scholarly journals Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Saima Ali Haider ◽  
Bashir Ahmad ◽  
Sajid Ali ◽  
Ali Haider ◽  
Shumaila Bashir ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Response Rate ◽  
Therapy Response ◽  
Khyber Pakhtunkhwa ◽  
Direct Acting Antiviral ◽  
Liver Ultrasound ◽  
Treatment Naïve ◽  
Direct Acting

Background: Approximately 3% of the population worldwide is infected with Hepatitis C Virus (HCV). Different regimens have been used to treat HCV, each of which has its side effects and efficacy. Sofosbuvir, a direct-acting antiviral drug, has replaced all previous regimens with the highest response rate. However, its response is not fully covered in Pakistan, especially Khyber Pakhtunkhwa. Objectives: The study aimed to examine the response to Sofosbuvir and Ribavirin combination therapy in chronic HCV patients infected with various HCV genotypes. Methods: This study was conducted in Tertiary Care Hospitals, Peshawar, Pakistan. The patients were enrolled from January 2016 to March 2017. A total of 80 patients (57 naïve and 23 non-responder) were enrolled in this study. The age range was 16 - 70 years, and the mean age was 36 ± 2 years. Genotyping, biochemical profile, PCR tests, and liver ultrasounds were done for all of the enrolled subjects at the start and end of therapy. All patients were given direct-acting antiviral drugs for six months and then, the end of treatment response was noted. Results: A total of 80 subjects with HCV infection took part in the study, including 57 (71.25%) treatment-naïve and 23 (28.75%) treatment non-responding patients. The end of therapy response was reported after 24 weeks of treatment. Among the 80 patients, 72 (90%) patients achieved the end of therapy response. The highest end of therapy response (100%) was noted in genotype 1 and mixed genotypes and patients with normal liver ultrasound. The lowest end of therapy response (70%) was found in un-type genotype and patients with an abnormal texture of liver ultrasound. The end of therapy response rate was higher in females than in males. Conclusions: In the current study, the minimal response was found in un-type genotypes and genotypes that did not respond to INF, as compared to treatment-naïve subjects. Further research is needed to understand the relevant host and viral factors, with particular attention to relapsed patients and non-responders that are difficult to treat in the Pakistani population.

scholarly journals Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Fabián Aldunate ◽  
Natalia Echeverría ◽  
Daniela Chiodi ◽  
Pablo López ◽  
Adriana Sánchez-Cicerón ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
South American ◽  
Genotype 1 ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Before And After ◽  
Treatment Naïve ◽  
Direct Acting

Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

scholarly journals Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhanyi Li ◽  
Ying Liu ◽  
Ying Zhang ◽  
Xiaoqiong Shao ◽  
Qiumin Luo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Ns5a Region ◽  
Treatment Naïve ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

Background and Objective. The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

scholarly journals Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment

2012 ◽  
Vol 87 (3) ◽  
pp. 1544-1553 ◽  
Author(s):  
Doug J. Bartels ◽  
James C. Sullivan ◽  
Eileen Z. Zhang ◽  
Ann M. Tigges ◽  
Jennifer L. Dorrian ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Viral Response ◽  
Allosteric Inhibitors ◽  
Resistant Variant ◽  
Direct Acting Antiviral ◽  
Treatment Naïve ◽  
Variant Frequency ◽  
Direct Acting ◽  
Ns5b Polymerase

ABSTRACTThe prevalence of naturally occurring hepatitis C virus (HCV) variants that are less sensitive to direct-acting antiviral (DAA) inhibitors has not been fully characterized. We used population sequence analysis to assess the frequency of such variants in plasma samples from 3,447 DAA-naive patients with genotype 1 HCV. In general, HCV variants with lower-level resistance (3- to 25-fold increased 50% inhibitor concentration [IC50]) to telaprevir were observed as the dominant species in 0 to 3% of patients, depending on the specific variant, whereas higher-level resistant variants (>25-fold-increased IC50) were not observed. Specific variants resistant to NS5A inhibitors were predominant in up to 6% of patients. Most variants resistant to nucleo(s/t)ide active-site NS5B polymerase inhibitors were not observed, whereas variants resistant to non-nucleoside allosteric inhibitors were observed in up to 18% of patients. The presence of DAA-resistant variants in NS5A, NS5B, or NS3 (including telaprevir-resistant variants), in baseline samples of treatment-naive patients receiving a telaprevir-based regimen in phase 3 studies did not affect the sustained viral response (SVR). Treatment-naive patients with viral populations containing the telaprevir-resistant variants NS3 V36M, T54S, or R155K at baseline achieved a 74% SVR rate, whereas patients with no resistant variants detected prior to treatment achieved a 76% SVR rate. The effect of specific resistant variant frequency on response to various DAA treatments in different patient populations, including interferon nonresponders, should be further studied.

scholarly journals Experience of a Portuguese Center: Effectiveness of Direct-Acting Antiviral Therapy for Hepatitis C

2019 ◽  
Vol 32 (3) ◽  
pp. 189 ◽  
Author(s):  
Fátima Falcão ◽  
Carla Lopes ◽  
Erica Viegas ◽  
Rita Perez ◽  
Isabel Aldir ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Sustained Virologic Response ◽  
Response Rate ◽  
Virologic Response ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antiviral ◽  
Direct Acting

Introduction: In late 2014, Portugal implemented a national program for the treatment of patients with chronic hepatitis C with directacting antiviral agents. This program has made Portugal one of the first European countries to implement a structured measure of treatment to eliminate this serious public health problem. The aim of this study was to assess the effectiveness of direct-acting antiviral therapy in the treatment of patients with chronic hepatitis C virus infection.Material and Methods: A retrospective observational study was conducted at Centro Hospitalar de Lisboa Ocidental on the national online platform from December 2014 until February 2017 and included patients with hepatitis C virus infection who underwent treatment. The primary endpoint was sustained virologic response at least 12 weeks post treatment. Data was analyzed with the SPSS 17.0 program.Results: During the study period, 820 patients completed therapy and achieved sufficient follow-up time to assess sustained virologic response with an overall response rate of 97.2% (n = 797) and a response rate of 98.0%, 99.5%, 90.9%, 95.1% and 94.2% for genotypes 1a, 1b, 2, 3 and 4, respectively. Data suggested that advanced fibrosis (F3/F4), human immunodeficiency virus co-infection and treatment failure with interferon and ribavirin were not negatively related with sustained virologic response in our population. Most patients (80.1%) completed treatment with ledipasvir/sofosbuvir ± ribavirin. The most common adverse events were fatigue and insomnia followed by headache and weight loss.Discussion: Patients predominantly had genotype 1 infection which correlates with HCV distribution in Europe, but we found a major proportion in genotype 4 which can be explained by immigration from African countries. Our patients’ ages ranging from 22 to 90 years, reflected a new approach with no upper age limit. Direct-acting antivirals regimens resulted in remarkably high SVR rates compared to interferon-based regimens, which were consistent with clinical trials data.Conclusion: Our data showed that direct-acting antiviral-based regimens are safe and have a high success rate in the treatment of patients with hepatitis C virus infection in a real-world setting.

New Epidemiologic Data Regarding Hepatitis C Virus Infection in Romania

2017 ◽  
Vol 26 (4) ◽  
pp. 381-386
Author(s):  
Mircea Manuc ◽  
Carmen M. Preda ◽  
Corneliu P. Popescu ◽  
Cristian Baicuș ◽  
Theodor Voiosu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Users ◽  
Antiviral Agent ◽  
Virologic Response ◽  
Advanced Fibrosis ◽  
Direct Acting Antiviral ◽  
Genotype 1B ◽  
Direct Acting ◽  
End Stage

Background & Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania.Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address.Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanța (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramureș (8.8/105) (p<0.001).Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.Abbreviations: BMI: body mass index; DAA: direct-acting antiviral agent; GT: genotype; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; IDU: intravenous drug users; MELD: model for end stage liver disease; NASH: non-alcoholic steatohepatitis; SVR; sustained virologic response.

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