Low Hepatitis C Virus RNA Research Articles

Second hepatitis C virus transmission by blood components since introduction of mandatory NAT screening in Germany.

Viral safety of blood products in Germany has improved significantly over the last two decades. We describe the second documented transfusion-transmitted (TT) episode for the hepatitis C virus (HCV) in Germany since mandatory nucleic acid amplification techniques (NAT) screening was introduced in 1999. When a repeat donor who had tested negative for anti-HCV tested positive for HCV RNA by NAT in a minipool (MP) of eight, a look-back procedure was initiated. Qualitative, quantitative and genotyping assays were used to investigate the titers of the quarantined fresh frozen plasma (FFP) from the donor and a serum sample from the recipient of the pooled platelet concentrate (PPC). Amplified products of 5'UTR and HVR1 were used for sequence comparison to characterize the HCV genomic identity of donor and recipient samples. All NAT tests utilized in this procedure were able to detect a low HCV RNA titer (~15 IU/ml) in the FFP from the donation. Dilution of FFP by factor 8 was performed to mimic an MP, and the detection rate correlated well with the claimed sensitivity of the tests. Analysis of donor and recipient samples revealed genotype 3a viral transmission confirmed by sequence analysis. This TT HCV case could have been prevented by individual donation (ID) NAT. However, a low titer blood donation in the window period (WP) is very rare. Residual risk calculation for TT HCV in the WP revealed that, compared to MP-NAT testing, ID-NAT would improve blood safety only marginally.

Treatment of interferon treated relapsers and non- responder chronic hepatitis C cases with Directly acting antivirals

To determine the response rate to sofosbuvir and ribavirin in chronic Hepatitis C Virus (HCV) patients who did not respond or relapsed with interferon therapy. A case series study was performed at Jinnah Postgraduate Medical Centre (JPMC), Karachi from January 2017- January 2019. HCV RNA positive were initiated in eligible patients with sofosbuvir 400mg once daily and ribavirin 400mg orally according to body weight for six months. Rapid viral response (RVR) [normal/undetectable ALT and AST level or very low HCV RNA at 4-6 weeks]. HCVRNA, CP, ALT were checked after 3 months of stopping treatment to confirm sustained virologic response (SVR). Of 100 cases, 16 (16%) were non-responders while relapse was observed in 84 (84%) patients. Among the 13 cirrhosis patients, 11 (84.6%) achieved SVR. Females had a significantly higher response rate as compared to males (p value 0.034). The sustained virological response rate in interferon treated chronic hepatitis C patients retreated with sofosbuvir and ribavirin was found satisfactory. &nbsp

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release.

Hepatitis C virus (HCV) causes acute hepatitis C and can lead to life-threatening complications if it becomes chronic. The HCV genome is a single plus strand of RNA. Its intracellular replication is a spatiotemporally coordinated process of RNA translation upon cell infection, RNA synthesis within a replication compartment, and virus particle production. While HCV is mainly transmitted via mature infectious virus particles, it has also been suggested that HCV-infected cells can secrete HCV RNA carrying exosomes that can infect cells in a receptor independent manner. In order to gain insight into these two routes of transmission, we developed a series of intracellular HCV replication models that include HCV RNA secretion and/or virus assembly and release. Fitting our models to in vitro data, in which cells were infected with HCV, suggests that initially most secreted HCV RNA derives from intracellular cytosolic plus-strand RNA, but subsequently secreted HCV RNA derives equally from the cytoplasm and the replication compartments. Furthermore, our model fits to the data suggest that the rate of virus assembly and release is limited by host cell resources. Including the effects of direct acting antivirals in our models, we found that in spite of decreasing intracellular HCV RNA and extracellular virus concentration, low level HCV RNA secretion may continue as long as intracellular RNA is available. This may possibly explain the presence of detectable levels of plasma HCV RNA at the end of treatment even in patients that ultimately attain a sustained virologic response.

