Sustained Virological Response Rates Research Articles

Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

Evaluación del valor clínico y económico de sofosbuvir/velpatasvir (SOF/VEL) en pacientes con hepatitis C crónica en España durante los últimos 5 años

Objective: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain.Methods: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied.Results: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197Meuro.Conclusion: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV)

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Adherence in HCV Treatment: What We Know.

Although therapy with direct-acting antiviral (DAA) agents achieves high HCV cure rates and is forgiving of missed doses, certain patient populations, such as people who inject drugs (PWID), are often denied therapy because of a perceived high risk of nonadherence. However, a relationship between adherence to DAAs for various patient populations and efficacy has not been well defined. The lack of a standardized method for evaluating adherence complicates making comparisons between studies, making it difficult to develop and implement novel measures that may improve adherent behavior. Traditional methods for assessing adherence may overestimate medication adherence, while newer, technology-based methods may assist with accurately assessing and maintaining patient adherence to therapy. Data demonstrate that special populations of patients with HCV, such as PWID, can be successfully treated, with relatively high rates of sustained virologic response (SVR) despite less-than-optimal adherence. While rates of adherence, and subsequently SVR, can be improved, antiviral therapy should not be withheld because of fear of nonadherence. This paper addresses medication adherence and forgiveness of DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, in different patient populations with HCV. Considerations in evaluating adherence in HCV therapy and available methods for assessing adherence are detailed.

Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents.

Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n=1169) and post-DAA (after 2014, n=780) groups. Changes in clinical features and prognosis were assessed. Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69years), lower levels of AST (40 vs 56IU/L), ALT (31 vs 46IU/L), and AFP (11.7 vs 23.6ng/mL), higher platelet count (13.5 vs 10.8×104/μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P<0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6years, P<0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P<0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P=1.0). The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.

Antiviral activity of lactoferrin: a focus on hepatitis C chronic

Introduction: The Hepatitis C virus (HCV) is one of the main causes of chronic liver disease in the world, and despite having a treatment with sustained virologic response rate, this therapy is not resolutive for all patients. Objectives: To carry out a literature review on the action of bovine lactoferrin (bLf) on chronic hepatitis C to find evidence of its antiviral effect for a possible treatment associated with conventional therapy. Methodology: 49 articles were found according to the descriptors “lactoferrin” “immunotherapy” “chronic hepatitis C” in the pre-selected databases and seven were chosen according to the inclusion and exclusion criteria for writing the review in question. Results: The benefit of bLF use was related to the reduction of serum HCV RNA levels (1106 kIU/ml to 612 kIU/ml), plasma 8-isoprostane (8.6 ± 3.7 to 6.9 ± 2.1 pg/ml) and alanine aminotransferase (ALT) values (85 ± 80 to 63 ± 55 IU/l). Conclusion: The studies showed a possible antiviral effect of bovine lactoferrin that should be explored, through further studies, for adjuvant use in patients with chronic hepatitis C who do not show complete efficacy with the pre-established treatment for the disease.

Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study.

In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

High Hepatitis C Cure Rates Among Patients With Alcohol Use at a Safety-Net Hepatitis C Clinic.

We set out to examine several aspects of the relationship between alcohol use and hepatitis C virus (HCV) among a cohort of patients treated at an HCV clinic within a safety net hospital. We examined (1) the prevalence of alcohol use among patients treated for HCV, (2) the likelihood of being started on treatment among patients who reported drinking alcohol compared with those who did not, and (3) the associations between alcohol use and HCV cure. We performed a retrospective chart abstraction study using data from the Grady Liver Clinic, a specialty HCV clinic colocated in Grady Memorial Hospital's primary care clinic and run by general internists. Nine hundred fifty-four patients were included. The sustained virologic response rate among those with 12-week posttreatment measurement was 99.2%, with only 5 patients experiencing virologic failure. None of the alcohol use indicators significantly impacted sustained virologic response or loss to follow-up. Estimates of alcohol use ranged from 28.9% (by International Classification of Diseases, Tenth Revision, code) to 48.9% (clinician documentation). Treatment initiation rates were the same among those who did and did not report alcohol use. Alcohol use was not associated with decreased HCV cure rates. Our findings validate the inclusion of patients with alcohol use in HCV treatment programs.

