Hyperuricemia affects long-term prognosis in metabolic dysfunction–associated steatotic liver disease: a multinational study

Late-Onset Wilson’s Disease

The Glucagon-Like Peptide-1 Receptor Agonist Exendin 4 Has a Protective Role in Ischemic Injury of Lean and Steatotic Liver by Inhibiting Cell Death and Stimulating Lipolysis

Background and AimThe molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking.MethodsThis was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives.ResultsA total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant‐free survival.ConclusionOur study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

BackgroundNon-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality.MethodsWe used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction–associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed.ResultsAmong the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3–17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27–1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09–1.60), CVD (HR = 2.06, 95% CI = 1.61–2.63) or other causes (HR = 1.21, 95%CI = 0.97–1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality.ConclusionsOur findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Background and aimsThe effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population. MethodsWe assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020. Using an as-treated exposure definition, we compared DOACs to VKAs and apixaban to rivaroxaban. After inverse probability of treatment weighting, Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95 % confidence intervals (CIs) of ischemic stroke and major bleeding. Site-specific estimates were pooled using random-effects models. Analyses were repeated among NVAF patients with cirrhosis. ResultsThere were 11,881 NVAF patients with liver disease (2683 with cirrhosis). Among those, 8815 initiated DOACs (4414 apixaban, 2497 rivaroxaban) and 3696 VKAs. The HRs (95 % CIs) for DOACs compared to VKAs were 1.01 (0.76–1.34) for ischemic stroke and 0.87 (0.77–0.99) for major bleeding. Results were consistent among patients with cirrhosis. The HRs (95 % CIs) for apixaban compared to rivaroxaban were 0.85 (0.60–1.20) for ischemic stroke and 0.80 (0.68–0.95) for major bleeding. This decreased bleeding risk was not observed among patients with cirrhosis (HR, 1.01; 95 % CI 0.72–1.43). ConclusionsAmong NVAF patients with liver disease, DOACs were as effective and slightly safer than VKAs, and apixaban was as effective but safer than rivaroxaban. The safety benefit with apixaban was not present among patients with cirrhosis.

Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Selecting the initial antiviral regimen for chronic hepatitis B (CHB) requires balancing patients' comorbidities and long-term safety. This study examines the differences in patient and disease-related factors that guide clinicians to prescribe either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) as the initial treatment. The study included treatment-naïve CHB patients aged 18 or older who had been diagnosed for at least 1 year since 2010 and initiated on antiviral therapy. The data included variables such as age, gender, body mass index (BMI), comorbidities, liver disease activity, biopsy results, cirrhosis, hepatic steatosis, hepatitis B e antigen status, hepatitis B virus DNA levels, triglycerides, cholesterol, renal function, and baseline bone mineral density (BMD), which were assessed by dual-energy x-ray absorptiometry (DEXA). Among 2259 patients (61.6% male), 1270 patients (56.22%) received TDF, while 989 patients (43.78%) received ETV as first line therapy. The TDF was more commonly prescribed to patients with a lower BMI (median 25.7 vs. 26.2, P = .001) and lower baseline creatinine (0.75 vs. 0.80 for ETV, P < .001). Clinicians preferred ETV among patients with an estimated glomerular filtration rate (eGFR) < 60 (n = 36), (P < .001). The BMD was evaluated in 365 patients (16.3%). The DEXA scans were performed for 116 patients (11.8%) in the ETV group and 249 patients (19.8%) in the TDF group (P < .001). This national multicenter study emphasizes that patient-related factors, including gender, age, baseline renal function, and liver disease severity, significantly influence the choice of first-line antiviral therapy for CHB, often outweighing disease-specific factors. Cite this article as: Yamazhan T, Zerdali E, Önlen Y, et al. A national multicenter study on initial antiviral treatment preferences on chronic hepatitis B: Entecavir versus tenofovir disoproxil fumarate. Turk J Gastroenterol. 2026;37(2):179-185.

ABSTRACTMetabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease globally. Previous studies have shown that MASLD is an independent risk factor for chronic kidney disease (CKD), but the variations in estimated glomerular filtration rate (eGFR) levels across countries with different ethnic backgrounds have not been extensively reported. We enrolled 3308 participants with biopsy‐proven MASLD from 34 centers in this multinational study and analyzed the associations between eGFR and histological severity of liver fibrosis in different countries. European participants had lower eGFR levels (92.2 ± 20.7 vs. 104.7 ± 17.3 mL/min/1.73 m2) and significant liver fibrosis (61.4 vs. 32.4%) than Asian individuals. In Asia, Chinese participants had the highest mean eGFR level at 105.8 mL/min/1.73 m2, while Malaysian participants had the lowest at 87.3 mL/min/1.73 m2 (p < 0.001). In Europe, French participants had the highest mean eGFR level at 95.3 mL/min/1.73 m2, while Romanian individuals had the lowest at 81.1 mL/min/1.73 m2 (p < 0.001). eGFR levels were inversely associated with liver fibrosis in Asian individuals (OR: 0.793, 95%CI: 0.685–0.917, p = 0.002), even after adjusting for traditional renal risk factors, but not in Europeans. Our findings provide the basis for further investigation of the burden of MASLD on CKD risk in different countries.

AimsThe PREVIEW lifestyle intervention study (http://clinicaltrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type‐2 diabetes. We hypothesized that the initial, fixed low‐energy diet (LED) would induce different metabolic outcomes in men vs women.Materials and methodsAll participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2) individuals with pre‐diabetes according to ADA‐criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat‐free mass (FFM) and metabolic syndrome Z‐score.ResultsIn total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow‐up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA‐IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z‐score, C‐peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo‐glycaemia.ConclusionsAn 8‐week LED induced different effects in women than in men. These findings are clinically important and suggest gender‐specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.

In an experimental murine liver clamping model, we aimed to investigate the efficacy of real-time confocal microscopy (RCM) in assessing viability of steatotic livers in comparison to standard assessment tools, including histopathological evaluation. C57Bl/6 mice were subjected to a methionine-choline-deficient diet causing nonalcoholic fatty liver disease or to Lieber DeCarli diet causing ethanol-induced liver injury. Untreated animals served as controls. Liver biopsies were analyzed following challenge with 45 min of warm ischemia time and either 4 h of reperfusion or 24 h of cold storage. Organ quality assessment was performed at defined time points by RCM, histological staining, measurement of serum alanine aminotransferase activity, and expression analyses of proinflammatory cytokines. Additionally, survival analysis was performed. Cold as well as warm ischemia time resulted in a significant decrease in cell viability when compared with naive livers as well as nonischemic-challenged steatotic livers (P < 0.05) as assessed by RCM. Furthermore, RCM revealed the actual cellular damage at early time points, while established methods including H&E-staining and serum transaminase profile failed. In a translational attempt, we demonstrate that RCM is a suitable diagnostic tool to obtain information about functional damage of the liver apart from standard approaches.

Late Onset Wilson Disease Frequently Overlooked

Hepatocellular carcinoma (HCC) remains a major health burden in Asia. Advances in antiviral therapies are reshaping the etiological landscape of HCC. This study evaluated temporal shifts in HCC etiology across Asian countries and their clinical implications. This multinational study analyzed 6,261 newly diagnosed HCC patients registered in the APASL Hepatology/Oncology Consortium (A-HOC) from 19 centers across seven Asian countries and regions between 2013 and 2023. Data on demographics, tumor characteristics, etiology, and treatment patterns were collected. Etiologies included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), MAFLD plus excess alcoholic intake (MAFLD + eAL), autoimmune liver disease, cryptogenic, and others. Temporal trends and regional variations were assessed. In many countries, HBV remained predominant (43.3%-69.5%) and relatively stable throughout the period, while HCV showed only modest reductions. In Japan, HCV was the leading cause of HCC (33.1%), with a significant decline over time, accompanied by a rise in MAFLD-related HCC. ALD-related HCC increased in South Korea, and MAFLD-related HCC rose in Turkey. Tumor size and stage at diagnosis varied by etiology and region, affecting treatment strategies. Early-stage diagnosis was more frequent in Japan and Taiwan, whereas advanced-stage HCC was common in China and Indonesia. Distinct regional patterns and temporal changes in HCC etiology across Asia highlight the need for tailored prevention and surveillance measures. The growing burden of MAFLD-related HCC emphasizes its emerging role in liver cancer development, particularly in regions with declining viral hepatitis.

Cardiovascular disease and its associated comorbidities, including diabetes mellitus, obesity and dyslipidemia, represent a significant socioeconomic burden, particularly in low- to middle-income countries. Pharmacological intervention with statins, which reduce low-density lipoprotein–cholesterol levels, has been demonstrated to reduce cardiovascular risk. This study assessed the prevalence of lipid abnormalities as well as risk factors for dyslipidemia in Egyptian patients on chronic statin treatment. DYSIS is a cross-sectional, observational, multinational study. Key eligibility criteria were age of at least 45 years and stable statin treatment for at least three months. In the Egyptian DYSIS cohort, a total of 1466 patients, 920 men and 532 women, were enrolled in 24 different centers. Patient characteristics and lipid measurements were documented, and multivariate regression modeling was used to assess factors associated with dyslipidemia. Most patients (85%) were defined as being at very-high risk of cardiovascular disease. Gender-specific differences included higher rates of tobacco smoking and metabolic syndrome in men and women, respectively. Goal LDL–C levels were not achieved by 67.2% of the population, rising to 72% in both high- and very-high risk patients. Factors independently associated with LDL–C levels not being at goal included diabetes mellitus, ischemic heart disease, and high blood pressure. Despite chronic statin treatment, two-thirds of patients in the DYSIS-Egypt study had elevated LDL–C levels. A dual strategy, comprising modification of lifestyle factors together with novel treatment options, appears to be necessary to combat the rise in cardiovascular-related morbidity and mortality.

When is steatosis too much for transplantation?

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?