Mean Hepatitis C Virus RNA Levels Research Articles

Hepatitis C Treatment by Directly Acting Antiviral Agents and Its Impact on Glycemic Control

Objective: To evaluate Hepatitis C treatment by directly acting antiviral agents and its impact on glycemic control. 
 Study Design: This is an observational study.
 Setting: This study was conducted in Medicine department Civil Hospital Karachi from March 2018 to December 2019.
 Materials and Methods: Patients visiting the outpatient department of the hospital having documented HCV infection having type 2 diabetes mellitus were included in the study. All participants were given directly acting antiviral treatment for 12 weeks. After treatment they were assessed for achievement of sustained virological response (SVR). Pre-treatment and post treatment fasting blood glucose levels and HbA1c levels were checked. SVR is defined as serum HCV RNA which is undetectable (<50IU/ml) after 12 weeks of antiviral treatment.
 Results: Around 332 patients matched our inclusion criteria. Amongst these there were 219 males and 113 females. The mean age of patients was 39.44 ± 2.19 years. All the selected participants started therapy on Sofosbuvir-velpatasvir (pangenotypic NS5A-NS5B inhibitor single-pill combination regimen that has potent activity against hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, and 6.) plus ribavirin. After treatment with directly acting antiviral therapy 231 (69.57%) patients achieved sustained virological response. Patients who achieved SVR showed improved glycaemic control than those who didn’t. Patients with cirrhosis showed decreased chances of attainment of SVR. Fasting blood glucose levels and HbA1c were also decreased, decreasing the amount of insulin required for diabetes control. 
 Conclusion: Our study showed that treatment with directly acting antiviral treatment improved glycaemic control in HCV infected patients. Other factors like BMI, presence of cirrhosis, mean serum HCV RNA levels and adherence to treatment were major predictors for achievement of SVR.

Serum‑derived hepatitis C virus can infect human glioblastoma cell line SF268 and activate the PI3K‑Akt pathway.

Extra‑hepatic manifestations are frequently observed in hepatitisC virus (HCV)‑infected patients; however the underlying mechanisms remain largely unknown. In the present study, the human glioblastoma SF268 cell line (the precise origin of the cell type is not clear) was infected with HCV using HCV‑positive serum, and viral replication was assessed by immunofluorescence, reverse transcription‑polymerase chain reaction (PCR), quantitative PCR and western blotting following infection. HCV core protein and HCV RNA were detected in HCV‑positive serum‑infected SF268 cells at day4 post‑infection, while no infection was observed in cells exposed to HCV‑negative serum. The mean HCV RNA levels at day 4 post‑infection were up to 5.00IU/ml log10; however, HCV RNA and immunostaining for core protein were negative when cultured to day6 or longer. The data suggest that human glioblastoma SF268 cells were transiently infected with HCV. AKT serine/threonine kinase phosphorylation was also detected in HCV‑infected SF268 cells at day4 post‑infection. To the best of our knowledge, this is the first demonstration that a human glioblastoma cell line can be infected with serum‑derived HCV. The results provide evidence that HCV infection can occur in cells of the central nervous system. Neurological disorder‑associated phosphoinositide3‑kinase‑AKT signaling pathway was activated in parallel with HCV infection, suggesting that SF268 may serve as an invitro model for investigating HCV‑nervous system cell interactions.

Hepatitis C virus load in parenchyma cells correlates with hepatic injury in infected patients

