Higher HCV RNA Levels Research Articles

Sofosbuvir-based regimens for HCV in stage 4–stage 5 chronic kidney disease. A systematic review with meta-analysis

BackgroundHepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD. Study aims and designWe performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. ResultsThirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I2=99.8%) and 0.09 (95% CI, 0.05; 0.13, I2=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I2=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, −0.01; 0.04, I2=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I2=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I2=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found. ConclusionsSOF-based regimens appear safe and effective in patients with stage 4–5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.

Sofosbuvir-based regimens for HCV in stage 4–stage 5 chronic kidney disease. A systematic review with meta-analysis

BackgroundHepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD. Study aims and designWe performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. ResultsThirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I2=99.8%) and 0.09 (95% CI, 0.05; 0.13, I2=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I2=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, −0.01; 0.04, I2=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I2=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I2=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found. ConclusionsSOF-based regimens appear safe and effective in patients with stage 4–5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.

Thiol-disulphide balance and total oxidant-antioxidant status in patients with chronic hepatitis C.

To assess the dynamic thiol/disulphide homeostasis (DTDH) and total oxidant/antioxidant status in patients with hepatitis C virus (HCV) infection and to evaluate their association with HCV-RNA levels. Levels of serum total thiol (TT), native thiol (NT), disulphide (DS), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) as oxidative stress markers were determined in 162 individuals, including 74 patients with HCV infection and 88 non-HCV controls. HCV genotypes and HCV-RNA levels of the patients were recorded. The NT, TT and TAS levels and NT/TT ratio were significantly lower in the HCV group compared with the control group. On the contrary, DS, TOS and OSI levels and DS/NT and DS/TT ratios were significantly higher. Patients with high HCV RNA levels (> 650000IU/mL) had higher DS levels than patients with low HCV-RNA levels (<650000IU/mL). Genotype 1 was observed in 68.9% of patients with HCV. Levels of oxidative stress parameters were similar between genotype 1 and other genotypes (2, 3 and 5). No significant correlations were found between oxidative stress markers and albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin and HCV-RNA levels in patients with HCV infection. A negative correlation was found only between OSI and albumin. Our results suggest that DTDH shifts towards the DS direction because of thiol oxidation in HCV-infected patients. Furthermore, DS levels were significantly higher in patients with high HCV-RNA levels compared with patients with low HCV-RNA levels.

The incidence of resistance-associated variants to NS5A in HCV subtypes 1a and 1b in Taiwan

BackgroundResistance-associated variants (RAVs) to direct-antiviral agents (DAAs) may hamper treatment. There was a lack of data on the natural prevalence of RAVs in Taiwanese HCV-infected patients. We investigated the real-life presence of RAVs in the nonstructural 5A (NS5A) region in HCV genotype 1a and 1b in chronically infected individuals in Taiwan. MethodsIn this single-center cohort study, nested polymerase chain reaction and direct sequencing analysis was used to determine the frequency of RAVs in the HCV NS5A region in patients with HCV genotype 1a (n = 55) and 1b (n = 525). ResultsIn genotype 1a strains, the incidence of RAVs was 16.4% (9/55) in the NS5A region (M28V/T, n = 6, 10.9%; Q30L, n = 1, 1.8%; Y93N/H, n = 3, 5.5%). In genotype 1b, the incidence of RAVs was 17.5% (92/525) in the NS5A region (L31I/M/V, n = 7, 1.3%; Y93 H/S, n = 87, 16.5%). Patients with RAVs had significantly higher HCV RNA levels (6.1 ± 0.7 vs 5.9 ± 0.8 log IU/mL, p = 0.001) and lower rGT levels (28.9 ± 18.9 vs. 42.9 ± 57.0 U/L, p = 0.001) compared to those without RAVs. Multivariate analysis identified HCV RNA levels (odds ratio = 1.145, 95% CI: 1.060–1.237, p = 0.001) and rGT (OR = 0.989, 95% CI: 0.978–0.999, p = 0.035) as risk factors that are associated with the presence of RAVs. Importantly, there is no association between the presence of RAVs and no SVR (3.8% in patients with RAVs, 15.9% in patients without RAVs, p = 0.32). ConclusionRAVs, especially M28V and Y93H in the NS5A region, were highly prevalent in patients with genotype 1a and 1b HCV, respectively, in Taiwan, and they were linked to high HCV RNA levels and low rGT levels. Before using the NS5A inhibitors, the presence of mutated HCV variants should be taken into consideration.

