Hepatitis C Virus (HCV) RNA Level Determined by Second-Generation Branched-DNA Probe Assay as Predictor of Response to Interferon Treatment in Patients with Chronic HCV Viremia

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype 1b and 37 genotype 2a) with chronic HCV viremia received 24-week IFN- treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype 1b patients [5.4 × 10⁶ HCV genome equivalent (Meq)/ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype 1b patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level 1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype 1b patients with level 1.0 Meq/ml (57.6%) than in those with level >1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of 1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.     

Viraemia,cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus

OBJECTIVES: The clinical features of hepatitis C virus (HCV) infection depend on the immune and autoimmune reactions induced by the virus. Chronic renal failure might alter the pattern of these reactions. The aim of this study was to determine the prevalence of cryoglobulinaemia, the frequency of autoantibodies and HCV viral load in HCV infected Greek patients on chronic haemodialysis. METHODS: Seventy-three HCV Ab(+) patients on maintenance haemodialysis and 87 otherwise normal patients with chronic HCV infection were evaluated for the presence of cryoglobulins, autoantibodies and viral markers. RESULTS: Cryoglobulins were detected in 22/73 (30.1%) haemodialysis patients and in 23/87 (26.4%) patients with normal renal function (NS). The mean cryocrit value was significantly lower in the haemodialysis group ( = 0.002). Haemodialysis patients had significantly higher levels of C4 component of complement and lower incidence of rheumatoid factor than those of patients with normal renal function. Serum HCV RNA levels were found significantly lower in the haemodialysis group (median, 2.20 Meq/ml; range, 119.9 Meq/ml) than in the group with normal renal function (median, 4.50 Meq/ml; range, 114.9 Meq/ml; = 0.046). The distribution of genotypes was not different between the two groups. CONCLUSIONS: There are subtle differences in autoimmune features of HCV infection if the patients are also haemodialysed for renal failure. HCV viral load is lower in haemodialysis patients, with no difference in the HCV genotype prevalence. The clinical significance of these findings is unknown.     

Low HCV replication levels in end-stage hepatitis C virus-related liver disease.

BACKGROUND/AIMS: The relationship between HCV RNA levels and the severity of HCV-related liver disease has been addressed in a few studies, which has led to conflicting results. To clarify this point, we studied serum HCV RNA levels in patients with HCV liver disease at various stages, using a second-generation branched DNA (bDNA) assay. METHODS: One hundred and forty-eight patients with chronic HCV infection were classified into 3 groups: group A included 92 patients with chronic active hepatitis (CAH) without cirrhosis; group B included 30 patients with CAH and compensated cirrhosis; group C included 26 patients with end-stage cirrhosis. In all patients, serum HCV RNA was sought by qualitative PCR and quantified using second-generation bDNA assay. HCV RNA was also quantified after liver transplantation in 22 patients from group C. HCV genotype was determined in all patients. RESULTS: HCV RNA was detected by PCR in 100%, l00% and 92% of the patients from groups A, B and C, respectively (NS). The proportion of patients with HCV RNA levels higher than the cut-off of bDNA assay was significantly lower in patients from group C than in patients from groups A and B (50% vs 94% and 93% respectively, p<0.0001). The mean HCV viremia was lower in group C than in groups A and B (1.35+/-0.24 MEq/ml vs 5.00+/-6.04 MEq/ml and 5.85+/-7.70 MEq/ml, respectively, p<0.0001). This difference was independent of HCV genotype. In the patients from group C, post-transplant HCV RNA levels were significantly higher than pretransplant HCV RNA levels (14.90+/-26.40 vs 1.35+/-0.24 MEq/ml, p=0.0065). CONCLUSIONS: HCV RNA levels do not appear to differ significantly among patients with CAH with or without compensated cirrhosis. In contrast, HCV RNA levels seem to be significantly lower in patients with end-stage HCV-related liver cirrhosis. In these patients, high levels of replication are restored after liver transplantation, suggesting that low pretransplant viral loads are not due to the intrinsic characteristics of the infective viral strains, but rather to the severity of liver disease.     

Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection

BACKGROUND/AIMS: End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. METHODS: Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9+/-10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. RESULTS: HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0+/-9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. CONCLUSIONS: Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.     

