UNASSIGNED: Telehealth has emerged as an important mode of cirrhosis care delivery, but its use and satisfaction among vulnerable populations (eg, racial/ethnic minorities, socioeconomically disadvantaged, substance use disorders) are unknown. We evaluated digital capacity, telehealth use, satisfaction and associated factors among patients receiving hepatology care via telehealth (telehepatology) across 2 Veterans Affairs and 1 safety-net Healthcare systems.
UNASSIGNED: English- and Spanish-speaking adults with cirrhosis (N = 256) completed surveys on telehealth use and satisfaction, quality of life, pandemic stress, alcohol use and depression. Logistic regression analyses assessed telehealth use and general linear models evaluated telehealth satisfaction.
UNASSIGNED: The mean age was 64.5 years, 80.9% were male and 35.9% Latino; 44.5% had alcohol-associated cirrhosis; 20.8% had decompensated cirrhosis; 100% had digital (phone/computer) capacity; and 75.0% used telehepatology in the prior 6 months. On multivariable analysis, participants with alcohol-associated (vs not) cirrhosis were less likely and those with greater pandemic stress were more likely to use telehepatology (odds ratio = 0.46 and 1.41, respectively; P < .05). Better quality of life was associated with higher telehepatology satisfaction and older age was associated with lower satisfaction (β = 0.01 and -0.01, respectively; P < .05). Latinos had higher satisfaction, but alcohol use disorder was associated with less satisfaction with telehepatology visits (β = 0.22 and -0.02, respectively; P < .05).
UNASSIGNED: Participants had high telehepatology capacity, yet demographics and alcohol-related problems influenced telehepatology use and satisfaction. Findings underscore the need for interventions to enhance patient experience with telehepatology for certain vulnerable groups including those with alcohol-associated cirrhosis in order to optimize care delivery.

OBJECTIVE: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been introduced. However, research on this new nomenclature and definition remains limited. This study aims to assess the impact of cardiometabolic risk factors and alcohol consumption on all-cause mortality in MASLD and its subgroups.
RESULTS: We included 2408 participants with MASLD in NHANES III and their linked mortality through 2019. MASLD patients were divided into two groups based on alcohol consumption: Pure MASLD and MetALD. The Cox proportional hazard model was used to assess the association between factors and all-cause mortality. During the median 26.0-year follow-up, there were 1040 deaths. The multivariable Cox regression analysis revealed a significant increase of over two-fold in the all-cause mortality rate among patients with four or more cardiometabolic risk factors compared to those with only one. When focusing on each component of cardiometabolic risk factors individually, only diabetes and hypertension were significantly associated with all-cause mortality (p < 0.05). In a subgroup analysis, each additional cardiometabolic factor was linked to an increase in all-cause mortality in both pure MASLD (hazard ratio 1.16; 95% CI 1.06-1.28; p = 0.002) and MetALD (HR 1.77; 95% CI 1.26-2.49; p = 0.001). Notably, an elevation in alcohol consumption was significantly associated with an increase in all-cause mortality rate only in the MetALD (p < 0.001).
CONCLUSIONS: This study found that the presence of diabetes or hypertension was significantly associated with all-cause mortality. We also explored the different impacts of these factors and alcohol consumption within MASLD subgroups.

Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.

OBJECTIVE: Non-invasive tests (NITs) for liver fibrosis have been recognized for their clinical utility in metabolic dysfunction-associated steatotic liver disease (MASLD). However, their diagnostic efficacy in detecting liver fibrosis is notably reduced in patients with alcohol-related liver disease. Therefore, ascertaining the reliability of NITs in patients with MASLD with moderate alcohol intake (MetALD) is essential.
METHODS: In this cross-sectional study, we reviewed data from 7,918 health check-up participants who underwent both magnetic resonance elastography (MRE) and ultrasound for the diagnosis of hepatic steatosis. The participants were categorized into MASLD and MetALD groups, and the performance of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were assessed. Advanced hepatic fibrosis (F3) was defined as MRE ≥3.6 kPa.
RESULTS: The prevalence of MetALD was 5.8% in this health check-up cohort, and 1.5% of these patients exhibited advanced hepatic fibrosis. Both MetALD and MASLD displayed similar metabolic profiles and hepatic fibrosis burdens. The diagnostic performance of FIB-4 and NFS for MRE ≥3.6 kPa showed no noticeable differences in the area under the receiver-operating characteristic values between the two groups (0.85 vs. 0.80 in FIB-4). Moreover, the sensitivity (71.4%), specificity (77.3%), and both positive (4.6%) and negative (99.4%) predictive values of NITs for MetALD closely mirrored those observed for MASLD.
CONCLUSIONS: FIB-4 performed well for the initial screening of advanced hepatic fibrosis in MetALD, demonstrating reasonable sensitivity and negative predictive values.
UNASSIGNED: In this cross-sectional study, data from 7,918 participants who underwent MRE were analyzed to assess the performance of fibrosis-4 (FIB-4) and non-alcoholic fatty liver disease fibrosis scores in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with moderate alcohol intake (MetALD). We found that FIB-4 had high diagnostic accuracy in the newly identified MetALD group, similar to that in the MASLD population. These results highlight the potential of FIB-4 as a reliable screening tool for MetALD, even when specific subgroups are considered. Therefore, FIB-4 is a valuable screening tool for identifying advanced fibrosis in the MetALD population.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

