Search Results (332)

Background/Objectives: Hepatocellular carcinoma (HCC) remains a leading cause of global cancer mortality, with increasing incidence and persistently poor survival. Hepatitis C virus (HCV) is a major risk factor for HCC, and while the advent of direct-acting antivirals (DAAs) has significantly altered HCV-related hepatocellular cancer (HCC-HCV) risk, the global burden remains substantial. With the World Health Organization (WHO) aiming to reduce hepatitis-related deaths by 2030, we set out to evaluate global HCC-HCV trends from 1990 to 2021, stratified by sex, WHO region, and sociodemographic index (SDI), using data from the Global Burden of Disease (GBD) 2021 study. Methods: We analyzed age-standardized incidence (ASI), deaths, and disability-adjusted life years (DALYs) due to HCV-HCC from 1990 to 2021 using GBD 2021 data. Trends were stratified by WHO region, sociodemographic index (SDI), and sex. Joinpoint regression modeling was used to identify statistically significant temporal inflection points and calculate the annual percent change (APC) in unique time segments and average annual percent change (AAPC) over the entire study period (1990 to 2021). Results: Globally, deaths and DALYs attributable to HCV-HCC increased over the study period while ASI declined modestly. The region of the Americas exhibited the highest AAPC in all three metrics, potentially driven by an aging HCV-infected population, rising comorbidities (e.g., obesity, diabetes), and improved case detection. Nevertheless, on a global level, high-SDI regions showed the most favorable trends, particularly after 2016, likely reflecting the earlier adoption of DAAs and a differential success of WHO goals. Lower-SDI regions continued to exhibit increasing burden. Notably, ASI began to rise again between 2019 and 2021, suggesting an ongoing need to critically evaluate and restructure our approach to reducing HCV and HCV-HCC. Conclusions: Our findings underscore the urgent need for equity-driven, region-specific strategies to achieve better control of this highly morbid disease. Full article

Background/Objectives: Chronic hepatitis C virus (HCV) infection is associated with a wide spectrum of extrahepatic manifestations, involving the immune, dermatologic, endocrine, vascular, and neuropsychiatric systems. Among these, mixed cryoglobulinemic vasculitis (CryoVas) remains one of the most clinically relevant complications. This work aims to provide a structured overview of HCV-related extrahepatic conditions and to analyze the clinical and virological outcomes of direct-acting antivirals (DAAs) in CryoVas patients. Methods: We first categorized and reviewed extrahepatic manifestations of HCV across five major domains: immune, inflammatory/metabolic/vascular, dermatological, thyroid, and neuropsychiatric. Subsequently, we conducted a comparative analysis of five clinical studies evaluating the impact of DAA therapy in patients with CryoVas. Data on demographics, clinical symptoms, treatment regimens, sustained virological response, and clinical response were extracted and summarized. Results: HCV was found to be associated with numerous extrahepatic conditions, including mixed cryoglobulinemia, non-Hodgkin lymphoma, autoimmune thyroiditis, insulin resistance, and neurocognitive symptoms. In the CryoVas subgroup analysis, virological response rates were uniformly high (88.9–100%), but clinical remission varied significantly. Complete response ranged from 39% to 90%, highlighting a discrepancy between viral eradication and extrahepatic symptom resolution. These findings underscore the need for individualized follow-up and further investigation into persistent immunological dysfunction post-sustained virological response (SVR). However, clinical outcomes were more variable: complete response (CR) varied between 39% and 90%, partial response (PR) ranged from 4% to 42%, and no response (NR) was reported in 0% to 40% of cases. Although significant improvement in key manifestations such as purpura, arthralgia, and neuropathy was frequently observed, a subset of patients continued to exhibit residual or refractory symptoms despite achieving SVR. Conclusions: HCV infection exerts multisystemic effects that extend beyond liver pathology. While DAAs offer near-universal virological clearance, the heterogeneous clinical response in CryoVas underscores the need for closer monitoring of extrahepatic outcomes. Future research should assess whether combining DAAs with immunomodulatory strategies can improve symptom control and long-term outcomes in patients with severe or refractory CryoVas. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the hepatitis C virus (HCV) and has recently been incorporated into the Korean healthcare system. This study aimed to evaluate the real-world efficacy and safety of these antivirals in the South Korean population. Methods: This prospective, multicenter, observational study enrolled patients with chronic HCV treated with SOF/VEL-based regimens at six hospitals between November 2022 and January 2024. DAA-naïve patients received SOF/VEL ± ribavirin for 12 weeks. Patients who had failed prior DAA therapy received SOF/VEL/VOX for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 101 patients treated with SOF/VEL, the mean age was 64.71 years, and 40.9% were male. Genotypes 1b and 2 were identified in 40.6% and 59.4% of patients, respectively. Two patients had a history of interferon-based treatment. The mean baseline HCV RNA level was 3,088,097 IU/mL. Cirrhosis was observed in 26.7% of patients (21.8% compensated; 5.0% decompensated). Of the 101 patients, 12 were lost to follow-up. Among the 89 patients who completed follow-up, SVR12 was achieved in 100.0% (89/89), including 5 patients with decompensated cirrhosis. In the SOF/VEL/VOX group, 17 patients were treated. The mean age was 61.84 years, 29.4% were male, and four had compensated cirrhosis. One patient was lost to follow-up. SVR12 was achieved in 100.0% (16/16) of the patients who completed follow-up. No serious adverse events (≥grade 3) were reported in either group during the DAA treatment period. Conclusions: In this first prospective real-world study in South Korea, SOF/VEL-based regimens demonstrated excellent efficacy and safety, achieving 100% SVR12 in the per-protocol population, including patients with cirrhosis and prior treatment failure. Full article

In HCV-coinfected people with HIV (PWH), there are still conflicting data regarding the long-term metabolic impact of HCV eradication. The aim of the study is to investigate long-term changes in controlled attenuation parameter (CAP) and metabolic profile after sustained virological response (SVR) post-direct acting antivirals (DAAs) in PWH. This is a retrospective observational study including individuals with HIV/HCV coinfection, followed as outpatients at San Raffaele Hospital, who achieved SVR post-DAAs. Individuals were assessed for metabolic parameters before and after the start of DAAs. Univariate and multivariate mixed linear models were calculated to estimate crude mean changes in CAP, metabolic parameters, and weight; slopes were reported with the corresponding 95% confidence intervals (95% CI). Overall, during a median follow-up of 4.02 years (interquartile range, IQR 3.04–4.80), the mean percent increase in CAP was 2.86/year (p < 0. 0001), and the mean decrease in stiffness was –4.28 (p = 0.003). Additionally, total cholesterol (p < 0.0001), high-density lipoprotein (HDL) cholesterol (p = 0.001), triglycerides (p < 0.0001), glucose (p < 0.0001), and Body Mass Index (BMI) (p < 0.0001) increased over time. A long-term follow-up in PWH with SVR post-DAAs showed an overall significant increase in CAP and worsening of the metabolic profile, suggesting a higher risk of developing liver steatosis and metabolic alterations over time. Full article

Background: Hepatitis C virus (HCV) remains a significant public health concern in Thailand, with genotype-specific, drug-dependent variations influencing treatment response and disease progression. Despite the availability of pan-genotypic direct-acting antivirals (DAAs), genotype surveillance remains essential for optimizing national elimination strategies. This study thus aims to characterize the molecular distribution of HCV genotypes in northern Thailand. Methods: We conducted a retrospective molecular epidemiological study on 1737 HCV-infected patients who attended the Clinical Microbiology Service Unit (CMSU) Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University between April 2016 and June 2024. HCV genotyping was performed using Sanger sequencing and reverse hybridization line probe assay (LiPA). Results: Genotype 3 was the most prevalent (36.6%), followed by genotype 1 (35.8%) and genotype 6 (27.2%). Subtype 3a (27.2%) predominated, along with 1a (22.1%), 1b (12.6%), and genotype 6 subtypes including 6c to 6l (13.5%) and 6n (6.6%). Males had a higher prevalence of genotype 1, while genotype 3 was more common among females. Temporal analysis revealed a relative increase in genotype 6 prevalence since 2021. Genotype 6 also exhibited significantly higher median viral loads compared to genotypes 1 and 3 (p < 0.0001). Conclusions: This study provides updated evidence on the shifting distribution of HCV genotypes in northern Thailand, particularly the increasing prevalence of genotype 6. These findings underscore the importance of continued molecular surveillance to guide genotype-specific treatment strategies and support Thailand’s 2030 HCV elimination goals. Full article

Backgrounds: Direct-acting antiviral (DAA) therapy, which achieves a high sustained virological response (SVR) rate, has been established as a standard treatment for patients with hepatitis C virus (HCV) infection. However, the risk factors for postoperative recurrence in patients with HCV-related hepatocellular carcinoma (HCC) detected after the achievement of an SVR by DAAs are unknown. Methods: The clinical records of 95 patients with initial HCV-related HCC detected after DAA-SVR achievement, who underwent liver resection between September 2014 and December 2020, were retrospectively reviewed. Patients with major vascular invasion and/or SVR achievement induced by interferon-based therapy were excluded. In this study, the patients were divided into two groups according to their alcohol intake status: without alcohol abuse (<80 g of ethanol each day for at least 5 years, n = 85) and with (continuous) alcohol abuse (n = 10). The risk factors for recurrence after liver resection were investigated, with special reference to the alcohol intake status. Results: The 3- and 5-year disease-free survival (DFS) rates after liver resection were 68.7% and 55.3%, respectively. Univariate and multivariate analyses identified alcohol abuse [hazard ratio (HR) 3.36, p = 0.004] and tumor size (HR 2.53, p = 0.010) as independent risk factors for postoperative recurrence. The 3- and 5-year postoperative DFS rates were 72.2% and 61.5% for patients without alcohol abuse and 40.0% and 13.3% for those with alcohol abuse (p = 0.001). Conclusions: Continuous alcohol abuse is a risk factor for recurrence after surgery of HCC detected after the achievement of DAA-SVR. Full article

Background/Objectives: Direct-acting antiviral (DAA) therapy has been highly successful in treating chronic hepatitis C (CHC). The nationwide Treatment as Prevention of Hepatitis C (TraP HepC) initiative that was launched in Iceland in 2016 utilized liver stiffness measurements (LSM) to assess liver fibrosis at baseline and follow-up. We aimed to determine changes in liver stiffness among patients following treatment with DAAs and evaluate risk factors associated with hepatic fibrosis. Methods: Eligible CHC patients with liver stiffness of >9.5 kilopascals (kPa) before DAA treatment were invited for a follow-up visit in 2024. Risk factors for cirrhosis were registered, LSM performed, and liver enzymes, blood lipids, and glucose levels measured. Changes in liver stiffness were compared to baseline measurements, and correlations with risk factors were analyzed. Results: A total of 96 patients had LSMs > 9.5 kPa at treatment initiation. During the follow-up period, 61 were eligible for participation, 38 consented, and 34 (35%) died. The total follow-up was 258.3 person-years. The median follow-up period between measurements was 7.1 years. The median liver stiffness decreased from 17.2 kPa to 7.3 kPa (p < 0.01), and 80% of those with cirrhosis (>12.5 kPa) regressed to non-cirrhotic values. High BMI and daily alcohol consumption were significantly associated with increased liver stiffness in 8% of patients. Conclusions: In this single-arm, pre-post pilot study, liver stiffness regressed significantly in 92% of patients who were cured of CHC. Patients with other persistent risk factors following cure, such as obesity and alcohol abuse, were the only patients who had increased liver stiffness at the end of follow-up. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases. Aims: We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years. Methods: In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset. Results: Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient’s risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU). Conclusions: Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (>25 kPa), showed the lowest reduction of NIT scores, and developed events in 80/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score ≥ 8 demonstrated a significant incidence of HCC (37/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU. Full article

Background: There is still debate whether ribavirin should be added to direct-acting antivirals (DAAs) for the management of treatment-experienced individuals with non-genotype-1 hepatitis C. This study compared the efficacy and safety of adding ribavirin to sofosbuvir-based combinations compared to sofosbuvir-based regimens alone in treating non-genotype 1 hepatitis C virus (HCV) in individuals who have been previously treated. Methods: We searched Cochrane CENTRAL, PubMed, SCOPUS, CINAHL and preprint databases from inception to September 2023 for randomized controlled trials (RCTs) that compared sofosbuvir-based regimens with ribavirin to sofosbuvir-based regimens alone in previously treated individuals with non-genotype 1 HCV infection. Data extraction and quality of study assessments were performed by two independent authors, and synthesis was performed using bias-adjusted models, heterogeneity using I2, and publication bias using funnel plots. Results: Eight RCTs compared sofosbuvir-based combinations with and without ribavirin were included. Overall, the addition of ribavirin to sofosbuvir, compared to sofosbuvir alone, did not show a benefit in achieving sustained virological response (SVR) (OR 0.91, 95% CI 0.26–3.17, I2 = 70.0%) with moderate certainty in Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence. In subgroup analysis, there was no benefit of adding ribavirin to sofosbuvir in individuals with non-genotype 1 HCV. The additional ribavirin was associated with increased adverse events (OR 2.03, 95% CI 1.58–2.6, I2 = 8.0%) and treatment discontinuation (OR 1.81, 95% CI 0.78–4.28, I2 = 0.0%). Conclusions: The moderate certainty evidence suggests that adding ribavirin to sofosbuvir-based regimens may not confer benefit in achieving SVR in previously treated individuals with non-genotype 1 HCV but increases the odds of adverse events and treatment discontinuation. More evidence is needed on the effect of additional ribavirin in achieving SVR in individuals with decompensated cirrhosis. Registration: The protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022368868). Full article

Background: The triglyceride-glucose (TyG) index has emerged as a novel surrogate marker of insulin resistance, but its changes after hepatitis C virus (HCV) eradication remain unclear. This study aimed to evaluate changes in the TyG index following direct-acting antiviral (DAA) treatment. Methods: HCV-infected patients achieving sustained virological response 12 weeks post-treatment (SVR12) were prospectively enrolled from May 2015 to June 2023. Exclusion criteria included the following: (1) failure to achieve SVR12; (2) use of anti-diabetes or anti-hyperlipidemia medications; and (3) hepatitis B virus or human immunodeficiency virus co-infection. Changes in lipid profiles, TyG index, and homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated from baseline to SVR12. Insulin resistance was defined as HOMA-IR ≥ 2.5. The optimal TyG index cut-off for predicting insulin resistance was determined using the Youden Index. Results: A total of 111 patients (median age: 61.0 years; 45.9% male) were included. The TyG index correlated positively with HOMA-IR (Pearson’s r = 0.32, p < 0.001). Among patients with pre-existing insulin resistance, significant improvements were observed at SVR12 in both HOMA-IR (4.0 [IQR: 3.1–5.4] vs. 2.5 [IQR: 2.0–3.9]; p < 0.001) and TyG index (8.47 [IQR: 8.08–8.68] vs. 8.36 [IQR: 8.00–8.71]; p = 0.028). Using 8.27 as the optimal TyG index cut-off, similar improvements were noted in HOMA-IR (2.8 [IQR: 2.0–4.3] vs. 2.3 [IQR: 1.5–3.8]; p = 0.031) and TyG index (8.62 [IQR: 8.46–8.83] vs. 8.52 [IQR: 8.27–8.89]; p = 0.003). Conclusions: The TyG index is a valuable tool for monitoring changes in insulin resistance after HCV eradication, particularly in patients with baseline insulin resistance. Full article

Background: Chronic hepatitis C virus (HCV) infection significantly impairs health-related quality of life (HRQoL) and poses a substantial global health concern. Direct-acting antiviral (DAA) therapies have revolutionized HCV treatment, but their impact on HRQoL, particularly considering clinical and psychological factors, requires further investigation. This study aimed to evaluate the influence of DAA therapy on HRQoL in Romanian patients with chronic HCV infection, analyzing the effects of treatment on HRQoL and the role of associated factors. Methods: A prospective, single-center study was conducted on 90 HCV-infected patients treated with a 12-week DAA regimen (Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir). HRQoL was assessed at baseline (BSL), end of treatment (EOT), and 12 weeks post-treatment (SVR) using the WHOQOL BREF questionnaire. Clinical data, including fibrosis degree, prior PegIFN treatment, and psychological assessments (HADS, PSS), were collected. Statistical analyses examined HRQoL trends and associations with clinical and psychological parameters. Results: Significant improvements in HRQoL were observed across all domains over time (p < 0.0001). Gender and residence did not significantly influence HRQoL changes. Fibrosis severity and prior PegIFN treatment had no significant impact on HRQoL progression. However, comorbidities such as anemia and chronic kidney disease moderated improvements in specific HRQoL domains. Anxiety also affected HRQoL, while perceived stress and depression did not show significant effects. Conclusions: DAA therapy significantly enhances HRQoL in HCV-infected patients. While clinical and treatment-related factors had limited influence, comorbidities and anxiety played a moderating role. These findings underscore the importance of personalized care and integrated mental health assessments in HCV management. Full article

Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers of hepatocellular carcinoma (HCC). Despite the availability of an effective HBV vaccine since the 1980s, millions remain chronically infected due to the persistence of covalently closed circular DNA (cccDNA) as a reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs and interferon, effectively suppress viral replication but fail to eliminate cccDNA, underscoring the urgent need for innovative therapeutic strategies. Direct-acting antiviral agents (DAAs), which have revolutionized HCV treatment with high cure rates, offer a promising model for HBV therapy. A particularly attractive target is the intrinsically disordered region (IDR) of the HBx protein, which regulates cccDNA transcription, viral replication, and oncogenesis by interacting with key host proteins. DAAs targeting these interactions could inhibit viral persistence, suppress oncogenic signaling, and overcome treatment resistance. This review highlights the potential of HBx-directed DAAs to complement existing therapies, offering renewed hope for a functional HBV cure and reduced cancer risk. Full article

Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens. Full article