慢性丙型肝炎患者病毒基因分型与血清HCV RNA水平的关系探讨

目的研究HCV基因型的分布,以探讨不同基因型感染者血清HCV RNA载量的差异。方法采用PCR法检测218例慢性丙型肝炎患者血清HCV RNA;采用ELISA法检测抗-HCV抗体;使用全自动生化分析仪测定丙氨酸氨基转移酶;采用化学发光免疫分析法测定血清肝纤维化指标;采用基因芯片法进行HCV基因分型。结果在218例HCV RNA阳性血清中共检出9种基因型,分别是lb、2a、3a、3b、6型单基因型共208例和lb+2a、lb+3b、lb+6型、2a+3a共10例四种混合基因型,其中以lb型168例(77.1%)、2a型19例(8.7%)为主;在208例HCV单基因型感染患者中发现不同基因型感染者血清HCV RNA载量无统计学差异(F=0.932,P>0.05);在168例1b基因型和40例非lb基因型感染者,性别差异无统计学意义(x2=0.857,P>0.05),两型感染者之间肝纤维化指标差别比较也无统计学意义。结论我国HCV基因型以lb型为主,基因型与HCV RNA载量及ALT水平之间无相关性。     

血液透析患者丙型和庚型肝炎病毒感染的研究

为了解血液透析患者中丙型肝炎病毒(HCV)和庚型肝炎病毒(HGV)的感染情况,并探讨相对危险因素,对48例在302医院和武警总医院进行维持性血液透析的患者用逆转录聚合酶链(PCR)反应和酶联免疫法检测了血清中HCV RNA、HGV RNA及其抗体水平。结果显示,抗-HCV和HCV RNA阳     

Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study

BACKGROUND: The severity, clinical course, and risk of hepatitis C virus (HCV) related chronic liver disease are still rather poorly defined. AIMS: To investigate the prevalence, risk factors, and severity of HCV related liver disease in the general population, and investigate whether infection with a specific genotype is associated with an increased risk of cirrhosis or hepatocellular carcinoma. METHODS: HCV RNA determination by polymerase chain reaction (PCR) and HCV genotyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular carcinoma was established by liver biopsy in all cases. All the data were analysed by univariate and multivariate statistics in all the cohort. To investigate the natural history of HCV infection, anti-HCV positive subjects were followed up every six months for three years with liver function tests and ultrasonograms. RESULTS: The overall prevalence of HCV RNA positivity was 2.3%. Positivity increased progressively with age, and was higher in women (ratio of men to women = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intravenous drug use, blood transfusions received before 1990, history of previous hepatitis among the cohabiting, and history of animal (mainly dogs) bites were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, sex, and alcohol intake, genotype 1b infection, with or without coinfection with other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of follow up, 57 (35%) of the HCV RNA positive subjects had consistently normal alanine aminotransferase and gamma-glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcohol a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year). CONCLUSIONS: In the general population of Northern Italy, HCV infection is widespread, but only less than 50% of the anti-HCV positive subjects, particularly those infected with genotype 1b, are associated with a more severe liver disease. Alcohol consumption greater that 30 g a day significantly aggravates the natural course of the disease.     

Distribution of HCV Genotypes in Patients with End-Stage Renal Disease According to Type of Dialysis Treatment

The objective of this study was to investigate the effects of types of dialysis treatments on hepatitis C virus infection and the epidemiologic properties of hepatitis C virus (HCV) infection at three Baskent University hospitals, in Ankara, Adana, and Izmir, Turkey, in 655, 326, and 118 patients with end-stage renal disease, respectively. One hundred thirty patients with HCV viremia among 271 patients with end-stage renal disease seropositive for HCV were included in this cross-sectional study. HCV RNA-positive patients were classified according to the renal replacement therapies (hemodialysis or continuous ambulatory peritoneal dialysis), and viral load, transaminase levels, and distribution of genotypes were compared between these subgroups. In the continuous ambulatory peritoneal dialysis group, 26 of 165 patients (16%) were serum anti-HCV positive, and 11 of 26 patients (42%) were serum HCV RNA positive. Twenty-six percent of the patients undergoing hemodialysis were anti-HCV positive, and 49% were HCV RNA positive. The prevalence of genotype 1b was 68% and 73% for patients in the continuous ambulatory peritoneal dialysis and hemodialysis groups, respectively. No significant differences were found between the genotype 1b and the non-1b groups or between different dialysis types with regard to age and sex and serum aspartate transaminase, alanine aminotransferase, and HCV RNA levels. We conclude that HCV seropositivity may differ between different types of dialysis treatments, although viral load and genotypes may be similar in persons with end-stage renal disease and those without.     

Usefulness of combined application of double‐filtration plasmapheresis and twice‐daily injections of interferon‐β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load

Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and has been recognized as an important prognostic factor. Therefore, the aggressive antiviral therapy is necessary for HCV infection in HD patients. However, various treatment limitations exist in HD patients such as the inability to use ribavirin. We have previously reported that HCV RNA can be eradicated by administration of interferon (IFN)‐β during HD in patients with HCV infection caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA levels. In this case report, we tried to clarify the efficacy of combined application of double‐filtration plasmapheresis (DFPP) and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. We report two HD patients with HCV genotype 1b infection and high viral loads who were successfully treated by five sessions of DFPP undertaken prior to treatment with IFN‐β (twice‐daily injections for 2 weeks). HCV was eradicated by this combination therapy in both patients. We revealed the efficacy of combined application of DFPP and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. This combined therapy may be useful for the HD patients who are resistant to conventional IFN monotherapy.     

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。     

Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1–4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39±4 vs 3.6±8 Meq/ml,P<0.0001) but significantly lower ALT (56±11 vs 97±12 units/liter,P=0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.     

Recent approach for diagnosis of early HCV infection

Detection of HCV infection during the window phase of infection, before seroconversion, is important in blood screening. However, a significant delay exists between the time of infection and the development of antibodies. The delay in window period can last up to 70 days. The aim of the present study was to investigate the kinetics of HCV markers during early infection, with detection of HCV core antigen as an early method for diagnosis. The study included determination of HCV RNA by qualitative and quantitative PCR, HCV core antigen detection by enzyme linked immunosorbent assay (ELISA) and specific serological markers including anti-HCV IgG and IgM. The study was carried out on 34 patients diagnosed as non A non B acute hepatitis and proved to be hepatitis C by qualitative HCV RNA PCR. Sixteen healthy control subjects were also included. From each consenting patient and control, blood samples were collected and serum was separated and subjected to determination of AST and ALT and the following virological laboratory tests: HCV core antigen detection by ELISA, determination of specific anti-HCV IgM and specific anti-HCV IgG, qualitative and quantitative determination of HCV RNA by second version of PCR. In patients, the median quantity of HCV RNA was 739.1 x 10(3) lu/ml with minimum quantity 2.1 x 10(3) lu/ml and maximum 38352.3 x 10(3) lu/ml. A comparison between the different diagnostic methods revealed that the highest sensitivity was for HCV-core antigen detection (82.4%), specificity was 100% negative predictive value was 72.2% and positive predictive value was 100%. Specific anti-HCV IgG had moderate levels of sensitivity (58.5%), specificity (75%), negative predictive value (46.2%)and positive predictive value (83.3%). The least sensitive method was the specific anti-HCV IgM (29.4%) with negative predictive value 40% but had specificity and positive predictive value of 100% of each. From this study we could conclude the followings: From virological methods, serological detection of specific IgM anti-HCV had the least sensitivity limits, while it had the highest specificity and positive predictive value. Specific anti-HCV IgG had moderate sensitivity and specificity. The most sensitive and specific tool for diagnosis of early HCV viraemia was the detection of HCV core Ag by ELISA when compared to molecular biological methods.     

