Predictor Of Sustained Virological Response Research Articles

Predictors of hepatitis C cure among people who inject drugs treated with directly observed therapy supported by peer case managers in Kenya.

Directly observed therapy (DOT) maximizes adherence and minimizes treatment gaps. Peer case managers (PCM) have also shown promise as a component of integrated HCV treatment strategies. DOT and PCM-support have been underexplored, particularly in low- and middle-income countries (LMICs). The objective of this study was to evaluate predictors of sustained virologic response (SVR) among people who inject drugs (PWID) attending medication-assisted treatment (MAT) and needle and syringe programs (NSP) sites in Kenya. We recruited PWID accessing MAT and NSP in Nairobi and Coastal Kenya. PWID were treated with ledipasvir/sofosbuvir using DOT supported by PCMs. We used bivariate and multivariate logistic regression to examine the impact of sociodemographic, behavioral, and clinical factors on SVR. Among 92 PWID who initiated HCV treatment, 79 (86%) were male with mean age of 36.3 years (SD=±6.5); 38 (41%) were HIV-positive, and 87 (95%) reported injecting drugs in the last 30 days. Just over half of participants were genotype 1a (55%), followed by genotype 4a (41%) and mixed 1a/4a (3%). Most participants, 85 (92%) completed treatment and 79 (86%) achieved SVR. While sociodemographic and behavioral factors including recent injection drug use were not significantly associated with achieving SVR, being fully adherent (p=0.042), number of doses taken (p=0.008) and treatment completion (p= 0.001) were associated with higher odds of achieving SVR. DOT with PCM-support was an effective model for HCV treatment among PWID in this LMIC setting. Adherence was the most important driver of SVR suggesting DOT and PCM support can overcome other factors that might limit adherence. Further research is necessary to ascertain the effectiveness of other models of HCV care for PWID in LMICs given NSP and MAT access is variable, and DOT may not be sustainable with limited resources.

The relation between SNPs in the NME1 gene and response to sofosbuvir in Egyptian patients with chronic HCV

BackgroundHepatitis C virus (HCV) infection is considered one of the most urgent health problems in the world, with an incidence of approximately 71 million patients and 399,000 deaths per year from related liver diseases. In this study, we examined the association between 2 single nucleotide polymorphisms (SNPs) in the nucleoside diphosphate kinase 1 (NME1) gene (encoding one of the sofosbuvir metabolizing enzymes) and the response to the sofosbuvir plus daclatasvir regimen in Egyptian HCV-infected patients.ResultsOur data showed a similarity in the distribution of the CC, CT, and TT genotypes of NME1 rs2302254 C/T (p = 0.847) and the CC, TC, and TT genotypes of NME1 rs16949649 T/C (p = 0.937) among patients who were either treatment responders or relapsers. Based on the univariate and multivariate logistic regression analyses of the significant predictors for sustained virological response (SVR), five factors showed a robust predictive potency for the treatment outcome: age, fasting blood glucose level, platelets, albumin, and alpha-fetoprotein. Strikingly, there was a significant correlation between the rs16949649T/C polymorphism and serum creatinine (p = 0.023). Higher creatinine levels were observed among the CC carriers than the TC or TT carriers.ConclusionsThe 2 studied SNPs of NME1 had no significant association with SVR in Egyptian HCV-infected patients; however, the noticeable relation between rs16949649T/C and creatinine level might represent a foundation for future studies on the renal extra-hepatic manifestation of HCV and SNPs of NME1 gene.

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Efficacy and Safety of Sofosbuvir and Ribavirin in an Italian Cohort of HCV Genotype 2 Elderly Cirrhotic Patients.

