Predictor Of Sustained Virological Response Research Articles

Kinetic of Virologic Response to Pegylated Interferon and Ribavirin in Children With Chronic Hepatitis C Predicts the Effect of Treatment.

Chronic hepatitis C is a global health problem. Although new, highly effective and safe direct-acting antivirals have been approved for adults, the only drugs currently registered for children are pegylated interferon and ribavirin. The timelines for the pediatric approval of the new treatment regimens are far off. Three phase II-III pediatric trials with direct-acting antivirals are recruiting, and the estimated dates of completion of these studies range between April 2018 and January 2023. The aim of this study was to evaluate the value of on-treatment virologic response (VR) as predictor of sustained virologic response (SVR) in a cohort of Italian children with chronic hepatitis C and to establish possible stopping rules. Sixty-four children were enrolled (January 2012 to December 2015). SVR rate was 79.7% (51/64). VR at weeks 2 to 12 were shown to be robust predictors for the attainment of SVR. The positive predictive values of VR at weeks 8 and 12 were 98% and 92.7%, respectively. The negative predictive values at the same treatment weeks were 92.9% and 100%, indicating that no child who did not achieve VR at week 12 obtained SVR and that the likelihood of achieving SVR if still positive at week 8 was very low. Our results suggest for the first time that VR at week 8 could be considered a reliable predictor of SVR. Monitoring viral kinetics is useful for predicting the success of pegylated interferon and ribavirin therapy in children.

The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors.

Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3 genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P = 0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P = 0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens.

Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type 1 Infection.

Background: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. Methods: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV). Multivariate analysis of factors predicting sustained virological response (SVR) was conducted. Results: HLA-DMA rs1063478 and DMB rs23544 were independent factors of HCV treatment outcomes in Chinese Han population. Individuals who carried favorable genotypes of rs1063478TT and rs23544GG were more likely to achieve SVR {Dominant model: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.24–3.41; OR = 2.04, 95% CI =1.23–3.35, respectively}. Rs23544, rs1063478, baseline glucose, baseline platelet and T4 level were independent predictors of SVR. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.740. Conclusions: The genetic variation of rs1063478 and rs23544 are associated with the treatment outcomes in the Chinese Han population.

Real-world effectiveness and predictors of sustained virological response with all-oral therapy in 21,242 hepatitis C genotype-1 patients.

Predictors of sustained virological response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. We evaluated effectiveness and identified predictors of SVR for ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ±RBV) and ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ±RBV in patients treated in routine practice. Observational, intent-to-treat cohort of 21,142 genotype-1 patients initiating 8 or 12 weeks of LDV/SOF ±RBV or 12 weeks of OPrD ±RBV at any Veterans Affairs facility. Multivariate logistic regression models were constructed to model SVR and identify predictors. SVR was 91.2% (9,781/10,720) for LDV/SOF, 89.6% (3,266/3,646) for LDV/SOF+RBV, 91.7% (1,197/1,306) for OPrD and 87.8% (3,365/3,832) for OPrD+RBV. For LDV/SOF ±RBV, reduced odds of SVR occurred in African-Americans (0.80, 95% CI 0.70, 0.92, P<0.001), body mass index (BMI)<25 (0.77, 95% CI 0.66, 0.90, P<0.001), BMI≥30 (0.77, 95% CI 0.67, 0.89, P<0.001), proton pump inhibitors (PPIs; 0.81, 95% CI 0.71, 0.92, P<0.001), decompensated liver disease (0.58, 95% CI 0.45, 0.74, P<0.001) and FIB4>3.25 (0.60, 95% CI 0.53, 0.69, P<0.001). For OPrD ±RBV, FIB-4>3.25 negatively predicted SVR (0.72, 95% CI 0.59, 0.88, P<0.001). Detectable 4-week on-treatment HCV RNA≥15 IU/ml reduced SVR odds for both regimens (LDV/SOF ±RBV OR 0.49, 95% CI 0.41, 0.58, P<0.001; OPrD ±RBV OR 0.38, 95% CI 0.29, 0.50, P<0.001). Receipt of OPrD+RBV compared to LDV/SOF reduced odds of SVR (OR 0.70, 95% CI 0.62, 0.80, P<0.001). Mental health diagnosis did not impact likelihood of SVR. The diversity and size of this cohort allowed for extensive examination of regimen-specific predictors of SVR. FIB-4>3.25 and detectable 4-week on-treatment HCV RNA had the greatest negative impact. African-American race, low or high BMI, and PPIs negatively impacted odds of SVR for LDV/SOF ±RBV. Mental health diagnoses did not.

