Virological Response Rates Research Articles

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.

Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China.

Over the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC). A retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots. A total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p < 0.001). Significant improvements were observed in the levels of total bilirubin, ALT, AST, albumin, globulin, albumin/globulin ratio, gamma-glutamyl transferase, alkaline phosphatase, platelet, fibrosis-4 (FIB-4), and aspartate transaminase to platelet ratio index (APRI) between baseline and EOT (p < 0.05). SOF-based treatments achieved high virological and biochemical response rates in patients with HCV GT 6 infection.

Mutations in human cytymegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) UL97 gene lead to increase in viremia duration and poor antiviral response in recipients of allogeneic hematopoietic stem cells.

Human cytomegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) (HCMV) is one of the most commonly detected viruses in recipients of allogeneic hematopoietic stem cell (allo-HSCT) transplants. However, the emergence of resistance to antiviral drugs such as ganciclovir (GCV) poses a challenge in managing these patients. This study aims to investigate the prevalence and impact of mutations in the HCMV UL97 gene associated with resistance to GCV on the course of infection among allo-HSCT patients. The study examined the association between UL97 mutations and the clinical course of HCMV infection in allo-HSCT patients. Genetic sequencing was performed to identify mutations, and their impact on viral replication and resistance to GCV was assessed. Six mutations were identified (D490A, T502A, C592G, C592F, E596G, C603W). C592G, C592F, E596G, and C603W are associated with resistance to antiviral drugs, while D490A and T502A described for the first time. When comparing patients with wild-type and those carrying the mutant variant, several parameters of peripheral blood were significantly lower in the former group. The median time to peak viral load following allo-HSCT, duration of viremia, and rate of virological response to high-dose therapy also differed significantly between the two groups. It was shown that approximately one third (4 out of 14) of allogeneic stem cell transplant recipients had mutations associated with resistance to GCV. Patients carrying the mutant variant of HCMV had longer viremia and took longer to achieve a negative virological test result after starting high-dose therapy. Performing genotyping may help make more evidence-based therapeutic decisions.

Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis

BackgroundThe high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs).MethodsWe performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach.ResultsSix studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%).ConclusionThe 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%.

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.

Efficacy and safety of tenofovir amibufenamide in the treatment of patients over 65 years of age with chronic hepatitis B

Objective: To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis. Methods: We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results: The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline (P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased (P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased (P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment (P＞0.05), and no serious adverse events were observed. Conclusions: For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.

Nucleos(t)ide analogs to treat patients with positive hepatitis B virus deoxyribonucleic acid and normal alanine transaminase: protocol for an open-label single-center randomized parallel controlled trial

BackgroundDirect high-quality evidence remains absent on the benefits of HBeAg-negative chronic hepatitis B patients (CHB) with normal alanine transaminase (ALT) and positive HBV DNA after nucleos(t)ide analogs (NAs) treatment.MethodsThis is a single-center, open-label, randomized parallel controlled trial with a follow-up duration of 96 weeks. An estimated 300 patients will be recruited at West China Hospital of Sichuan University, China. After stratified by serum HBV DNA (< 2000 vs. ≥ 2000 IU/ml), eligible patients will be randomized (allocation ratio 1:1) to receive either antiviral therapy (the treatment group) or regular examination alone (the control group). The primary outcomes are rates of virological response and changes in the levels of serum HBV pregenomic RNA (pgRNA) and scores of health-related qualities of life.DiscussionThis randomized controlled trial focuses on HBeAg-negative patients with normal ALT, including those of the inactive carrier phase and the grey zone, whose antiviral treatment remains controversial. Additionally, a health-related quality of life scale is introduced to comprehensively estimate the benefit of antiviral treatment apart from virological response and adverse liver events. Meaningfully, the study findings will provide high-quality and direct evidence for optimal clinical management in such populations.Trial registrationThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300069391) on 15 March 2023.Graphical

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.

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.

Follow-up post-HCV virological response to DAA in advanced chronic liver disease.

Direct-acting antivirals (DAA) achieve high virological response rates with minimal side effects for many patients. Despite their significant impact on the progression and epidemiology of hepatitis C virus (HCV) associated liver disease, the global annual incidence of chronic infections is expected to remain relatively constant, averaging 1.42 million new cases each year until 2030. Furthermore, by 2030, there will be a 14-17% increase in end-stage liver disease outcomes such as liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis in adults aged 18 years and over. Although reductions in liver decompensation, HCC occurrence, and mortality have been shown in patients with advanced liver disease who achieved sustained virological response (SVR) with DAA, these benefits may be less significant in those with decompensated liver cirrhosis. This review aims to summarise the impact of the virological response to DAA on liver disease progression and outcomes in patients with advanced chronic liver disease, which appears to be crucial for defining patient-specific follow-up.

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.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

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

The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study.

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.

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.

Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis

Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2=100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2=79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2=10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. None.

Directly Acting Anti-Viral Drugs and Its Metabolic Side Effects in Patients with Chronic HCV

Abstract Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, with an estimated 170 million people infected worldwide. Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Aim of the Work The aim of this work is to study side effects of directly acting anti HCV drug (DAA) and its progression in metabolism of lipid profile, blood sugar level, and renal function. Patients and Methods This case study had been carried out on 200 subjects presented to Department of Internal Medicine at Kobbri ELkobba hospital inpatient and outpatient clinics between March 2016 and September 2016. Results sustained virological response (12 weeks) after end of the treatment in more than 90% of patients, Liver function parameters including albumin, bilirubin, and prothrombin time and liver enzymes Ast, Alt improved in the majority of patients during and after the end of therapy,but there is significant increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level. Conclusion Once-daily oral daclatasvir plus sofosbuvir with or without Ribavirin was associated with high rates of sustained virologic response among patients infected with HCV, including chronic cirrhotic patients and relapsers, successful treatment associated with Improvement of liver function parameters in the majority of patients, Increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level.

Safety and Efficacy of Directly Acting Antivirals (Sofosbuvir &amp; Daclatasvir) in Treatment of Chronic HCV

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Aim of the Work The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated HCV infection in patients with HCV and HIV co-infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included are chronic HCV infection and were receiving antiretroviral therapy for the HIV with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, the rate of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high (29/30, 96.67%). The most common adverse events were fatigue (73.33%), headache (46.67%), and there was a high safety profile on using DAAs. No patient discontinued treatment because of adverse events. No serious adverse events or mortality were reported. In this study, AST &amp; ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. Conclusion Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a very good safety profile. Moreover, the treated patients showed a significant increase in CD4 count. Accordingly, HIV/HCV co-infected patients should be treated with sofosbuvir and daclatesvir containing regimens.