Effect of hepatitis C virus treatment engagement on the skin and soft tissue infections healthcare burden among people who inject drugs in Quebec, Canada: a population-based interrupted time series study.

A Multicenter, open-label, randomized, non-inferiority trial of 8 versus 12 weeks of sofosbuvir/ravidasvir treatment in non-cirrhotic patients with chronic hepatitis C virus infection (EASE trial).

Mechanistic study of Hederagenin against liver injury by inhibiting AIM2-mediated PANoptosis via the JAK2/STAT3 signaling pathway.

Nepetin suppresses HBV-associated hepatocellular carcinoma metastasis by regulating the HBx/HIF-1α-mediated autophagy axis.

Florida has the second-highest rate of acute hepatitis C virus (HCV) infection cases in the United States. However, HCV care cascade outcomes among individuals seeking care in Florida emergency departments (EDs) remain unknown. To assess HCV care cascade outcomes and identify HCV infection predictors among individuals tested for HCV in Florida EDs. This retrospective study used electronic health records (2016-2023) linked to the Agency for Healthcare Research and Quality on Social Determinants of Health regional data. Adults aged 18-79 years tested for HCV infection in Florida EDs. Outcomes included the proportions of individuals completing each HCV care cascade step: (1) HCV screening; (2) HCV diagnosis; (3) linkage to care; and (4) treatment initiation. A multivariable logistic regression model was used to identify predictors of HCV infection. Among individuals seeking care in EDs, 4.98% (n=18,444) were tested for HCV, of whom 4.97% were confirmed HCV-positive. Among HCV-positive individuals, 11.24% were linked to care, and 2.84% initiated treatment. Significant predictors of HCV infection included having Medicaid insurance (OR=1.53, 95% CI: 1.14-2.07) or being uninsured (OR=2.88, 95% CI: 2.02-4.12), coinfection with human immunodeficiency virus (OR=28.99, 95% CI: 22.31-37.67), opioid injection drug use (OR=3.62, 95% CI: 2.76-4.75), opioid overdose (OR=3.89, 95% CI: 2.32-6.52), and residing in communities characterized by lower educational attainment (fourth quartile OR=1.95, 95% CI: 1.27-2.98). Significant gaps persist across the HCV care cascade among individuals tested in Florida EDs. Innovative public health interventions are needed to support these vulnerable populations.

Mechanistic insights into the inhibition of recombinant hepatitis E virus papain-like cysteine protease by Khaya grandifoliola hydro-Ethanolic extract: UHPLC-MS profiling, enzyme kinetics, computational modeling, and cell-based assays.

Diagnostic accuracy, satisfaction, and acceptability of point-of-care testing for syphilis, hepatitis B, and hepatitis C infections among Thai adolescents and young adults with sexual risk behaviors.

Hepatitis B viral infection status in HCV-endemic areas.

Chronic viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) remains a leading global public health burden, driving progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) through complex interactions between viral replication, host immune responses, and extracellular matrix (ECM) remodelling. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that serve as central regulators of ECM homoeostasis and immune modulation in the liver. While physiological MMP activity is essential for tissue repair and immune surveillance, dysregulation of the MMP/TIMP (tissue inhibitors of metalloproteinases) axis during viral hepatitis promotes hepatic fibrogenesis, immune evasion, and malignant transformation, positioning MMPs as both drivers of disease progression and promising therapeutic targets. This review comprehensively examines the molecular and cellular mechanisms governing MMP/TIMP dysregulation across the spectrum of viral hepatitis, with particular focus on HCV and HBV. We address the reciprocal interactions between these viruses and MMP/TIMP expression, the roles of MMPs in liver fibrosis, viral replication, hepatocarcinogenesis, and immunomodulation of the tumour microenvironment, and the accelerated fibrogenic mechanisms in HIV-HCV and HIV-HBV coinfection. The review also extends to acute viral hepatitis (HAV and HEV), where direct MMP/TIMP data remain scarce but mechanistic and indirect ECM evidence indicate significant involvement. Finally, we critically evaluate current and emerging MMP-targeted therapeutic strategies including selective inhibitors, nanoparticle delivery systems, and RNA-based approaches and highlight key unresolved questions to guide future research towards disease-tailored interventions against viral hepatitis-driven liver damage and malignant progression.

Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis worldwide and represents a uniquely severe threat in pregnancy in areas where genotypes 1 and 2 circulate. In low-resource tropical settings, and particularly in the World Health Organization (WHO) Southeast Asia region, HEV infection during pregnancy is associated with disproportionately high maternal case fatality, frequent progression to acute liver failure, and devastating foetal and perinatal outcomes. This narrative review synthesises contemporary evidence on epidemiology, pathogenesis, clinical presentation, maternal and foetal outcomes, management challenges, and prevention strategies with a focus on tropical practice. Critical gaps in diagnostic capacity, access to critical care, and vaccine deployment are highlighted, and practical recommendations are offered to clinicians and health systems working in endemic settings. Strengthened surveillance, outbreak preparedness, inclusion of pregnant women in vaccine policy deliberations, and improved antenatal counselling are essential to reduce preventable deaths from HEV in pregnancy.

Mutation of the proteolytic cleavage site enhances stability and yield of recombinant hepatitis C virus core protein in bacterial cells.

Sustained virological response (SVR) improves prognosis in patients with chronic hepatitis C virus (HCV) with compensated cirrhosis, but whether a similar benefit can be obtained in decompensated patients is controversial. We studied the association between SVR and liver-related events (LREs) in patients with decompensated HCV cirrhosis. We included patients with decompensated HCV cirrhosis (Child-Turcotte-Pugh [CTP] ≥7 and/or history of decompensation) treated with direct-acting antivirals. The association between SVR and LREs, and between SVR-related change in Model for End-stage Liver Disease (MELD) score and LREs were assessed. In total, 914 patients were included, with a median age of 54.7 years; 45% had alcohol use disorder, 87% CTP-B, and the median MELD score was 12.1. SVR was achieved in 834 patients (91.2%), with a median follow-up of 28 months. The 3-year cumulative incidence of LREs was 47.5% in patients with SVR compared with 58.6% in those without (P < .001). Findings were consistent in multivariable analysis (adjusted hazard ratio [aHR], 0.692; P = .011). SVR was associated with a reduced risk of LREs in patients with a pretreatment MELD <15 (44.4% vs 57.6%; aHR, 0.601; P = .004), but not among patients with MELD ≥15 (62.8% vs 58.9%; aHR, 0.936; P = .801). Among patients with SVR, a ≥2-point decrease in MELD was observed in 23.4% and was not associated with a reduced risk of LREs (52.1% vs 50.7%; P = .473). Findings were consistent in multivariable analysis (aHR, 0.730; P = .122), and in patients with a pretreatment MELD score ≥15. SVR was associated with a reduced risk of LREs in patients with decompensated HCV cirrhosis with a MELD score <15, whereas no clinical benefit was observed in those with higher MELD scores despite an SVR-associated MELD decrease.

Hepatitis E virus (HEV) infection is very frequent in Europe with more than 2 million annual infections. Patients with liver cirrhosis may face an increased risk of suffering from acute-on-chronic liver failure (ACLF) due to HEV infection. We explored the consequences and prevalence of HEV infection in individuals with liver cirrhosis. We retrospectively analysed the clinical outcome of all consecutive patients who were hospitalized at our center due to acute HEV infection and analysed their outcome between 2014 and 2024. Next, we tested 249 sera from 184 cirrhotic patients during individual episodes of acute hepatic decompensation for anti-HEV IgM and HEV-RNA to analyse the relevance of acute HEV infection as a triggering event. Finally, we established a single center cohort of patients with advanced liver cirrhosis, and assessed the anti-HEV IgG seroprevalence (n = 332). Over the past decade, 32 patients with liver cirrhosis who were hospitalized due to acute HEV infection were identified. Among these patients, 16 (50%) developed ACLF, resulting in five fatalities (31.3%) and three individuals (18.8%) requiring liver transplantation for survival. Of 249 sera obtained during acute hepatic decompensation, 11 (4.4%) were either HEV-RNA positive (n = 2) and/or anti-HEV IgM positive (n = 10), linking HEV infection to these acute decompensations. Screening of patients with liver cirrhosis for anti-HEV IgG showed that 67.2% of patients (223/332) were anti-HEV negative and thus at potential risk for future HEV infection. Patients with advanced liver cirrhosis are at risk of acute HEV infection, which is a relevant cause of hepatic decompensation and ACLF with high mortality in these patients. DRKS00010664; NCT04801290.

