High Sustained Viral Response Research Articles

Achieving High Sustained Viral Response in Difficult-to-Treat Hepatitis C-Infected Transfusion-Dependent Thalassemia Patients with Direct-Acting Antivirals

Achieving High Sustained Viral Response in Difficult-to-Treat Hepatitis C-Infected Transfusion-Dependent Thalassemia Patients with Direct-Acting Antivirals

Algorithm for early diagnosis of viral hepatitis C

Abstract Issue Viral hepatitis C (VH C) is a global problem of the public health. Different interventions for achieving the Global Health Sector Strategy on viral hepatitis targets (65% reduction in HCV-related deaths, 90% in new infections and 90% of infections diagnosed by 2030) were considered. Increased diagnosis and treatment rates would be required to achieve these targets in all countries, even with the introduction of high sustained viral response therapies. Description of the problem The latest global HCV disease burden estimates showed that about 71.1 million people worldwide are viremic, corresponding to a prevalence of 1%. The prevalence of HCV is not homogenous: the WHO Eastern-Mediterranean Region is with the highest number of infected subjects (15 millions), followed by the European Region (14 million). In Bulgaria, the incidence of VH C is 0.63-1.30 at 100 000 population (2008-2020) and in Pleven region is 0.38-3.8, respectively. Results Retrospective study was conducted upon epidemiological, demographic, clinical, laboratory and viral characteristics in fifty cases of VH C confirmed with positive anti-HCV, evaluated by ELISA. Thirty eight of cases were hospitalized in different clinics of the University Hospital “Dr Georgi Stranski”-Pleven (2017-2018) and remainders were blood-donors registered in Regional Center of Transfusion Hematology-Pleven. Surgical interventions (26.32%), blood infusions (23.68%) and hemodialysis (15.79%) were at highest risk for VH C. Twenty five hospital patients were with chronic VH C (66%), five with cirrhosis (13%) and eight (21%) with acute hepatitis C. Twenty of the patients (53%) were asymptomatic about hepatitis and were hospitalized because of different comorbidities (p < 0.0005). Lessons We propose an algorithm for early diagnosis of VH C based on mandatory screening for anti-HCV in risk groups, especially before invasive procedures. The early detection of HCV infection will reduce the complications and nosocomial infections. Key messages • Different scenarios developed to achieve the WHO Targets in all countries assume an implementation of national policies to prevent new infections and to diagnose current infections through screening. • The early detection of HCV infection will reduce the complications and nosocomial infections.

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services: real-world data.

There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). Natural experiment, evaluated using data from national biennial surveys of PWID and national clinical data. Services providing injecting equipment (2010-18) and HCV treatment clinics (2017-18) across Scotland. A total of 12 492 PWID who completed a questionnaire and provided a blood spot (tested for HCV-antibodies and RNA); 4105 individuals who initiated HCV treatment. The intervention was rapid DAA scale-up among PWID, which occurred in Tayside. The comparator was GGC/RoS. Trends in HCV viraemia and uptake of HCV therapy over time; sustained viral response (SVR) rates to therapy by region and treatment setting. Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR)=0.47, 95% confidence interval (CI)=0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR=0.89, 95% CI=0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population.

Erratum to: SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter Phase III Clinical Trial

BACKGROUND The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible. METHODS Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12). RESULTS There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent. CONCLUSIONS The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries. CLINICAL TRIALS REGISTRATION NCT03200184.

Assessment of thyroid function in patients with chronic hepatitis C virus infection before and after treatment with oral direct-antiviral drugs

Background There are laboratory and clinical associations between liver and thyroid diseases. Hepatitis C virus is known to be responsible for both hepatic and extrahepatic diseases. Direct-acting antivirals (DAAs) provide high sustained viral response rates and much reduced adverse effects and impaired health-related quality of life during treatment. Aim To assess thyroid function in patients with chronic hepatitis C (CHC) receiving DAAs before start treatment and after achieving of SVR. Patients and methods A prospective study was conducted on 300 patients with CHC infection who were recruited for the study after obtaining written informed consent. Full history was taken, as well as routine examination and special investigations were done for all patients before the start of the remedy and by the end of treatment with DAAs. Results PCR results revealed a statistically significant difference, as SVR was evident in 98% of patients. Analysis of thyroid function assessments in the present study showed that 277 (92.3%) patients were euthyroid and 23 (7.7%) patients had thyroid disorders, comprising seven (2.3%) patients with subclinical hypothyroidism, 14 (4.66%) patients with overt hypothyroidism, and two (0.7%) patients with subclinical hyperthyroidism. Conclusion Thyroid function in patients with CHC infections was not damaged with treatment with DAAs for hepatitis C virus treatment. Hypothyroidism is prevalent in patients with CHC, and after treatment with DAAs, thyroid dysfunction slightly improved, especially subclinical, after achievement of SVR.

Impact of different anti-HCV regimens on platelet count during treatment in Egyptian patients

BackgroundSide effects of antiviral therapies for hepatitis C, especially hematologic abnormalities, may decrease both therapeutic adherence and therapeutic success rate. Adherence to therapy is essential to achieve an early viral response (EVR), and this is vital for attaining a sustained viral response (SVR). Discontinuation of anti-viral therapy is the only way to prevent progressive thrombocytopenia; however, discontinuation of therapy may reduce the rate of viral clearance and SVR. Our aim is to study effects of antiviral therapy for HCV on platelet count. One hundred sixty eight adult patients with chronic hepatitis C were enrolled in this study and subcategorized into 3 groups: group (1) contains 56 patients receiving IFN, ribavirin and sofosbuvir (triple therapy); group (2) contains 55 patients receiving ribavirin and sofosbuvir (SOF/RBV); and group (3) contains 57 patients receiving simeprevir and sofosbuvir (SIM/SOF). HCV RNA by PCR were checked basically for all studied patients. Follow-up platelet count was done weekly during the first month then monthly till end of treatment. Follow-up of platelet count decrement was assessed at the 2nd week, 4th week and end of antiviral therapy for all studied groups.ResultsWe found that in the 2nd week and 4th week, most of patients (76.2%, 71.4%) showed platelet count decrement during antiviral therapy. The decrement of platelet at the 2nd week, 4th week and at end of treatment was much noticed with the SOF/RBV antiviral therapy studied group. None of the patients developed severe thrombocytopenia; none of the patients needed to stop antiviral therapy due to thrombocytopenia, only 6 patients needed dose modification, most of them were from the triple therapy group.ConclusionWe concluded that thrombocytopenia in chronic HCV infection has a multifactorial pathophysiology and remains a major problem. The recent change in direct-acting antiviral therapy (DAA) without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN-based antiviral therapy. DAAs, with high SVR and few haematological adverse effects, have been shown to improve thrombocytopenia associated with HCV infection as well as advanced hepatic disease.

High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia

Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF+DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF+DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF+DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12weeks post-treatment (SVR12) according to a modified intention-to-treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and nonserious adverse events (S/AE). Of 9158 patients, median age was 57years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n=8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF+DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.

Study the efficacy of sofosbuvir/daclatasvir in treatment of hepatitis C virus in Egypt

Objectives To evaluate the efficacy of combination therapy of sofosbuvir and daclatasvir with or without ribavirin as a treatment of chronic hepatitis C virus (HCV), estimated by the rate of achievement of sustained viral response 12 weeks. Background Direct-acting antiviral agents opened the gate to a new era for the management of HCV. These agents have shown high sustained viral response rates of ~90% in clinical trials, shorter therapies, less toxicity, and interferon-free regimens. Patients and methods This prospective, population-based study included 401 HCV-infected patients, 18–75 years of age, attending the Viral Hepatitis Unit of the National Committee for Control of Viral Hepatitis at Center of Cardiac and Digestive System, Sohag, who were divided into two groups: group I (easy to treat) was treated by sofosbuvir + daclatasvir for 3 months, and group II (difficult to treat) was treated by sofosbuvir + daclatasvir + ribavirin for 3 months. Results There was a high statistically significant difference between the studied groups regarding liver echo pattern, splenic size, fibrosis index based on the 4 factors, blood glucose, international normalized ratio, total bilirubin, serum albumin, aspartate transaminase, and platelet count (P 0.05). Conclusion The treatment regimen of sofosbuvir + daclatasvir with/without ribavirin for chronic HCV patients was of high efficacy.

Erratum to: SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial.

Erratum to: SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial.

1020 The Effect of Metabolic Syndrome Components on Liver Stiffness Measurement Values After HCV Eradication

INTRODUCTION: The availability of noninvasive fibrosis measures coupled with high sustained viral response (SVR) rates has shifted the paradigm in the management of HCV infection in the direct-acting antiviral (DAA) era. Although these noninvasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy, use of these measures in monitoring fibrosis regression after HCV eradication is currently limited. There is evidence that patients who achieve SVR after therapy have a reduced risk of liver-related complications.1 This is likely attributed to the regression of fibrosis after HCV eradication.2 Other comorbidities, such as obesity, nonalcoholic steatohepatitis and diabetes mellitus may also contribute to liver-related complications.3-4 The aim of this study is to evaluate the effect of metabolic syndrome components on liver stiffness measurement (LSM) after HCV eradication. METHODS: A retrospective study of 65 HCV monoinfected patients who received DAA and achieved SVR located in a safety net hospital in Cleveland. All Patients had pretreatment LSM of more than 7k Pa. Patient’s with Fibrosis stage F4 had CP class A. Fibrosis was evaluate within 12 months before treatment and 12-24 months after SVR using Transient Elastography. Other collected parameters included BMI, history of DM, HLD and HTN, HbA1c, LDL, HDL and TGs. Demographics and hepatitis C genotype (GT) were also collected. Statistical analysis was performed using descriptive analysis, Anova, Univariate regression and Multivariate regression to compare variables for statistical significance. RESULTS: Among all subjects (n = 65). 64.6% were male. 61.5% had Genotype 1a, 26.2% had genotype 1b and 6.2% had genotype 2. 33.8% were diabetic, 64.6% had hyperlipidemia, and 66.2% patients had hypertension. The mean pre-treatment LSM was 14.4kPa (SD 10.0) and the mean post-treatment LSM was 9.33 kPa (SD 5.3). The mean of delta-stiffness was 5.1 kPa (SD 9.7). 53.8% patients dropped their LSM by 3 kPa or more after SVR. In univariate logistic regression, age (P = 0.675), race (P = 0.11), genotype (P = 0.688), BMI (P = 0.709), diabetes (P = 0.661), hyperlipidemia (P = 0.743), and hypertension (P = 0.545) failed to show any significant correlation with significant drop (≥3kPa) in liver stiffness measurement. CONCLUSION: Sustained viral response after direct-acting antiviral (DAA) therapy leads to significant improvement in LSM within 48 months of therapy completion. Metabolic syndrome components has no significant effect on LSM improvement after SVR.

Efficacy of Atorvastatin Plus Pegylated Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin Alone in Chronic Hepatitis C Patients with Genotype-3a

Chronic hepatitis C infection has created a huge burden of disease causing serious healtheffects. The combination therapy used to treat hepatitis C virus (HCV) infection includes Pegylatedinterferon and Ribavirin. As cholesterol biosynthesis plays a pivotal role in HCV replication, the use ofvarious statins has been associated with higher sustained viral response Objective: To compare theefficacy of atorvastatin plus pegylated interferon and ribavirin versus pegylated interferon and ribavirinalone in patients of chronic hepatitis C with genotype-3a Methods: This Randomized controlled trial wasconducted at outpatient department, Mayo Hospital Lahore for six months i.e. May to November 2017.After ethical approval, 60 patients of ages 25 to 55 years of either gender with chronic hepatitis C withgenotype 3a were included in the study. Informed consent was taken from all patients. Then patients wererandomly allocated into two groups “A” and “B” using random number table. Patients in Group A receivedstandard of care treatment for chronic hepatitis C i.e. pegylated interferon and ribavirin while the patientsin Group B also received tab atorvastatin along with the standard treatment. Patients were follow up for 4week. Blood samples were collected and HCV RNA detection. All this information were entered inproforma Results: In standard therapy group, the mean age of patients was 39.50±8.39years. Inatorvastatin plus standard therapy group, the mean age of patients was 34.30±6.78years. In standardtherapy group, there were 25 (83.3%) males and 5 (16.7%) females. In atorvastatin plus standard therapygroup, there were 16 (53.3%) males and 14 (46.7%) females. After 4 weeks, Rapid Virological Response(RVR) was achieved in 4 (13.3%) patients in standard therapy group while in 14 (46.7%) in atorvastatin plusstandard therapy group. The difference was significant (p<0.05) Conclusions: Atorvastatin incombination with Pegylated interferon and ribavirin have better efficacy as compared to Pegylatedinterferon & ribavirin alone in chronic hepatitis C-3a.

HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1.

BackgroundThe efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV.MethodsWe compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV.ResultsUp to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020).ConclusionsThe results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.

Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection

Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.

Thyroid in patients receiving new direct-acting antiviral agents for treatment of hepatitis C virus

Objective The aim was to judge thyroid dysfunction in patients receiving new direct-acting antiviral agents (DAAs) for treatment of hepatitis C pathogen. Background Persistent hepatitis C is a gradually progressive disease. DAAs provide high sustained viral response rates and much reduced adverse effects and impaired health-related quality of life during treatment. Patients and methods The analysis included 100 patients with persistent hepatitis C contamination with normal thyroid functions before starting treatment with DAAs. After obtaining written informed consent, all patients were analyzed and clinically assessed. Laboratory investigations including complete blood picture, assessment of liver organ and kidney function, thyroid-stimulating hormone, and free thyroxin 4 were done for all patients before the start of the remedy, and by the end of treatment of direct-acting antiviral remedy. Results An evaluation of the analyzed patients who were obtaining direct-acting antiviral drugs for treatment of hepatitis C pathogen before and after remedy with respect to the PCR findings proved significant decrease of PCR values after treatment (P = 0.0001). There is no statistically significant difference before and after remedy with new DAA regarding laboratory findings as serum thyroid-stimulating hormone (P = 0.580) and serum free T4 (P = 0.279). Conclusion Thyroid function in patients with chronic hepatitis C infection was not afflicted with treatment with new direct-acting antiviral drugs for treatment of hepatitis C virus.

IL-28β gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients.

PEGylated interferon (PEG-IFN) in combination with ribavirin is the gold standard for chronic hepatitis C virus (HCV). The majority of patients received PEG-IFN/ribavirin achieve a sustained viral response (SVR), but few cases failed to respond. It was evident that host genetic factors determine the treatment-induced viral clearance as well as spontaneous response. In the current study, the rs12979860 polymorphism of IL28β gene was analyzed and its association with the virological response to PEG-IFNtreatment was determined. One hundred and fifty Egyptian patients with HCV genotype 4 treated with PEG-IFN/ribavirin were assessed at 12 and 24 weeks of therapy, the rs12979860 genotype was determined using TaqMan-based quantitative polymerase chain reaction. Although the CC genotype was the most frequent (58%), the higher SVR was achieved for patients with favorable CC genotype (93%) in contrast to CT and TT genotypes. we conclude that IL28B polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genotype 4 and patients who carry CC genotype have a higher chance of SVR.

Real-world treatment of hepatitis C with second-generation direct-acting antivirals: initial results from a multicentre Canadian retrospective cohort of diverse patients.

High hepatitis C cure rates have been observed in registration trials with second-generation direct-acting antivirals. Real-world data also indicate high sustained viral response (SVR) rates. Our objective was to determine real-world SVR rates for patients infected with hepatitis C virus (HCV) who were treated with second-generation direct-acting antivirals in the first 18 months of their availability in Canada. Four centres in Calgary contributed their treatment data for a diverse patient population including those who had or had not undergone liver transplantation, those coinfected with HIV and vulnerable populations. We included all patients documented to have started hepatitis C treatment with direct-acting antivirals between October 2014 and April 2016, with follow-up through October 2016. We used multivariate analysis to determine independent predictors of treatment failure. Outcome data were available for 351 patients, of whom 326 (92.9%) achieved an SVR (193/206 [93.7%], 57/59 [96.6%] and 44/51 [86.3%] for genotypes 1a, 1b and 3, respectively, p = 0.2). Independent predictors of not achieving SVR were older age (adjusted odds ratio [OR] 0.95 [95% confidence interval (CI) 0.90-1.00]), male sex (adjusted OR 0.30 [95% CI 0.10-0.89]) and, in patients with genotype 1a infection, history of hepatocellular carcinoma (adjusted OR 0.13 [95% CI 0.03-0.53]). In the entire cohort, the presence of cirrhosis, genotype and hepatocellular carcinoma were not associated with a lower SVR rate. There were no differences in SVR rate according to treatment centre, HIV coinfection or liver transplantation. Among patients with genotype 3 infection, a significantly lower SVR rate was observed for those treated outside of standard of care than for those treated within standard of care (33.3% v. 89.6%, p = 0.04). De novo hepatocellular carcinoma developed in 12 patients (3.4%) despite successful direct-acting antiviral therapy. We report high SVR rates in a real-world diverse cohort of HCV-infected patients treated with second-generation direct-acting antivirals. The results highlight the importance of conducting real-world analyses to elucidate clinical factors associated with poorer outcomes that may not be identified in registration trials.

Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon-β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy.

To improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead-in interferon (IFN)-β injections was formulated according to the types of resistance-associated substitutions (RAS) in the non-structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV). Thirty-three patients failing prior DCV/ASV received SOF/LDV for 12weeks. Patients with HCV carrying unfavorable NS5A-RAS and/or those previously treated with simeprevir were given lead-in IFN-β injections twice a day for 2weeks; sequential changes in the NS5A-RAS during the injection period were evaluated using deep sequencing. Lead-in injections were not undertaken in 27 patients; a sustained viral response (SVR) was achieved in 26 patients, while viral relapse occurred in 1 patient with HCV carrying NS5A-L28M/R30H/Y93H mutations. Among the 6 patients receiving lead-in injections, viral relapse occurred in 2 patients who had an unfavorable IFN-λ3-related gene single nucleotide polymorphism allele; both patients had been previously treated with simeprevir, and HCV carrying NS5A-L31V/Y93H mutations had emerged after DCV/ASV. Deep sequencing revealed no changes in the NS5A-RAS profiles during the lead-in injection period in either patient. In contrast, in a patient with a favorable allele who was infected with similar unfavorable HCV strains, NS5A-L31/Y93 wild-type strains appeared during the injection period, enabling an SVR. Using customized therapies based on the NS5A-RAS profiles, a high SVR rate was obtained after SOF/LDV in patients failing prior DCV/ASV. Lead-in IFN-β injections did not improve the efficacy in patients with HCV carrying unfavorable NS5A-RAS except in those with a favorable IFN-λ3-related gene allele.

Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n=74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n=1) in the NS3, and at L31 (n=4), Y93 (n=4), and L31/Y93 (n=1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n=12). Univariate analysis showed that a history of SMV (P<.01) and the presence of mutations in NS5A (P=.02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.

Sofosbuvir and velpatasvir for the treatment of hepatitis C

ABSTRACTIntroduction: Direct acting antivirals are revolutionizing the treatment of chronic hepatitis C. Specifically, the combination therapy sofosbuvir and velpatasvir offers a pangenotypic regimen with high sustained viral response (SVR).Areas covered: Reviewed here are the clinical trials that led to the FDA approval of sofosbuvir and velpatasvir combination therapy, the adverse events during registration trials, and drug-drug interactions. Sofosbuvir and velpatasvir is a fixed dose regimen that is both interferon- and ribavirin-free. It is administered for 12 weeks as a once-a-day pill, covers all genotypes of hepatitis C, and achieves SVR >95% in non-cirrhotic patients and patients with compensated cirrhosis. Addition of ribavirin is recommended for patients with decompensated cirrhosis (CTP B or C). Baseline resistance-associated substitutions do not appear to impair ability to achieve SVR with an initial course of treatment.Expert commentary: Availability of this highly efficacious, well tolerated, all oral regimen formulated as a single pill, can potentially simplify hepatitis C treatment. Its utility as a pangenotypic regimen additionally limits resource utilization.

SAT-221 - High sustained viral response among hepatitis C virus genotype 3 patients with advanced liver fibrosis - real-world data of HCV elimination program in Georgia

SAT-221 - High sustained viral response among hepatitis C virus genotype 3 patients with advanced liver fibrosis - real-world data of HCV elimination program in Georgia