Effect of Antiviral Drug on Viral Load Patients Infected with Hepatitis C Virus Genotype 3

Background: Hepatitis C Virus (HCV) genotype 3 is recognized for its rapid progression towards liver fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma, particularly in regions with high prevalence rates like Pakistan. Despite advances in treatment, understanding the efficacy and outcomes of direct-acting antiviral (DAA) therapy in this specific genotype remains crucial for optimizing clinical management and public health strategies. Objective: This study aims to evaluate the efficacy and safety of daclatasvir and sofosbuvir combination therapy in patients with HCV genotype 3 infection, focusing on sustained virologic response (SVR), viral load reduction, and treatment-related adverse events. Methods: A single-group, pretest-posttest design was utilized, involving 130 participants diagnosed with HCV genotype 3. Patients received a 12-week regimen of daclatasvir (60mg daily) and sofosbuvir (400mg daily). The study conducted thorough pre-treatment and post-treatment assessments, including ELISA for HCV antibodies, PCR for viral load determination, and genotyping. Statistical analyses were performed using SPSS version 25, with significance set at p&lt;0.05. Results: Of the 130 participants, 93% achieved SVR at 12 weeks post-treatment. The pre-treatment viral load ranged from 78,200 to 120,900,000 IU/mL, significantly decreasing post-treatment across the cohort. Genotype analysis confirmed HCV genotype 3 in 85.71% of cases. Treatment was well-tolerated, with no serious adverse events reported. Conclusion: The combination therapy of daclatasvir and sofosbuvir was highly effective and safe in treating patients with HCV genotype 3 infection, demonstrating a high rate of SVR and a significant reduction in viral load without severe adverse events. These findings support the use of this regimen as a viable treatment option for this challenging HCV genotype.

Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Natural history and clinical features of hepatitisC virus infection during childhood: A nationwide, observational survey in Japan.

Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitisC viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1years (range 0.9-7.2years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0months; p=0.0031). Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

The Association between Urinary Alcohol Metabolites on Hepatitis C Treatment and Response

Background: Direct-acting antiviral (DAA) medications for the treatment of chronic hepatitis C virus (HCV) infection has achieved higher rates of sustained virologic response (SVR) with shorter treatment durations and no alcohol abstinence prerequisite. Previous therapies required alcohol abstinence for at least 6 months. Methods: Our retrospective cohort study in Veterans with chronic HCV infection presenting for care at the Joseph Maxwell Cleland Atlanta VA medical center (AVAMC) between 1/1/2015 – 11/29/2017 examined the relationship between alcohol use, DAA initiation, and SVR. Results: The cohort included 1763 people that were mostly males (97%) with a mean age of 63 years and 70% Black. In multivariate analysis, the odds of receiving DAA were 0.7 (95% CI: 0.674, 0.9; p=0.0013) in those with “detectable” alcohol metabolites compared with those who had “undetectable” alcohol metabolites. The odds of achieving SVR were 0.7 (95% CI: 0.5, 1.0; p=0.0525) in those with “detectable” alcohol metabolites. Overall, 86% of patients who received DAA therapy achieved SVR. Conclusions: Alcohol use categorized using urine alcohol metabolite testing, during the study period was associated with a significantly lower odds of receiving DAA therapy but had no statistical significance on the odds of achieving SVR. While patients with chronic hepatitis C should be counseled on the risks of alcohol use, it is not associated with lower likelihood of achieving SVR and should not preclude the initiation of DAA therapy

Hepatitis C prevalence and cascade of care among patients in the decentralised opioid agonist therapy programme of the canton of St Gallen, Switzerland: a cross-sectional study.

