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The complex interplay between the gut microbiota, the intestinal barrier, the immune system and the liver is strongly influenced by environmental and genetic factors that can disrupt the homeostasis leading to disease. Among the modulable factors, diet has been identified as a key regulator of microbiota composition in patients with metabolic syndrome and related diseases, including the metabolic dysfunction-associated fatty liver disease (MAFLD). The altered microbiota disrupts the intestinal barrier at different levels inducing functional and structural changes at the mucus lining, the intercellular junctions on the epithelial layer, or at the recently characterized vascular barrier. Barrier disruption leads to an increased gut permeability to bacteria and derived products which challenge the immune system and promote inflammation. All these alterations contribute to the pathogenesis of MAFLD, and thus, therapeutic approaches targeting the gut-liver-axis are increasingly being explored. In addition, the specific changes induced in the intestinal flora may allow to characterize distinctive microbial signatures for non-invasive diagnosis, severity stratification and disease monitoring.

The term gut–liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a “chicken and egg” situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.

Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection. We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe). We included 30 HIV MASLD , 30 HIV MASLD and 20 HIV MASLD participants. Major butyrate producers, including , , and dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD , with MASLD participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV vs. HIV MASLD , q-value = 0.002; HIV MASLD vs. HIV MASLD , q-value = 0.930; and HIV MASLD vs. HIV MASLD , q-value < 0.001). The most abundant genera in MASLD- were , and . In contrast, the most enriched genera in MASLD+ were , and We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.

Acute-on-chronic liver failure (ACLF) is characterized by the acute decompensation of cirrhosis associated with organ failure and high short-term mortality. The key event in the pathogenesis is a dysfunctional immune response arising from exacerbation of the two main immunological alterations already present in cirrhosis: and . High-grade systemic inflammation due to predominant activation and dysregulation of the innate immune response leads to the massive release of cytokines. Recognition of acutely increased pathogen and damage-associated molecular patterns by specific receptors underlies its pathogenesis and contributes to tissue damage and organ failure. In addition, an inappropriate compensatory anti-inflammatory response over the course of ACLF, along with the exhaustion and dysfunction of both the innate and adaptive immune systems, leads to functional immune cell paralysis. This entails a high risk of infection and contributes to a poor prognosis. Therapeutic approaches seeking to counteract the immune alterations present in ACLF are currently under investigation.

Background and Aim Type 2 Diabetes mellitus (T2DM), age, and obesity are risk factors for metabolic dysfunction‐associated steatotic liver disease (MASLD). We aimed to assess the performance of non‐invasive tests (NITs) for the diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) and fibrosis in high‐risk subjects. Methods Multicentre cross‐sectional study that included 124 biopsy‐proven MASLD in more than 50 years‐old patients with overweight/obesity and T2DM. Vibration‐controlled transient elastography, Fibrosis‐4 index (FIB‐4), Non‐alcoholic fatty liver disease fibrosis score (NFS), OWLiver Panel (OWLiver DM2 + Metabolomics‐Advanced Steatohepatitis Fibrosis Score ‐MASEF) and FibroScan‐AST were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated. NITs were assessed individually and in sequential/parallel combinations. Results 35 (28.2%) patients had early MASH and 66 (53.2%) had MASH with significant fibrosis (at‐risk MASH). The OWLiver Panel correctly classified 86.1% as MASH, showing an accuracy, sensitivity, specificity, PPV, and NPV of 0.77, 0.86, 0.35, 0.85, and 0.36, respectively. Class III obesity, diabetes control, or gender did not impact on the performance of the OWLiver Panel (p > 0.1). NITs for at‐risk MASH showed an AUC > 0.70 except for NFS. MASEF showed the highest accuracy and NPV for at‐risk MASH (AUC 0.77 [0.68–0.85], NPV 72%) and advanced fibrosis (AUC 0.80 [0.71–0.88], NPV 92%). Combinations of NITs for the identification of at‐risk MASH did not provide any additional benefit over using MASEF alone. Conclusion One‐step screening strategy with the OWLiver Panel has high accuracy to detect MASH and at‐risk MASH in high‐risk subjects for MASLD.

Acute liver failure (ALF) is a rare and severe condition with high mortality. Liver transplantation (LT) has improved patient outcomes. This study analysed trends in aetiology, characteristics, and outcomes of ALF patients undergoing LT in Spain. We retrospectively reviewed 217 adult ALF-LT cases from 11 Spanish centers (2001 -2020), divided into two 10-year periods. Clinical, biochemical, and outcome data were collected, and predictors of mortality were identified. 217 adult ALF-LT patients were included (61.8% women, mean age: 41 years). Common aetiologies were cryptogenic (26.7%), autoimmune (26.3%), and viral (18%), with sex differences. Over time, autoimmune and drug-induced liver injury increased (22.3% vs 29.8% and 13.6% vs 21.1%), with a low prevalence of acetaminophen toxicity, and hepatitis B virus declined (23.3% vs 11.4%). Despite higher infection rates (52.5% vs 66.2%) linked to stronger immunosuppression, respiratory failure (29.1% vs 16.1%), chronic kidney disease (27.1% vs 13.6%), cardiovascular events (10.6% vs 1%), and mortality (37.6% vs 17.9%) decreased. Pre-LT hypertension, pre-LT acute kidney injury, and hypernatremia at LT were independently associated with worse survival. This large multicenter study revealed temporal changes in aetiologies, immunosuppressive treatment, and post-LT complications, with an improvement in outcome.

Background and Aim Elderly patients are frequently affected by gallstone-related disease. Current guidelines support cholecystectomy after a first acute biliary complication. In the aging, these recommendations are irregularly followed. Methods We analyzed data from patients 65 or older admitted between June 30, 2004 and June 30, 2013 with a diagnosis of acute pancreatitis, cholangitis, or cholecystitis. Diagnosis and severity assessment were defined according to current guidelines. Harms, mortality, and cholecystectomy rates were evaluated. Baseline factors independently predicting cholecystectomy were identified. Results A total of 491 patients were included. The median age was 78.8 years, and 51.7 % were women. Acute cholecystitis was present in 51.7 %, acute pancreatitis in 36.5 %, and acute cholangitis in 11.8 %. Cholecystectomy was performed in 47.1 %. Age, myocardial infarct, dementia, diabetes, nonmetastatic tumor, and severe liver disease were risk factors for not undergoing surgery. Complications related to hospital stay appeared in 33 % of patients. Surgery, cholecystostomy, and ERCP presented harms in 21–25 %. Overall mortality rate was 5.4 %: 10.4 % in acute cholangitis, 6.8 % in acute cholecystitis, and 2.2 % in acute pancreatitis. Mild cases presented a 1.3 % mortality, while 28.6 % of severe cases died. After discharge, 24.7 % of patients presented a new biliary complication, 9.7 % of them severe. Relapse was more frequent in patients managed without invasive procedures, 42.3 % than in cholecystectomy patients, 9.9 % ( p  < 0.001) and than in ERCP patients, 19.4 % ( p  = 0.01). Conclusions Cholecystectomy should be recommended to elderly patients after a first acute biliary complication. If not previously performed, ERCP should be offered as an alternative when surgery is contraindicated or refused.

Background Patients with recurrent cholangitis are at risk of developing life-threatening sepsis. Selective decontamination of the digestive tract (SDD) involving oral nonabsorbable antibiotics has been primarily applied to children undergoing Kasai portoenterostomy surgery. Methods In this study, SDD containing colistin, tobramycin, and nystatin was administered to eight patients with recurrent cholangitis, and the incidence density before and after SDD administration was analyzed. Results The overall incidence density of cholangitis requiring hospital admission was 0.37 per 100 patient days during the SDD period and was significantly lower than observed before SDD administration (1.05 per 100 patient days) [RR: 0.35 (95% CI: 0.21–0.59); p: <0.001, two-sided]. This was not associated with an increased risk of resistance during SDD administration. Conclusion In this study SDD reduced by 65% the frequency and severity of recurrent cholangitis. In addition, this procedure is patient-friendly and microbiologically safe.