in drug users in Saudi ArabiaJOURNAL OF MEDICAL VIROLOGY, Issue 8 2009Alhusain J. Alzahrani Abstract Injecting drug users are at increased risk of infection with hepatitis viruses and blood-borne pathogens. The aim of this study was to examine HBV, HCV, HDV, and TTV infections in Saudi drug users (N,=,344). Extraction of nucleic acid from serum, reverse-transcription, amplification of viral nucleic acids, and HBV and HCV genotyping were done using established techniques. Of the analyzed samples, 41 (12%) contained detectable HBV DNA, 131 (38%) contained detectable HCV RNA, and 174 (51%) had detectable TTV DNA. The predominant HBV genotype was found to be genotype D and the predominant HCV genotype was found to be genotype 1b. All the samples were negative for HDV. Twelve samples (3.5%) were found to contain mixed HBV and HCV genomes, 24 samples (7%) were found to contain mixed HBV and TTV genomes, 82 samples (24%) were found to contain mixed HCV and TTV genomes, and 9 samples (2.6%) were found to contain mixed HBV, HCV, and TTV genomes. Identification of various infections in drug users will help the control of these infections in this group as well as in the community. J. Med. Virol. 81:1343,1347, 2009. © 2009 Wiley-Liss, Inc. [source] Hepatitis C virus does not infect muscle, the intervertebral disk, or the meniscus in patients with chronic hepatitis CJOURNAL OF MEDICAL VIROLOGY, Issue 12 2007Javier Bartolomé Abstract Chronic infection with hepatitis C virus (HCV) is associated with several extrahepatic manifestations, including neuromuscular and joint disorders, and HCV RNA has been detected in muscle fibers of patients with myosistis and chronic hepatitis C. However, whether HCV infects muscle cells in patients without myosistis is unknown. The presence of HCV in other sites of the musculoskeletal system has not been investigated. In the present study the presence of HCV RNA was sought in muscle (2 cases), intervertebral disk (1 case) and meniscus (1 case) samples from patients with chronic hepatitis C. HCV RNA was not detected by reverse transcription and real-time polymerase chain reaction in any of the samples tested. In conclusion, the results do not support a direct role of HCV in musculoskeletal disorders associated with chronic hepatitis C. J. Med. Virol. 79:1818,1820, 2007. © Wiley-Liss, Inc. [source] Genetic characterization of hepatitis C virus strains in Estonia: Fluctuations in the predominating subtype with timeJOURNAL OF MEDICAL VIROLOGY, Issue 4 2007Tatjana Tallo Abstract During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994,2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5,-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5,UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999,2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P,<,0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia. J. Med. Virol. 79:374,382, 2007. © 2007 Wiley-Liss, Inc. 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