Sofosbuvir and ribavirin represented until recently the standard of care in hepatitis C virus genotype 2 cirrhotic patients. In registration trials, 12-16 week durations were associated with 90% sus- tained virological responses, although not confirmed by real-life studies. In Italy, various durations (12,16, 20, and 24 weeks) represent lawfully reimbursable healthcare practice. The aim is, therefore, to study the behavior of Italian clinicians and the possible impact of therapy durations on sustained virological responses and patient safety. Data of all consecutive genotype 2 cirrhotic patients who started sofosbuvir plus ribavirin therapy between January 2015 and March 2017 in 7 Italian liver clinics were collected retrospectively. Overall, 147 patients (138 Child-Pugh A, mean age: 71 years) were treated. The median treatment duration was 16 weeks, but marked differences were found among the clinicians; however, the 12-week duration was not considered by the vast majority of them. Rates of intention-to-treat and per-protocol sus- tained virological responses were 95.9% and 97.1%, respectively, and neither showed differences between the various durations. No independent, sustained virological response predictors could be found, but the median baselines for Child-Pugh and Model For End-Stage Liver Disease scores were higher in non-respond- ers. Anemia was not associated with treatment duration. One case of acute kidney injury attributed to the possible sofosbuvir effect was reported. In genotype 2 cirrhotic patients, sofosbuvir plus ribavirin was associated with real-life-sustained virological response rates of almost 96%, without a significant impact on treatment duration provided it was longer than 12 weeks.

Efficacy and safety of direct-acting antiviral therapies and baseline predictors for treatment outcomes in hepatitis C patients: A multicenter, real-world study in Guangdong, China.

The data on direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients in southern China with multiple genotypes circulating are limited. This study aims to evaluate the efficacy and safety of DAA regimens among CHC patients in Guangdong, China. A total of 220 patients receiving a variety of DAA were enrolled. The primary outcome was sustained virologic response (SVR) at 12 weeks. Resistance associated substitutions (RASs) were evaluated by deep sequencing. The overall SVR rate was 96.4%, and was 97.7% for genotype 1, 100% for genotype 2, 91.9% for genotype 3, 95.7% for genotype 6, and 100% for untyped. The overall incidence of adverse events (AEs) was 8.2% (18/220) and all the AEs were mild. Nonstructural proteins 5A RAS, 30K/31M, and Y93H were most prevalent at baseline and the end of treatment in non-SVR patients, respectively. Logistics regression showed that elevated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) at baseline were specifically associated with non-SVR in patients with genotype 3 and 6 infections (p = 0.029 and p = 0.017) but not genotype 1 infection (p = 0.746 and p = 0.971), and baseline AST was the best predictor for SVR in genotypes 3 and 6 patients (area under curve = 0.890).Our studies demonstrated all DAA regimens achieved ideal SVR and were well tolerated. NS5A RAS were prevalent in non-SVR patients. Elevated ALT and AST as baseline predictors for non-SVR in genotypes 3 and 6 infections warrant further research in a larger cohort.

History of alcohol use does not predict HCV direct acting antiviral treatment outcomes.

Hepatitis C virus (HCV) infection and excessive alcohol consumption are leading causes of liver disease worldwide. Direct acting antivirals (DAAs) are well-tolerated treatments for HCV infections with high sustained virologic response (SVR) rates. There are limited data assessing the influence of alcohol use on DAA uptake and cure. We performed a retrospective analysis of patients followed at The Ottawa Hospital Viral Hepatitis Program between January 2014 and May 2020 to investigate the effect of excessive alcohol use history on DAA uptake and SVR rates. Additionally, we evaluated the incidence of concurrent comorbidities and social determinants of health. Predictors of DAA uptake and SVR were assessed by logistic regression. Excessive alcohol use history was reported in 46.0% (733) of patients. Excessive alcohol use did not predict DAA uptake (OR 1.06, 95% CI 0.71 to 1.57), while employment (OR 2.10, 95% CI 1.29 to 3.42) and recreational drug use (OR 0.62, 95% CI 0.40 to 0.94) were predictors. Employment predicted SVR (OR 2.38, 95% CI 1.68 to 3.36) in those starting treatment. Excessive alcohol use history did not predict SVR. History of excessive alcohol use does not influence treatment initiation or SVR. Efforts to improve treatment uptake should shift to focus on the roles of determinants of health such as employment and recreational drug use on treatment initiation.

