Sustained Virological Response Rates Research Articles

Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study.

The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in BCLC stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study. We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for SVR and adjusted hazard ratio (aHR) for OS. Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were recruited. The sustained virological response (SVR) rates were 96.6% in the HCC group and 98.8% in the non-HCC group (p < 0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41, 95% CI 0.31-0.54; p < 0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46, 95% CI 0.35-0.60; p < 0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41, 95% CI 0.28-0.59; p < 0.001). The impact of SVR on OS persisted significantly across BCLC stages 0-A and stages B-C. High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.

Comparative Analysis of Host and Virus-Driven Variables Affecting Response to Ribavirin and Interferon Therapy in Hepatitis C Patients

Current guidelines advocate for individualized treatment approaches for the management of Hepatitis C, that incorporate baseline assessments of viral genotype, host comorbidities, and socioeconomic factors to maximize therapeutic success. Objectives: To analyze the impact of host and virus-driven variables on treatment response in patients receiving ribavirin and interferon therapy. Methods: This prospective cohort study was conducted on 138 patients aged 18–65 with confirmed chronic HCV infection who were eligible for interferon and ribavirin therapy. The patients were followed up to a 24-week post-treatment to assess recovery measured in terms of sustained virological response (SVR). The host-driven factors included age, gender, BMI, and the presence of IL28B polymorphism while virus-driven factors included HCV genotype and baseline viral load. Results: The study sample predominantly consisted of male (55.1%), and genotype 3 virus accounted for 68.1% of participants. A high proportion (76.1%) of participants achieved SVR. Factors associated with better treatment outcomes included younger age (90.7% in the 31–45 age group), gender (89.5% of male), normal BMI (91.2% of those with a BMI of 18.5–24.9), and the favorable IL28B polymorphism CC genotype (91.8%). Low baseline viral load was observed in 60.1% of patients, and those with genotype 3 had better SVR rates. Conclusions: It was concluded that younger age, male gender, normal BMI, favorable IL28B polymorphism along with low baseline viral load, and genotype 3 were positively associated with achieving SVR.

Unveiling Hepatitis C: Causes, Impact and advances in treatment

Hepatitis C Virus (HCV) infection continues to pose a major global health issue, with around 58 million chronic cases reported worldwide and about 1.5 million new infections each year. This virus is a primary contributor to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC), leading to approximately 290,000 deaths annually (WHO, 2022). The introduction of direct-acting antiviral (DAA) therapies has transformed HCV treatment, with sustained virologic response (SVR) rates surpassing 95% across various genotypes. However, challenges remain in meeting the World Health Organization's target of eliminating HCV as a public health threat by 2030. Key obstacles include low diagnosis rates, as only 21% of those infected with HCV are aware of their condition, and restricted access to treatment, especially in low- and middle-income countries (LMICs). This article reviews the latest epidemiological trends related to HCV, focusing on the disparities in disease burden and access to healthcare. It discusses innovative diagnostic methods, such as point-of-care testing, and emphasizes the importance of universal screening programs in areas with high prevalence. Additionally, we look at new therapeutic strategies, including pan-genotypic DAAs and their effects on marginalized communities. Lastly, we examine public health initiatives aimed at enhancing HCV prevention, such as harm reduction programs and vaccination efforts for co-infections like hepatitis B. By integrating findings from recent studies and reports, this article highlights the necessity for collaborative global efforts to address the challenges of HCV elimination. Strategies that emphasize prevention, early detection, and fair access to treatment are crucial for alleviating the HCV disease burden and reaching elimination goals.