The Role of Vitamin D During Therapy in Chronic Hepatitis C Virus Infection and Its Relation to CYP 27 B1-1260 Promoter Polymorphism

Objective: vitamin D is a potent immunomodulator. A number of genetic polymorphisms in the vitamin D pathway have been shown to affect vitamin D signaling, and stratification according to such polymorphisms has already being implemented in randomized controlled clinical intervention studies. Aim of the work: the study was attempted to examine whether vitamin D improved viral response and predicted treatment outcome in patients with chronic hepatitis C virus (CHCV) infection. Patients and methods: ninety two patients with CHCV, whose age ranged between 20 and 56 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before and after the treatment with pegylated interferon (PEG-IFN), ribavirin (RBV) and vitamin D supplementation drops; 2000 IU/day, 10 drops/day, six patients whom received identical therapy without vitamin D were included to serve as controls. All the patients had body mass index (BMI) ≤ 30, were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations. CBCs and analysis of the expression of CYP 27 B1-1260 gene, vitamin D receptor (VDR), and the levels of serum 25-hydroxyvitamin D before and after chronic hepatitis C virus treatment. Results: the treatment group with vitamin D had BMI ≤ 30 and high viral load 90900004.00 IU/ML, (P= 0.098). Sixty three percent of treated patients were HCV RNA negative at 48 weeks after treatment (SVR). Baseline serum vitamin D level was 8.5 minimum, mean level (32.9 ± 27 ng/mL). It increased after 48 wk vit D treatment, to a mean level of (54.9 ± 38 ng/mL). VDR show highly significant difference between patients and controls as regarding Ff=55.4% for patients (P=0.01), and 66.7% ff for the controls (P=0.006) alleles. CYP27B1 show non significant relation between patients and controls, with CYP27B1 genotype frequencies of the promoter polymorphism CC = 51.1% for patients, 66.7% for the control group, C allele frequency 69% for the patients, 83.3% for the controls, AC 35.9% for the patients, 33.3% for the controls. The majority of cases had A1F1 and A1F2 biopsy results. Conclusion: our study suggests a role of vitamin D in the response to treatment of chronic HCV patients. However, serum concentration is not a suitable predictor of treatment outcome. VDR had a predictive positive treatment outcome. CYP27B1-1260 was found to be an independent predictor of sustained virologic response (SVR). Recommendations: The level of recommended supplementation of vitamin D depends on the patient’s individual deficiency, although 2000 IU daily is a common dose. Patients taking vitamin D supplements should have serum measurements made after starting therapy to determine whether they are reaching target levels.

Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

The lower limits of virus detection of hepatitis C virus (HCV) RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR)] in predicting sustained virological response (SVR) in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN) and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90) and detectable but not quantifiable (< 12 IU/mL, n = 27). All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA) HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001). We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002) and a good predictor of SVR [area under the curve (AUC) = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks) with PEG-IFN and ribavirin.

ASSOCIATION BETWEEN THE IL28B rs12979860 POLYMORPHISM AND THERAPY RESPONSE IN PATIENTS INFECTED WITH GENOTYPE 1 OF HEPATITIS C VIRUS IN CENTRAL BRAZIL

Polimorfismos de nucleotídeo único (SNPs) relacionados ao gene IL28B têm sido associados à eliminação espontânea do vírus da hepatite C (VHC) e à resposta virológica sustentada (RVS) no tratamento da infecção pelo VHC. Este estudo teve como objetivo investigar a associação entre o SNP IL28B rs12979860 e a RVS em pacientes com hepatite C no Brasil Central. Um total de 101 pacientes crônicos monoinfectados com o genótipo 1 do VHC, tratados com interferon peguilado e ribavirina (PEG-IFN/RBV), foi estudado na cidade de Goiânia, estado de Goiás, Brasil Central. A análise de rs12979860 mostrou que o genótipo mais prevalente foi CT (57,4%), seguido por CC (23,8%) e TT (18,8%). A taxa global de 28,7% (IC 95%: 20,4-38,7) para a RVS foi encontrada na população estudada. Na análise multivariada, somente o genótipo CC para o SNP rs12979860 (OR: 3,77; IC 95%: 1,13- 12,60; p = 0,031) mostrou-se independente associado à RVS. Estes achados mostram que o SNP IL28B rs12979860 é um forte preditor de RVS no tratamento com PEG-IFN/RBV nos pacientes infectados com o genótipo 1 do VHC no Brasil Central.

Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy.

Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.

Favorable efficacy of daclatasvir plus asunaprevir in treatment of elderly Japanese patients infected with HCV genotype 1b aged 70 and older.

The combination of daclatasvir and asunaprevir is efficacious in the treatment of hepatitis C virus (HCV) infection, but its efficacy and predictors of efficacy in the elderly (≥70 years) remain unclear. In this study, 844 patients with chronic HCV genotype 1b infection, were treated with daclatasvir (60 mg once daily) plus asunaprevir (100 mg twice daily) for 24 weeks. Using the intention-to-treat analysis, the sustained virological response (SVR) rates were 87% and 88% for all 844 patients and 411 elderly (>70 years of age), respectively. In both groups, multivariate analysis identified NS5A-Y93H mutation (<20%), pretreatment (failure of treatment except for triple therapy with simeprevir, or treatment naive), and level of viremia (<6.0 log IU/ml) as independent predictors of SVR. Direct sequencing showed a significantly higher rate of NS3-D168 mutation at baseline in non-responders to triple therapy with simeprevir (44%) than others (2%). Alfa-fetoprotein (AFP) level and liver stiffness were significantly lower after end of treatment than at baseline, in both the SVR and non-SVR groups. In conclusion, daclatasvir-asunaprevir combination achieved high SVR in HCV genotype 1b patients, including elderly patients. Viral factors negatively influenced the response to treatment. Treatment improved AFP level and liver stiffness (surrogate markers of hepatocellular carcinoma), regardless of treatment efficacy. J. Med. Virol. 89:91-98, 2017. © 2016 Wiley Periodicals, Inc.

Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients.

Real-world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions. The uptake of ledipasvir/sofosbuvir (LDV/SOF) regimens across health care settings has been rapid, but variations often occur in clinical practice. The aim of this study was to assess sustained virologic response (SVR) of LDV/SOF±ribavirin (RBV) in routine medical practice. This observational, intent-to-treat cohort was comprised of 4,365 genotype 1, treatment-naive, HCV-infected veterans treated with LDV/SOF±RBV. SVR rates were 91.3% (3,191/3,495) for LDV/SOF and 92.0% (527/573) for LDV/SOF+RBV (P = 0.65). African American race (odds ratio 0.70, 95% confidence interval 0.54-0.90, P = 0.004) and FIB-4 >3.25 (odds ratio 0.56, 95% confidence interval 0.43-0.71, P < 0.001) were independently associated with decreased likelihood of SVR; age, sex, body mass index, decompensated liver disease, diabetes, genotype 1 subtype, and regimen did not predict SVR. In models limited to those who completed 12 weeks of treatment, African American race was no longer a significant predictor of SVR but FIB-4 >3.25 (odds ratio 0.35, 95% confidence interval 0.24-0.50, P < 0.001) remained. Among those without cirrhosis (defined by FIB-4 ≤3.25) and with baseline HCV RNA<6,000,000 IU/mL, SVR rates were 93.2% (1,020/1,094) for those who completed 8 weeks of therapy and 96.6% (875/906) for those who completed 12 weeks of therapy (P = 0.001). In this real-world cohort, SVR rates with LDV/SOF±RBV nearly matched the rates reported in clinical trials and were consistently high across all subgroups; those without cirrhosis but with HCV RNA<6,000,000 IU/mL were less likely to achieve SVR with 8 weeks compared to 12 weeks of therapy, although the numeric difference in SVR rates was small. (Hepatology 2016;64:405-414).

Distribution of IL28B Polymorphism in a Cohort of Italians and Immigrants with HCV Infection: Association with Viraemia, Stage of Fibrosis and Response to Treatment.

Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9% males, 27.1% females) is 50years. 91.5% % of patients are Caucasian, 8.5% African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8% respectively. As regards ethnic group, African people have a prevalence of 35.5% for CC, while Caucasians have a prevalence of 23.8% for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges.