Hepatitis C virus micro-elimination within a clinic for people with HIV: challenges in the home stretch.

To describe a pharmacist-led campaign aimed at reducing the proportion of people with HIV with ongoing chronic hepatitis C virus (HCV) infection and delineating barriers to HCV care in this patient population. An electronic report and retrospective chart review were used to identify patients who remained with HCV infections after a previous treatment initiative. A clinical pharmacist and pharmacy resident approached the remaining HCV patients during their routine visits for HIV care to offer and coordinate direct-acting antiviral (DAA) treatment. The primary end-point was to compare the prevalence of chronic HCV before and after the intervention period. Barriers to care were also evaluated, with logistic regression performed to identify predictors of sustained virologic response (SVR) attainment. Forty-six patients were included in the analysis (4.2% of clinic population), with HCV prevalence falling to 0.6% (six patients) by the end of the study (p<0.0001). The HCV care cascade in the cohort was as follows: 70% agreed to and received DAA therapy, 63% initiated therapy, and 50% achieved SVR. The top barriers to care at baseline included recreational drug use (67%), poor engagement in care (61%), and mental health disorders (28%). Poor engagement in care and active recreational drug use were associated with decreased odds of achieving SVR in bivariate analysis. A coordinated effort can make strides towards reducing the overall burden of HCV in this challenging population. The HCV care cascade remains tied to the HIV continuum of care, with poor engagement in care remaining an important rate-limiting step impeding micro-elimination.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

831. Hepatitis C Virus Micro-elimination Within a Human Immunodeficiency Virus Clinic: Challenges in the Home Stretch

BackgroundHepatitis c virus (HCV) eradication among persons with HIV (PWH) is alluring since DAAs efficacy is high regardless of HIV status and PWH in care are usually screened for HCV. Despite the potential, barriers to care have prevented many from achieving sustained virologic response (SVR). We performed a pharmacist-led campaign to reduce the proportion of PWH with active HCV and describe the barriers to care. MethodsThis retrospective review evaluated patients receiving care at a Ryan White-funded clinic from 07/2018 to 12/2020. Patients were eligible if HCV diagnosed ≥1 year and receiving HIV care. The primary endpoint was to compare the prevalence HCV before and after a pharmacy initiative to target the remaining patients at the clinic not treated during first 3 ½ year period of oral DAA therapy availability. Secondary analysis was to identify barriers to care, measure the proportion of patients in each step of the HCV care cascade, and determine predictors of SVR. Among barriers to care, inconsistent engagement was defined as patients with habitual missed appointments. Logistic regression and Chi-square tests were performed.Results46 of 1,100 PWH had active HCV for ≥1 year. Median age, years since HIV and HCV diagnoses were 58.5 years of age, 17 years, and 11.5 years, respectively. Most patients were male (70%), Black (61%), Latinx (28%), HCV genotype 1 (90%), had an HIV RNA < 200 copies/mL (72%), & had Medicaid (87%). 32/46 patients agreed to therapy, with all getting insurance approval and DAAs delivered. Glecaprevir/pibrentasvir (73%) was the preferred by payors, followed by sofosbuvir/velpatasvir (15%). Eight remained with active HCV and 19 achieved SVR. The prevalence rate dropped from 4.2% to 0.7% (P < 0.0001). Active drug use, inconsistent engagement, mental health disorder and nonadherence were initial barriers to care. After multivariate analysis, patients with inconsistent engagement continued to be less likely achieve SVR compared to those we remained consistently in care (aOR: 0.062, 95 CI: 0.009-0.421).HCV care cascade in PWH within a Ryan White-funded clinic Active HCV includes 46 patients with chronic HCV infection receiving HIV in care at clinic, DAA approval process describes patients agreeing to HCV treatment along a continuum of pending laboratory results or pending prior authorization requests, DAA procurement depicts patients that have received approval and delivery of medications, DAA initiation describes patients who started treatment (27 patients), and SVR documented defines patients with an undetectable HCV RNA 12 weeks after therapy (19 patients).ConclusionPharmacists can impact the burden of HCV among PWH receiving care. The HCV care cascade remains tied to the HIV continuum of care, with disengagement from care remaining an important rate-limiting step impeding micro-elimination.Disclosures All Authors: No reported disclosures