To eliminate chronic hepatitis C virus (HCV) infection by 2030, 90% of those infected must be diagnosed and 80% treated. In Switzerland, >40% of the estimated 32,000 infected people are still undiagnosed. In the canton of St Gallen, HCV prevalence and cascade of care have only been studied in the centralised opioid agonist therapy (OAT) setting (institutions), although about 80% of OAT patients are treated decentrally (general practitioner [GP] or pharmacy). To describe HCV prevalence and cascade of care among patients in the decentralised OAT programme of the canton of St Gallen, Switzerland, and compare it to contemporaneous data from the centralised setting. For each patient receiving his/her OAT from a GP or pharmacy on 1 April 2021, the cantonal medical office sent a questionnaire to the prescribing GP. Patient characteristics, HCV antibody (Ab)/RNA screening uptake, HCV Ab/RNA prevalence and HCV treatment uptake were obtained and compared to those of patients of the Medizinisch-soziale Hilfsstelle 1 in St Gallen (centralised setting). Of the 563 OAT patients under the care of 127 GPs, 107 patients from 41 GPs could be analysed (median age: 48 years [IQR: 40-56]; ongoing intravenous drug use: 25%; OAT provider: 66% GP, 34% pharmacy). HCV Ab screening uptake was 68% (73/107) with an HCV Ab prevalence of 68% (50/73) among those tested. Of the HCV Ab-positive patients, 84% (42/50) were HCV RNA-tested, among whom 57% (24/42) were viraemic. HCV treatment uptake was 83% (20/24), with 95% (19/20) achieving a sustained virological response. Non-uptake of HCV screening and treatment tended to be higher among patients receiving OAT at the pharmacy vs at the GP's office: 37% vs 26% (p = 0.245) for screening and 30% vs 7% (p = 0.139) for treatment. The proportion never HCV Ab-tested and the proportion of HCV Ab-positives never HCV RNA-tested was significantly higher in the decentralised compared to the centralised setting: 32% vs 3% (p <0.001) never Ab-tested and 16% vs 0% (p = 0.002) never RNA-tested. In contrast, HCV treatment uptake (83% vs 78%), sustained virological response rate (95% vs 100%) and residual HCV RNA prevalence among the HCV Ab-positive (12% vs 14%) were comparable for both settings. In the decentralised OAT setting of the canton of St Gallen, HCV Ab prevalence is high. Since HCV Ab and RNA screening uptake are markedly lower than in the centralised setting, potentially >40% of patients with chronic HCV are not diagnosed yet. HCV screening in the decentralised setting needs improvement, e.g. by increasing awareness and simplifying testing. High HCV treatment uptake and cure rates are possible in centralised and decentralised settings.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study

BackgroundSelf-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold.MethodsThis study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold.ResultsThe self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis.ConclusionsSelf-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study.

Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded. To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR. Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC. HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn't show protective efficacy. DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong

Background & aimTo evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality.MethodsThree hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development.ResultsDuring a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3–8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy.ConclusionsThe risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with HepatitisC and Cirrhosis.

In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitisC (HCV) in patients with cirrhosis. We used data from the Chronic HepatitisCohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with pvalue < 0.05. The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-weekand 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.

Beyond genotype-4: Direct-acting antiviral agents in patients with chronic hepatitis C infection from the Eastern Province of Saudi Arabia.

Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting. This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0. Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects. Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.

Profile of Sofosbuvir and Velpatasvir Combination in the Treatment of Chronic Hepatitis C in Children and Adolescents: Current Evidence.

Chronic hepatitis C (HCV) affects up to 3.25 million children and adolescents. Early treatment of HCV in children and adolescents reduces progression to advanced liver disease and cancer. Treatment for HCV has evolved to highly effective direct acting antiviral therapy in adults and now in children ≥3 years of age. This review focuses on the role of sofosbuvir and velpatasvir (SOF/VEL), a newer treatment of children and adolescents with chronic HCV. SOF/VEL is a pangenotypic DAA with primary clearance via the liver and biliary excretion. It has been studied in children and adolescents and is approved in the US for use in children and adolescents ≥3 years of age. Although the data are currently limited, SOF/VEL has demonstrated sustained viral response rates similar to comparable DAAs in the range of 95-98%. To date, side effects have been minimal.