We evaluated cardiac extracellular volume (ECV) fraction, a sign of inflammation and fibrosis, in 10 individuals with chronic Hepatitis C virus (HCV) infection prior to treatment using cardiac magnetic resonance (CMR) at 3 T. Compared to age-matched, healthy volunteers, HCV-infected individuals had significantly increased ECV fraction (0.30 ± 0.03 vs. 0.26 ± 0.03, p = 0.0036) regardless of myocardial damage markers, hypertension as a comorbidity, smoking pack-years or fibrosis stage. Our results show that untreated hepatitis C is associated with the development of extrahepatic manifestations even before the onset of liver fibrosis, highlighting that early HCV treatment is prudent to reduce all-cause morbidity.

Role of ferroptosis in liver diseases and its implications for therapeutic strategies.

Hepatocellular carcinoma (HCC), which is mostly caused by chronic liver illnesses such as cirrhosis, non-alcoholic steatohepatitis, and viral hepatitis, continues to be one of the major causes of cancer-related death globally. Serum alpha-fetoprotein (AFP) is frequently used for diagnosis; however, because of its poor sensitivity and specificity, new trustworthy biomarkers must be found. According to recent data, glycoproteins show promise as a means of enhancing HCC diagnosis and treatment targeting. Changes in fucosylation and sialylation are examples of aberrant glycosylation that have a significant impact on immunological evasion, tumour development, and metastasis. Key glycoproteins, including hemopexin, endosialin, pentraxin 3, haptoglobin, and ceruloplasmin, are summarised in the current review along with their structural traits, expression patterns, and functions in the pathophysiology of HCC. Although increased haptoglobin glycosylation improves early diagnostic potential, cereuloplasmin increases tumour cell survival by regulating ferroptosis. Endosialin promotes stromal remodelling and immune evasion in the tumour microenvironment, while hemopexin helps control oxidative stress. Pentraxin 3 has a dual, context-dependent activity as a pro-tumorigenic factor and a tumour suppressor. These glycoproteins have the potential to greatly enhance illness stratification and diagnostic accuracy when paired with conventional indicators like AFP. The precise mapping of glycosylation patterns made possible by emerging multi-omics and spatial technologies provides a clearer understanding of their mechanistic functions and translational significance. When combined, glycoprotein-based biomarkers and therapeutic targets offer new possibilities for early identification and individualised HCC treatment, hence representing a potential area for precision oncology.

When viruses meet cystic fibrosis: Insights into host-pathogen dynamics.

Reliable data on viral hepatitis-related deaths remain limited, challenging assessment of progress towards the WHO elimination targets for mortality. To address this gap, we estimated hepatitis B- and C-attributable mortality in Italy, Romania, and Spain for 2022. Retrospective hospital data on decompensated cirrhosis and hepatocellular carcinoma cases were collected from sentinel sites in each of three countries using standard WHO protocol. The data were used to calculate fractions of these diseases attributable to hepatitis B and C. Adjusted and weighted attributable fractions were applied to national vital statistics data on deaths from cirrhosis and hepatocellular carcinoma from Eurostat to produce national hepatitis mortality estimates. A total of 1733 cases of decompensated cirrhosis and hepatocellular carcinoma cases were enrolled into the study from sentinel sites across Italy, Romania, and Spain. We estimated that the share of decompensated cirrhosis deaths attributed to hepatitis B was: 8.7% in Italy, 16.8% in Romania and 1.8% in Spain. The respective share of hepatocellular carcinoma deaths attributed to hepatitis B was 19.0% in Italy, 31.2% in Romania and 4.9% in Spain. Hepatitis C accounted for 61.6% of hepatocellular carcinoma deaths in Italy, 36.5% in Romania, and 31.1% in Spain, as well as 32.9% of decompensated cirrhosis deaths in Italy, 18.8% in Romania and 12.7% in Spain. Overall, hepatitis B-related mortality per 100 000 population was 3.1 in Italy, 12.0 in Romania and 0.6 in Spain. Hepatitis C-related mortality was 11.4 per 100 000 population in Italy, 13.8 in Romania and 3.7 in Spain. Our study yielded empirical data needed to estimate hepatitis mortality for assessing the impact of hepatitis strategies. Whilst our results indicate a reduction in deaths related to hepatitis B and C in Italy and Spain, none of the three countries was meeting the WHO's 2025 target for hepatitis C-related mortality, although the hepatitis B-related mortality target was met by Italy and Spain. Our findings highlight the need for countries to continue strengthening efforts to prevent and control viral hepatitis and to integrate such assessments into national surveillance to guide effective targeting of interventions and monitoring of progress towards the elimination targets.