Shelter-Based Integrated Model Is Effective in Scaling Up Hepatitis C Testing and Treatment in Persons Experiencing Homelessness.

Hepatitis C virus (HCV) prevalence is high among people experiencing homelessness, but barriers to scaling up HCV testing and treatment persist. We aimed to implement onsite HCV testing and education and evaluate the effectiveness of low‐barrier linkage to HCV therapy among individuals accessing homeless shelters. HCV rapid testing was performed at four large shelters in San Francisco (SF) and Minneapolis (MN). Sociodemographic status, HCV risk, barriers to testing, and interest in therapy were captured. Participants received information about HCV. Those testing positive underwent formal HCV education and onsite therapy. Multivariable modeling assessed predictors of receipt of HCV therapy and sustained virologic response (SVR). A total of 766 clients were tested. Median age was 53.7 years, 68.2% were male participants, 46.3% were Black, 27.5% were White, 13.2% were Hispanic, and 57.7% had high school education or less; 162 (21.1%) were HCV antibody positive, 107 (66.0%) had detectable HCV RNA (82.1% with active drug use, 53.8% history of psychiatric illness), 66 (61.7%) received HCV therapy, and 81.8% achieved SVR. On multivariate analysis, shelter location (MN vs. SF, odds ratio [OR], 0.3; P = 0.01) and having a health care provider (OR, 4.1; P = 0.02) were associated with receipt of therapy. On intention to treat analysis, the only predictor of SVR when adjusted for age, sex, and race was HCV medication adherence (OR, 14.5; P = 0.01). Conclusion: Leveraging existing homeless shelter infrastructure was successful in enhancing HCV testing and treatment uptake. Despite high rates of active substance use, psychiatric illness, and suboptimal adherence, over 80% achieved HCV cure. This highlights the critical importance of integrated models in HCV elimination efforts in people experiencing homelessness that can be applied to other shelter settings.

Direct-acting antiviral treatment uptake and sustained virological response outcomes are not affected by alcohol use: ACANUHCanalysis.

Alcohol use and hepatitis C virus (HCV) are two leading causes of liver disease. Alcohol use is prevalent among the HCV-infected population and accelerates the progression of HCV-related liver disease. Despite barriers to care faced by HCV-infected patients who use alcohol, few studies have analyzed uptake of direct-acting antiviral (DAA) treatment. We compared rates of treatment uptake and sustained virological response (SVR) between patients with and without alcohol use. Prospective data were obtained from the Canadian Network Undertaking against Hepatitis C (CANUHC) cohort. Consenting patients assessed for DAA treatment between January 2016 and December 2019 were included. Demographic and clinical characteristics were compared between patients with and without alcohol use by means of t-tests, χ2 tests, and Fisher's Exact Tests. Univariate and multivariate analyses were used to determine predictors of SVR and treatment initiation. Current alcohol use was reported for 217 of 725 (30%) patients. The proportion of patients initiating DAA treatment did not vary by alcohol use status (82% versus 83%; p= 0.99). SVR rate was similar between patients with alcohol use and patients without alcohol use (92% versus 94%; p= 0.45). Univariate and multivariate analysis found no association between alcohol use and SVR or treatment initiation. Patients engaged in HCV treatment have highly favourable treatment uptake and outcomes regardless of alcohol use. Public health interventions should be directed toward facilitating access to care for all patients irrespective of alcohol use. Research into high-level alcohol use and DAA outcomes is needed.