Prevalence of Hepatitis C Virus Infection in a Surgical Population of Southeast China: A Large-Scale Multicenter Study.

Background Chronic HCV infection affects 80 million people globally and may progress to advanced liver disease. The present study aims to investigate the present epidemiology of HCV infection in a southeastern Chinese surgical patient cohort. Methods Blood samples obtained from 78,484 surgical patients from 18 different city and county hospitals were enrolled. The incidence of serum HCV antibody positivity, HCV RNA load, and HCV genotyping, as well as demographics and relevant clinical history, were investigated. Data were stratified using the multistage cluster random sampling method and further analyzed using the SPSS-20 package. Results HCV antibody positivity was detected in 0.15% of the population (95% confidence interval (CI): 0.12%–0.18%). Genotype 1b (55.74%) was the dominant type. The HCV infection peaked in the age groups of 16–20, 41–50, and 61–65 years, and it was higher in males than in females (0.19% vs. 0.13%, P < 0.05). The geographical distribution of infection rates differed: 0.19% (95% CI: 0.14%–0.24%), 0.18% (95% CI: 0.13%–0.23%), and 0.06% (95% CI: 0.03–0.09%) in plain areas, islands, and valley regions, respectively. Patients with transfusion history and urban residence were associated with high HCV RNA levels (adjusted odds ratio = 11.24 and 6.20, P < 0.05). Conclusion The prevalence of HCV infection in this cohort from southeast China was 0.17%, which is lower than the reported 0.43% infection rate in China in 2006. This result can be (partially) explained by the improvement of blood donor screening and the successful campaign for the use of disposable syringes and needles.

LOW CONCENTRATIONS OF HEPATITIS C VIRUS RNA IN SEROLOGICALLY MILD INFECTION

Occult HCV infection (OCI) provides significant interest recently. HCV RNA in this case can be detected not in plasma, but in blood cells and/or in liver tissue. In case of antibody genesis impairment anti-HCV detection may lead to negative or "uncertain" result. The aim of the study was to estimate infection type in blood donors and patients with hematological diseases by exploration of samples with uncertain anti-HCV detection results. Blood samples of 30 180 potential blood donors' and 4322 patients with hematological diseases were tested. Comparative analysis of wide pattern of HCV markers was performed. 33 blood donors and 42 patients were enrolled in follow-up examination. Uncertain results of Anti-HCV detection in donors' samples were in 0.18% of cases. Follow-up examination of 33 donors provided discordant results using immunochemiluminescence assay and ELISA. 15.2% donors' samples contained HCV RNA in low concentration. Follow-up observation of 42 patients with incomplete antiviral antibody pattern showed HCV RNA presence in 40.5% cases (21.4% high viremia and 19.0% low viremia). Samples with low RNA concentration contained low titers of anti-core antibodies. Samples with high titers of anti-core antibodies contained high HCV RNA level. Uncertain results of anti-HCV in 15.2% of potential blood donors' samples were confirmed by detection of HCV RNA in low concentration. It proved OCI presence in these individuals and called for testing for wide pattern of HCV markers in addition to routine screening. Patients with hematological diseases showed low level of HCV RNA along with low titers of antibodies against one or two viral antigens.