The association between serum hepatitis C virus (HCV) load and hepatic injury in HCV-infected patients has been extensively investigated. The present study aimed to investigate the association between HCV load in hepatic parenchyma cells and hepatic injury in HCV-infected patients. A total of 56 HCV-infected patients were included in the present retrospective study. The serum HCV mRNA was determined using quantitative polymerase chain reaction, while the hepatic parenchyma cell volume and HCV mRNA in hepatic parenchyma cells were also determined. Hepatic injury was evaluated on the basis of the severity of inflammation and fibrosis. The results demonstrated that there were evident differences in the mean serum HCV RNA levels and the HCV load/parenchyma cell volume among the various grades of hepatic inflammation (G1-G4) when groups with the least and most inflammation were compared (G1 vs. G4; P<0.05). Significant differences in the HCV load existed between groups divided according to the fibrosis grade; in addition, differences existed between fibrosis grades S1 and S2, and S2 and S4 when comparing serum HCV RNA levels (P<0.05). Similarly, differences existed between every two fibrosis stages (S0 vs. S4, S2 vs. S3, and S2 vs. S4; P<0.05) when viral loads and parenchyma cell volumes were compared (F=2.860, P<0.05). Furthermore, the fibrosis staging was correlated with the viral load/parenchyma cell volume (F=2.670, P<0.05). In conclusion, hepatic fibrosis grade was found to be associated with HCV load in parenchyma cells. The results of the present study demonstrated that the viral load in parenchyma cells is a more appropriate index compared with the serum viral load for evaluating HCV replication in hepatocytes, and may function as an important factor in HCV-infected hepatic injury evaluation.

Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.

A Pilot Study Examining the Safety and Tolerability of Valacyclovir in Veterans With Hepatitis C Virus/Herpes Simplex Virus Type 2 Coinfection

IntroductionWe performed a pilot study examining the safety and tolerability of valacyclovir in veterans with herpes simplex virus type 2 and hepatitis C virus (HCV) coinfection. MethodsWe performed a randomized double-blind, placebo-controlled, crossover clinical trial in U.S. veterans with genotype 1 HCV/herpes simplex virus type 2 coinfection. Patients were randomized 1:1 in blocks of 10 to receive either 1g twice-daily valacyclovir or matching placebo for 8 weeks followed by a 2-week washout phase with daily placebo. The alternate therapy (valacyclovir or placebo) was given for an additional 8-week period. Safety assessments were performed every 2 weeks. Changes in HCV RNA and alanine aminotransferase (ALT) were estimated using linear mixed models (SAS Proc Mixed). ResultsThirty patients were enrolled. Valacyclovir was not associated with toxicity or adverse events. ALT levels declined 6% to 10%; mean HCV RNA levels were reduced 24% (1.3 million IU/mL [0.21 log10 IU/mL]) during the valacyclovir phase (P=0.08) with no carryover effect observed (P=0.21). ConclusionsValacyclovir 1g twice daily showed no evidence of hepatotoxicity in U.S. veterans with hepatitis C. A modest reduction in serum levels of ALT and plasma levels of HCV RNA was observed.

The effect of cryoglobulinemia on the antiviral therapy in patients with chronic hepatitis C

To investigate the possible influence of cryoglobulinemia on the antiviral effect in chronic hepatitis C patients, who were treated with combination therapy of pegylated interferon alpha-2a and ribavirin. Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with ribavirin. Baseline cryoglobulins were detected in the sera by cryoprecipitation. Hepatitis C virus (HCV) genotyping was performed and HCV viral load was detected at baseline, and at 4, 12 weeks during treatment, 24 weeks after cessation of treatment. Eighteen (45.0%) patients infected with HCV were cryoglobulins positive at baseline. Mean serum HCV RNA level in cryoglobulins positive patients was higher than that in cryoglobulins negative patients (6.36+/-0.63 vs. 5.70+/-1.20, P = 0.032). The rapid virological response (RVR) rate was statically different between cryoglobulins positive patients and cryoglobulins negative ones (6/18, 33.3% vs. 15/22, 68.2%, P = 0.028). In contrast, no difference was found in early virological response (EVR) rate between the cryoglobulins positive patients and cryoglobulins negative ones (14/17, 82.4% vs. 18/21, 85.7%, P = 1.0). Sustained virological response (SVR) rate in cryoglobulins positive and cryoglobulins negative was different (0/3, 0 vs 6/6, 100%, P = 0.012). The rate of patients achieved RVR was different between the patients infected with HCV genotype 1 b of two groups (cryoglobulins positive: 2/13, 15.4% vs cryoglobulins negative 14/21; 66.7%, P = 0.005). However, the rate of EVR in patients infected HCV genotype 1 b was not statistically different (cryoglobulins positive: 9/12, 75.0% vs. cryoglobulins negative 17/20; 81.2%, P = 0.647). The rates of RVR and SVR achievement in cryoglobulinemia positive CHC patients are lower than those in cryoglobulinemia negative CHC patients.

Identifying HCV genotype 1 patients at risk of relapse

The objective of this analysis was to identify predictors of relapse in genotype 1 patients after 48 weeks of treatment with peginterferon plus ribavirin. Retrospective analysis of data from treatment-naive genotype 1 patients with an end-of-treatment response after 48 weeks of treatment with peginterferon alpha-2a plus ribavirin 1000/1200 mg/day in the Canadian Pegasys Expanded Access Program. Among treatment-naive genotype 1 patients with an end-of-treatment response (n = 432), the sustained virological response status was known for 405 individuals (sustained virological response n = 328, 81%; relapse n = 77, 19%). Early virological response rates at week 12 were similar in relapsers (98.7%) and sustained responders (98.5%). More relapsers (12 of 77, 15.6%) than sustained responders (15 of 328, 4.6%) had quantifiable hepatitis C virus (HCV) RNA (>or=600 IU/ml) at week 12 and, among these patients, mean and maximum HCV RNA levels were higher in relapsers, although the median values were similar. Factors significantly associated with relapse in the multiple logistic regression analysis include older age (odds ratio: 1.48 per decade, 95% confidence interval: 1.06-2.07; P = 0.023), Caucasian ethnicity (odds ratio: 3.23, confidence interval: 1.25-8.33; P = 0.016), higher baseline serum HCV RNA level (P = 0.005), the drop in HCV RNA between baseline and week 12 (P = 0.026), and the interaction between baseline HCV RNA level and the decrease in HCV RNA between baseline and week 12 (P = 0.032). Older age, Caucasian ethnicity, and high baseline HCV RNA level, and a smaller decrease in HCV RNA between baseline and week 12 predict a relapse in genotype 1 patients.

Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients

Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa-2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was cloned from HCV genotype 1-infected patients (n = 22). A mean number of 47 clones were sequenced before, at the end, and after treatment with 400 mg boceprevir twice or three times daily for 14 days for genotypic, phenotypic, and viral fitness analysis. At the end of treatment, a wild-type an NS3 protease sequence was observed with a mean frequency of 85.9%. In the remaining isolates, five previously observed resistance mutations (V36M/A, T54A/S, R155K/T, A156S, V170A) and one mutation (V55A) with unknown resistance to boceprevir were detected either alone or in combination. Phenotypic analysis in the HCV replicon assay showed low (V36G, T54S, R155L; 3.8- to 5.5-fold 50% inhibitory concentration [IC(50)]), medium (V55A, R155K, V170A, T54A, A156S; 6.8- to 17.7-fold IC(50)) and high level (A156T; >120-fold IC(50)) resistance to boceprevir. The overall frequency of resistant mutations and the level of resistance increased with greater declines in mean maximum HCV RNA levels. Two weeks after the end of treatment, the frequency of resistant variants declined and the number of wild-type isolates increased to 95.5%. With the exception of V36 and V170 variants all resistant mutations declined by more than 50%. Mathematical modeling revealed impaired replicative fitness for all single mutations, whereas for combined mutations a relative increase of replication efficiency was suggested. During boceprevir monotherapy, resistance mutations at six positions within the NS3 protease were detected by way of clonal sequence analysis. All mutations are associated with reduced replicative fitness estimated by mathematical modeling and show cross-resistance to telaprevir.

Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.

Interferon Treatment in Hemodialysis Patients With Chronic Hepatitis C Virus Infection: A Systematic Review of the Literature and Meta-analysis of Treatment Efficacy and Harms

Hepatitis C virus (HCV) infection is prevalent in patients undergoing hemodialysis and is associated with greater mortality. We determined the efficacy and harms of interferon (IFN) and pegylated IFN (PEG-IFN) treatment of hemodialysis patients with chronic HCV infection and identified factors associated with these outcomes. Meta-analysis and meta-regression of randomized controlled trials, uncontrolled trials, and prospective observational studies. Hemodialysis patients with chronic HCV infection. MEDLINE indexed studies since 1966, sample size greater than 10. IFN-based treatment, including PEG-IFN with and without ribavirin. Sustained virological response (SVR) 6 months after treatment, rate of treatment discontinuation caused by adverse events, and factors associated with these outcomes. 20 studies of 459 IFN-treated patients, 3 studies of 38 PEG-IFN-treated patients, and 2 studies of 49 PEG-IFN and ribavirin-treated patients met inclusion criteria. The overall SVR rate was 41% (95% confidence interval [CI], 33 to 49) for IFN and 37% (95% CI, 9 to 77) for PEG-IFN. Treatment discontinuation rates were 26% (95% CI, 20 to 34) for IFN and 28% (95% CI, 12 to 53) for PEG-IFN. SVR was higher with 3 million units (MU) or higher of IFN 3 times weekly, with lower mean HCV RNA, and with lower rates of cirrhosis, HCV genotype 1 or elevated transaminase, but these findings were not statistically significant. Treatment discontinuation rates were greater in studies using larger doses. Publication bias, few randomized controlled trials, and limitations in generalizability to all hemodialysis patients. IFN treatment of hemodialysis patients results in an SVR rate of 41%. Higher dose, lower mean HCV RNA level, and lower rates of cirrhosis, transaminase level increase, and HCV genotype 1 may be associated with greater SVR rates, but additional studies using individual patient data are needed.

Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C

Aims:Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients...

Associations of tumour necrosis factor alpha promoter polymorphisms at position −308 and −238 with clinical characteristics of chronic hepatitis C

The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions -308 (TNF308.2) and -238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF-alpha variants were determined in 250 biopsy-proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of -308 and -238 TNF-alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels (<800 000 IU/mL; P = 0.031) and severe fibrosis stage (F3-F4; P = 0.006) and higher mean fibrosis score (P = 0.007). The higher cytokine production (with one or two TNF308.2 alleles) was correlated significantly with lower pretreatment HCV RNA levels with a lower mean HCV RNA level (P = 0.024) and increased frequency of lower pretreatment HCV RNA levels (<800 000 IU/mL; P = 0.017). Stepwise logistic regression showed that higher fibrosis score and low HCV RNA levels were independently related to the TNF308.2 allele [odds ratio (95% CI): 1.385 (1.127-1.702) and 0.698 (0.488-0.990)]. We conclude that inheritance of the TNF-alpha promoter genotype at the position -308 appears to be associated with variability in severity of fibrosis and viral load in chronic HCV infection.

Hepatitis C Virus (HCV) Genotypes and Disease Progression in HIV/HCV‐Coinfected Patients

The relationship between hepatitis C virus (HCV) genotype and HCV and human immunodeficiency virus (HIV) type 1 disease is not well defined. The present study analyzed data from a cohort of 207 HIV-1-infected and 126 HIV-1-uninfected children and adolescents with hemophilia who enrolled in the Hemophilia Growth and Development Study and were followed for 7 years. The mean HCV RNA level was higher in the participants in the HCV genotype 1 group than in the participants the HCV non-genotype 1 group, among both the HIV-1-infected (difference, +0.33 log 10 copies/mL; P = .038) and HIV-1-uninfected (difference, +0.59 log 10 copies/ mL; P = .008) participants. Although HCV genotype was not associated with differences in HIV-1 RNA level, a significantly lower mean CD4 + T cell count (difference, -127 cells/μL; P =.026) and percentage of CD4 + T cells (difference, -4.3%; P =.027) were observed in the participants in the HCV genotype 1 group, compared with those in the participants in the HCV non-genotype 1 group. In addition, the participants in the HCV genotype 1 group were at increased risk for progression to AIDS-related mortality (hazard ratio, 2.44; P = .037). The present study suggests that HCV infection and genotype may influence the natural history of HCV and HIV-1 disease.

Effect of Hepatitis C Virus (HCV) Genotype on HCV and HIV‐1 Disease

The relationship between hepatitis C virus (HCV) genotype and HCV and human immunodeficiency virus (HIV) type 1 disease is not well defined. The present study analyzed data from a cohort of 207 HIV-1-infected and 126 HIV-1-uninfected children and adolescents with hemophilia who enrolled in the Hemophilia Growth and Development Study and were followed for 7 years. The mean HCV RNA level was higher in the participants in the HCV genotype 1 group than in the participants the HCV non-genotype 1 group, among both the HIV-1-infected (difference, +0.33 log(10) copies/mL; P=.038) and HIV-1-uninfected (difference, +0.59 log(10) copies/mL; P=.008) participants. Although HCV genotype was not associated with differences in HIV-1 RNA level, a significantly lower mean CD4(+) T cell count (difference, -127 cells/ microL; P=.026) and percentage of CD4(+) T cells (difference, -4.3%; P=.027) were observed in the participants in the HCV genotype 1 group, compared with those in the participants in the HCV non-genotype 1 group. In addition, the participants in the HCV genotype 1 group were at increased risk for progression to AIDS-related mortality (hazard ratio, 2.44; P=.037). The present study suggests that HCV infection and genotype may influence the natural history of HCV and HIV-1 disease.

Early Hepatitis C Viral Response (EVR) to Peginterferon Alfa 2a and Ribavirin in Patients with β Thalassemia.

Hepatitis C virus (HCV) infection is an important cause of liver failure and death in patients with thalassemia who received frequent blood transfusions before HCV screening became routine. Severe transfusion-related iron overload may accelerate the progression of liver disease, influence response to therapy, and increase the risk of antiviral treatment in these patients. An open-label, single arm trial of peginterferon alfa 2a (180 ug weekly) and ribavirin (1200 mg/day for > 75 kg, 1000 mg/day 50 to 75 kg, 800 mg for < 50kg) was initiated in August, 2003 in the NIH-sponsored Thalassemia Clinical Trials Network to examine safety and efficacy in adult patients. Although the study is still enrolling patients, we are presenting viral response data for the first 16 patients (mean age: 33 yrs, range 22 to 44, 50% female, 75% genotype 1). Iron burden was assessed by chemical analysis of liver biopsy and HCV RNA levels were measured using the Roche COBAS HCV Tests (qualitative and quantitative). These analyses were performed by a central laboratory. HCV levels were measured at baseline, weeks 1, 2, 3, 4, 12 and 24.Early Virologic ResponsesWeek 1Week 2Week 3Week 4Week 12Week 24N*16161616116Non-d**122375>2-log567731% >2 log38%50%56%63%91%100%*number with result available; **non-detectable; ***greater than 2 log decreaseFour patients discontinued between weeks 4 through 12 (1 death, 1 persistent cough, 1 extreme fatigue, and 1 pregnancy (spouse). These patients had all achieved > 2 log drop by week 4. The mean liver iron at baseline was 10.1 mg/gm dry wt (range: 1.1 to 21.2) and the mean log HCV RNA level was 5.8 (range 4.0 to 6.8). The median time to > 2 log decrease was 1 week for patients with genotype 2 and 4 weeks for patients with genotype 1 (p=0.004). There was no correlation either between baseline iron or baseline HCV level and time to > 2 log decrease. Transfusion requirement increased 52% as assessed at 12 weeks and did not predict earlier viral response. In summary, there is EVR (>2 log drop) in 63% at 4 weeks and 91 % at 12 weeks, comparable to those seen in patients without thalassemia. Quantitative hepatic iron concentration at baseline was not a predictor of EVR. Completion of the study is planned to determine whether the EVR predicts sustained viral response and whether the iron overload or increased transfusion requirements during therapy pose significant safety issues.

Assessment of correlation between serum titers of hepatitis C virus and severity of liver disease.