Rapid virologic response in chronic hepatitis C genotype 1: Evaluation of pretreatment factors in patients

Background and study aimsRapid virologic response (RVR) is defined as undetectable hepatitis C virus (HCV) RNA in serum after 4 weeks of treatment for chronic hepatitis C (CHC). Paritaprevir/ritonavir/ombitasvir (PRO) and/or dasabuvir (D), with or without ribavirin [PRO (D) ± ribavirin], which are direct-acting antivirals (DAAs), is the currently approved treatment regimen for CHC genotype 1; this regimen can also be used in patients with end-stage renal failure (ESRF). In this study, we aimed to evaluate the effect of pretreatment factors on RVR in patients treated with PRO (D) ± ribavirin. Patients and methodsThis study included 60 patients with CHC genotype 1 who were treated with PRO (D) ± ribavirin and achieved RVR. Patients’ demographic data; baseline HCV RNA levels; HCV genotype information; biochemical, histologic, and radiologic results; and previous treatment history were recorded. Patients were categorized into two groups: virologic responses achieved in the first week (group 1) and in the first to the fourth week (group 2). Pretreatment factors were compared between the groups. ResultsPatients in group 1 who achieved ultraRVR (undetectable HCV RNA after 1 week of treatment) had significantly lower mean pretreatment HCV RNA levels and lower prevalence of ESRF than patients in group 2. ConclusionsRVR has been indicated to be a robust positive predictor of sustained virologic response. We concluded that some pretreatment factors such as low HCV RNA level and absence of ESRF might lead to faster RVR and shorter treatment duration with DAAs for CHC.

Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C.

Background/AimsThis study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection.MethodsThis retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment.ResultsSVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001).ConclusionsYoung age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

Clinical implication of serum uric acid level in pegylated interferon and ribavirin combination therapy for chronic hepatitis C infection.

Background/AimsCombined treatment of pegylated interferon-α (PEG-IFN) and ribavirin (RBV) has long been accepted as the standard treatment for chronic hepatitis C virus (HCV) infection. Many predictive factors for treatment response have been identified. The aim of this study was to evaluate the efficacy and safety of combined PEG-IFN plus RBV and to examine the value of serum uric acid as a predictive factor in the treatment of chronic hepatitis C.MethodsA total of 74 patients chronically infected with HCV were enrolled between December 2004 and June 2009. Patients received subcutaneous PEG-IFN (α-2a: 180 μg once a week) in combination with RBV (1,000 to 1,200 mg daily depending on body weight). We evaluated treatment responses represented by early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and relapse, as well as diverse adverse events. Various viral and host features were also assessed to clarify factors associated with treatment response.ResultsDuring treatment, EVR was achieved in 26 patients (26/33, 78.8%) with HCV genotype 1. ETR and SVR were achieved in 59 (77.6%) and 56 patients (73.6%), respectively, across all genotypes. Genotype 2/3, lower HCV RNA, and lower uric acid were associated with higher SVR.ConclusionsThe treatment response to combination therapy with PEG-IFN plus RBV was effective, especially in genotype 2/3. Uric acid might be useful as a predictive factor for response to therapy for chronic hepatitis.

Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study.

This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).

High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease

Associations between chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD) remain controversial. Here we aimed to clarify the association between HCV viral load, genotype, and CKD in 13,805 participants aged 30-65 years enrolled in the REVEAL-HCV Study, a community-based prospective study conducted in 1991-1992. CKD was defined by consecutive proteinuria oran estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2. Chronic HCV infection was defined by detectable HCV viral load. Logistic regression models were used to estimate prevalence odds ratio of CKD for chronic HCV infection after adjusting for other risk factors. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio (95% confidence interval) for CKD was significantly increased to 1.91 (1.27-2.88) for chronically HCV-infected participants. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio of CKD was 1.21 (0.54-2.70), 1.40 (0.66-3.00) and 3.44 (1.92-6.14) for chronically HCV-infected participants with low to high tertiles of serum HCV RNA, respectively. The adjusted prevalence odds ratios of CKD were 0.54 (0.17-1.75) for participants with low HCV RNA and genotype 1, 1.80 (0.84-3.87) for those with low HCV RNA and genotype 2, 2.62 (1.11-6.17) for those with high HCV RNA and genotype 1 and 4.99 (2.25-11.06) for those with high HCV RNA and genotype 2, compared with non-chronically HCV-infected participants. Thus, chronic HCV infection is associated with an increased risk of CKD. High HCV viral load and HCV genotype 2 are strong CKD predictors.