Hepatitis C Virus Core Antigen for On-treatment Prediction of Sustained Virological Response to Direct Acting Antivirals in Chronic Hepatitis C

Background and Aim: Cirrhotic patients have lower response rates to DAAs with increased frequency of adverse events. This study aims to evaluate the value of HCVcAg as an early predictor of SVR to DAAs in cirrhotic patients to justify the treatment and avoid side effects.&#x0D; Patients and Methods: This prospective cohort study was conducted on 85 treatment-naive HCV cirrhotic patients who had fulfilled the inclusion and exclusion criteria of the National Treatment Protocol of chronic HCV infection. HCVcAg detection was done on 10th day of treatment. Predictivity of HCVcAg for SVR was assessed in terms of specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy rates. ROC curve was conducted to assess predictivity of HCVcAg as well.&#x0D; Results: SVR12 was (91.76%). HCVcAg was negative in 79 patients; 78 of them achieved SVR, while it was positive in 6 patients; all of whom did not achieve SVR. HCVcAg had sensitivity, specificity, PPV, NPV and accuracy rates of 100%, 98.73%, 85.71%, 100% and 98.82% respectively in prediction of SVR. With AUC of 0.929. There was a positive strong significant correlation between HCVcAg and SVR12 (r = 0.898, P = 0.015).&#x0D; Conclusion: HCVcAg is a sensitive, specific, accurate, easily available, and affordable on- treatment predictor of SVR in cirrhotic patients with chronic HCV with possible future treatment regimen modification to improve efficacy and tolerability in difficult to treat cirrhotic patients.

WITHDRAWN: Analysis of host genetic variations associated with response to anti-HCV therapies in global populations

Abstract Hepatitis C virus (HCV) is a global health issue infecting 71 million people chronically. Host genetic variants have significant role in the prediction of better treatment response as well as the modulation of the side effects of anti-HCV therapies. Assessment of frequencies of such genetic variants in global populations has not been performed so far. In current study, we highlight the allele/genotype frequency pattern of SNPs associated with the prediction of sustained virologic response (SVR) to antiviral therapies such as sofosbuvir, daclatasvir, pegylated (PEG)-IFN and ribavirin (RBV) across the global populations. We compiled a list of genes (n = 203) involved in the host immunity, inflammatory response, surface receptor for virus attachment and pharmacogenes by using deep literature survey and manually curated databases such as Pharmacogenomics Knowledge Base (PharmGKB), and PharmacoGenomic Mutation Database (PGMD). We identified 200 SNPs in 66 genes associated with the treatment response with different combinations of PEG-IFN/RBV, sofosbuvir and daclatasvir antiviral therapies reported in different continental populations. Several variants such as rs12979860, rs368234815, rs12980275, rs4273729 significantly involved in the prediction of better treatment response to direct acting viral agents and PEG-IFN/RBV. The genotype frequency of variants such as rs12979860 “CC”, rs368234815 “TT”, rs4803217 “CC”, and s12980275 “AA” was found high (up to 84%) in Asian populations followed by European (~60%) and American populations (~50%) whereas low in African populations (~20%) by using the whole genome sequence data of 1000 genomes project. Genetic differentiation analysis using the prioritized variants illustrated that African populations are well differentiated with other continental populations. Hence, this study compiles a comprehensive landscape of variants associated with HCV treatment, and may be useful in clinical decision to explore suitability of current and future therapies in different populations.

Interferon-γ inducible protein-10 and interleukin 28B gene polymorphism as predictive markers for genotype 4 hepatitis C virus treatment response.

HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P<0.05). CC genotype in IL28B polymorphism (rs12979860) was the favorable genotype as 65.8% achieved SVR, while TT genotype in IL-28B polymorphism (rs8099917) was the favorable genotype as 81.5% achieved SVR. Baseline IP-10 was significantly correlated to genotypes CC in rs12979860 and TT in rs8099917. Combined use of serum baseline IP-10 levels with IL-28B polymorphisms could improve the prediction of SVR to PEG-IFNα/RBV therapy in Egyptian chronic HCV infection patients with genotype 4.

Predictors of Sustained Virological Response in Chronic Hepatitis C Patients Treated with Current Direct Acting Antiviral Drugs

Predictors of Sustained Virological Response in Chronic Hepatitis C Patients Treated with Current Direct Acting Antiviral Drugs

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.

English hepatitis C registry data show high response rates to directly acting anti-virals, even if treatment is not completed.

In England, choice of hepatitis C therapy is determined by national contracts that change with time, facilitating comparisons between different regimens. England has a diverse population with hepatitis C including large proportions of uncommon viral genotypes. To evaluate efficacy of directly acting anti-viral treatments for hepatitis C in England using real-world data from the national treatment registry. Sustained virological response (SVR) rates 12weeks after treatment completion for patients treated between 2014 and August 2018 who attended for SVR tests were analysed in univariate subgroups using Chi-squared tests. Multivariate models were constructed with clinically relevant variables to determine predictors of SVR and evaluate the impact of treatment regimens. SVR data were available on 14,603 treated patients. The overall SVR rate was 95.59% [95% CI 95.25%-95.91%]. Multivariable regression modelling in patients with genotype 1 infection showed that the odds of SVR with elbasvir/grazoprevir were higher than for those treated with sofosbuvir/ledipasvir (OR 1.891, 95% CI 1.072-3.336, P=0.028). For genotype 3, we found no significant difference between any of the treatment regimens. Patients who completed at least one third of the planned treatment duration achieved SVR rates in excess of 80%. All of the currently licensed hepatitis C direct-acting anti-viral regimens had similar efficacy (>95%) in an unselected population. Noncompletion of planned treatment duration still resulted in over 80% SVR rates provided that more than one third of treatment was completed.

Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan.

This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.

Association between IFN-λ 3 Gene Polymorphisms and Outcome of Treatment with Direct Acting Antivirals in Chronic HCV-Infected Egyptian Patients

ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection. Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection. Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group. Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype). Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.

IL-28B - Predictor of Sustained Virological Response for IFN-based Regimens in Chronic Hepatitis C and Criteria for Optimizing DAAs Indication

Chronic viral infections affecting the liver represents a global burden for medical comunities. More than 170 million individuals are infected chronically with hepatitis C virus (HCV), this accounting about 2�3% of the world�s population. Despite numerous progresses aquired in viral pahogenesis and treatment, chronic hepatitis C management is influenced by a multitude of factors. Interleukin IL-28 beta subunit (IL28B) demonstrated to be involved in both sustained virological response (SVR) to treatment, but even with spontaneous viral clearance without any therapy. In the era of direct antiviral agents (DAAs) we aimed to find out what was the real influence of IL28B phenotypes over the response to Peg-IFN and Ribavirin treatment in patients with chronic hepatitis C, many of theses being non-responders or relapsers, and as consequence, to optimize the referal of patients to more expensive and efficient treatments. In a retrospectively manner, we analyzed the IL28B phenotype and its influence over the rapid viral response (RVR), early viral response (EVR) and sustained viral response (SVR), in 250 patients HCV treated patients. We made correlations between the treatment response rates and the IL28B polymorphism.TT phenotype was correlated negatively with all parameters studied, while CC phenotype was correlated with the best response rates. We concluded that IL28B phenotypes interfere with the EVR and SVR rates, IL28B phenotype being an independent prognostic factor for antiviral treatment response in our patient groups, and according to this characteristics, we created the premise to optimize the patients referal to expensive therapies as DAAs.