The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels. Moreover, a direct association has been observed between serum titers of HCV and transmission rates of the virus. The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. Fifty patients with HCV infection were included in the study. These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics. Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique. Linear regression analysis was performed between serum viral titers and liver tests. In addition, for the purpose of comparison, the subjects were divided into two groups: those with low viral titers (< or = 50 genome mEq/mL) and high titers (> 50 mEq/mL). All subjects were men, with a mean +/- SD age of 47 +/- 7.8 years. The mean HCV RNA level in the blood was 76.3 x 10(5) +/- 109.1 genome equivalents/mL. There was no correlation between HCV RNA levels and age of the patients (r = 0.181), and the history or amount (g/d) of alcohol consumption (r = 0.07). Furthermore, no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r = 0.175), bilirubin (r = 0.217), ALT (r = 0.06) and AST (r = 0.004) levels. Similarly, no significant difference was observed between patients with low viral titers and high titers with respect to any of the parameters. Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus. These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.

Pretreatment hepatitis C virus dynamics for predicting virological response to interferon-α2b monotherapy in patients with chronic hepatitis C virus infection

One hundred and forty-one patients with chronic hepatitis C virus (HCV) infection treated with 6 MIU of interferon (IFN)-α2b for 24 weeks were studied to compare pretreatment viral dynamics during 1 month before the initiation of treatment (ΔHCV) with other predictive factors. The patients were classified into three groups according to ΔHCV: the Increase group (ΔHCV >0.20 log copies/ml/month), the Stable group (−0.20≤ΔHCV≤0.20 log copies/ml/month) and the Decrease group (ΔHCV<−0.20 log copies/ml/month). The sustained response (SR) rates were 0/40 (0%) in the Increase group, 6/54 (11.1%) in the Stable group and 25/47 (53.2%) in the Decrease group ( P<0.0001). Based on the HCV RNA level at baseline, the SR rates were lower in the Increase group than that in the Decrease group in less than 5.0 log copies/ml (0% vs. 100.0%, P=0.0132) and at 5.00–5.49 log copies/ml (0% vs. 81.8%, P=0.0270), respectively. The pretreatment HCV RNA decrease was determined as independent predictors of SR by multivariable logistic regression analysis ( P<0.0001). For serial assays of HCV RNA during treatment, there was not significant difference in mean HCV RNA level at baseline but was significantly different on day 14 between the Decrease and the Nondecrease groups (1.15 vs. 2.21 log copies/ml, P=0.0417). These results suggest that ΔHCV is independently associated with the IFN response and is useful for determining the indication of IFN treatment.

Comparative analysis of viral titers and histologic features of Pakistani patients infected with hepatitis C virus type 3

Background: Serum hepatitis C virus (HCV) RNA levels and genotypes are considered to be important determinants of the response to interferon treatment. Generally, patterns of viral loads have been reported for HCV type 1 infections and categorized as low- or high-level viremia. We studied the distribution of HCV RNA levels in patients predominantly infected with HCV type 3 and correlated it with hepatic damage. Methods: Serum HCV RNA levels and HCV serotypes were determined in 245 anti-HCV-positive patients representing all the major ethnic groups of Pakistan. Patients were grouped according to their HCV RNA levels as: level I (up to 50th percentile); level 11 (50th to 75th percentile); and level III (>75th percentile). Results: Sixty-one patients (25%) had high-level viremia (level 111) of 13.9 mega equivalent per milliliter (MEq/mL) or greater. These were more likely to be males (48 versus 13, P<0.05). A higher viral load correlated with advanced levels of fatty changes in liver. HCV type 3 was found in 68% of the samples, and type 1 in 14%; the rest were undefined. Mean HCV RNA levels were lower in patients infected with HCV type 3 than in patients infected with HCV type 1 (8.63 MEq/mL versus 37 MEq/mL; P < 0.001). Conclusions: Most patients with HCV type 3 infection had viremia that was significantly lower than that in HCV type 1-infected patients. This may be the reason for the better response to treatment usually seen in such cases. The severity of histologic changes was not associated with HCV type 3 viremia levels.

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 lb and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-alpha 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 lb patients [5.4 x 10(6) 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 lb patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level < or = 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 lb patients with level < or = 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 < or = 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of < or = 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.

Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto-antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.