Multicenter Comparison Study of both Analytical and Clinical Performance across Four Roche Hepatitis C Virus RNA Assays Utilizing Different Platforms

ABSTRACTThe efficacy of antiviral treatment for chronic hepatitis C virus (HCV) infection is determined by measuring HCV RNA at specific time points throughout therapy using highly sensitive and accurate HCV RNA assays. This study compared the performances of two recently developed real-time PCR HCV RNA assays, cobas HCV for use on the cobas 6800/8800 systems (cobas 6800/8800 HCV) and cobas HCV for use on the cobas 4800 system (cobas 4800 HCV), with those of two established assays, the Cobas AmpliPrep/Cobas TaqMan HCV quantitative test, version 2 (CAP/CTM v2) and the Cobas TaqMan HCV test, version 2 for use with the High Pure system (HPS/CTM v2). The limits of detection (LODs) and linearity at lower concentrations (5 to 1000 IU/ml) were assessed for cobas 6800/8800 HCV and cobas 4800 HCV using WHO standard traceable panels representing HCV genotypes (GT) 1 to 4. Pairwise assay comparisons were also performed using 245 clinical samples representing HCV GT 1 to GT 4. Results from cobas 6800/8800 HCV and cobas 4800 HCV were linear at low HCV RNA concentrations (<0.3 log10 IU/ml difference between expected and observed results) with LODs of 8.2 IU/ml and 11.7 IU/ml, respectively, for GT 1. The new assays showed excellent agreement with results from CAP/CTM v2 and HPS/CTM v2 in samples with quantifiable viral loads. The concordances using the 6 million IU/ml cutoff were high among all four assays (90 to 94%). In conclusion, the cobas 6800/8800 HCV and cobas 4800 HCV tests are sensitive and linear and correlate well with the established Roche assays used in clinical practice.

Clinical value of on-treatment HCV RNA levels during different sofosbuvir-based antiviral regimens

The European Association for the Study of the Liver (EASL) guidelines recommend HCV RNA measurements at specific time points during sofosbuvir(SOF)-therapy. However, it remains unclear, how these results should be interpreted. We aimed to analyze whether on-treatment HCV RNA levels predict relapse comparing the CobasAmpliPrep/CobasTaqMan v2.0 (CAP/CTM) and Abbott RealTime HCV (ART) assays. Samples were collected from 298 patients (HCV genotypes; GT1-5) at weeks (w) 0, 1, 2, 4, 8, 12, 16, 20 and 24 during SOF-based therapy at two university clinics and tested for HCV RNA level by CAP/CTM and ART. Patients were treated with SOF/ribavirin (RBV) 12/24 w (n=99), pegylated-interferon-alfa (PegIFN)/SOF/RBV 12 w (n=51), SOF/simeprevir (SMV)±RBV 12 w (n=69) or SOF/daclatasvir±RBV 12/24 w (n=79). HCV RNA levels during the first 4weeks of SOF/RBV therapy were significantly lower in GT3 patients who achieved SVR compared with those who relapsed. All GT3 patients with a week 2 result <45IU/ml by CAP/CTM achieved SVR but only 33% of those with ⩾45IU/ml (p=0.0003). Similar results were documented with ART and 60IU/ml as cut-off (SVR: 100% vs. 29%; p=0.0002). In contrast, HCV RNA levels during early treatment phases were not significantly related to relapse in patients treated with other SOF-based regimens. Residual HCV RNA was frequently detected by ART at later stages of therapy. However, SVR rates remained high in these patients. At the end of SOF/SMV±RBV therapy HCV RNA was detectable with ART in 20% of patients, of whom 92% achieved SVR. HCV RNA levels assessed at week 2 of SOF/RBV therapy can predict relapse in GT3-patients. Detectable HCV RNA results at later stages during SOF-based therapy may occur frequently with the more sensitive ART. However, this should not lead to treatment extension. We analyzed the predictive value of hepatitis C virus (HCV) RNA levels measured at different time points for treatment efficacy. We found that the level of HCV RNA measured at week 2 of antiviral therapy can be used to predict treatment success in patients with HCV genotype 3 infection treated with sofosbuvir and ribavirin but not in patients treated with other sofosbuvir-based regimens. Low level HCV RNA is frequently detected by the RealTime HCV assay during later stages of antiviral therapy. However, this is not associated with reoccurrence of HCV RNA after the end of treatment.