P-2207. HCV Reinfection is Associated with Cocaine Use and Ongoing Injection Drug Use in People with OUD: Outcomes from the ANCHOR and LOOP Studies

Abstract Background Despite achieving sustained virologic response (SVR), people with HCV, opioid use disorder (OUD) and ongoing injection drug use (IDU) remain at risk of reinfection. Identification and retreatment of reinfected individuals is critical to HCV elimination. We sought to evaluate the rate of HCV reinfection, factors associated with reinfection, and retreatment in a cohort of people who inject drugs (PWID).Table 1.Bivariate analysis of baseline sociodemographic characteristics. Methods The ANCHOR study provided HCV treatment for 198 people with chronic HCV, OUD, and recent opioid use. Those who achieved SVR underwent screening for HCV reinfection, with retreatment initiated per standard of care. At each visit, surveys were administered to evaluate ongoing risk behaviors and medication for OUD (MOUD) status. Patients were followed for 96 weeks with optional enrollment in a 2-year extension study (LOOP).Table 2.Bivariate (IRR) and multivariable (aIRR) analyses of factors associated with HCV reinfection. Results 158 individuals achieved SVR and were followed after treatment completion for 353 person-years, median 90 weeks (IQR 84-160 weeks). Subjects were predominantly male (69%), Black (84.2%), middle-aged (58 years), and HIV-negative (94.9%). Twenty individuals (12.7%) were reinfected a median of 77 weeks (IQR 60-105 weeks) after HCV treatment, at a rate of 5.7/100 person-years. Reinfection was associated with cocaine use (p&amp;lt; 0.001) and IDU in the past month (p=0.005). Of the 20 reinfected individuals, 16 (80%) initiated HCV re-treatment a median of 26 weeks after detection (IQR 4-64 weeks), with 12 (75%) achieving SVR, 1 currently on treatment, and 5 deaths.Figure 1.Kaplan-Meier reinfection free survival curve assessing associations of cocaine use with HCV reinfection. Conclusion In this cohort of people with OUD recently cured of HCV, we observed moderate rates of HCV reinfection associated with cocaine use and past month IDU, with high rates of retreatment uptake and SVR. These data highlight that in people with active drug use, longitudinal follow-up for retesting and retreatment is critical for HCV elimination. Enhanced accessibility to and engagement with harm-reduction services – such as syringe service programs - and interventions specifically addressing polysubstance use are crucial to reducing ongoing HCV transmission and reinfection. Disclosures Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support

A Comprehensive Review of Antiviral Therapy for Hepatitis C: The Long Journey from Interferon to Pan-Genotypic Direct-Acting Antivirals (DAAs)

The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally.

Predictors of response to daclatasvir in addition to sofosbuvir in hepatitis C virus-infected patients with stage 4 and 5 chronic kidney disease and patients on maintenance hemodialysis

BackgroundThe FDA authorized the use of sofosbuvir-based therapy in persons with chronic kidney disease (CKD) stages 4 and 5 and in those on maintenance hemodialysis (HD). It has been known that treatment efficacy might be affected by virus- and host-related parameters. The aim of this study was to identify the response rate of sofosbuvir plus daclatasvir in CKD stage 4/5 and HD patients. The secondary aim was to identify the predictors of treatment failure.MethodsThis cross-sectional study was conducted on 55 HCV-infected patients recruited from Alexandria University hospitals. The study included patients on maintenance HD or CKD stages 4–5. Baseline characteristics and SNP genotyping of the IFNL4 rs368234815 variant were addressed as possible predictors of response. The participants received sofosbuvir alongside daclatasvir with or without ribavirin for 3–6 months, according to the EASL guidelines. The response was evaluated by testing serum HCV RNA using PCR 12 weeks after treatment.ResultsOnly 29 patients achieved sustained virologic response (SVR) (52.7%). Non-responders had statistically significantly lower hemoglobin, platelets, and albumin, while they had higher INR, liver enzymes, bilirubin, and APRI scores. FIB-4 scores were significantly lower among responders (1.64 ± 0.74 versus 4.81 ± 1.82) (p < 0.001). Among those with treatment failure, 13 patients (50%) had the TT/G genotype, while only 3 patients (11.5%) of the TT/TT genotype failed to achieve SVR12. Only 13.8% of patients with the G/G genotype achieved SVR12 (P = 0.001). Multivariate regression revealed that higher FIB-4 was the only predictor of failure to achieve SVR12. FIB-4 at a cutoff level of 2.63 has a sensitivity, specificity, PPV, and NPV for prediction of treatment failure of 88.46%, 93.10%, 92%, and 90%, respectively.ConclusionsFIB-4 above 2.63 is a predictor of lower SVR rates among patients with advanced CKD stages.

