Tommaso Sarcina

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health burden, with hepatic fibrosis being the strongest determinant of clinical outcomes. While genetic variants such as PNPLA3 and TM6SF2 are recognized drivers of disease progression, the downstream molecular mediators linking genetic susceptibility to fibrogenesis remain unclear. This study investigated the role of the stress-response co-chaperone BAG3 as a circulating biomarker of hepatic fibrosis and its association with PNPLA3 and TM6SF2 genotypes. In a well-characterized Southern European cohort of 146 MASLD patients, liver fibrosis was assessed using the FIB-4 index, serum BAG3 levels were quantified by ELISA, and genotyping for PNPLA3 and TM6SF2 variants was performed. BAG3 concentrations were significantly higher in patients with advanced disease and correlated positively with FIB-4 values. Carriers of the TM6SF2 risk allele exhibited increased BAG3 levels, and a cumulative increase was observed with multiple PNPLA3 and TM6SF2 risk alleles. These findings suggest that BAG3 may represent a potential, non-invasive biomarker reflecting fibrogenic burden and a mechanistic link between genetic risk and hepatic fibrosis in MASLD.

Background: Hepatitis C Virus (HCV) remains a global health challenge as WHO elimination targets are not achievable in most countries, mainly due to the high number of undiagnosed individuals. In Italy, where national elimination efforts are ongoing, regional disparities further hinder progress. This study aimed to characterize the hidden burden of chronic HCV infection across t he territory of the Province of Salerno, Southern Italy, to suggest a novel municipal-level screening approach, with implications for national strategies. Methods: We analyzed records of residents diagnosed with chronic HCV infection and linked to care between 2015 and 2022. Data included age, sex, municipality of residence, HCV genotype, and fibrosis stage. Observed prevalence was compared with expected prevalence derived from national/regional benchmarks. Municipalities were categorized as urban or rural based on the resident population. Results: A total of 3528 cases were identified across 139 municipalities. Patients had a mean age of 63 years, and 54% were male. Half were diagnosed at an advanced stage (F3–F4), with genotype 1b being predominant. The hidden burden increased with age and showed a higher prevalence in rural areas compared to urban ones, with values of about 7 vs. 3 per 1000 inhabitants respectively. Logistic regression analysis identified age, male sex, urban residence, and genotype 1b as factors associated with advanced fibrosis or cirrhosis. Conclusions: This is the first Italian study to apply a standardized municipal-level classification to quantify the hidden burden of HCV. The model identifies underdiagnosed areas, highlights urban–rural disparities (a higher degree of underdiagnosis in rural areas versus a higher frequency of late diagnosis in urban ones), and provides a replicable tool for precision public health. Its adoption could enhance national HCV elimination efforts by supporting targeted screening, optimized resource allocation, and equitable access to care.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on 298 MASLD patients: 148 from a Hepatology Unit and 150 from a Bariatric Surgery Unit. Genotyping was performed for the PNPLA3, TM6SF2, MBOAT7, and GCKR variants. A PRS was calculated and used to stratify patients by genetic risk. Liver fibrosis was assessed using the FIB-4 index, and a subset also underwent transient elastography. Clinical, biochemical, and anthropometric data were analyzed across genetic strata. PRSs showed positive correlations with AST, ALT, and FIB-4, indicating increased liver injury and fibrosis risk with higher genetic burden. Transaminases increased significantly across PRS quartiles (p < 0.05), and individuals with PRS > 0.532 exhibited elevated AST, ALT, and borderline FIB-4. Variant-specific associations included PNPLA3 with increased AST and MBOAT7 with higher hepatic steatosis (CAP). Subgroup analyses revealed distinct genetic and phenotypic patterns between the two clinical cohorts. These findings support the additive role of genetic risk in MASLD progression and underscore the value of polygenic profiling for the early identification and personalized management of high-risk patients.

Hepatitis C is a disease for which in approximately 30 years we have gone from the discovery of the causative agent in 1989, to the introduction of direct-acting antiviral (DAAs) therapies starting from 2011, and to a proposal for its elimination in 2016, with some countries being on track for this goal. Elimination efforts, in the absence of a vaccine, rely on prevention measures and antiviral therapies. However, treatment rates have declined in recent years and are not considered adequate to achieve this goal at a global level. This poses a great epidemiological challenge, as HCV in many countries still causes a significant burden and most infected people are not yet diagnosed. Consequently, efforts are needed at different levels with common purposes: to facilitate access to screening and diagnosis and to improve linkage to care pathways. In this review, we discuss the latest epidemiological findings on HCV infection, the obstacles to its elimination, and strategies that are believed to be useful to overcome these obstacles but are applied unevenly across the world.