Higher hepatitis C virus‐viral loads and complex sexual partners in hepatitis C virus‐human immunodeficiency virus coinfected injection drug users: A case‐control study

Injection drug users (IDUs) are likely contributors to hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infections. However, little is known about the HCV viral loads of IDUs with HCV‐HIV coinfection. The aim of this prospective study was to investigate the HCV viral loads among IDUs with HCV infection, HCV‐HIV coinfection, and HCV‐HBV coinfection. Among the 45 IDUs recruited to the study, 27 were HCV monoinfected; 9 were HCV‐HIV coinfected; 7 were HCV‐HBV coinfected; and 2 were seronegative for HCV, HBV, or HIV infection. A control group of 180 age‐ and gender‐matched chronic HCV‐infected patients were enrolled using the propensity score method. A standardized case record form was used to collect demographic, clinical, laboratory, and virological data. The HCV RNA levels in IDUs with HCV‐HIV coinfection were significantly higher than those in the control group, IDUs with HCV monoinfection, and IDUs with HCV‐HBV coinfection (P &lt; 0.001, P &lt; 0.001, and P &lt; 0.001, respectively). The HCV‐RNA levels in the control group were higher than those in IDUs with HCV monoinfection and HCV‐HBV coinfection (P = 0.04 and P = 0.039, respectively). After analyzing the risk factors related to these viral infections in IDUs, a complex sexual partner was more prevalent among IDUs with HCV‐HIV coinfection than those with HCV monoinfection or HCV‐HBV coinfection (P = 0.02 and P = 0.035, respectively). IDUs with HCV‐HIV coinfection demonstrated extremely high HCV‐RNA levels. Antiviral therapy, especially in the directly acting antiviral era, is indicated. In addition, IDUs with a complex sexual partner had a significantly higher risk of HIV infection. Therefore, the measure to curb this transmission is more important for infectious control.

HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype.

The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

Burden of Liver Disease among Community-Based People Who Inject Drugs (PWID) in Chennai, India.

Background and ObjectiveWe characterize the burden of liver disease in a cohort of PWID in Chennai, India, with a high prevalence of HCV.Materials and Methods1,042 PWID were sampled through community outreach in Chennai. Participants underwent fasting blood draw, questionnaire and an examination that included liver stiffness assessment using transient elastography (Fibroscan) and assessment of steatosis via ultrasound.ResultsThe median age was 39 years, all were male, 14.8% were HIV infected and 35.6% were HCV antibody positive, of whom 78.9% were chronically infected (HCV RNA positive). Median liver stiffness was 6.2 kPA; 72.9% had no evidence of or mild stiffness, 14.5% had moderate stiffness, and 12.6% had evidence of severe stiffness/cirrhosis. Prevalence of severe stiffness/cirrhosis was significantly higher among persons who were older, had a longer duration of injecting drugs, higher body mass index, higher prevalence of insulin resistance, higher prevalence of steatosis, higher HCV RNA levels and evidence of alcohol dependence. An estimated 42.1% of severe stiffness/cirrhosis in this sample was attributable to HCV. 529 (53.0%) had some evidence of steatosis. Prevalence of steatosis was higher among those who had larger waist circumference, insulin resistance, higher HDL cholesterol and a history of antiretroviral therapy.ConclusionsWe observed a high burden of liver disease in this relatively young cohort that was primarily driven by chronic HCV infection, metabolic factors (insulin resistance and steatosis) and heavy alcohol use. Interventions to improve access to HCV treatment and reduce alcohol use are needed to prevent further progression of liver disease.

HCV-HIV coinfected pregnant women: data from a multicentre study in Italy.

To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels.

Hepatitis C virus (HCV) infection is associated with chronic inflammation; yet studies show greater interleukin (IL)-6, but lower C-reactive protein (CRP) levels. We determined whether liver fibrosis severity and HCV replication affect the ability of IL-6 to stimulate the production of CRP from the liver. We used multivariable generalized linear regression to examine the association of HIV, HCV and transient elastography-measured liver stiffness with IL-6 and CRP in participants (164 HIV-monoinfected; 10 HCV-monoinfected; 73 HIV/HCV-coinfected; 59 neither infection) of the Women's Interagency HIV Study. Significant fibrosis was defined as liver stiffness greater than 7.1 kPa. IL-6 was positively correlated with CRP levels in all women, but CRP levels were lower in HCV-infected women (with and without HIV infection) at all levels of IL-6. HCV-infected women with fibrosis had nearly 2.7-fold higher IL-6 levels compared to controls [95% confidence interval (CI 146%, 447%]; HCV-infected women without fibrosis had IL-6 levels that were similar to controls. By contrast, CRP was 28% lower in HCV-infected women with fibrosis (95% CI -55%, 15%) and 47% lower in HCV-infected women without fibrosis (95% CI -68%, -12%). Among the HCV-infected women, higher HCV-RNA levels were associated with 9% lower CRP levels per doubling (95% CI -18%, 0%). Liver fibrosis severity is associated with greater IL-6 levels, but the stimulatory effect of IL-6 on CRP appears to be blunted by HCV replication rather than by liver fibrosis severity. Investigation of the potential CRP rebound after HCV-RNA eradication and persistent liver fibrosis on organ injury is needed.

Tu1013 On-Treatment HCV RNA As a Predictor of Sustained Virologie Response in HCV Genotype 3 - Infected Patients Treated With Daclatasvir and Sofosbuvir: Analysis of Phase 3 Ally-3 Study

A S L D A b st ra ct s rates in patients treated with DCV/ASV/BCV combined with RBV and in patients with GT1b subtype. Other baseline factors such as age, gender, BMI, IL28B genotype, HCV RNA >800,000 IU/mL, and platelet count <100 × 109/L did not appear to impact SVR12 rates in either cohort (Table). Similarly, race did not appear to influence SVR12 rates; of the 20 black patients enrolled in the study, all 20 achieved SVR12. Prior null response to pegIFN did not significantly impact outcome in the treatment-experienced cohort. Baseline resistanceassociated variants (RAVs) in NS5A (28, 30, 31, 93) or NS3 (168) did not impact SVR: 26/ 28 patients with NS5A RAVs and 2/2 patients with NS3 RAVs achieved SVR12. NS5B-P495 was not detected at baseline. Among patients with virologic failure, RAVs were detected in NS5A (Q30, Y93, L31), NS3 (R155, D168) and NS5B (P495, P421). Conclusion: The alloral fixed-dose combination of DCV, ASV, and BCV achieved high rates of SVR12 in patients with HCV genotype 1 infection and compensated cirrhosis. The strongest predictors of SVR12 were GT1b and use of RBV. Factors often associated with reduced responses to less potent regimens, such as advanced age, black race, prior null response to pegIFN, high baseline HCV RNA levels, low platelet counts, non-CC IL28B genotype, and baseline NS5A or NS3 RAVs did not appear to impact SVR12 rates.

Tu1015 MALACHITE-II: Phase 3b Trial of Ombitasvir/Paritaprevir/R and Dasabuvir + Ribavirin or Telaprevir + Peginterferon/Ribavirin in Peginterferon/Ribavirin Treatment-Experienced Adults With HCV Genotype 1

A S L D A b st ra ct s rates in patients treated with DCV/ASV/BCV combined with RBV and in patients with GT1b subtype. Other baseline factors such as age, gender, BMI, IL28B genotype, HCV RNA >800,000 IU/mL, and platelet count <100 × 109/L did not appear to impact SVR12 rates in either cohort (Table). Similarly, race did not appear to influence SVR12 rates; of the 20 black patients enrolled in the study, all 20 achieved SVR12. Prior null response to pegIFN did not significantly impact outcome in the treatment-experienced cohort. Baseline resistanceassociated variants (RAVs) in NS5A (28, 30, 31, 93) or NS3 (168) did not impact SVR: 26/ 28 patients with NS5A RAVs and 2/2 patients with NS3 RAVs achieved SVR12. NS5B-P495 was not detected at baseline. Among patients with virologic failure, RAVs were detected in NS5A (Q30, Y93, L31), NS3 (R155, D168) and NS5B (P495, P421). Conclusion: The alloral fixed-dose combination of DCV, ASV, and BCV achieved high rates of SVR12 in patients with HCV genotype 1 infection and compensated cirrhosis. The strongest predictors of SVR12 were GT1b and use of RBV. Factors often associated with reduced responses to less potent regimens, such as advanced age, black race, prior null response to pegIFN, high baseline HCV RNA levels, low platelet counts, non-CC IL28B genotype, and baseline NS5A or NS3 RAVs did not appear to impact SVR12 rates.

Tu1014 Single-Center Real-World Experience of Sofosbuvir Plus Simeprevir for 12 Weeks for Genotype 1 Chronic Hepatitis C With Advanced Fibrosis

A S L D A b st ra ct s rates in patients treated with DCV/ASV/BCV combined with RBV and in patients with GT1b subtype. Other baseline factors such as age, gender, BMI, IL28B genotype, HCV RNA >800,000 IU/mL, and platelet count <100 × 109/L did not appear to impact SVR12 rates in either cohort (Table). Similarly, race did not appear to influence SVR12 rates; of the 20 black patients enrolled in the study, all 20 achieved SVR12. Prior null response to pegIFN did not significantly impact outcome in the treatment-experienced cohort. Baseline resistanceassociated variants (RAVs) in NS5A (28, 30, 31, 93) or NS3 (168) did not impact SVR: 26/ 28 patients with NS5A RAVs and 2/2 patients with NS3 RAVs achieved SVR12. NS5B-P495 was not detected at baseline. Among patients with virologic failure, RAVs were detected in NS5A (Q30, Y93, L31), NS3 (R155, D168) and NS5B (P495, P421). Conclusion: The alloral fixed-dose combination of DCV, ASV, and BCV achieved high rates of SVR12 in patients with HCV genotype 1 infection and compensated cirrhosis. The strongest predictors of SVR12 were GT1b and use of RBV. Factors often associated with reduced responses to less potent regimens, such as advanced age, black race, prior null response to pegIFN, high baseline HCV RNA levels, low platelet counts, non-CC IL28B genotype, and baseline NS5A or NS3 RAVs did not appear to impact SVR12 rates.

BMI, male sex and IL28B genotype associated with persistently high hepatitis C virus RNA levels among chronically infected drug users up to 23 years following seroconversion.

The natural course of serum HCV RNA levels during chronic infection remains unclear. We investigated HCV RNA levels and factors associated with HCV RNA levels for the entire course from HCV seroconversion. We measured HCV RNA levels of 54 HCV seroconverters from the Amsterdam Cohort Studies among drug users at yearly intervals up to 23 years using bDNA (VERSANT 3.0, lower limit of detection 615 IU/mL). Samples below the cut-off of the assay were tested by TMA (Siemens VERSANT, detection limit 5 IU/mL). We used a latent class linear mixed model to examine the HCV RNA patterns and factors associated with HCV RNA levels. The median follow-up time was 10.8 years (IQR 6.5-14.9). We found two distinct HCV RNA patterns characterized by 45/54 cases and 9/54 cases. In multivariable analyses, HCV RNA levels were 0.41 log(10) IU/mL (95% confidence interval (CI) 0.06-0.75) higher for males as compared to females. Individuals with the IL28B CC genotype had 0.40 log(10) IU/mL (95% 0.08-0.73) higher HCV RNA levels than individuals with IL28B CT/TT genotypes. Body mass index (BMI) was associated with higher HCV RNA levels, 0.055 log(10) IU/mL per BMI point (95% CI 0.027-0.083). In this unique study, which examines the HCV RNA patterns over an extended period and following seroconversion, male sex, IL28B CC genotype and BMI were independently associated with higher average HCV RNA levels. These results contribute to defining the natural history of HCV infection and could play an important part in clinical decision-making.

Efficacy and safety of interferon-based therapy in the treatment of adult thalassemic patients with chronic hepatitis C: a 12 years audit

Background. HCV infection and transfusional iron overload in Thalassemic patients may result in liver disease. HCV treatment in Thalassemia has raised safety concerns.Aim. Estimate effectiveness and tolerability of interferon-based therapy in HCV-infected Thalassemic patients.Material and methods. Over a 12-year period, consecutive patients with β Thalassemia major (TM) and chronic hepatitis C received treatment. Liver biopsy, HCV-RNA and genotyping were performed beforehand. Sustained virological response (SVR) was defined as negative HCV-RNA 6 months post-treatment. Forty eight patients (26 M-22 F, mean age 39.8) were enrolled. Twenty nine patients were treated with conventional interferon alpha (IFNa) for 48 weeks (group A). Nineteen patients (10 naïve-9 previously IFNa experienced) received pegylated interferon (PEG-IFN) (group B).Results. HCV-1 was found in 44%, HCV-2 in 14%, HCV-3 in 23% and HCV-4 in 19%. Group A: ten patients (38.5%) achieved SVR, 2 (7.5%) relapsed and 17 (54%) were non responders. Group B: five (28%) achieved SVR, 8 (44%) relapsed and 6 (28%) never responded. High HCV-RNA levels, genotype 1 and advanced liver fibrosis were independently associated with no response. Four patients (3 treated with IFNα, 1 with PEG-IFN) had to discontinue treatment due to complications.Conclusions. The response rate of IFN monotherapy in multi-transfused, HCV-infected Thalassemic patients is not inferior to that in non-multi-transfused patients. IFNa administration is well-tolerated and should be recommended as initial treatment schedule in this setting.

Identification of Novel HCV Deletion Mutants in Chronic Hepatitis C Patients

The HCV genome consists of a positive 9.6 kb single-strand of RNA. Nucleotide substitutions in the HCV genome are common and a 2 kb deletion has been reported. A total of 117 chronic hepatitis C (CHC) patients who were treated with pegylated interferon plus ribavirin combination therapy were enrolled in this study. Total RNA was extracted from the patients' sera and reverse transcription and PCR were performed. Statistical analysis was performed to evaluate the effects of HCV deletion mutants on treatment with combination therapy. By amplifying entire HCV genomes using long-distance PCR, novel large deletion mutants were identified. Sequence analysis revealed that these deletions extended approximately 6 kb from the core/E2 region to the NS5A region and that there are three kinds of deletions that are identical at their 3' and 5' extremities. The subgenome virus particles appeared to coexist with full-genome virus particles in the sera of CHC patients despite lacking essential components for HCV viral replication. These short fragments were detected in 26 of 117 patients and were associated with significantly higher HCV RNA levels (P=0.018) and poor response to combination therapy (P=0.043). Moreover, the existence of HCV deletion mutants was significantly associated with virological relapse following combination therapy (P=0.046, OR=3.4). HCV deletion mutants may affect the HCV life cycle and reduce the antiviral effects of interferon therapy for CHC.

Co-infections with torque teno viruses in HCV infection

Background/Aim: The potential role of co-infections with novel hepatitisviruses such as torque teno viruses (SENV and TTV) is not clear in HCVinfection. We determined the prevalence and clinical significance of theseagents in different forms of HCV infection. Patients: a total of 365 HCVinfected individuals have been studied. Out of them 33 were symptomfree HCV carriers with persistently normal alanine aminotransferase (ALT), 97suffered from chronic hepatitis C not treated with interferon (IFN)-basedtherapy, 48 patients (pts) had chronic hepatitis C and treated with IFN+ ribavirin (RBV) for one year, 76 pts previously treated with IFN+RBVand achieved sustained virological response (SVR) and 111 were non-responders to IFN +RBV. One hundred and eight healthy volunters served as controls for TTV studies and 40 for SENV investigations. Methods: HCVRNA was detected using Roche Cobas Amplicor Monitor 2.0 test, TTV DNA, SENV-D and SENV-H DNA by PCR method. Results: Prevalance of both SENV-D, SENV-H and TTV was higher in HCV pts than in healthy controls (SENV-D: 43.7% vs. 7.5%; SENV-H 66.6% vs. 35.0% and TTV: 77.7% vs. 18.5%, respectively). Both SENV and TTV carriers have lower serum ALT and higher HCV RNA levels than SENV negative and TTV negative pts. IFN+RBV treated pts with SVR, after the therapy showed lower frequency of SENV-D (10.5%) and TTV (3.9%) than not treated ones. HCV pts with SENV-D achieved lower SVR (33%) than SENV-D negative pts (45%). Conclusion: Torque teno viruses can be accidental tourists in HCV infection, and though they may interfere with HCV, their pathogenetic role in liver injury is questionable. They may be IFN (+RBV?) sensitive agents.

Rapid virological response as a predictor of sustained response in HCV-infected patients with persistently normal alanine aminotransferase levels: A multicenter study

Rapid virological response (RVR) is now considered the strongest predictor of sustained virological response (SVR) in patients with HCV undergoing antiviral treatment, and thus, shorter antiviral treatment for these patients has been suggested. However, no data exist on the predictive value of RVR in HCV carriers with normal ALT values. A total of 137 patients with persistently normal ALT treated with peginterferon alfa 2a and ribavirin were studied. Fifteen patients dropped out early because of side effects, and in 10 patients with HCV-1 treatment was discontinued because of lack of early virological response (EVR). RVR was observed in 68% of the patients (42% patients with HCV-1, 90% HCV-2 and 64% HCV-3). An end-of-treatment response was observed in 86% of the patients (68% HCV-1, 100% HCV-2 and 91% HCV-3). SVR was maintained in 91 patients (46% HCV-1, 97% HCV-2 and 82% HCV-3). Overall, 92% patients with rapid response did obtain HCV eradication vs only 38% of those without rapid response. HCV-1 patients with baseline HCV RNA <400×10(3) IU/mL were more likely to achieve RVR and SVR than those with higher HCV RNA levels. We conclude that patients with genotype 1 and normal ALT who achieve HCV RNA negativity at week 4 may have a higher probability of eradicating their infection. Because of the concomitant favourable demographic and virological features often found in this particular subset of patients, the duration of therapy in these people might be shortened in the case of RVR. Persistently normal alanine aminotransferase levels patients with genotype 2 or 3 have a high chance of achieving SVR, so retesting of HCV RNA during treatment may have no additional practical value in these subjects.

Treatment of chronic hepatitis C: The efficacy and predictors of response to therapy

Background: The current standard for therapy of chronic hepatitis C (CHC) is combination of pegylated interferon alpha (PEG IFN-&2a or PEG IFN-&2b) and ribavirin (RBV). It is universally accepted that achievement of Sustained Virological Response (SVR) means successful treatment. Certain factors are good predictors of treatment outcome and they provide optimal, individual therapeutic approach. Objectives: Evaluation of efficacy of CHC treatment and predictors of treatment response. Methods: 194 patients with CHC were treated with combination therapy (PEG IFN-&2a + RBV).Virological examinations: anti-HCV antibodies (ELISA), serum HCV RNK levels and HCV genotypes (PCR technique). Liver biopsy specimens were staged in accordance with the Metavir score. Predictor with influence on treatment outcome were estimated by multivariable logistic regression analysis. Results: There were more patients of male gender (59.3%), older then 40 years (58.2%), with high basal HCV-RNA level (> 800.000 IU/ml, 63%), with G1 HCV (67%) in treated group of patients with CHC. Bridging fibrosis and cirrhosis (F3, F4) were found in 54 (27.8%) of patients. SVR was achieved in 69.2%, relapse was found in 11.9% of patients. 19.8% of patients had no response on therapy. Predictors for achievement of SVR were: non-1 HCV genotype p = 0.002, OR 5.9 95% CI (1.9–18.0), achievement of early virological response (EVR) p = 0.000, OR 0.92, 95% CI (2.73–35.97), and patients younger the 40 years p = 0.005, OR 3.66 95% CI (1.48-9.0). Predictors for failure of therapy for patients who didn’t respond to treatment were: G1 HCV p = 0.005, OR 3.9, 95 CI (1.5–10.3), high basal viral load p = 0.013, OR 3.45, 95% CI (1.29–9.19) and interupted continuity of treatment p = 0.002, OR 4.49, 95% CI (1.72–11.76). Conclusion: The current standard antiviral therapy was efficient in 127/194 (69.2%) of our patients. The most important predictors for successful treatment (SVR) were: non-1 HCV genotype, achievement of EVR for G1 HCV and patients age. Predictors for failure of treatment were: G1 HCV, high basal viral load, older age (>40 years), presence of cirrhosis and discontinuity of treatment. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive