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Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

Background Methods Results: Conclusion: There is limited literature describing the real‐world practice of delayed initiation and shortened duration direct‐acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1‐week post‐transplant.Retrospective study of HCV‐negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections.102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. Methods: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. Results: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00–1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34–2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30–2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). Conclusion: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC. [ABSTRACT FROM AUTHOR]

Porphyrias are rare, mostly inherited disorders resulting from altered activity of specific enzymes in the haem synthesis pathway that lead to accumulation of pathway intermediates. Photocutaneous symptoms occur when excess amounts of photoreactive porphyrins circulate in the blood to the skin, whereas increases in potentially neurotoxic porphyrin precursors are associated with neurovisceral symptoms. Current therapies are suboptimal and their mechanisms are not well established. As described here, emerging therapies address underlying disease mechanisms by introducing a gene, RNA or other specific molecule with the potential to cure or slow progression of the disease. Recent progress in nanotechnology and nanoscience, particularly regarding particle design and formulation, is expanding disease targets. More secure and efficient drug delivery systems have extended our toolbox for transferring specific molecules, especially into hepatocytes, and led to proof‐of‐concept studies in animal models. Repurposing existing drugs as molecular chaperones or haem synthesis inhibitors is also promising. This review summarizes key examples of these emerging therapeutic approaches and their application for hepatic and erythropoietic porphyrias. [ABSTRACT FROM AUTHOR]

Purpose of Review: The hepatitis C virus (HCV) is a major cause of liver-related morbidity and mortality, and a major risk factor of hepatocellular carcinoma (HCC) around the world. Early detection, continued prevention of transmission, and antiviral treatment of chronically infected persons are the pillars to decrease incidence and mortality of HCV. The widespread access to safe and effective direct acting anti-viral agents (DAA) has allowed the elimination of the infection possible in almost all treated patients, thus leading to a significant reduction of liver-related and overall mortality due to HCV in the cured population. Treatment of HCV does not completely eradicate HCC risk in populations with advanced liver disease and those with cofactors known to promote liver carcinogenesis such as diabetes, obesity, and excessive alcohol consumption. Recent Findings: Molecular-based biomarkers are expected to overcome the limits of liver disease severity, thus improving the identification of screening candidates. Summary: The implementation of risk-stratified surveillance programs coupled with the identification of biomarkers to predict HCC in HCV cured patents is deemed necessary for implementing the cost-effective management of these patients. [ABSTRACT FROM AUTHOR]

Hepatitis C viral infections present a significant global health challenge, carrying substantial economic implications. These infections manifest in various clinical forms, including acute and chronic hepatitis, liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC emerge as the primary contributors to mortality in hepatitis virus-induced liver diseases. To alleviate the public health impact of this disease, it is imperative to enhance the diagnosis and treatment rates among hepatitis C virus-infected individuals. The advent of direct-acting antivirals (DAAs), especially pan-genotypic regimens such as a combination of sofosbuvir and velpatasvir, has shown remarkable progress in achieving hepatitis C cure. However, potential obstacles, such as drug adverse effects and resistance-associated substitutions (RASs), warrant attention. Managing chronic hepatitis C (CHC) requires tailored treatment plans, vigilant monitoring, and judicious re-treatment strategies.

Background: Non-invasive biomarkers have largely replaced liver biopsy in assessment of liver fibrosis in chronic HCV. Autotaxin (ATX) is a novel serum marker that may be related to liver fibrosis. Aim: to clarify the role of ATX as a biomarker for the estimation of hepatic fibrosis and to compare its sensitivity and specificity to the well-known fibrosis-4 score (FIB-4) and the AST-to-Platelet Ratio Index (APRI) before treatment with direct-acting antiviral drugs (DAAs) for chronic HCV as well as six months after the end of treatment. Methods: Plasma samples were obtained from 86 chronic HCV patients with different degrees of liver fibrosis. Routine laboratory, transient elastography (TE) and ultrasonographic assessments were done. Enzyme-linked immunosorbent assay (ELISA) technique was used to detect ATX. Results: ATX, FIB-4, and APRI had AUC of 0.57, 0.95, and 0.92, respectively for the detection of cirrhosis (F4). Baseline ATX was higher in cirrhotic group vs. noncirrhotic group (250 vs. 210) pg/ml, although the difference was not significant (p= 0.3). Significant improvement of all the laboratory parameters, APRI, FIB-4 and liver stiffness occurred at sustained virological response after 24 weeks (SVR24). Nonsignificant increase of ATX level was noted six months after the end of treatment. Conclusion: ATX should be considered cautiously as a diagnostic marker for liver fibrosis in patients with chronic HCV. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. Methods PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. Results Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. Conclusions Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. Registration PROSPERO CRD42020180793.

Introduction: Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment. Methodology: The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients. Results: At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients. Conclusions: It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs. [ABSTRACT FROM AUTHOR]

Aims: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct‐acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction‐associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. Methods: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α‐fetoprotein (AFP), Fibrosis‐4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. Results: A total of 86 patients (6.7%) developed HCC during the follow‐up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04–1.11, P = 0.0008), Fibrosis‐4 index (HR 1.17, CI 1.08–1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40–6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis‐4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. Conclusion: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL. [ABSTRACT FROM AUTHOR]

Background: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. Methods: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. Results: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. Conclusions: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. Registration: PROSPERO CRD42020180793. [ABSTRACT FROM AUTHOR]

The prognosis of patients with hepatitis C virus infection depends not only on liver lesions, but also on extrahepatic sequelae. Direct-acting antiviral agents (DAAs), as the first-line drugs in the treatment of hepatitis C, have helped more and more patients achieve sustained virologic response and clinical cure, but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure. [ABSTRACT FROM AUTHOR]

There is no established rescue therapy for hepatitis C patients with decompensated cirrhosis who experience treatment failure on 12-week sofosbuvir (SOF)/velpatasvir (VEL) therapy that is the only approved regimen for decompensated cirrhosis in Japan. We experienced a patient with decompensated cirrhosis who showed virologic relapse at post-treatment week 7 following 12-week SOF/VEL therapy. She had resistance-associated substitutions (RASs) against VEL before therapy but did not achieve new RASs against VEL or SOF after therapy. We considered rescue therapy following strong demand from her and her family. The drug adherence of therapy was 100%, and the treatment was well tolerated. Because we prioritized the safety and drug adherence of the regimen, we performed prolonged 24-week SOF/VEL therapy without ribavirin at her own expense with the approval of the ethics board in the hospital where the first author belongs. Fortunately, a sustained virologic response 24 was achieved without any adverse events. Hepatocellular carcinoma that had developed after 12-week SOF/VEL therapy recurred and was treated near the end of rescue therapy, but hepatic functional reserve improved. Although this was a single case report and was assumed to be very rare, the same regimen might be effective for treatment failure with 12-week SOF/VEL therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. Aim: the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. Methods: A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. Results: Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. Conclusion: according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients. [ABSTRACT FROM AUTHOR]

The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8-12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p = .016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p = .002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p = .002). Anti-GPIIb/IIIa antibodyproducing B cells were positively correlated with plasma BAFF levels in these patients (r = 0.669, p = .039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia. [ABSTRACT FROM AUTHOR]

Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95 %, making HCV the only curable viral disease. The successful treatment of chronic hepatitis C has greatly reduced, but not eliminated, the risk of HCC. Certain individuals, especially those with cirrhosis already present, remain vulnerable to HCC after achieving a sustained virological response (SVR). This article systematically reviews the recent studies on the risk and mechanisms of HCC development after HCV viral cure, the screening and predictive value of biological markers, and patient surveillance. Factors such as older age, diabetes, hepatic fat accumulation, alcohol use, and lack of fibrosis reversal are linked to increased HCC risk after HCV cure. The mechanism of HCC development after DAAs treatment remains unclear, but the possible mechanisms include immune cell dysfunction during HCV infection, cytokine network imbalance, epigenetic alterations, and host factors. Several biological markers and risk prediction models have been used to monitor the risk of HCC in CHC patients who have achieved SVR, but most still require validation and standardization. The implementation of risk-stratified surveillance programs is becoming urgent from a cost-effective point of view, but the availability of validated biomarkers to predict HCC in cured patients remains an unmet clinical need. Additionally, managing CHC patients who achieve SVR is becoming a growing challenge as an increasing number of HCV patients are cured.

Abstract Background and Aim The aim of this study was to identify the factors associated with liver‐related and non‐liver‐related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct‐acting antiviral agents (DAAs). Methods We conducted a retrospective, single‐center cohort study of HCV patients cured by DAAs. Results A total of 330 patients with SVR to DAAs were eligible. The median follow‐up period was 3.38 years (inter‐quartile range: 2.03–4.58). The cumulative liver‐related or non‐liver‐related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver‐related deaths, 9 of the 10 were from liver cancer. Among the non‐liver‐related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81–61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76–59.2), independently predicted liver‐related death. No variables were associated with non‐liver‐related death. Conclusion Our findings suggest that DM and a history of HCC are risk factors for liver‐related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.

Background: Hepatitis C virus (HCV) is a worldwide health challenge that imposes urgent interventions for prevention and control. We aimed to assess the response rate for the direct-acting antiviral agents (DAAs) regimen in HCV-infected patients attending the public health centers/hospitals in the Western region of Saudi Arabia. Methods and Results: A retrospective study was followed, including data from the electronic medical records of HCV-infected adult patients in the period 2018-2020. Patients underwent HCV health education and treatment with DAAs according to the regional protocols. The type of treatment regimens provided to the included patients was recorded with the outcome (respondent vs. non-respondent) after 12 weeks post completion of treatment (SVR12) based on negative results (or less than the minimum detection levels using the specified assay) of HCV-RNA detected by polymerase chain reaction. The SVR12 was used for predicting SVR as it was reported to be applicable as SVR24. All cases with discontinuations, treatment modifications, and/or deaths were excluded. Included were a total of 505 adult patients recorded in 13 primary healthcare units and hepatitis treatment specialty clinics of hospitals in the Eastern region of Saudi Arabia during the specified period of the study. The patients were aged 30–73 years (mean age of 48.1±9.1 years), of which 229(45.3%) were females and 276(54.7%) males. Most patients received sofosbuvir/daclatasvir (86.1%), followed by glecaprevir/pibrentasvir (11.5%), and elbasvir/grazoprevir (2.4%). Overall, the SVR rate was 97.4% in the study population. Sofosbuvir/daclatasvir had an SVR12 of approximately 98.4%, while the rate of glecaprevir/pibrentasvir was 93.1%. Conclusion: The present findings show an overall HCV cure rate of 97.4% of patients with HCV in response to the elimination program with DAAs in the Eastern region of Saudi Arabia, as indicated by high SVR12. This is an example of treating patients with HCV in a structured, supportive setting to help in the HCV elimination program.

Copyright of Journal of Tepecik Education & Research Hospital / İzmir Tepecik Eğitim ve Araştırma Hastanesi Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing. [ABSTRACT FROM AUTHOR]

Renal transplantation is the most beneficial treatment in patients with chronic kidney disease (CKD), increasing life expectancy and improving quality of life. A better understanding of organ and tissue functions, the development of surgical techniques, and new and effective immunosuppressive and antimicrobial drugs increase the success of transplantation. However, the number of renal transplantations from living and cadaveric donors is not at the desired frequency. Among the leading causes of the restrictions for transplantation are both the recipients' and donors' chronic diseases. While hepatitis B and C infections are a significant problem affecting the number and success of renal transplantations, the innovation of hepatitis C virus treatments has improved outcomes. Thus, the recipient and donor hepatitis B and C virus infections are no longer considered as relative contraindications for renal transplantation. This review discusses the management of patients and donors with hepatitis B and hepatitis C in renal transplantation. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. Aim: the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. Methods: A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. Results: Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. Conclusion: according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.

Background: Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated. Aim: This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C. Method: The US FDA Adverse Event Reporting System database was searched for GADR cases reported from 01 to 2012 to 30 September 2021. Twelve DAA types used for hepatitis C virus were included. The top 30 GADRs were assessed based on the use of DAAs, number of cases, and clinical features. A case–non-case disproportionality approach was used to confirm pharmacovigilance signals, whereby reporting odds ratios (ROR) with 95% CI were calculated. Results: Nausea (70.01/1000), diarrhoea (39.10/1000), and vomiting (31.68/1000) accounted for the highest number of cases. The pooled median time-to-onset of the top 30 GADRs was 13 days (Q1-Q3: 2–38) and the proportion of drug discontinuation was 19.17%. The highest number of DAA-related cases involved ledipasvir/sofosbuvir (21.86%), sofosbuvir/velpatasvir (21.77%), and sofosbuvir (13.41%). When DAAs were considered as a class drug, after adjusting for age, sex, concomitant diseases and drugs that potentially induced GADRs, significant RORs for specific GADRs were noted, including abdominal discomfort (1.62, 95% CI 1.32–1.99), constipation (1.54, 95% CI 1.26–1.89), dyspepsia (1.25, 95% CI 1.01–1.55), abdominal distension (1.36, 95% CI 1.05–1.75), faeces discoloured (1.77, 95% CI 1.15–2.73), and gastric ulcer (2.37, 95% CI 1.28–4.41). Conclusion: Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8–12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p =.016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p =.002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p =.002). Anti-GPIIb/IIIa antibody-producing B cells were positively correlated with plasma BAFF levels in these patients (r = 0.669, p =.039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia. What is the context? Production of antiplatelet antibodies is one of the mechanisms underlying thrombocytopenia in patients with chronic hepatitis C. Antiplatelet antibodies against platelet membrane glycoprotein (GP) IIb/IIIa are commonly detected in hepatitis C virus-associated immune thrombocytopenia. Hepatitis C virus elimination by direct-acting antiviral agents (DAA) improves thrombocytopenia in patients with hepatitis C; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. What is new? In this study, we determined whether DAA treatment can alter the autoimmune response against platelets and improve platelet count. The frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly from the baseline following DAA treatment in chronic hepatitis C patients with thrombocytopenia. DAA treatment reduced the levels of B-cell-activating factor, a cytokine associated with autoantibody production. What is the impact? The study provides evidence that DAA treatment diminishes the autoimmune response to GPIIb/IIIa and, therefore, improves platelet counts in chronic hepatitis C patients with thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to identify the factors associated with liver‐related and non‐liver‐related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct‐acting antiviral agents (DAAs). Methods: We conducted a retrospective, single‐center cohort study of HCV patients cured by DAAs. Results: A total of 330 patients with SVR to DAAs were eligible. The median follow‐up period was 3.38 years (inter‐quartile range: 2.03–4.58). The cumulative liver‐related or non‐liver‐related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver‐related deaths, 9 of the 10 were from liver cancer. Among the non‐liver‐related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81–61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76–59.2), independently predicted liver‐related death. No variables were associated with non‐liver‐related death. Conclusion: Our findings suggest that DM and a history of HCC are risk factors for liver‐related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection. Among haemophilic (H) men, HCV is the leading cause of liver disease. Direct‐acting antiviral agents (DAA) reduce HCV viral load, but impact on HCC is unknown. Methods: This was a retrospective study of adult H and nonhaemophilic (NH) male discharges, with and without HCC, identified by ICD‐10 codes in the National Inpatient Sample (NIS) database, 2016–2018, with DAA availability. Analyses included discharge‐level weights to reflect national estimates. Categorical variables were assessed by Rao‐Scott chi‐square and continuous variables by weighted simple linear regression. HCC correlates were determined by weighted multivariable logistic regression. Results: Among 7,674,969 adult male discharges, 3730 H (.04%) were identified in 2016–2018, of whom 10.06% had HCV and 1.07% had HCC, significantly higher than NH (1.22% and.27%, respectively) all P <.001. Annual HCC rates were similar during the 3‐year period (2016–2018) in H and NH. Among H, HCC is associated with older age and higher rates of HCV, HBV, NASH, end‐stage liver disease, and Charlson comorbidity (CCI), each P <.001. Among HCC, H were younger and more likely HIV+, each P <.001, but less likely alcoholic (P =.018) or hyperlipidaemic (P =.008) compared to NH. In multivariable regression, risk factors for HCC among H included NASH (OR 21.6), HCV (OR 3.96), CCI (OR1.54), all P <.001, while HIV and hyperlipidaemia were protective. Conclusion: From 2016 to 2018, HCC rates did not change significantly in haemophilia discharges. NASH, HCV, and CCI are significant risks for HCC in haemophilia during the DAA‐era. [ABSTRACT FROM AUTHOR]

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Background and Aim: Several studies have suggested that treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) may be associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the incidence and risk factors of HCC in HCV patients who achieved a sustained virologic response (SVR) following DAA therapies. Materials and Methods: The medical data of patients who were diagnosed with HCV and received DAA therapy in two tertiary centers in Turkey were retrospectively collected. Results: Among them, 75 patients (52.4%) were noncirrhotic and 68 patients (47.6%) were cirrhotic. The overall SVR rate was 97.2% (139/143). It was 100% in noncirrhotic and 94.1% in cirrhotic patients. HCC was developed in 5 (7.4%) patients, all of whom had baseline cirrhosis. The annual rate of HCC occurrence was 2.94%, and the 5-year cumulative incidence of HCC was 7.3%. The mean Child-Pugh score (CPS) and Model for End-Stage Liver Disease (MELD) score significantly decreased after DAA treatment (CPS 7.0 vs 5.9, p=0.001; MELD 10.8 vs 9.5, p=0.003). Conclusion: There was no significant increase in the rate of HCC in cirrhotic HCV patients treated with DAAs. This treatment led to a remarkably high SVR rate and lowered CPS and MELD scores in cirrhotic HCV patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95 %, making HCV the only curable viral disease. The successful treatment of chronic hepatitis C has greatly reduced, but not eliminated, the risk of HCC. Certain individuals, especially those with cirrhosis already present, remain vulnerable to HCC after achieving a sustained virological response (SVR). This article systematically reviews the recent studies on the risk and mechanisms of HCC development after HCV viral cure, the screening and predictive value of biological markers, and patient surveillance. Factors such as older age, diabetes, hepatic fat accumulation, alcohol use, and lack of fibrosis reversal are linked to increased HCC risk after HCV cure. The mechanism of HCC development after DAAs treatment remains unclear, but the possible mechanisms include immune cell dysfunction during HCV infection, cytokine network imbalance, epigenetic alterations, and host factors. Several biological markers and risk prediction models have been used to monitor the risk of HCC in CHC patients who have achieved SVR, but most still require validation and standardization. The implementation of risk-stratified surveillance programs is becoming urgent from a cost-effective point of view, but the availability of validated biomarkers to predict HCC in cured patients remains an unmet clinical need. Additionally, managing CHC patients who achieve SVR is becoming a growing challenge as an increasing number of HCV patients are cured., Competing Interests: Conflicts of interests None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Abstract Background Chronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD. Patients and methods The present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment. Results A total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2–100%). Conclusion Hepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

Abstract Background Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. Results Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. Conclusion Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P

Introduction: As a country that is heavily burdened by hepatitis C, China's successful responses to this public health threat have significant implications for the achievement of the global elimination goal. Methods: This article reviews China's strategies for prevention, screening, diagnosis, access to direct-acting antiviral agents (DAA) therapy, and patient management of hepatitis C. It also analyses the major challenges and summarizes the valuable successful international experiences that have implications for China to achieve the elimination goal. Results: To promote the achievement of elimination, China has taken a series of proactive measures to promote the prevention and treatment of hepatitis C. Compared with other middle-income countries, there is still much room for China to achieve universal screening, diagnosis and treatment based on a streamlined disease management procedure. A stronger role of primary care in an integrated healthcare delivery system and integration of hepatitis C with other infectious disease programs should also be the focus of China's efforts. Conclusions: As a developing country with a large population, a "micro-elimination" strategy with focused screening and proactive diagnosis and treatment for the vulnerable population may be a more practical approach to eliminating hepatitis C in China. Continued efforts are needed to fully overcome the intellectual property barriers of sofosbuvir for forming the more competitive pan-genotype DAA combinations based on the locally developed DAAs. Meanwhile, the safety net for patients in economic hardship needs to be further strengthened. More importantly, it is necessary to promote patients' willingness and compliance with standard treatment through increased awareness of hepatitis C. The development of an integrated healthcare delivery system, a disease management procedure which is suitable for primary care, and full compliance of the primary care providers are also important to achieve effective cascade care management. [ABSTRACT FROM AUTHOR]

Today, hepatitis C virus infection affects up to 1.5 million people per year and is responsible for 29 thousand deaths per year. In the 1970s, the clinical observation of unclear, transfusion-related cases of hepatitis ignited scientific curiosity, and after years of intensive, basic research, the hepatitis C virus was discovered and described as the causative agent for these cases of unclear hepatitis in 1989. Even before the description of the hepatitis C virus, clinicians had started treating infected individuals with interferon. However, intense side effects and limited antiviral efficacy have been major challenges, shaping the aim for the development of more suitable and specific treatments. Before direct-acting antiviral agents could be developed, a detailed understanding of viral properties was necessary. In the years after the discovery of the new virus, several research groups had been working on the hepatitis C virus biology and finally revealed the replication cycle. This knowledge was the basis for the later development of specific antiviral drugs referred to as direct-acting antiviral agents. In 2011, roughly 22 years after the discovery of the hepatitis C virus, the first two drugs became available and paved the way for a revolution in hepatitis C therapy. Today, the treatment of chronic hepatitis C virus infection does not rely on interferon anymore, and the treatment response rate is above 90% in most cases, including those with unsuccessful pretreatments. Regardless of the clinical and scientific success story, some challenges remain until the HCV elimination goals announced by the World Health Organization are met. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis C infections (HCV) are associated with an increase in morbidity and mortality. The aim of this study is to update the results of treatment with direct-acting antiviral agents (DAAs) using a larger population of healthcare personnel (HP) and a longer observation period. Methods Secondary data analysis of DAA treatment administered to HP (with confirmed occupational acquired HCV infection) between 1 January 2014 and 30 December 2018, is based on statutory accident insurance data from Germany. The end points of the study were results of a monitoring carried out 12 and 24 weeks after the end of treatment (sustained virological response, SVR), as well as side effects and the assessment of reduced work ability after treatment. Multivariate logistic regression models were constructed to investigate predictors of SVR. Results The study population (n = 305) mainly comprised HP with a genotype 1 infection. The average age was 63 (SD 10) and 77% were female. Two thirds of the HP suffered from fibrosis or cirrhosis, and had experience of treatment. Statistically, men were significantly more likely to suffer from cirrhosis than women (60% compared to 21%, p

BackgroundIncreased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy.MethodsWe measured the dynamic changes of IP-10 in samples from 90 patients with CHC. The serum IP-10 levels, intrahepatic expressions of IP-10 mRNA, and protein were determined, respectively. For the in vitro experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting.ResultsPatients with chronic hepatitis C had increased baseline IP-10 levels, intrahepatic IP-10 mRNA, and protein expression. After initiating DAAs therapy, serum IP-10 levels decreased gradually in patients who achieved cure, whereas in patients who failed the therapy, IP-10 levels did not change significantly or recovered from the initial decline. Multivariate logistic regression analysis confirmed that baseline IP-10 level ≤ 450 pg/ml and decline >30% at 12 weeks independently predicted the SVR in patients with CHC who received DAAs. In vitro, the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels.ConclusionIP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC.

Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84–127) × 103/mm3 vs. 120 (87–153) × 103/mm3(P =

Objectives: Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct‐acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. Methods: T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. Results: In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low‐density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. Conclusions: HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed. [ABSTRACT FROM AUTHOR]

The advent of direct-acting antiviral drugs (DAAs) was a breakthrough in the treatment of patients with chronic hepatitis C, yet high viral replication errors can lead to the development of resistance associated variants (RAVs). Thus, assessment of RAV in infected patients is necessary to monitor treatment effectiveness. The aim of our study was to investigate the presence of primary resistance mutations in the NS3 and NS5 regions of HCV in treatment-naive patients. Samples were taken from 42 patients with HCV who had not previously received DAA treatment. In the present study, we used the method for determining drug resistance mutations based on direct sequencing of the NS3, NS5A, and NS5B genes developed by the Saint Petersburg Pasteur Institute. Primary mutations associated with resistance were detected in 5 patients (12%). According to the Geno2pheno [hcv] 0.92 database, nucleotide substitutions were identified in various viral genes conferring resistance or decreased sensitivity to the respective inhibitors. This study has shown different mutations in the analyzed genes in patients with HCV who had not previously received DAA treatment. These mutations may increase the likelihood of treatment failure in the future. [ABSTRACT FROM AUTHOR]

Background and Objective: Hypoglycemia induced by direct‐acting antiviral agents (DAAs) for chronic hepatitis C virus (HCV) infection is a rare but potentially life‐threatening adverse reaction, which led to warnings by competent authorities. We therefore aimed to examine the hypoglycemic safety signal for DAAs. Methods: Reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 1 October 2012 to 31 March 2020 were analyzed. The Medical Dictionary for Regulatory Activities was used to identify hypoglycemia cases. A case by non‐case disproportionality approach was used whereby reporting odds ratio (ROR) with 95% confidence intervals (CI) were calculated. Results: In HCV infection with diabetes patients, the cumulative frequency of hypoglycemic ADRs was 21.85/1000 for reports involving DAAs versus 13.50/1000 for reports involving other medications; For DAAs as a class drug, a nearly double increased reporting odds for hypoglycemia was observed (ROR: 1.63, 95% CI: 1.11–2.41). However, in DAAs subgroup analysis, only telaprevir (ROR: 1.66, 95% CI: 1.01–2.74) and elbasvir/grazoprevir (ROR: 2.25, 95% CI: 1.05–4.83) were associated with increased reporting risk of hypoglycemia during corresponding marketing period; when combined with insulins and sulfonylureas, DAAs were associated with increased reporting risk for hypoglycemia (ROR: 1.98, 95% CI: 1.36–2.88; ROR: 1.62, 95% CI: 1.06–2.48), but concomitant biguanides, dipeptidyl peptidase IV (DPP‐4) inhibitors or glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) were not significant. Conclusions: This study supports the current recommendation for cautious about hypoglycemic risk relating to the use of DAAs. Treatment with DAAs and antidabetic agents (especially insulins and sulfonylureas) will increase hypoglycemia reporting risk. Physicians and pharmacists should be aware of this risk when prescribing DAAs for patients suffering from diabetes, advanced age or liver decompensation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users. [ABSTRACT FROM AUTHOR]

Abstract Background Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. Methods From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO. Results This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32–149) × 103/µL at BL to 116.5 (40–196) and 118.0 (35–275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P

Background: Hepatitis C virus can be eradicated with antiviral therapy, thus reducing the risk of disease progression and death associated with the final stage of liver disease.

Background: Ministry of National Guard–Health Affairs in Saudi Arabia developed a new policy for the use of direct antiviral agents (DAAs) for hepatitis C. The present study was conducted to evaluate prescribers' compliance and the impact of the policy on DAAs appropriate use. Materials and Methods: This study was conducted at King Abdul Aziz Medical City in Jeddah, Saudi Arabia. The study compares patients' data during 1 year before and 1 year after policy initiation. The primary outcomes were compliance to monitoring parameters, appropriateness of treatment and treatment eligibility. Secondary outcomes included sustained virologic response at 12 weeks, documentation of potential drug–drug interactions and treatment costs. Independent samples t-test and Chi-square test were used when applicable. A P < 0.05 was considered statistically significant. Results: One hundred and three patients were included in analysis (46 before and 57 after policy). Prescriber compliance to baseline monitoring parameters was 67.4% before policy and 82.5% after-policy (P = 0.076). International normalized ratio (INR) was requested in 84.8% of cases before policy compared to 96.5% after-policy (P = 0.036). Treatment options offered to patients were appropriate in 52.2% of cases before policy and in 82.5% after-policy (P = 0.001). Conclusion: There is a significant improvement in the baseline monitoring of INR. Treatment options offered after policy implementation were significantly more appropriate.

Background and Aims: Chronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies. Methods: We screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients' baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment. Results: High IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039). Conclusions: There were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience. [ABSTRACT FROM AUTHOR]

Background: Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. Results: Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. Conclusion: Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis. [ABSTRACT FROM AUTHOR]