Background and AimsThe risk of disease progression in MASH increases proportionally to the pathological stage of fibrosis. This latter is evaluated through a semi-quantitative process, which has limited sensitivity in reflecting changes in disease or response to treatment. This study aims to test the clinical impact of Artificial Intelligence (AI) in characterizing liver fibrosis in MASH patients.MethodsThe study included 60 patients with clinical pathological diagnosis of MASH. Among these, 17 received a medical treatment and underwent a post-treatment biopsy. For each biopsy (n = 77) a Sirius Red digital slide (SR-WSI) was obtained. AI extracts >30 features from SR-WSI, including estimated collagen area (ECA) and entropy of collagen (EnC).ResultsAI highlighted that different histopathological stages are associated with progressive and significant increase of ECA (F2: 2.6% ± 0.4; F3: 5.7% ± 0.4; F4: 10.9% ± 0.8; p: 0.0001) and EnC (F2: 0.96 ± 0.05; F3: 1.24 ± 0.06; F4: 1.80 ± 0.11, p: 0.0001); disclosed the heterogeneity of fibrosis among pathological homogenous cases; revealed post treatment fibrosis modification in 76% of the cases (vs 56% detected by histopathology).ConclusionAI characterizes the fibrosis process by its true, continuous, and non-categorical nature, thus allowing for better identification of the response to anti-MASH treatment.

Background and aimSignificant weight loss is the only proven therapy for patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to identify factors that predict significant weight loss - exceeding 7% of the initial weight - in MASLD outpatients.MethodsWe included all MASLD patients referred to four Italian tertiary liver centres between January 2019 and December 2021. They received advice on lifestyle changes according to current guidelines, with reassessment of anthropometric measures after 18 to 24 months.ResultsAfter evaluating 908 patients meeting the inclusion criteria, the majority were found to be male (518/908, 57%) with a mean age of 61.7 ± 13.31 years and a mean baseline body mass index (BMI) of 30.31 ± 4.49 kg/m2. Over a mean follow-up period of 21.88 ± 6 months, only 166 (18.3%) patients achieved significant weight loss. Unadjusted regression analysis revealed significant correlations between dyslipidaemia, baseline BMI ≥ 30kg/m2, and the use of GLP-1 (glucagon-like peptide 1) agonists with significant weight loss (p<0.05). Multivariate regression analysis identified only BMI ≥ 30 kg/m2 (OR = 1.96, 95% CI: 1.37-2.8) and dyslipidaemia (OR = 0.6, 95% CI: 0.44-0.88) as independent predictors of significant weight loss.ConclusionsA baseline BMI ≥ 30 kg/m2 and the absence of dyslipidemia emerged as significant predictors of achieving substantial weight loss in MASLD patients. These findings highlight the need for personalized interventions to improve the effectiveness of weight management strategies in MASLD.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

IntroductionNonalcoholic fatty liver disease (NAFLD) is replacing viral hepatitis as the leading cause of chronic liver disease and hepatocellular carcinoma (HCC) in many Western countries. NAFLD-associated HCC usually affects older patients with multiple comorbidities, frequently develops in the absence of cirrhosis, and is often diagnosed later with worse chance of survival. The worse prognosis is also due to limited surveillance strategies and a lower efficacy of standard treatments.Areas coveredWe evaluate the available literature to understand the current surveillance strategies and treatment limitations in the workup of NAFLD-associated HCC, focusing on the differences with HCC associated with other liver diseases.Expert opinionIn this review we discuss epidemiology and risk factors for HCC in NAFLD patients and address key HCC surveillance and management issues. Although most data are still preliminary, the detection of non-cirrhotic NAFLD patients at increased risk for HCC and the potential adoption of novel screening tools could lead to accurate and suitable HCC surveillance and management strategies for NAFLD patients.

Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.