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors. MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model. ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR=4.65, 95% CI=3.36–6.42, P<0.00001) but not in HCV-2/3-infected Caucasian patients (OR=1.44, 95% CI: 0.89–2.33, P=0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR=0.49, 95% CI: 0.38–0.64, P<0.00001), regardless of the HCV genotype. ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.

Prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for estimation of efficiency of therapy with the use of pegylated interferon a-2 and ribavarin in patients with chronic genotype 1 hepatitis C

To estimate the prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for the achievement of sustained virologic response (SVR) to antiviral therapy (AVT) with the use of pegylated interferon α-2 and ribavarin in patients with chronic genotype 1 hepatitis C (CHC-1). The secondary aim was to evaluate the influence of these genetic factors on the progress of hepatic fibrosis in case of failure of the above treatment. A total of 146 patients with CHC-1 were examined. We studied the RNA genotype of hepatitis C virus, blood group specificity, IL-28B gene polymorphism, and severity of hepatic fibrosis (puncture biopsies). Dynamics of hepatic fibrosis was followed up in 40 patients who failed to develop the virologic response. 20 control patients did not receive AVT. The multifactor significance criterion was used to identify the initial factor that produced the highest effect on SVR. SVR was observed in 56.8% of the patients. Its efficiency was most significantly influenced by. the combination of blood group specificity and interleukin 28B gene polymorphism (p = 0.000024). Combination of blood group (0)1 with C/C or T/T IL-28B genotypes, A(II) with C/T or T/T and B(III) with T/G was associated with SVR in 100, 88.2, and 94.4% cases respectively. It was absent in patients with blood group A(II) in combination with double-nucleotide substitution in rs8099917 of the IL-28B gene (TG and GG genotypes); these patients suffered progressive fibrosis. SVR occurred in 83.8% of the patients with blood group B(III). The knowledge of blood group in patients with CHC-1 and IL-28B gene polymorphism treated with the use of pegylated interferon α-2 and ribavarin allows to predict SVR with a probability of 100% in case of blood group 0(1) and C/C or T/T genotypes, 88.2% in case of blood group A(II) and single-nucleotide C>Tsubstitution in rs8099917 locus of the IL-28B gene, 94.4% in case of blood group B(II) and single-nucleotide T>G substitution in the rs809991.7 locus, 83.8% in case of blood group B(III). Treatment of patients with these genetic traits with antiviral drugs of direct action has no appreciable advances over treatment with AVT in combination with pegylated interferon α-2 and ribavarin (SVR above or around 85%). Patients with blood group A(II) and single- or double-nucleotide substitution in rs8099917 (TG or GG genotypes) have minimal chances to produce SVR to the above treatment. Simultaneous progression of hepatic fibrosis suggest that such therapy is undesirable in these cases. They should be regarded as main candidates for interferon-free therapy. Combination of blood group specificity and interleukin 28B gene polymorphism is a simple and reliable predictor of SVR and dynamics of fibrosis in patients with CHC-I receiving AVT with pegylated interferon α-2 and ribavirin; also, it may be an instrument of selection of patients for interferon-free therapy.

Elevated on-treatment levels of serum IFN-gamma is associated with treatment failure of peginterferon plus ribavirin therapy for chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.

Course of hepatitis C virus (HCV) RNA and HCV core antigen testing are predictors for reaching sustained virologic response in liver transplant recipients undergoing sofosbuvir treatment in a real-life setting.

Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.

Predictors of sustained virological response in patients with hepatitis C virus genotype 3 infection.

Aim of the studyTo assess predictors of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) genotype 3 treated with standard therapy.Material and methodsWe retrospectively investigated data of 116 consecutive treatment-naïve patients chronically infected with HCV genotype 3, treated with pegylated interferon alpha (PegIFNα) and ribavirin (RBV) for 24 weeks. HCV RNA at week 4 (rapid virological response – RVR) and week 12 (early virological response – EVR) were measured in 85 and 105 patients respectively. Liver biopsy data were available for 103 patients. The variables were compared between patients with an SVR and those without.ResultsOverall 70.7% of patients achieved an SVR. Pretreatment factors including younger age, mild liver fibrosis as well as normal values of gamma-glutamyl transferase (GGT) and platelet count were significantly associated with higher SVR rate in univariate analysis. In the multivariate analysis only baseline platelet count > 140 000/µl and normal GGT activity were correlated with higher SVR rate. At weeks 4 and 12 HCV RNA was undetectable in 34.1% and 84.8% of patients respectively. The SVR rate was significantly higher in patients with an RVR compared to those without (p = 0.002). Only 2 patients with a rapid and early virological response did not achieve an SVR; both had negative pretreatment prognostic factors.ConclusionsIn treatment-naïve patients with genotype 3 HCV infection, low baseline platelet count and elevated GGT activity were significantly associated with poor response to PegIFNα and RBV. Achieving a rapid and early virological response was associated with higher likelihood of an SVR.