Outcomes of Direct-Acting Antivirals Versus Interferon-Based Therapy in Chronic Hepatitis C Infection.

This systematic review evaluates the outcomes of direct-acting antivirals (DAAs) compared to interferon-based therapies in patients with chronic hepatitis C infection. DAAs consistently demonstrate higher sustained virologic response (SVR) rates and better safety profiles across various patient populations, including those with cirrhosis and treatment-experienced individuals. The studies included highlight the superior efficacy of DAAs, with fewer adverse events such as anemia and fatigue, making them more tolerable and suitable for long-term treatment. These findings reinforce the clinical importance of DAAs as the standard of care for managing hepatitis C virus (HCV), particularly in special populations. Although interferon-based therapies remain relevant in resource-limited settings, this review emphasizes the need for broader access to DAAs to improve global health outcomes and reduce HCV-related morbidity and mortality.

Real-World Experience, Effectiveness, and Safety of Direct-Acting Antivirals for the Treatment of Hepatitis C in Oman: A Cross-Sectional, Multicenter Study.

Background: The advent of direct-acting antiviral (DAA) therapy has revolutionized the treatment landscape of the hepatitis C virus (HCV) infection. This study aimed to provide a comprehensive research study of the real-world effectiveness and safety of DAA treatment, representing the first study conducted in the Omani population. Methods: A cross-sectional study was conducted including 375 HCV patients with different genotypes, treated using different DAA regimens, with or without ribavirin, between January 2012 and December 2020 at the Sultan Qaboos University Hospital and the medical city for military and security services, two tertiary hospitals in Muscat, Oman. The rate of sustained virologic response 12 weeks after completing the regimen (SVR-12) was analyzed as the primary outcome. Secondary outcomes included treatment safety and adverse events related to DAA therapy, as reported by patients and treating physicians. Results: A total of 375 patients were included in the study, with a mean age of 47.3 ± 15.4 years. Most were male (59.2%) and treatment-naïve (71.7%). The prevalence of liver cirrhosis was 19.7%, while 4.0% had hepatocellular carcinoma (HCC). The SVR-12 rate among treatment-naïve and treatment-experienced patients was 95.0% and 93.4%, respectively. Several parameters were associated with DAA treatment failure, including liver cirrhosis (p = 0.004) and active HCC (p = 0.009). Following SVR-12, significant improvements were observed in alanine transaminase, bilirubin, and albumin levels, Fibrosis-4 Index, and liver stiffness measurements compared to baseline (p <0.001 each). No significant adverse effects were reported. Conclusions: Based on our real-world experience, DAAs are highly effective in treating patients with HCV infection in Oman, with an excellent tolerability and safety profile.

Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years

ObjectiveDirect-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. MethodsAn 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. ResultsSOF/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 197M€. ConclusionSOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy.

The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.

Factors involved in gastroesophageal varix-related events in patients with hepatitisC virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitisC virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. We conducted a multicenter study using prospective data from 478 hepatitisC virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. The median age was 70years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p<0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p=0.120). Across 35.7months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p=0.001). In the multivariate analysis, high-risk varix (p<0.001), high baseline gamma-glutamyl transpeptidase levels (p<0.001), and virologic failure (p=0.004) were significantly involved in varix-related events. The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C.

Hepatitis C virus (HCV) infection is a major global health burden, with an estimated 58 million people chronically infected worldwide, according to the World Health Organization (WHO).While many people remain asymptomatic during the early stages of infection, chronic hepatitis C can cause long-term liver damage, significantly increasing the morbidity and mortality associated with the disease. The primary objective of this technical report is to find the efficacy of novel antiviral therapies in treating hepatitis C in a tertiary care hospital in Lahore. This technical report was done in Shalamar Hospital, Lahore, from June 2023 to June 2024. Data for the report were collected retrospectively from 500 patients through a review of patient medical records from the hospital. Medical and electronic health records provided the patient demographics (age, gender, ethnicity), hepatitis C genotype, liver disease stage (fibrosis or cirrhosis staging), previous treatment history, and type of antiviral therapy administered (direct-acting antivirals (DAA)).Out of 500, there were 280 (56%) male and 220 (44%) female patients. The mean age of the patients was 41.23±5.67 years. Patients were divided among mild, advanced, and post-liver transplant as 320 (64%), 150 (30%), and 30 (6%), respectively.Among the DAA regimens, sofosbuvir-based therapies had the highest sustained virologic response (SVR) rate of 95%, followed by glecaprevir/pibrentasvir at 93%. Ledipasvir/sofosbuvir and other DAAs showed slightly lower SVR rates, at 89% and 87%, respectively, indicating high overall efficacy across different therapies. This report concluded that DAAsare highly effective in treating hepatitis C, with an overall SVR rate of 92% and good tolerability across most patient groups. However, patients with genotype III, advanced liver disease, or post-liver transplant status may require personalized treatment approaches due to slightly lower efficacy.

HCV-HIV co-infection in people who inject drugs: Barriers to treatment and cure of HCV infection in the era of DAAs, a prospective study in Athens, Greece.

HIV/hepatitis C virus (HCV) co-infection among people who inject drugs (PWID) remains a global health problem. The goal of our study was to evaluate, in a real-world setting, success rates of sustained virological response (SVR) using direct-acting antivirals (DAAs) to treat a population of PWID living with HCV/HIV. This was a prospective single-center observational study. We collected demographic, socioeconomic, and clinical data pertaining to HIV and HCV infection in PWID with several barriers to care. We identified risk factors for SVR failure. Among 130 individuals retained to HIV care, we planned HCV treatment in 119/130 (91.5%); 106/119 (89.1%) started treatment with DAAs and 100/106 (94.3%) completed treatment. People not starting treatment were more often in active opioid drug use (odds ratio [OR] 0.25; 95% confidence interval [CI] 0.07-0.97, p = 0.045) and benzodiazepine abuse (OR 0.25; 95% CI 0.07-0.95, p = 0.042). Only 86/100 (86%) were tested for SVR at 12 weeks (SVR12) and 72/86 (83.7%) achieved SVR. PWID in opioid substitution programmes tended to return for SVR12 testing more often (54.7% vs. 30%, p = 0.081). Individuals in active opioid drug use (OR 0.226; 95% CI 0.064-0.793, p = 0.02) or with poor adherence (OR 0.187; 95% CI 0.043-0.814, p = 0.025) were less likely to achieve SVR. At the end of our study period, 113/119 (95%) treatment-eligible patients remained alive. HCV infection was cured in 68/113 (61.1%) people. Our findings underscore the importance of prioritizing combatting substance use to achieve HCV elimination goals. A systematic approach with effort to overcome barriers to receiving and completing treatment and encourage to enrol in opioid substitution programmes if not possible to completely abstain from use, can help increase chances of HCV cure.

Enhancing Hepatitis C Care in Primary Care: A Nurse Practitioner–Led Intervention

This quality improvement (QI) project at a Federally Qualified Health Center explores enhancing hepatitis C (HCV) treatment in primary care settings. It focuses on nurse practitioner (NP)-led interventions to improve sustained viral response (SVR) rates among high-risk groups. The project, conducted from June 2021 to January 2023, identified challenges in treatment uptake and continuity, emphasizing the role of NPs in bridging care gaps. Innovative approaches, including simplified treatment algorithms and integrated behavioral health services, were implemented. The project highlights the potential of primary care settings in managing HCV, aligning with the World Health Organization’s goal of eliminating HCV by 2030.