Clinical efficacy of pegylated interferon in patients co-infected with HIV and HCV who failed standard interferon therapy

To investigate the efficacy and safety of pegylated interferon-alpha (PEG-INF-α) combined with ribavirin in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who failed prior standard interferon therapy. A prospective study was performed to analyze HCV RNA load, liver function, and CD4+ count at weeks 0 (baseline), 12, 24, and 48 of treatment and at 24 weeks after drug discontinuation in 20 patients co-infected with HIV and HCV who failed standard interferon therapy and were then treated with PEG-INF-αand ribavirin. Among the 20 patients, 14 were infected with HCV genotype 1b, 3 with HCV genotype 2a, and 3 failed sequencing. At baseline, the mean CD4(+)count, mean CD8(+)count, and mean CD4(+)/CD8(+)ratio were 406.45 ± 210.83 cells/ml, 1 076.45 ± 716.18 cells /ml, and 0.43 ± 0.17, respectively; the mean HCV RNA load was 6.01 ± 1.13 log10IU/ml; 12 patients (60%) had abnormal liver function. A total of 14 patients (70%) achieved complete early virologic response, 15 (75%) achieved end-of-treatment virologic response, 7 (35%) achieved sustained virologic response (SVR), and 8 (40%) experienced recurrence. The incidence rate of drug-related adverse events during the treatment was 50% (10/20); no serious adverse events occurred, and no patient withdrew from the treatment due to adverse events. At week 48, both CD4(+)and CD8(+)counts of all patients declined significantly compared with the baseline values (P= 0.001 and 0.001), but the CD4(+)/CD8(+)ratio increased significantly (P= 0.032). The SVR group had a significantly lower mean baseline HCV RNA load than the non-SVR group (4.95 ± 1.18 log10IU/ml vs 6.59 ± 0.53 log10IU/ml,t= 3.49,P= 0.009). In the patients co-infected with HIV and HCV who failed standard interferon therapy, PEG-INF-αcombined with ribavirin has good efficacy and safety, and the patients with a low baseline HCV RNA load are more likely to achieve SVR.

The genotype distribution of hepatitis C in southeastern Taiwan: Clinical characteristics, racial difference, and therapeutic response

The genotypes of hepatitis C virus (HCV) are associated with the therapeutic response. The racial diversity of Taitung, Taiwan is heterogeneous and a distinguishing feature; how such racial differences influence the genotype distribution and treatment outcome has not been well studied. The objective of this study is to elucidate the HCV genotype distribution in southeastern Taiwan and to analyze the racial differences influencing genotypes and clinical implications. In this retrospective cohort study, we included 343 patients who had been treated with peginterferon-alpha plus ribavirin. The predominant HCV genotype in the southeastern area was type 1 (43.7%), followed by type 2 (37.0%). The proportion of patients mixed with genotype 1 was lower in indigenous vis-à-vis nonindigenous groups (46.1% and 60.2%, p = 0.02). The prevalence of genotype 6 (5.2%) seems higher than in the general population of Taiwan and showed no difference between indigenous and nonindigenous people. The sustained virological response rate was higher in patients without genotype 1, low baseline HCV RNA (≤ 400,000 IU/mL), and in patients who achieved rapid virological response. Racial differences did not influence the therapeutic response. In this retrospective study, the proportion of HCV genotype 6 appeared slightly higher in southeastern areas than in the general population in Taiwan. The prevalence of genotype 1 in indigenous people was statistically lower than in nonindigenous people. Sustained virological response rate did not show any significant difference between indigenous and nonindigenous people in the current study.

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

Efficacy of 24-week pegylated interferon alpha and ribavirin combination therapy in highly selected patients infected with hepatitis C virus genotype 1.

Background:Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.Objectives:The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.Patients and Methods:In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.Results:The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).Conclusions:The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.

Impact of alloimmune T cell responses on hepatitis C virus replication in liver transplant recipients

We investigated the influence of alloimmune T cell responses on hepatitis C virus (HCV) replication in HCV-infected patients after liver transplantation (LT). To monitor the immune-status in 27 HCV-infected LT recipients, we routinely performed mixed lymphocyte reaction (MLR) assays within 4weeks after LT. HCV RNA titers in most patients fluctuated in inverse proportion to the stimulation index (SI) of anti-donor reactive T cells early after LT. Two weeks after LT, recipients with high HCV RNA titers (>1000KIU/mL) displayed a significantly lower SI for anti-donor reactive T cells than recipients with low HCV RNA titers did (<1000KIU/mL). An in vitro transwell assay mimicking the anatomical features of the interaction between HCV-infected hepatocytes and alloreactive T cells in allograft livers demonstrated that interferon (IFN)-γ was necessary to suppress HCV replication. This study proves the significant impact of alloimmune T cell responses on HCV replication in HCV-infected LT recipients.

Factors associated with sustained virological response in 24‐week telaprevir‐based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype

Single nucleotide polymorphisms (SNP) near the interleukin-28B (IL28B) gene affect the outcome of 24-week telaprevir-based triple therapy with telaprevir, pegylated interferon-α and ribavirin for chronic hepatitis C virus (HCV) genotype 1b patients. We aimed to identify factors associated with treatment outcomes in patients with the unfavorable minor IL28B SNP genotype, who have poor response to combination therapy. Pretreatment and on-treatment factors associated with sustained virological response (SVR) for 24-week telaprevir-based triple therapy were analyzed using multiple logistic regression analysis in 106 HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype (non-TT). Of the 106 non-TT patients, 62 (58.5%) achieved SVR. Of the 44 remaining patients, 22 experienced relapse, 13 experienced viral breakthrough and nine were non-responders. Pretreatment factors such as treatment-naïve/prior treatment response (P = 0.0041), high fasting serum low-density lipoprotein cholesterol (LDL-C) concentration (P = 0.0068) and low serum HCV RNA levels (P = 0.0088) were significantly and independently associated with SVR. On-treatment factors such as achievement of rapid virological response (RVR) were significantly and independently associated with SVR (P = 0.0001). For both pre- and on-treatment factors, treatment-naïve/prior treatment response (P = 0.0018), low pretreatment serum fasting LDL-C (P = 0.0062) and achieving RVR (P = 0.0021) were significantly and independently associated with SVR. In HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype, evaluating prior treatment response and achieving RVR and pretreatment serum fasting LDL-C concentrations were useful for predicting SVR achievement after 24-week telaprevir-based triple therapy.

Peginterferon alfa-2a and peginterferon alfa-2b combined with ribavirin in patients with genotype 1 chronic hepatitis C: Results of a prospective single-centre study

PurposeThis prospective, randomized, single-centre study compared peginterferons alfa-2a and alfa-2b, combined with ribavirin, in treating patients infected with hepatitis C virus (HCV) genotype 1. Material/methodsHundred-and-one patients received 48 weeks of open-label treatment with peginterferon alfa-2a (180μg/week) and 111 patients received peginterferon alfa-2b (1.5μg/kg/week). All patients received the same dose of ribavirin 1000/1200mg/day, depending on weight. The primary efficacy endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50IU/mL) 24 weeks after the end of treatment. ResultsEarly virologic response (EVR), defined as at least 2log10IU/mL reduction of viral load at 12 weeks, was more common in patients treated with peginterferon alfa-2a (88% vs. 74.8%; p=0.04). However, the difference in SVR was not statistically significant (49.5% vs. 44.1%; p=0.43). ConclusionsPeginterferon alfa-2a treated patients were also more likely to be HCV RNA negative at the end of treatment (67.3% vs. 57.7%), but this difference did not reach statistical significance. Multivariate logistic regression analysis found that SVR was associated with low fibrosis stage (F1–2 by Scheuer; p=0.001) and low serum HCV RNA level (<400,000IU/L; p=0.023). While both forms of peginterferon showed similar efficacy as measured by SVR, use of peginterferon alfa-2b could lower the number of patients receiving unnecessary treatment beyond 12 weeks.

Assessment of health‐related quality of life and how it predicts the outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C

Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045). HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients.

Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N=1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50IU/mL] by week 4 of treatment (rapid virologic response) and 24weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p<0.1×10(-30)) was stronger than that between METAVIR (p=3.86×10(-13)) or APRI (p=5.48×10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40KD)/ribavirin.

In routine clinical practice, few physicians use early viral kinetics to guide HCV dual therapy treatment decisions

PROPHESYS is a large, multinational, non-interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on-treatment virological response (VR). This PROPHESYS subanalysis is restricted to treatment-naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono-infected patients who received peginterferon alfa-2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria. The likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non-RVR/EVR patients with HCV RNA>400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB-4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa-2a dose, but a high proportion received a higher-than-recommended ribavirin dose. Despite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.