The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C.

Background:A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC).Materials and Methods:In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing.Results:Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients’ body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study.Conclusion:IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients.

Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study.

Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that investigated sustained virological response (SVR) rates by these drugs yielded different outcomes. The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon alpha plus ribavirin in patients who were treatment-naïve. A multicenter, retrospective observational study. The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with peginterferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients' data were collected from 22 centers via a standard form, which has been prepared for this study. The data included demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (duration of treatment, outcomes, discontinuations and adverse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient's demographic characteristics, baseline viral load, genotype, and fibrosis scores. The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 patients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to histologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early virological response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%). Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish patients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.

Noninvasive prediction of HCV-4 SVR by 2D US: a randomized study using data mining algorithm

Objective and aim Hepatitis C virus (HCV) can cause both acute and chronic hepatitis. Antiviral therapy is the cornerstone for the treatment of chronic HCV infection once diagnosis is confirmed by PCR. The goal of antiviral therapy is to eradicate HCV RNA or attain sustained virological response (SVR). In many countries worldwide, including Egypt, HCV infection is treated with a combination of pegylated interferon α and ribavirin (RBV). Liver fibrosis/cirrhosis stage influences the response to pegylated interferon α and RBV. Even with new oral therapies such as Sovaldi many patients have to continue to be on combination regimens of interferon/RBV or RBV alone. In the current study, we aimed to use data mining analysis to determine sonographic pictures that can successfully predict SVR in HCV-4 patients before the antiviral therapy. Methods Eighty-two patients were enrolled in this study and they underwent two-dimensional ultrasound examination before the antiviral therapy. The sonographic data obtained were analyzed with Rapidminer version 4.6 to create a decision tree algorithm for the prediction of SVR. Results The absence of significant liver fibrosis was a predictive parameter of SVR mainly in those patients without a sonographic picture of cirrhosis. The resulting tree yielded an accuracy, sensitivity, and specificity of 85.82 ± 10.79, 68.75, and 96.00%, respectively, upon 10-fold cross-validation. Conclusion In the current study we used decision tree algorithm, one of the most important computational methods and tools for data analysis and predictive modeling in applied medicine, to predict SVR in HCV-infected patients. Two-dimensional ultrasound can give predictive information regarding the treatment outcome before interferon therapy for HCV-4.

Prevalence of interleukin-28B single nucleotide polymorphism genotypes in patients with hepatitis C infection in Isfahan, Iran.

Background:Hepatitis C infection is one of the most common causes of liver-related morbidity and mortality. Due to limited efficacy and side-effects of treatment, identification of the determinants of response to treatment is an important issue. Nowadays, genotyping of interleukin (IL)-28B is one of the strongest tests used for prediction of sustained virological response. The prevalence of IL28B genotypes varies across different ethnicities. This study presents data on IL28B single nucleotide polymorphism (SNP) (rs12979860) in a group of Iranian hepatitis C virus (HCV)-infected patients in Isfahan.Materials and Methods:One hundred patients already diagnosed for hepatitis C enrolled the study. Genomic DNA was extracted from whole blood samples. Specific primers were used to amplify IL28B gene (rs12979860). The rs129679860 SNP was genotyped by real-time polymerase chain reaction using TaqMan® probes.Results:The mean age of patients was 33.16 years (25–42 years). Ninety-nine subjects were male and 1 was female. The frequency of HCV genotypes was as follows: Genotype 3a: 53%, genotype 1a: 42%, genotype 1b: 2%, mixed genotype (1a + 3a): 1% and 2%: Nontypable.IL28B rs12979860 genotypes were TT in 17 patients (17%), CT in 41 patients (41%), and CC in the remaining 42 patients (42%).Conclusion:The prevalence of C allele is much higher in our population study than in African American HCV patients (62.5% and 40% respectively), which can explain better response to treatment in our patients.