Background and Aims:Metabolic dysfunction drives hepatic progression in metabolic dysfunction-associated steatotic liver disease (MASLD), yet conventional binary metabolic syndrome (MetS) definitions may obscure dose-response risk of fibrosis. We evaluated the association between MetS severity and advanced fibrosis probability in a representative US MASLD cohort. Methods:Adults aged 20-74 years with ultrasound-defined MASLD in the Third National Health and Nutrition Examination Survey were analyzed. Exposure was the validated MetS severity Z-score (quartiles, percentile categories, and continuous percentile with restricted cubic splines). Outcome was the Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS)-defined advanced fibrosis probability (intermediate-to-high: NFS ≥ -1.455; high: NFS > 0.676). Complex survey logistic regression estimated adjusted odds ratios (aORs). Results:Among 3036 participants, 29.6% had intermediate fibrosis probability and 5.2% had high advanced fibrosis probability. High fibrosis probability was most prevalent in non-Hispanic Black adults (8.0%) and least in Mexican Americans (2.6%; P value <.001). Approximately 2.5% of the low MetS severity group had a high probability of advanced fibrosis compared with 11.4% in the very high MetS severity group (P value <.001). Each one-quartile decrease in MetS severity was associated with 21% (aOR = 0.79; 95% confidence interval [CI]: 0.68-0.91) and 32% (aOR = 0.68; 95% CI: 0.48-0.96) lower odds of intermediate-to-high and high probability of advanced fibrosis, respectively. In dose-response analyses, advanced fibrosis risk rose modestly through midrange severities and accelerated beyond the 70th severity percentile, reaching aOR of 3.59 (95% CI: 2.74-4.70) at the 90th vs the 50th percentile. Conclusion:MetS severity demonstrates a graded and nonlinear association with advanced fibrosis probability in MASLD. A continuous metabolic-burden measure may enhance upstream triage and risk stratification alongside existing noninvasive pathways.

ABSTRACT Background Hepatocellular carcinoma (HCC) survival in the United States varies sharply by neighborhood disadvantage. Aim To determine whether residence in persistently impoverished or low‐SES census tracts is independently associated with lower all‐cause and HCC‐specific survival. Methods We identified 51,323 adults with HCC using a population‐based retrospective cohort from the Surveillance, Epidemiology, and End Results Research Plus Specialized Database (2006–2020). Two census tract‐level socioeconomic exposures were defined: persistent poverty (≥ 20% living below the poverty line for approximately 30 years) and low SES (Yost Index first quintile). Overlap Propensity Score Weighting, combined with marginal structural models, estimated the 1‐, 5‐, 10‐, and 15‐year risks of all‐cause and HCC‐specific mortality. Results The median follow‐up was 16 months, 6058 (11.8%) lived in persistently impoverished tracts, and 9863 (19.5%) lived in low‐SES tracts. After weighting, residents of persistently impoverished areas had a 1‐year all‐cause mortality risk of 46.0% vs. 40.3% (RD, 5.6%; 95% CI, 4.4% to 6.9%; RR, 1.14; 95% CI, 1.11 to 1.17) and an HCC‐specific mortality risk of 33.3% vs. 28.6% (RD, 4.8%; 95% CI, 3.2% to 6.3%; RR, 1.17; 95% CI, 1.11 to 1.22). Living in low‐SES tracts raised 1‐year all‐cause mortality risk to 32.5% vs. 30.1% (RD, 4.8%; 95% CI, 3.6% to 6.0%; RR, 1.12; 95% CI, 1.09 to 1.15) and HCC‐specific mortality risk to 32.5% vs. 30.1% (RD, 2.5%; 95% CI, 1.4% to 3.5%; RR, 1.08; 95% CI, 1.05 to 1.12). Conclusions Both persistent neighborhood poverty and contemporary low SES independently contribute to significant increases in mortality risk after HCC diagnosis.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Epidemiological evidence indicates that MASLD is associated with an increased risk of developing colorectal cancer (CRC). MASLD and CRC share many common risk factors and pathophysiological mechanisms, but an optimal strategy for identifying and managing CRC risk in individuals with MASLD remains lacking.Objective This study aimed to achieve consensus on the risk of CRC in individuals with MASLD.Design A Delphi survey was conducted by a multidisciplinary panel of 35 international experts from diverse medical fields across Asia, Europe, North America, South America, Oceania and Africa. Experts evaluated 17 statements across three domains: epidemiology, pathogenesis and management.Results Consensus was achieved on all 17 statements. MASLD is associated with an increased risk of CRC, and metabolic burden further increases this risk. Furthermore, the severity of MASLD is associated with worse outcomes in patients with MASLD and CRC. The gut-liver axis and gut dysbiosis play key roles in the development of MASLD and CRC, while leptin and adiponectin may also be involved. Weight loss with lifestyle interventions, early CRC screening, bariatric surgery and use of GLP-1 receptor agonists are highlighted as potential risk-reduction strategies.Conclusion The expert panel emphasises the need for greater clinical vigilance for CRC among individuals with MASLD. This consensus supports a paradigm shift towards earlier, risk-adapted screening and integrated metabolic management to reduce the burden of CRC in the MASLD population.