Chronic hepatitis D is the most severe form of viral hepatitis. Despite recommendations for systematic screening of HBsAg-positive individuals, hepatitis D infection remains underdiagnosed. Standard HDV virological markers are classically assessed in serum or plasma specimens obtained through venous whole blood sampling. This approach is costly and challenging in resource-limited settings. Dried blood spot (DBS) sampling offers a practical alternative for large-scale screening, diagnosis, and monitoring of viral hepatitis. The goal of the study is to evaluate the performance of commercially available HDV diagnostic assays using DBS. Plasma and DBS-collected whole blood specimens from individuals chronically infected with HBV or coinfected with HBV and HDV were analysed for HDV antibody detection, HDV RNA quantification, HBsAg levels, and HDV genotyping. HDV antibodies were reliably detected in DBS after threshold adjustment, with the LIAISON XL Murex Anti-HDV assay showing superior sensitivity (99.3%) compared to HDV Ab DIA.PRO (90.3%), while both assays exhibited excellent specificity. HDV RNA was quantifiable in 86.8% of DBS specimens from patients with active infection, although levels were about 1.5 log10 lower than plasma, showing a strong correlation (r = 0.786; p < 0.0001). HBsAg was detectable and quantifiable in all DBS samples, correlating closely with plasma values (r = 0.98). DBS-based HDV genotyping was successful in 84.8% of samples and concordant with plasma results. DBS collection of whole blood from DBS appears to be a promising and practical alternative to conventional venous blood sampling for HDV screening, diagnosis, and monitoring.

Liver fibrosis is a shared pathological phenotype of chronic liver diseases of diverse etiologies, including viral hepatitis, alcohol-associated liver disease and metabolic dysfunction-associated steatohepatitis (MASH), as well as cholestatic liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis, and may progress to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Despite advances in etiological treatments, effective therapies for established fibrosis remain limited. Increasing evidence indicates that liver fibrosis is a dynamic and potentially reversible process. The Wnt/β-catenin pathway is central to both liver regeneration and fibrogenesis and has traditionally been interpreted in terms of quantitative activation. Recent studies demonstrate that β-catenin-dependent transcription is qualitatively regulated by its nuclear coactivators, CREB-binding protein (CBP) and p300. CBP- and p300-associated transcriptional programmes exert distinct biological effects, promoting fibrogenic or regenerative states, respectively. These findings support a broader conceptual framework in which liver fibrosis can be viewed as a transcriptionally regulated and potentially reversible pathological state. In this review, we first summarize the molecular basis of canonical Wnt/β-catenin signalling and its transcriptional regulation by CBP and p300. Then, we discuss the pathophysiological relevance of CBP- versus p300-dependent β-catenin transcription in liver fibrosis of various etiologies, including cholestatic injury, and review experimental and early clinical evidence suggesting that selective modulation of CBP-associated transcription may promote early functional recovery, potentially preceding measurable regression of fibrotic burden. We close by considering implications for clinical trial design and the importance of function-oriented endpoints in antifibrotic drug development.