Nationwide registry of glecaprevir plus pibrentasvir in the treatment of HCV in Taiwan

The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan

About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2–3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.

Glecaprevir/ Pibrentasvir in the Treatment of Chronic Hepatitis C Patients – A Real-World Nationwide HCV Registry Program (TACR) in Taiwan

Background/AimsThe study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan.MethodsThe Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3,144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). ResultsThe overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). ConclusionsThe results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Efficacy and safety of ledipasvir/sofosbuvir for hepatitis C among drug users: a systematic review and meta-analysis

Background and aims Limited data is available on the efficacy of direct acting anti-viral drugs on hepatitis C in drug users. The aim of this meta-analysis was to comprehensively analyze the efficacy and safety of LDV/SOF in drug users infected with the hepatitis C virus (HCV). Methods The PubMed, Cochrane library, Embase and Web of Science databases were searched for articles published till April 2021 on HCV-positive drug users who were treated with ledipasvir/sofosbuvir (LDV/SOF). The primary endpoint was pooled sustained virological response at 12 weeks (SVR12) with 95% confidence interval (95% CI). Funnel plots and Egger’s test were used to assess the publication bias. Results A total of 12 studies and 711 subjects treated with LDV/SOF-based regimen for HCV were included, and the pooled SVR12 rate was 89.8% (95% CI 85.9–92.7). The pooled SVR12 rate of genotype 1 drug users was 92.4% (95% CI 88.6–95.0). Subgroup analysis showed that pooled SVR12 rates of patients treated with LDV/SOF and LDV/SOF ± RBV were 89.2% (95% CI 83.4–93.1), 90.4% (95% CI 83.6–94.5) respectively. In addition, the SVR12 rates were 88% (95% CI 70.7–95.7) for 8 weeks, 89.9% (95% CI 81.0–94.9) for 12 weeks and 82.2% (95% CI 24.9–98.5) for 24 weeks of treatment. Conclusion LDV/SOF is a safe and relatively effective treatment for hepatitis C in drug users.

An updated systematic review and meta-analysis on efficacy of Sofosbuvir in treating hepatitis C-infected patients with advanced chronic kidney disease

Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite adequate. The aim of this study was to evaluate the efficacy and safety of Sofosbuvir-based therapy without Ribavirin for all hepatitis C virus genotypes among patients with advanced CKD. We conducted an updated systematic literature search from the beginning of 2013 up to June 2020. Sustained virologic response (SVR) rate at 12 and/or 24 weeks after the end of treatment, and adverse events in HCV-infected patients with advanced CKD were pooled using random effects models. We included 27 published articles in our meta-analyses, totaling 1,464 HCV-infected patients with advanced CKD. We found a substantial heterogeneity based on the I2 index (P = 0.00, I2 = 56.1%). The pooled SVR rates at 12 and 24 weeks after the end of Sofosbuvir-based treatment were 97% (95% Confidence Interval: 95–99) and 95% (89–99) respectively. The pooled SVR12 rates were 98% (96–100) and 94% (90–97) in patients under 60 and over 60 years old respectively. The pooled incidence of severe adverse events was 0.11 (0.04–0.19). The pooled SVR12 rate after completion of the half dose regimen was as high as the full dose treatment but it was associated with less adverse events (0.06 versus 0.14). The pooled SVR12 rate was 98% (91–100) in cirrhotic patients and 100% (98–100) in non-cirrhotic patients. The endorsement of Sofosbuvir-based regimen can improve the treatment of hepatitis C virus infection in patients with advanced CKD.

Directly Acting Antiviral-Based Treatment for HCV-Infected Persons Who Inject Drugs: A Multicenter Real-Life Study

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. Results: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). Conclusions: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

Sofosbuvir-based therapies achieved satisfactory virological response in Chinese with genotypes 3 and 6 infection: a real-world experience from a centre

