BACKGROUND & AIMS:Steatotic liver disease encompasses metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and a mixed type (metabolic dysfunction-associated and alcohol-related liver disease). We investigated the course of compensated advanced chronic liver disease across steatotic liver disease subtypes, the impact of clinically significant portal hypertension, and the role of noninvasive tests. METHODS:This study included patients with steatotic liver disease and compensated advanced chronic liver disease from 17 centers undergoing hepatic venous pressure gradient and noninvasive test assessment through December 2023. Primary outcomes were first hepatic decompensation and liver-related mortality. RESULTS:Among 696 patients (alcohol-related liver disease, 22%; metabolic dysfunction-associated and alcohol-related liver disease, 20%; metabolic dysfunction-associated steatotic liver disease, 58%), 94% had Child-Pugh A, and 60% had clinically significant portal hypertension. Over a median follow-up of 3.8 years, 170 patients decompensated, and 137 died (58% liver-related). The 3-year cumulative decompensation incidence was highest in alcohol-related liver disease (26%), followed by metabolic dysfunction-associated and alcohol-related liver disease (21%) and metabolic dysfunction-associated steatotic liver disease (15%); yet differences were no longer significant after adjusting for age, sex, Model for End-stage Liver Disease, albumin, and hepatic venous pressure gradient. Similarly, liver-related mortality did not differ by steatotic liver disease subtype in adjusted models. Clinically significant portal hypertension independently predicted decompensation across all subtypes. The ANTICIPATE-NASH model showed high and comparable diagnostic accuracy for clinically significant portal hypertension across alcohol-related liver disease, metabolic dysfunction-associated and alcohol-related liver disease, and metabolic dysfunction-associated steatotic liver disease (area under the receiver operating characteristic curve = 0.831-0.894). An ANTICIPATE-NASH probability ≥60% for ruling-in clinically significant portal hypertension outperformed the original ANTICIPATE model in all subtypes and independently predicted decompensation with similar effect sizes (adjusted subdistribution hazard ratio, 2.57-2.71). CONCLUSIONS:Higher crude decompensation rates in alcohol-related liver disease and metabolic dysfunction-associated and alcohol-related liver disease reflect more severe liver disease at presentation, yet outcomes are comparable across the steatotic liver disease spectrum after accounting for disease severity. ANTICIPATE-NASH accurately identifies clinically significant portal hypertension across steatotic liver disease subtypes, and both invasive and noninvasive measures of portal hypertension predict decompensation and liver-related death.

La hemocromatosis (HC) es una de las enfermedades hereditarias más frecuentes, caracterizada por una acumulación excesiva de hierro en el organismo que puede causar daño estructural y funcional en diversos órganos e incluso la muerte si no se trata. La forma más común de HC se debe a la mutación homocigota C282Y en el gen HFE. El diagnóstico se basa en la evaluación clínica y de los parámetros de hierro en plasma, junto con las pruebas genéticas y de imagen. El diagnóstico apropiado y oportuno de la HC es fundamental, ya que intervenciones simples, como la flebotomía, pueden prevenir o revertir el daño orgánico causado por la sobrecarga de hierro. Hemochromatosis (HC) is one of the most common hereditary diseases. It is characterized by an excessive accumulation of iron in the body that can cause structural and functional damage to various organs and death if left untreated. The most common form of HC is due to a homozygous C282Y mutation in the HFE gene. The diagnosis is based on a clinical evaluation and plasma iron parameters together with genetic and imaging tests. The proper and timely diagnosis of HC is essential, given that simple interventions, such as phlebotomy, can prevent or reverse organ damage caused by iron overload.

AbstractBackgroundPreliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis.ObjectiveWe aimed to investigate the prevalence of significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population‐based cohort from the same region.MethodsThis was a single‐center, cross‐sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013‐February 2017. These patients were propensity score matched (ratio 1:4) with a population‐based cohort from the same region (PREVHEP‐ETHON study; NCT02749864; N = 5988).ResultsOf 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP‐ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p = 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts.ConclusionsOur findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver‐related causes of fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and its incidence has been increasing in recent years because of the high prevalence of obesity and metabolic syndrome in the Western population. Alcohol-related liver disease (ArLD) is the most common cause of cirrhosis and constitutes the leading cause of cirrhosis-related deaths worldwide. Both NAFLD and ArLD constitute well-known causes of liver damage, with some similarities in their pathophysiology. For this reason, they can lead to the progression of liver disease, being responsible for a high proportion of liver-related events and liver-related deaths. Whether ArLD impacts the prognosis and progression of liver damage in patients with NAFLD is still a matter of debate. Nowadays, the synergistic deleterious effect of obesity and diabetes is clearly established in patients with ArLD and heavy alcohol consumption. However, it is still unknown whether low to moderate amounts of alcohol are good or bad for liver health. The measurement and identification of the possible synergistic deleterious effect of alcohol consumption in the assessment of patients with NAFLD is crucial for clinicians, since early intervention, advising abstinence and controlling cardiovascular risk factors would improve the prognosis of patients with both comorbidities. This article seeks to perform a comprehensive review of the pathophysiology of both disorders and measure the impact of alcohol consumption in patients with NAFLD.

Portal vein thrombosis constitutes the most common thrombotic event in patients with cirrhosis, with increased rates in the setting of advanced liver disease. Despite being a well-known complication of cirrhosis, the contribution of portal vein thrombosis to hepatic decompensation and overall mortality is still a matter of debate. The incorporation of direct oral anticoagulants and new radiological techniques for portal vein recanalization have expanded our therapeutic arsenal. However, the lack of large prospective observational studies and randomized trials explain the heterogenous diagnostic and therapeutic recommendations of current guidelines. This article seeks to make a comprehensive review of the pathophysiology, clinical features, diagnosis, and treatment of portal vein thrombosis in patients with cirrhosis.

ABSTRACT Background TURANDOT is the first prospective trial to compare BEV combined with either paclitaxel (PAC) or capecitabine (CAP). We report the planned interim analysis (IA) of efficacy. Methods Patients with HER2-negative mBC who had received no prior chemotherapy for mBC were randomised to receive either BEV–PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m d1, 8 & 15 q4w) or BEV–CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m bid d1–14 q3w) until disease progression or unacceptable toxicity. The primary objective is to demonstrate non-inferior overall survival (OS) with BEV–CAP vs BEV–PAC. Interim and final OS analyses were planned after 175 and 389 deaths, respectively, in the per-protocol (PP) population to reject the null hypothesis of inferiority (hazard ratio [HR] ≥1.33) with 80% power and overall α = 0.025. Secondary endpoints include response rate (RR), progression-free survival (PFS), safety and quality of life. Results Median follow-up was 19 months at data cut-off for this IA (1 Sep 2011). Baseline characteristics were generally similar in the 2 treatment arms. BEV-PAC (n = 285) BEV–CAP (n = 279) Median age, years 59 59 Visceral metastases, % 65 73 Prior (neo)adjuvant taxane, % 20 18 OS a Events, % 33 35 1-year OS rate, % b 81 79 HR (97.5% RCI c ) for non-inferiority 1.04 (-∞ to 1.69) p = 0.0593 d RR Overall, % 44 27 CMH test (superiority) p  PFS Events, % 62 77 Median, months 11.0 8.1 HR (95% CI) 1.36 (1.09 to 1.68) Log-rank (superiority) p = 0.0052 RCI = repeated confidence interval a PP population (n = 533) b Kaplan–Meier estimate c Using O'Brien–Fleming boundaries d Non-inferiority not shown as p > 0.00105 (α at IA) AEs were consistent with the known safety profiles of BEV, PAC and CAP. The most common grade ≥3 AEs were neutropenia (18%), peripheral neuropathy (14%) and leucopenia (7%) with BEV–PAC and hand-foot syndrome (16%), hypertension (6%) and diarrhoea (5%) with BEV–CAP. Conclusion In this planned IA, the non-inferiority criterion has not been met but OS results do not indicate relevant differences. Final results are expected in 2014. PFS and RR were better with BEV–PAC and very similar to previous data for BEV–PAC (E2100) and BEV–CAP (RIBBON-1). Disclosure R. Greil: RG has received research support and honoraria from Roche. S. Beslija: SB has received research support and honoraria from Roche. D. Messinger: Employee of IST GmbH, CRO which is providing various services and consultancies for Hoffmann-La Roche and CECOG. T. Brodowicz: TB has received honoraria from Roche. All other authors have declared no conflicts of interest.