A recent Delphi consensus proposed a new definition for metabolic dysfunction associated steatotic liver disease (MASLD) and introduced a disease entity called MetALD, a condition in which steatotic liver disease (SLD), metabolic dysfunction and moderate alcohol intake coexist. Given the limited available data on the prognostic implications of these disease entities, we performed a systematic review and meta-analysis of available cohort studies to evaluate the association of MASLD and MetALD with hard clinical outcomes. We included 5 studies for a total of 9 824 047 participants. Compared with participants without SLD, increased rates of all-cause mortality and incident cardiovascular disease were present for both MASLD and MetALD. Moreover, MetALD was also associated with significantly higher risks of cancer-related mortality (n = 2 studies, random-effects HR 2.10, 95% CI 1.35-3.28) and cardiovascular mortality (n = 3 studies, random-effects HR 1.17, 95% CI 1.12-1.22). Although preliminary, available evidence indicates a more unfavourable prognosis for patients with MetALD compared with those with MASLD.

BACKGROUND: The gut microbiome modulates the liver immune microenvironment and is deeply integrated into the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). Appendectomies, which are performed in almost all patients diagnosed with appendicitis, cause long-term alterations to the gut microbiome, providing a potential link with the development of MASLD. We therefore investigated a potential link between appendicitis and the presence of MASLD in a large cohort of outpatients in Germany.
METHODS: The present study included 26,717 individuals with and 26,717 without appendicitis. Univariable Cox-regression analyses were conducted to assess the association between appendicitis and MASLD.
RESULTS: During the long-term follow-up, 4.8% of patients with appendicitis and 3.4% of those in the non-appendicitis group were diagnosed with MASLD (p < 0.001), corresponding to an incidence of 5.4 (appendicitis cohort) versus 3.5 (non-appendicitis cohort) cases per 1000 patient years. These findings were confirmed in regression analysis, revealing a strong and statistically significant association between appendicitis and the development of MASLD (HR: 1.57; 95% CI: 1.39-1.78). This link was observed for all age groups and was independent of patients\' sex.
CONCLUSIONS: We provide evidence from a large cohort of outpatients in Germany suggesting a link between appendicitis and MASLD. This might help to better stratify patients according to their individual risk for the development of chronic liver diseases.

Alcohol use is the most important determinant of the development of alcohol-associated liver disease (ALD) and of predicting long-term outcomes in those with established liver disease. Worldwide, the amount, type, and pattern of use of alcohol vary. Alcohol use and consequent liver disease have been increasing in certain ethnic groups especially Hispanics and Native Americans, likely due to variations in genetics, cultural background, socio-economic status, and access to health care. Furthermore, the magnitude and burden of ALD have been increasing especially in the last few years among females and young adults who are at the prime of their productivity. It is critical to recognize the problem and care for these patients integrating cultural aspects in liver clinics. At the federal level, a societal approach is needed with the implementation of public health policies aiming to reduce alcohol consumption in the community. By addressing these challenges and promoting awareness, we can strive to reduce the burden of ALD, especially in high-risk demographic groups to improve their long-term health outcomes. Finally, we need studies and quality research examining these changing landscapes of demographics in ALD as a basis for developing therapeutic targets and interventions to reduce harmful drinking behaviours in these high-risk demographic groups.

The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes.
We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations.
FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs.
The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.

OBJECTIVE: Alcohol overconsumption is a risk factor for disease progression in patients with presumed metabolic dysfunction-associated steatotic liver disease (MASLD). How commonly this occurs and how it affects progression to major adverse liver outcomes (MALOs) is not well known.
METHODS: We did a register-based cohort study, including all patients with a diagnosis of MASLD in Sweden between 1987 and 2020. Patients were stratified on co-occurrence of diagnoses of alcohol-related liver disease (ALD) or alcohol use disorder (AUD) prior to MASLD diagnosis. Incident MALOs were derived from national registers. Cox regression was used to calculate hazard ratios (HRs) for incident MALO.
RESULTS: A total of 15,107 patients with MASLD were identified. The median age was 55 years, and 52% were female. Of the patients, 1843 (12%) had a prior diagnosis of ALD or AUD. During follow-up, a further 787 patients (5.2%) received a diagnosis of ALD or AUD. Patients with previous ALD or AUD diagnoses at or before baseline had considerably higher rates of MALOs compared with patients without (19.5% vs 7.8%; adjusted HR, 3.12; 95% confidence interval, 2.74-3.55). Acquiring an ALD or AUD diagnosis after MASLD diagnosis was associated with higher rates of MALOs (adjusted HR, 5.81; 95% confidence interval, 4.90-6.88).
CONCLUSIONS: ALD or AUD is commonly diagnosed prior to or after MASLD diagnosis. Such patients have considerably higher rates of progression to MALOs. Correctly separating between MASLD and ALD is vital to assess prognosis.