BackgroundAs previously shown by others, sofosbuvir-based regimens yield high sustained virological response rates in patients with HCV infection except for genotype 3b complicating with cirrhosis. The real-world study aims to explore efficacy and safety of sofosbuvir-based regimens in genotypes 3 and 6 infected patients, especially the impact of ribavirin co-administration on sustained virological response in cirrhotic patients with genotype 3b infection. MethodsA retrospective cohort study included 173 patients initiated on sofosbuvir-based regimens. Main endpoint of treatment was sustained virological response at post-treatment week 12 (SVR12).Results92 patients with sufficient follow-up were included. Overall, SVR12 rate was 96.7% (89/92), including 62 patients treated with addition of ribavirin to sofosbuvir-based regimens, given superior SVR12 rate (98.4%) than ribavirin free regimens (93.3%). SVR12 rates were 96.3% and 96.7% in patients infected with genotype3 (54) and genotype 6 (38) Among patients with genotype 3b infection, SVR12 was achieved in 97.1%, and 100% when complicating with cirrhosis. SVR12 rate was achieved in 96.6% among patients with cirrhosis (28/29), 100% with ribavirin co-administration regimens and 87.5% without ribavirin. Totally, three patients failed to achieve SVR12, including 2 non-cirrhotic patients with genotype 3b and 6a infection treated with sofosbuvir+ribavirin and sofosbuvir/velpatasvir regimen, one cirrhotic patient with genotype 3k infection treated with SOF/VEL regimen. No sever adverse events occurred.ConclusionsReal-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infection. Addition of ribavirin to sofosbuvir-based regimens may improve efficacy, especially in patients with genotype 3 infection and cirrhosis.Trial registrationNot applicable.

Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for HCV NS5A-inhibitor experienced patients with difficult to cure characteristics

Background In clinical trials, HCV salvage treatment with Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of &gt;95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. Methods We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). Findings Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n=46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n=82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n=18/18, GT1b n=2/4), 89% in GT3 (n=59/66) and 100% in GT6 (n=3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were four serious AEs including one death and three hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. Conclusion This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most however serious AEs can occur in those with advanced liver disease.

The efficacy and safety of direct-acting antiviral agents in patients with chronic HCV infection and UGT1A1*28 polymorphism

Objective. To determine the efficacy and safety of direct-acting antiviral agents (DAA) in patients with chronic HCV infection and UGT1A1*28 polymorphism. Materials and Methods. An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n = 143) with chronic hepatitis C (CHC) and liver cirrhosis and UGT1A1*28 polymorphism was performed. A total of 139 patients with chronic HCV infection were included in the efficacy analysis (absence of HCV RNA in blood by PCR) by the rate of sustained virologic response at week 12 (SVR12). Results. The SVR12 rate in patients with CHC and HCV-CP was 92.5% and 87.9%, respectively (p = 0.508), regardless of the presence of UGT1A1*28 polymorphism. The SVR12 rate in patients with chronic HCV infection and (TA)7/(TA)7 was 84.8%, with (TA)6/(TA)7 – 92.2% compared with (TA)6/ (TA)6 – 90,5% (p = 0.518). The rate of SVR12 in patients with CHC and (TA)7/(TA)7 or (TA)6/(TA)7 was 80% and 95%, respectively, with (TA)6/(TA)6 – 95.2%. The rate of SVR12 in patients with liver cirrhosis and (TA)7/(TA)7 or (TA)6/(TA)7 was 92.3% and 87.5%, respectively, with (TA)6/(TA)6 – 85.7%. The rate of SVR12 in patients with 12- and 24-week treatment duration was 88.2% and 96.6%, respectively (p = 0.30). As many as 96.2% of patients with the previous treatment with interferon and ribavirin had SVR12 compared to 88.5% of patients who have not previously taken antiviral drugs (p = 0.486). Grade 1 adverse events (AE) occurred in 24% of patients with chronic HCV infection treated with DAA; two patients developed Grade 4 AE. Conclusions. The treatment with DAA was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.

REAL-LIFE RESULTS OF SOFOSBUVIR BASED THERAPY FOR PATIENTS WITH HEPATITIS C

Purpose of the study. The sofosbuvir (SOF) based regimes for the treatment of patients infected with hepatitis C virus (HCV) hasimproved rates of sustained virological response (SVR) considerably in recent trials. There is only limiteddata concerning the efficacy and safety in a real-life cohort. We analyzed the treatment outcome of SOF based regimes for chronic hepatitis C patients in a real life setting. Materials and methods. This retrospective study analyzed 205 patients with chronic HCV infection. The following treatments were given according national guidelines: SOF + pegylated interferon alpha-2b + ribavirin for 12 weeks; SOF + ribavirin for 12–24 weeks. Results. Among 3 patients withgenotype 1a HCV the SVR12 rate was 100%, among 100 patients with genotype 1bHCV the SVR12 rate was 92%, among 11 patients with genotype 2 HCV the SVR12 rate was 90.9% and among 91 patients with genotype 3a HCV the SVR 12 rate was 96,7%. Treatment was safe, most of the side effects and laboratory abnormalities (anemia, neutropenia) found during this study were associated with pegylated interferon or ribavirin. Conclusion. In real life setting treatment regimens for chronic hepatitis C patients with SOF based regimens are highly effective and safe, including patients with cirrhosis and treatment experienced patients. Keywords: hepatitis C, genotype, sofosbuvir, ribavirin, pegylated interferon.