Performance of Elecsys® HCV Duo Immunoassay for Diagnosis and Assessment of Treatment Response in HCV Patients with or without HIV Infection

Background/Objectives: The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings.

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up

Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. Methods and findings Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. Conclusion The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies. Clinicaltrials.gov: NCT03434470 Abbreviations AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound

Prospective Assessment of Serum Lipid Alterations in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals: Insights Six Months Post Sustained Virological Response.

Background and Objectives: Chronic hepatitis C virus (HCV) infection is intricately linked with dysregulation of lipid metabolism. In particular, cholesterol plays a crucial role in HCV replication. Direct-acting antiviral agents (DAAs) therapy has revolutionized the hepatitis C treatment landscape, achieving high rates of sustained virological response (SVR). However, viral clearance comes with some alterations in lipid-related markers. This prospective study aimed to evaluate the impact of HCV clearance on lipid homeostasis and non-invasive liver fibrosis markers in hepatitis C patients treated with DAAs. Material and Methods: Fifty-two patients with varying degrees of fibrosis treated with DAAs therapy were evaluated at baseline and 24 weeks post-SVR. Lipid profiles and non-invasive liver fibrosis markers were assessed. Results: Our findings revealed an increase in total cholesterol, triglyceride, and LDLc (low-density lipoprotein cholesterol) levels at 24 weeks post-SVR, alongside an improvement in serum liver enzymes. Although improvements in liver stiffness were observed in non-invasive tests, there was an increase in lipid-related markers post-SVR. Conclusions: This suggests a potential increased cardiovascular risk despite improvements in liver function and fibrosis, highlighting the necessity for statin therapy in some cases and extended follow-ups for these patients. These findings underscore the importance of closely monitoring lipid profiles in chronic hepatitis C patients post-SVR, as well as the potential need for statin therapy to mitigate cardiovascular risk. Additionally, extended follow-up is essential to assess long-term outcomes and ensure the optimal management of these patients.

Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals

Background/PurposeThere are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. MethodsFrom March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. ResultsAmong the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). ConclusionFor DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.

Update on Hepatitis C Virus (HCV) Vaccine Candidates in Clinical Trials: A Systematic Literature Review

Introduction: Hepatitis C virus (HCV) infection remains a significant global health challenge, affecting over 71 million people worldwide and leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of highly effective direct-acting antiviral (DAA) therapies achieving sustained virologic response (SVR) rates exceeding 90%, high costs and limited accessibility impede global eradication efforts. Additionally, DAAs do not confer immunity against reinfection, highlighting the need for a prophylactic vaccine. Methods: This systematic literature review follows the PRISMA guidelines. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for articles published between January 2010 and March 2024, focusing on HCV vaccine candidates in clinical trials. Data on study characteristics, participant demographics, vaccine characteristics, vaccine platforms and key outcomes were extracted. Results: Nine studies met the eligibility criteria, covering various phases of clinical trials (Phase I, II, and II/III). Key findings included: Vaccine platforms: The studies primarily utilized three types of vaccine platforms: Viral Vector-Based Vaccines, Peptide-Based Vaccines and Recombinant Protein Vaccines Immunogenicity: Vaccines targeting non-structural proteins (NS3, NS4, NS5) induced robust T-cell responses. Chimpanzee adenovirus (ChAd) and Modified Vaccinia Ankara (MVA) vector-based vaccines showed high polyfunctional CD8+ and CD4+ T-cell levels. Safety: Most adverse events were mild to moderate, including flu-like symptoms and injection site reactions. Severe adverse events were noted with TG4040 when combined with PEG-IFNα and RBV. Efficacy: Significant reductions in viral load and improvements in liver function were reported. Personalized peptide vaccines demonstrated enhanced immune responses and improved overall survival in HCV-positive advanced HCC patients. Conclusion: HCV vaccine development has made significant strides, with several candidates demonstrating strong immunogenicity, acceptable safety, and promising efficacy in clinical trials. Continued research is essential to address challenges such as viral genetic variability, durability of immune responses, and global accessibility.