Artificial intelligence and machine learning are transforming hepatology by integrating clinical, laboratory, imaging, and wearable data for earlier diagnosis, risk prediction, and patient management. These technologies enable personalized care and noninvasive monitoring across metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatitis C, liver transplantation, and hepatocellular carcinoma. Ongoing advances in digital health and interpretability will enhance adoption and outcomes.

Background & aims Previous studies have examined the effects of metabolic syndrome (MetS) rather than its severity on race and ethnic disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We used the MetS severity score, a validated sex-race-ethnicity-specific severity measure, to examine the effects of race/ethnicity on the association between MetS severity and MASLD. Methods This study included 10,605 adult participants from the Third National Health and Nutrition Examination Survey. The MASLD diagnosis was based on ultrasound findings in patients without excessive alcohol intake or other liver diseases. MetS severity Z-scores were calculated and stratified into four categories low (1st-50th), moderate (>50th-75th), high (>75th-90th), and very high (>90th+)]. Multivariable adjusted logistic regression models with complex survey methods were used to test the effect of MetS severity on MASLD. Results The age-adjusted MASLD prevalence was 17.4%, 25.7%, 42.5, and 54.9% in adults with mild, moderate, high, and very high MetS severities, respectively (P-trend <0.001). MetS severity was significantly higher in patients with MASLD than in those without [mean percentile 60th vs. 44th, P<0.001]. Among patients with MASLD, Mexican-American and Black non-Hispanic females had significantly higher age-adjusted MetS severity (68th and 61st, respectively) than White non-Hispanic females 54th, while Black non-Hispanic males had significantly lower MetS severity (56th) than White non-Hispanic males (70th) (P-Interaction = 0.02). Adults with high and very high MetS severity had 2.27 (95% CI:1.70 to 3.03) and 3.12 (95% CI:2.20 to 4.42), respectively, higher adjusted odds of MASLD than those with mild MetS severity. Conclusions Racial/ethnic disparities in MetS severity play a pivotal role in the risk of MASLD. Our findings highlight the potential clinical utility of the MetS severity score in identifying at-risk individuals, which will help guide targeted prevention and tailoring management strategies to mitigate the MASLD burden.

The epidemiology of Hepatitis B virus (HBV) has drastically changed in recent decades due to public health initiatives, including universal infant vaccination programs,urbanization driving global travel, and migration patterns. Despite screening of pregnant women and newborns significantly reducing the rate of perinatal transmission in certain parts of the world, other, perhaps more uncommon, routes (e.g., parenteral) have led to outbreaks in specific areas affected by the opioid epidemic and injection drug use. Although our current understanding of the effect of genetic variants of HBV is lacking, we review current knowledge and patterns of genetic variants with geographical predominance, pathophysiology, and clinical manifestations. Serologic and molecular markers are used to screen, identify phase and activity of infection, and monitor response to antivirals and/or reactivation. This review will provide the most up-to-date summary of the epidemiology, transmission, genotype, replication, and current methods of screening to follow the various phases of HBV, including immunotolerance and reactivation.

BACKGROUND/AIMS:We examined the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) initiation on long-term Adverse Liver Outcomes (ALO) in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) cirrhosis and type 2 diabetes using real-world data from the MarketScan database. METHODS:We conducted a retrospective cohort study of patients with MASLD cirrhosis and type 2 diabetes between 2012 and 2020. Cox proportional hazard models examine the association between GLP-1RAs initiation, modelled as time-dependent, and the risk of ALO, a composite endpoint defined by the first occurrence of hepatic decompensation(s), portal hypertension, hepatocellular carcinoma (HCC) or liver transplantation (LT). We used Overlap Propensity Score Weighting (OPSW) to account for confounding. The study included 459 GLP-1RAs and 4837 non-GLP-1RAs patients. RESULTS:The non-GLP-1RAs patients presented with 1411 (29%) ALO over 7431.7 person years, while GLP-1RAs patients had 32 (7%) ALO over 586.6 person years - risk rate difference 13.5 (95% CI: 11.4-15.7) per 100 person-years. The OPSW-adjusted risk of ALO was reduced by 36% (hazard ratio [HR]: 0.64; 95% CI: 0.54-0.76) in patients with vs. without GLP-1RAs initiation. GLP-1RAs initiation was associated with significant reductions in the adjusted risk of hepatic decompensation (HR: 0.74; 95% CI: 0.61-0.88), portal hypertension (HR: 0.73; 95% CI: 0.60-0.88), HCC (HR: 0.37; 95% CI: 0.20-0.63) and LT (HR: 0.24; 95% CI: 0.12-0.43). CONCLUSION:The use of GLP-1RAs was associated with significant risk reductions in long-term adverse liver outcomes, including hepatic decompensation, portal hypertension, HCC and LT, in MASLD cirrhosis patients with type 2 diabetes.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that is observed primarily in patients with liver disease. The pathophysiology is complex and involves many factors including ammonia toxicity, dysregulation of central nervous system activity, and excess inflammatory cytokines. Symptoms of HE range from subclinical to debilitating. HE can be difficult to treat and represents a large burden to patients, their caregivers, and the health-care system because of associated resource utilization. This review article provides an overview of the current understanding of the pathophysiology behind HE and where the current research and treatments are pointing toward.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that is observed primarily in patients with liver disease. The pathophysiology is complex and involves many factors including ammonia toxicity, dysregulation of central nervous system activity, and excess inflammatory cytokines. Symptoms of HE range from subclinical to debilitating. HE can be difficult to treat and represents a large burden to patients, their caregivers, and the health-care system because of associated resource utilization. This review article provides an overview of the current understanding of the pathophysiology behind HE and where the current research and treatments are pointing toward.

INTRODUCTION AND OBJECTIVES:Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MATERIALS AND METHODS:We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. RESULTS:The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. CONCLUSIONS:Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

Background Rifaximin and/or lactulose therapy is widely used in cirrhotic patients for the prevention and treatment of hepatic encephalopathy. The incidence of gastrointestinal cancers in these patients on lactulose, rifaximin, and/or combination therapy is unknown. We investigated the possible effect of lactulose and rifaximin on cancer risk in patients with cirrhosis using the MarketScan database. Methods A retrospective cohort study was conducted using the Truven Health MarketScan Commercial Claims databases from 2007-2017. An index date was defined for each participant as the earliest date of cirrhosis diagnosis. A baseline period for each participant was defined as the 12 months prior to the first medication date while the study follow-up period represented the period from the initiation of the medication to its cessation. ANOVA was used to compare all continuous measures of age and duration of medication. Wald Chi-square tests were performed to test the associations between the study groups. Results A total of 12,409 patients were included in our study. The rifaximin only cohort had the greatest reduction in risk of developing colon cancer, esophageal cancer, and stomach cancer compared to the other groups. Rifaximin reduced the risk of colon cancer and esophageal cancer by 59.42% and 70.37%, respectively, compared to patients taking lactulose only. Patients in the lactulose plus rifaximin cohort had the highest rate of development of pancreatic cancer (lactulose plus rifaximin vs rifaximin only vs lactulose only, 0.45% vs 0.24% vs 0.21%; P < 0.0001) and liver and intrahepatic bile duct cancers (11.73% vs 5.84% vs 5.49%; P < 0.0001). Conclusion Colon, esophageal, and gastric cancers had a marked incidence reduction in the rifaximin only cohort compared to the other cohorts studied.

Background: Patients with cirrhosis are at increased risk of complications following surgery due to multiple factors, including portal hypertension and alterations in hemostasis. Improvements in perioperative management as well as risk stratification scores have helped improve outcomes, but gaps remain in our understanding of the cost and morbidity of cirrhotic patients who undergo surgery. Methods: We conducted a case-control study using the IBM Electronic Health Record (EHR) MarketScan Commercial Claims (MSCC) database from January 1, 2007 to December 31, 2017. Nonalcoholic cirrhotic patients who underwent surgery were identified based on International Classification of Diseases, Ninth Revision (ICD-9)/Tenth Revision (ICD-10) codes for multiple surgical categories and matched with controls with cirrhosis who did not undergo surgery in this time period. A total of 115,512 patients were identified with cirrhosis, of whom 19,542 (16.92%) had surgery. Medical history and comorbidities were compiled, and outcomes in the six-month period following surgery were analyzed between matched groups. A cost analysis was performed based on claims data.Results: Nonalcoholic cirrhotic patients who underwent surgery had a higher comorbidity index at baseline compared with controls (1.34 vs. 0.88, P<0.0001). Mortality was increased in the surgery group (4.68% vs. 2.38%, P<0.001) in the follow-up period. The surgical cohort had higher rates of adverse hepatic outcomes, including hepatic encephalopathy (5.00% vs. 2.50%, P<0.0001), spontaneous bacterial peritonitis (0.64% vs. 0.25%, P<0.001), and higher rates of septic shock (0.66% vs. 0.14%, P<0.001), intracerebral hemorrhage (0.49% vs. 0.04%, P<0.001), and acute hypoxemic respiratory failure (7.02% vs. 2.31%, P<0.001). Healthcare utilization analysis revealed increased total claims per patient in the surgical cohort (38.11 vs. 28.64, P<0.0001), higher inpatient admissions (6.05 vs. 2.35, P<0.0001), more outpatient visits (19.72 vs. 15.23, P<0.0001), and prescription claims per patient (11.76 vs. 10.61, P<0.0001) in the postsurgical period. The likelihood of at least one inpatient stay was higher in the surgical cohort (51.63% vs. 22.32%, P<0.0001), and inpatient stays were longer (4.99 days vs. 2.09 days, P<0.0001). The total cost of health services was significantly increased per patient in the postoperative period for patients undergoing surgery ($58,246 vs. $26,842, P<0.0001), largely due to increased inpatient costs ($34,446 vs. $10,789, P<0.0001).Conclusion: Nonalcoholic cirrhotics undergoing surgery experienced worse outcomes with respect to adverse hepatic events and complications, including septic shock and intracerebral hemorrhage. Claims and cost analysis showed a significant increase in health expenditure in the surgical group, largely due to the cost of more frequent and longer inpatient admissions.

Conclusion: Our study shows the clinical characteristics, outcomes, and prevalence of cardiac complications among patients with PBC in the USA using an inpatient healthcare database. Data on cardiac complicationsofPBCarescarce