Hepatitis C Virus RNA Levels Determined by Branched DNA Probe Assay Correlated with Levels Assessed Using Competitive PCR

Objective: To search for comparative differences, levels of hepatitis C virus (HCV) RNA were examined by branched DNA (bDNA) probe assay and by competitive polymerase chain reaction (PCR). Methods: The study population included 234 patients (chronic hepatitis 146, cirrhosis 36, hepatocellular carcinoma 52), all of whom were positive for HCV RNA, as determined by PCR. We quantified HCV RNA levels of all serum samples by both bDNA probe and competitive PCR. Results: HCV RNA was detected in serum samples by bDNA assay in 142 (60.7%) of the 234 patients; this rate was significantly higher in 106 (73.6%) of the 144 patients of genotype II than in 20 (41.7%) of 48 of genotype III and in 16 (38.1%) of 42 of genotype IV (p < 0.001, respectively). The median HCV RNA levels by bDNA assay (×10⁶eq/ml) were 0.1,0.1,0.4,1.4, and 5.3 among patients with HCV RNA levels <3, 4, 5, 6, and 7, respectively, by competitive PCR (logarithmic transformation copy numbers/50 μl). A significant correlation was found between HCV RNA levels by bDNA and competitive PCR ( r = 0.5747, p < 0.001). There was a correlation among patients of genotype II and genotype III but not genotype IV. Conclusion: We recommend bDNA assay for use in clinical practice because the procedure is not difficult and is less contamination-prone. The HCV RNA levels determined using this assay correlated with those examined by competitive PCR.     

Hepatitis C virus (HCV) Infection Rate among Seronegative Hemodialysis Patients Screened by Two Methods; HCV Core Antigen and Polymerase Chain Reaction

Background

End-stage renal disease patients on chronic hemodialysis are among high risk groups for hepatitis C virus (HCV) infection for whom routine HCV screening is recommended. Anti-HCV antibody (ab) testing may not be reliable to detect all infected cases because of the blunted ab response due to depressed immune state in these patients. Using a more reliable, cost-effective and non-complex HCV screening test may be necessary in this group of patients for case finding and management, and also for prevention of infection spread.

Objectives

The aim of this study was to find the prevalence of HCV infection in HCV ab negative hemodialysis patients by Real time PCR and total HCV core antigen (ag) test and comparing the results of the two tests.

Patients and Methods

From a single hemodialysis center, 181 anti- HCV ab negative patients were screened by total HCV core ag using an ELISA kit. Real time PCR was used for determination of the virus and viral load quantity.

Results

Among the 181 anti-HCV ab negative patients, 13 (7.2%) were positive for HCV core ag and 11 (6%) had detectable HCV RNA with a range of 40-336543 IU/ml by PCR. The two tests had a high measurement agreement (Kappa=0.82, P<0.001). Of the 13 patients with positive HCV core ag test results, 3 were negative for HCV RNA. Considering real time PCR for HCV RNA as the gold standard for HCV infection determination in this patient population, HCV core ag assay yielded a sensitivity of 90.9%, specificity of 98.2%, positive predictive value of 76.9% and negative predictive value of 99.4%.

Discussion

The rate of HCV infection among HCV ab negative hemodialysis patients was high. HCV core ag testing could be used as a sensitive method for HCV infection screening in this group of patients.     

Characteristics of complete responders to interferon among patients with chronic hepatitis C with high serum levels of RNA

Patients with chronic hepatitis C with high serum levels of HCV RNA are less likely to show a complete response to IFN therapy than those with a low serum levels of HCV RNA. The characteristics of patients with high serum levels of HCV RNA who show a complete response to IFN therapy have not been evaluated in detail. We retrospectively analyzed the 121 patients with high serum levels of HCV RNA (≥ 1.0 Meq/ml) before IFN therapy to determine the characteristics of complete responders. A complete response to IFN was observed in 12 (9.9%) of 121 patients. There was no difference between complete responders and non-responders in age, the result of liver function tests, or liver histology. In all complete responders, pretreatment serum level of HCV RNA was less than 5.0 Meq/ml, which was significantly lower than the level in the non-responders (P < 0.01). The fluctuation of HCV RNA level less than 0.5 Meq/ml was observed in ten of the 12 complete responders. The frequency of serotype 2 was significantly higher in the complete responders compared with the non-responders (P < 0.05). These findings suggest that complete responders are rare among patients with serum levels of HCV RNA ≥5.0 Meq/ml. In planning IFN therapy, fluctuations in the HCV RNA level, as well as the serotype, should be considered.     

Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19–68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 × 10⁶ eq/ml; range <0.2–69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (3 × 10⁶ eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 × 10⁶ eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels 3 × 10⁶ eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels 3 × 10⁶ eq/ml and grade 3–4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury.     

Liver steatosis in hepatitis C positive hemodialysis patients and factors affecting IFN-2a treatment

OBJECTIVE: Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD) patients. It is well known that HCV causes approximately 50% of hepatosteatosis in patients with normal renal function and that this rate is higher in patients infected with genotype 3. The aim of this study was to investigate the rate of steatosis, the regression in steatosis with interferon (IFN) treatment and factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C (CHC). MATERIAL AND METHODS: Thirty-seven HD patients with CHC were included in the study. All patients received hemodialysis treatment three times a week during the follow-up period. Patients were treated with 3 million units (MU) of IFN-alpha 2a monotherapy for at least 6 months. All patients were evaluated by liver biopsy before therapy and 16 were evaluated at 12-month follow-up. RESULTS: Mean age of the 37 patients (23 M, 14 F) was 44+/-11.6 years and body mass index was 21.8+/-1.8 kg/m2. Twenty-eight of the patients included in the study (75.7%) were of genotype 1b. RNA response after treatment was 78.4% and sustained response after the follow-up period of 14.9+/-8 months was 54%. Total cholesterol values were directly proportional to RNA response (p<0.003) and inversely correlated with resistance to treatment (p<0.008). Triglyceride values were inversely correlated with resistance to treatment (p<0.041). At evaluation of steatosis scores in baseline liver biopsy, severe and mild to moderate steatosis was found in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there was no steatosis. The rate of steatosis was found to be 44% in control biopsies. While there was no regression in the rates of steatosis (p=0.499), it was found that steatosis regressed after IFN treatment in two patients infected with genotype 3. No correlations were observed between HCV genotype, sustained response and liver steatosis. CONCLUSIONS: Response and sustained response rates of HD patients with HCV in a Turkish population were found to be high after IFN monotherapy. With the exception of two patients infected with genotype 3a, the rate of liver steatosis was found to be high and did not change after IFN treatment in HD patients with CHC.     

No Significant Changes in Levels of Hepatitis C Virus (HCV) RNA by HCV Infection Competitive Polymerase Chain Reaction in Blood Samples from Patients with Chronic

To determine if levels of hepatitis C virus(HCV) RNA change over a several-year period, wequantified the amount of HCV RNA by competitivepolymerase chain reaction. The population studiedincluded 44 residents of a rural area with chronic HCVinfection, 39 had chronic hepatitis C and 37 werepatients on hemodialysis. All these Japanese patientshad HCV RNA of genotype II. Blood samples were collected once a year from 1992 to 1995. From 1993 to1995 between the groups, there was no significantdifference in change of HCV RNA levels of 44 residentswith chronic HCV infection, with and without liverdysfunction, nor was there any change in the 31 hemodialysispatients from 1992 to 1995. The HCV RNA levels in the 25with chronic hepatitis who did not respond tointerferon-alpha during 1992-1993 returned topretreatment levels after the cessation of interferontreatment. In two of six hemodialysis patients who wereinfected with HCV during this observation period, HCVRNA was eliminated within one year, and the remaining four became HCV carriers. HCV RNA levels in thelatter rose rapidly after infection and were sustainedat a high level throughout the study period. Thus, HCVRNA level did not change remarkably during a three-year period, a finding which supportsthat it does not correlate with deterioration of liverdamage and aging of HCV carriers.     

HCV RNA levels in a multiethnic cohort of injection drug users: human genetic, viral and demographic associations

In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV enzyme immunoassay were tested for HCV viremia by a branched-chain DNA assay. HCV genotype was determined by sequencing the HCV nonstructural 5B protein region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1,701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). Human immunodeficiency virus type 1 (HIV-1) prevalence was 13.9%. The overall median HCV RNA level was 6.45 log(10) copies/mL. In unadjusted analyses, higher levels were found with older age, male gender, African-American ancestry, hepatitis B virus infection, HIV-1 infection, and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotypes 3 or 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype, and IL28B rs12979860 genotype were all independently associated with HCV RNA. CONCLUSION: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors.