Log Hepatitis C Virus RNA Research Articles

Alcohol Consumption and Hepatitis C Virus (HCV) RNA Levels in HIV/HCV Coinfected Patients.

Background: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited. Methods: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels. Results: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [β (95%CI): −0.04 (−0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (−0.24, 0.38), p = 0.66). Conclusions: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients.

Eradication of hepatitis C virus infection in kidney transplant recipients using direct-acting antiviral therapy: Qatar experience.

IntroductionHepatitis C virus (HCV) infection has detrimental effects on patient and graft survival after kidney transplantation. In the pre‐direct‐acting antiviral (DAA) era, treatment of HCV infection was associated with low response rates, poor tolerance, and increased risk of allograft rejection. However, DAAs have revolutionized HCV treatment. The aims of this study were to determine the impact of DAA on the sustained virologic response (SVR), renal function, and calcineurin inhibitor (CNI) levels and assess the tolerability to treatment in kidney transplant recipients with HCV infection in Qatar.MethodsThis retrospective study included the medical records of all kidney transplant recipients with confirmed HCV infection before January 1, 2020. All data were obtained from the patients’ electronic medical records; these included patient demographics; virologic responses to treatment; serum creatinine levels during treatment; urine protein to creatinine ratios and CNI levels before, during, and after treatment; and side effects related to DAA therapy.ResultsA total of 27 kidney transplant recipients with HCV were identified, 23 of whom received DAA therapy. The length of treatment ranged from 12 to 24 weeks, and 52% of patients had HCV genotype 1 infection. The median log10 HCV RNA was 6.6 copies per milliliter. None of the patients had liver cirrhosis, and all of them achieved SVR. There was no statistically significant difference in the glomerular filtration rate before, during, and after treatment. Most patients had stable CNI trough levels during treatment and did not require dose adjustment.ConclusionsHCV infection was successfully eradicated by DAA therapy in kidney transplant recipients, with a 100% SVR rate. Moreover, DAA therapy was well‐tolerated, and kidney function remained stable without an increased risk of rejection. These results are expected to drive the eradication of hepatitis C from the entire country.

Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection.

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross-sectional study, blood samples were taken from 249 recently diagnosed HCV-infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV-RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut-off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV-RNA load. Regression model: log viral load = 7.69 - 1.01 × G3 - 0.7 × G1 + 0.002 × ALT - 0.86 × fatigue.

Treatment efficacy of ledipasvir/sofosbuvir for 8 weeks in non-cirrhotic chronic hepatitis C genotype 4 patients.

Background/Aims:Ledipasvir/sofosbuvir (LDV/SOF) combination is administered for 12 to 24 weeks to treat hepatitis C virus (HCV); guidelines recommend 8 weeks treatment duration for HCV genotype (GT) 1 infection based on the patient's baseline characteristics. Data on treating HCV GT4 with LDV/SOF are limited. In this prospective cohort study, the efficacy and safety of 8 weeks treatment duration with LDV/SOF was evaluated in HCV GT4 patients in Saudi Arabia.Patients and Methods:Treatment-naïve, non-cirrhotic HCV GT4 patients received LDV/SOF for 8 weeks. HCV RNA levels and laboratory evaluations were recorded at baseline and at Weeks 4, 8, and 20. The primary endpoint was sustained virologic response 12 weeks after the end of the treatment (SVR12). Safety data were also recorded.Results:Forty-five patients with a mean age of 43.9 ± 17.2 years participated, of whom 57.8% were male. Mean log10 HCV RNA was 6.26 ± 6.32 IU/mL and most (91.1%) had baseline HCV RNA levels <6 million IU/mL. The most frequent comorbidities were hypertension and diabetes mellitus (20.0% each). Concomitant medication was taken by 18 patients (40.0%), of whom two took proton pump inhibitors. Overall, SVR12 was 97.8% (95% confidence interval [CI]: 88.2%–99.9%); one patient (2.2%) relapsed post treatment. No serious adverse events or discontinuations were reported. Eighteen patients (44.4%) had 38 adverse events related to LDV/SOF; the most frequent was headache.Conclusions:An 8-week regimen of LDV/SOF was well tolerated and efficacious in this treatment-naïve, non-cirrhotic HCV GT4–infected population. This study provides valuable information on a short treatment regimen for HCV GT4 infection in a real-world setting.

Evaluation of Dried Blood Spots as a Feasible Alternative to Plasma for the Detection and Quantification of Hepatitis C Virus in a Tropical Setting: A Pilot Study

AbstractIntroduction: Confirmatory diagnosis of hepatitis C virus (HCV) infection (HCV RNA detection) is essential before start of the therapy. HCV RNA detection is not available in many parts of India. Shipment of plasma from distant places to referral laboratories may affect HCV RNA titres. Dried blood spots (DBS) provide an easy alternative for transporting samples to centres where HCV RNA testing is done. Aim: Evaluation of DBS as a feasible alternative to plasma for HCV diagnosis. Methods: In this cross-sectional study, 40 consecutive patients’ blood samples were collected from patients referred from the Liver Clinic. Whole blood was spotted onto two Whatman 903TM cards. One card was incubated at ≥37°C and other at 4°C for 15 days, after drying. DBS was eluted and run in Abbott RealTime HCV assay. HCV was also quantified using the Abbott ARCHITECT HCV core antigen assay for 29 of the study patients. Results were compared with normal plasma values. Results: The median log HCV RNA value (in log10 IU/mL) of plasma was 5.74, with normalised DBS it was 4.92 (≥37°C) and 4.66 (4°C); difference in plasma and DBS median log values was 0.82 (≥37°C) and 1.08 (4°C) logs, respectively. Interclass correlation values were 0.943, P < 0.0001 (≥37°C) and 0.950, P < 0.0001 (4°C), showing high agreement. The median HCV core antigen value (in fmol/L) for plasma was 325.35, whereas it was 4.77 (≥37°C) and 4.64 (4°C) for DBS samples. Conclusions: DBS can be used for sampling patients from distant resource-limited settings as an alternative to plasma for HCV RNA estimation. Larger studies are required to evaluate the feasibility of DBS in the Indian subcontinent, especially for HCV core antigen estimation.

Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study.

The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR12 ) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC0-6 h ) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC0-6 h of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR12 rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log10 HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.

Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals.

We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients.

The Investigation of HCV RNA in Tear Fluid and Aqueous Humor in Patients with Anti-HCV Antibody Positive Who Underwent Cataract Surgery

Purpose: To obtain aqueous humor and tear fluid samples during cataract surgery of the hepatitis C virus (HCV)-antibody-positive patients in order to analyze them for HCV RNA and compare these measurements with serum HCV RNA levels.Methods: Twenty-nine anti-HCV-positive patients were included this study. HCV RNA viral load levels were determined by commercial real-time polymerase chain reaction system. Antibodies to HCV were screened with the enzyme-linked immunosorbent assay (ELISA) using anti-HCV test kit.Results: Log10 HCV RNA levels were found to be 6.00 ± 1.06 IU/mL in serum, 2.76 ± 0.36 IU/mL in the aqueous humor, and 1.91 ± 0.93 IU/mL in tear fluid. No correlation was detected between samples for HCV RNA positivity (p = .390, κ = .102). We have observed that, viral RNA was detected in the aqueous humor, while not in serum in one case, whereas viral RNA was detected in tear fluid but not in serum in another case.Conclusions: Although viral load detected in aqueous humor and tear fluid samples was considerably lower compared to the serum samples, it can still be important in terms of infectivity.

Understanding the effect of the HCV polymerase inhibitor mericitabine on early viral kinetics in the phase 2 JUMP‐C and PROPEL studies

The aim was to evaluate early viral kinetics in patients receiving mericitabine [hepatitis C virus (HCV) nucleoside polymerase inhibitor] with peginterferon alfa-2a (40KD) and ribavirin in two clinical trials (PROPEL and JUMP-C). We examined rapid virological responses (RVRs; week 4 HCV RNA <15 IU ml(-1) ) and complete early virological responses (cEVR; week 12 HCV RNA <15 IU ml(-1) ) in HCV genotype 1/4-infected patients receiving mericitabine (500 or 1000 mg) or placebo twice daily plus peginterferon alfa-2a and ribavirin. Among IL28B rs12979860 CC genotype patients receiving 500 or 1000 mg mericitabine or placebo, respectively, RVR rates were 64.3% (95% confidence interval: 38.8-83.7%), 95.1% (83.9-98.7%) and 33.3% (20.2-49.7%), and cEVR rates were 100% (78.5-100%), 100% (91.4-100%) and 80.6% (65.0-90.3%). Among non-CC genotype patients, RVR rates were 26.5% (14.6-43.1%), 52.3% (43.0-61.3%) and 5.7% (2.2-13.8%), and cEVR rates were 76.5% (60.0-87.6%), 84.6% (76.6-90.1%) and 28.6% (19.3-40.1%), respectively. In multiple regression analysis, IL28B genotype (P < 0.0001), mericitabine dose (P < 0.0001) and bodyweight (P = 0.0009) were associated with first-phase (α) slope (change in log10 HCV RNA from baseline to week 1). Mericitabine-containing triple therapy reduces the impact of IL28B genotype on RVR and cEVR compared with peginterferon alfa-2a and ribavirin dual therapy. The IL28B genotype, mericitabine dose and bodyweight are the most important factors associated with the α slope, and there is no evidence of a pharmacokinetic drug-drug interaction between mericitabine and ribavirin.

Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women.

To investigate the safety/efficacy of Boceprevir-based triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEG-IFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used. After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (P = 0.250), in 44% F0-F2 vs 54% F3-F4 (P = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only (6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.

Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders

Patients with chronic hepatitis C virus (HCV) infection and prior null response (<2 log HCV RNA decline after ⩾ 12 weeks of PegIFN/RBV) have limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir in non-cirrhotic genotype 1 null responders. In this randomized, phase 2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60 mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200mg) twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir twice-daily plus ribavirin (TRIPLE B3). The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (sustained virologic response, SVR12). Across all groups, mean HCV RNA was ⩾ 6 log IU/ml, and 99% of patients had a non-CC IL28B genotype. SVR12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2). In B3, most genotype 1a patients experienced virologic breakthrough. The most common adverse events were headache, diarrhea, and asthenia. Grade 3-4 aminotransferase elevations were infrequent and not treatment-limiting. In genotype 1 null responders, daclatasvir plus twice-daily asunaprevir DUAL therapy is effective for most genotype 1b patients, and daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for genotype 1a patients. Interferon-free regimens including daclatasvir and twice-daily asunaprevir for genotype 1 null responders should be tailored to subtype.

Boceprevir dosing for late responders and null responders: The role of bridging data between treatment-naïve and -experienced subjects

Boceprevir dosing for late responders and null responders: The role of bridging data between treatment-naïve and -experienced subjects

Viral Kinetics of the Y448H HCV NS5B Polymerase Mutant in Patients Treated with the HCV Inhibitor Tegobuvir (GS-9190)

Tegobuvir (GS‑9190) is a novel hepatitis C virus (HCV) non‑nucleoside NS5B polymerase inhibitor that effectively inhibits HCV replication in HCV-infected genotype (GT) 1 patients. The NS5B Y448H mutation was the most frequent mutation selected in patients receiving tegobuvir. In this study, we employed allele-specific PCR (AS-PCR) to monitor Y448H kinetics and estimate the pre-existing Y448H levels in HCV-infected patients and replicon cells. Y448H ASPCR was developed with a 0.5% assay cut-off to test replicon cells treated with tegobuvir and samples from HCVinfected GT 1 patients who received 8-days of tegobuvir monotherapy. By population sequencing, Y448H was not detected at baseline in serum samples from any of the 65 patients enrolled in the study. Using the more sensitive AS-PCR, Y448H was assessed in 62/65 patients at baseline and detected at >0.5% in 5/62 patients. Longitudinal patient samples were tested to monitor the Y448H replication kinetics during the 8-day tegobuvir monotherapy. The replication kinetics of the mutant virus were used to extrapolate a median baseline Y448H frequency of 0.025% (-3.6 log10). For the in vitro selection of GT 1b tegobuvir-treated replicon cells, pre-existing Y448H levels were similarly estimated at 0.015% (-3.8 log10). Pre-existing levels of the drug-resistant variant Y448H suggest a maximal 3.6 log10 HCV RNA reduction during monotherapy with optimal doses of NS5B non-nucleoside polymerase inhibitors that select for Y448H. These results aid in the prediction of the patient viral response and study designs to best achieve maximal antiviral response.

Sustained virologic response rates with telaprevir by response after 4 weeks of lead-in therapy in patients with prior treatment failure

For hepatitis C virus (HCV)-infected patients who have not responded to previous PegIFN/ribavirin treatment, it is unclear whether subsequent direct-acting antiviral therapy outcomes are better predicted by prior treatment response or by on-treatment response to a PegIFN/ribavirin lead-in. In REALIZE, treatment-experienced patients randomized to the lead-in telaprevir arm received 4 weeks of PegIFN-α-2a (180 μg/week) and ribavirin (1000-1200 mg/day), then 12 weeks of telaprevir (750 mg every 8h) plus PegIFN-α-2a/ribavirin, followed by 32 weeks of PegIFN-α-2a/ribavirin. This subanalysis only included patients in the lead-in telaprevir arm with available week 4 on-treatment response data (n=240). After 4weeks of PegIFN/ribavirin, 90% of relapsers, 60% of partial responders, and 41% of null responders in the lead-in telaprevir arm had ⩾1 log(10) HCV RNA reduction. Sustained virologic response (SVR) rates for telaprevir-treated patients with ≥1 versus <1 log(10) HCV RNA reduction after the PegIFN/ribavirin lead-in were 94% versus 62% in relapsers, 59% versus 56% in partial responders and 54% versus 15% in null responders. In prior relapsers and partial responders there is no apparent benefit of assessing response after a PegIFN/ribavirin lead-in with the aim of guiding telaprevir-based treatment. For patients known to be prior null responders, on-treatment response after a 4-week PegIFN/ribavirin lead-in may provide clinically useful prognostic information. However, withholding telaprevir-containing therapy in uncategorised treatment-experienced patient populations (i.e., that could include prior relapsers or partial responders), using response after a PegIFN/ribavirin lead-in could potentially exclude some patients with a high chance of SVR.

Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options

Improved therapeutic options for chronic hepatitis C virus (HCV) infection are needed for patients who are poor candidates for treatment with current regimens due to anticipated intolerability or low likelihood of response. In this open-label, phase 2a study of Japanese patients with chronic HCV genotype 1b infection, 21 null responders (<2 log₁₀ HCV RNA reduction after 12 weeks of peginterferon/ribavirin) and 22 patients intolerant to or medically ineligible for peginterferon/ribavirin therapy received dual oral treatment for 24 weeks with the NS5A replication complex inhibitor daclatasvir (DCV) and the NS3 protease inhibitor asunaprevir (ASV). The primary efficacy end point was sustained virologic response at 12 weeks post-treatment (SVR₁₂). Thirty-six of 43 enrolled patients completed 24 weeks of therapy. Serum HCV RNA levels declined rapidly, becoming undetectable in all patients on therapy by week 8. Overall, 76.7% of patients achieved SVR₁₂ and SVR₂₄, including 90.5% of null responders and 63.6% of ineligible/intolerant patients. There were no virologic failures among null responders. Three ineligible/intolerant patients experienced viral breakthrough and four relapsed post-treatment. Diarrhea, nasopharyngitis, headache, and ALT/AST increases, generally mild, were the most common adverse events; three discontinuations before week 24 were due to adverse events that included hyperbilirubinemia and transaminase elevations (two patients). Dual therapy with daclatasvir and asunaprevir, without peginterferon/ribavirin, was well tolerated and achieved high SVR rates in two groups of difficult-to-treat patients with hepatitis C virus genotype 1b infection.

Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin

The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24-72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.

Is Hepatitis C Virus Core Antigen an Adequate Marker for Community Screening?

A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115 (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was significantly correlated with HCV RNA according to the following equation: (log HCV RNA) = 2.08 + 1.03 (log HCV Ag) (R(2) = 0.94; P < 0.001). As determined using a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter) as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%, and 99%, respectively. In conclusion, for a community study, HCV Ag showed good correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can provide the best result validity.

Pioglitazone decreases hepatitis C viral load in overweight, treatment naïve, genotype 4 infected-patients: a pilot study.

BackgroundInsulin resistance (IR) is induced by chronic hepatitis C virus (HCV) genotypes 1 and 4 infections. It is not known whether drugs that affect IR such as Pioglitazone and Prednisone also affect serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment. The primary aim was to assess whether Pioglitazone by improving IR and/or inflammation decreases HCV viral load independently of standard of care HCV treatment. A secondary aim was to assess whether Prednisone, a drug that induces insulin resistance and stimulates HCV viral entry and replication in replicon culture systems, increases HCV viral load in this population.Methodology/Principal FindingsWe designed a two-arm, parallel Pilot Study of overweight, treatment naïve genotype 4 HCV-infected patients at a public referral Liver Clinic in Giza, Egypt. The subjects received Pioglitazone (30 mg/day for 14 days) or Prednisone (40 mg/day for 4 days) in a randomized fashion, but the two arms can be considered independent pilot studies. Only changes from baseline within each arm were assessed and no contrasts of the interventions were made, as this was not an aim of the study. Among 105 consecutive HCV genotype 4 patients, 39 were enrolled based on the optimal sample size and power analysis according to the CONSORT statement; 20 to the Pioglitazone group and 19 to the Prednisone group. Pioglitazone was effective in decreasing serum HCV RNA at day-14 (n = 10; difference of means = 205,618 IU/ml; 95% CI 26,600 to 384,600; P<0.001). Although Prednisone did increase serum HCV RNA at day-4 (n = 10; change from baseline = −42,786 IU/ml; 95% CI −85,500 to −15,700; P = 0.049), the log10 HCV RNA titers were statistically not different from baseline day-0.Conclusion/SignificanceThis is the first documentation that Pioglitazone decreases the serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment. The novel findings of our Study provide the foundation for basic and clinical investigations on the molecular mechanisms responsible for the Pioglitazone-induced decrease in HCV genotype 4 RNA titers.Trial RegistrationClinicalTrials.gov NCT01157975

Effectiveness of biweekly low‐dosage peginterferon treatment on the improvement of serum alanine aminotransferase and α‐fetoprotein levels

The purpose of this clinical study was to determine the effect of a biweekly low-dosage peginterferon α-2a treatment program on serum alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels. Fifty-five patients participated in the study. The inclusion criteria included chronic genotype 1b hepatitis C virus (HCV) infection, liver cirrhosis, or the absence of cirrhosis in subjects 65 years old or above, and interferon therapy naivety or a lack of sustained response to therapy with interferon-plus-ribavirin or peginterferon-plus-ribavirin. Patients were divided into naïve, relapser, and non-responder groups. The median age of the patients was 70 years, and 73% of patients had cirrhosis. All patients were treated with peginterferon α-2a at 90 µg biweekly. The rates of normalization (≤30 IU/l) of ALT levels at week 24 in the relapser group and the ≥2 log(10) HCV RNA decline group were high (74% and 68%, respectively). However, the ALT and AFP levels decreased significantly in each group, including the non-responder group. The ALT levels decreased significantly even in patients in whom the HCV RNA levels did not decrease. Furthermore, the AFP levels decreased significantly in the patients showing no decline in the ALT and HCV RNA levels. Only three patients discontinued treatment within 48 weeks due to adverse events, and more than 70% of the patients experienced no subjective symptoms during treatment. A biweekly low-dosage peginterferon α-2a therapy is effective for reducing the serum levels of ALT and AFP and may reduce hepatocarcinogenesis in patients with liver cirrhosis and in the elderly individuals.

Relationship Between Adherence to Hepatitis C Virus Therapy and Virologic Outcomes

Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined. To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence. Retrospective cohort study. National Veterans Affairs Hepatitis C Clinical Case Registry. 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation. Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of ≥2 log(10) HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment). Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with ≤40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with ≤40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy. This was an observational study without standardized timing for outcome measurements. Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin.