Arpan Mohanty

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and related fibrosis are increasingly prevalent conditions. The relation of the American Heart Association’s (AHA) cardiovascular health (CVH) metric Life’s Essential 8 (LE8) with MASLD, MetALD, and hepatic fibrosis remains unclear. We aimed to investigate the associations of CVH with MASLD, MetALD, and hepatic fibrosis. Methods: We defined significant hepatic fibrosis as a liver stiffness ≥8.2 kPa measured by vibration-controlled transient elastography. MASLD was defined as steatosis (controlled attenuation parameter of ≥274 dB/m) with ≥1 cardiometabolic risk factor and mild alcohol intake (≤140 g/week [women]; ≤210 g/week [men]). MetALD was defined as steatosis with ≥1 cardiometabolic risk factor and moderate alcohol intake (141–350 g/week [women]; 211–420 g/week [men]). Data from 2962 participants in the Framingham Heart Study (mean age 59 years, 57% women) were used in multivariable-adjusted logistic regression models, accounting for demographic and clinical covariates to relate CVH and liver outcomes. Results: Our study included 2704 participants with mild and 258 with moderate alcohol use. MASLD and MetALD prevalence was 34% and 40%, respectively, and 9% had significant hepatic fibrosis. Each 10-point increase in LE4 score (composite of diet, sleep health, physical activity, and smoking) was associated with 16% lower odds of MASLD (Odds Ratio [OR] 0.84; 95% CI: 0.80–0.90; p < 0.001) but not MetALD. Each 10-point increase in LE8 score was associated with 17% lower odds of hepatic fibrosis (OR 0.83; 95% CI: 0.78–0.89; p < 0.001). Conclusions: Better CVH is related to lower odds of MASLD and significant hepatic fibrosis.

Objective: The study aimed to compare the cost‐effectiveness of various strategies for screening for MASLD‐related advanced hepatic fibrosis (fibrosis stage > 2) using the fibrosis‐4 index (FIB‐4) and liver stiffness measurement (LSM) by transient elastography (TE) in persons with obesity.Methods: We created a decision‐analytic model comparing three screening strategies: no screening, TE, and FIB‐4 followed by TE. We used a Markov transition model to track liver state, with prevalence and transition probabilities specific to the population with obesity. If MASLD was detected, patients were treated with resmetirom.Results: We found an incremental cost‐effectiveness ratio (ICER) of $234,781 (95% CI: $232,581, $235,608) when comparing TE to no screening with a 10‐year interval. We note the ICER of $234,673 (95% CI: $234,033, $235,072) when comparing TE to FIB‐4+TE. In multivariate simulations, we found no screening was most likely to be cost‐effective for willingness‐to‐pay for QALY below approximately $250,000.Conclusions: Our results suggest routine screening for MASLD in obesity clinics is not cost‐effective with resmetirom as the available treatment. A prescreening with FIB‐4 before TE did not increase economic efficiency.

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Background Fecal immunochemical test (FIT) is less effective in detecting advanced adenomas (AA) than colonoscopy. Increase in FIT for colorectal cancer (CRC) screening may lead to an increased number of undetected AAs which may develop into future CRCs. Aim We determined the potential impact of FIT expansion on missed AAs and future CRC diagnoses in an urban, tertiary-care, safety-net hospital. Methods CRC and AA diagnoses were identified in patients undergoing colonoscopy for average-risk CRC screening or positive FIT between 2017 and 2019 at Boston Medical Center. Poisson regression modeling was used to estimate the frequency of AAs per year by age group using data from 2017 to 2019, assuming average outpatient volume and proportion of screening colonoscopies. Total number of patients who received FIT was extrapolated from those who underwent colonoscopy for positive FIT. We estimated AAs per year if ‘one-time’ FIT was used for screening in 75% and 100% of the population and subtracted this from the estimated AAs per year under the Poisson model to determine missed AAs. We used previously described, age and gender specific estimates of the annual progression of AA to CRC. Results The estimated number of CRCs detected per year is 4.6/1785 males and 4.6/2086 females screened. With 75% FIT expansion, we estimate an additional 3.5 (95% CI 1.3, 9.5) and 2.2 (95% CI 0.64, 7.6) CRCs; with 100% FIT expansion, we estimate an additional 7.4 (95% CI 3.7, 14.9) and 4.2 (95% CI 1.7, 10.5) CRCs, in 5 years, in males and females, respectively. Conclusion Expansion of FIT may substantially increase CRC incidence. Graphical Abstract

Background: Acute variceal hemorrhage is a major decompensating event in patients with cirrhosis and is associated with high 6-week mortality risk. Many prognostic models based on clinical and laboratory parameters have been developed to risk stratify patients on index bleeding presentation, including those based on the Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP). However, consensus on model performance remains unclear. Methods: Using a large US multicenter cohort of hospitalized patients with cirrhosis who presented with acute variceal hemorrhage, this study evaluates, recalibrates, and compares liver severity index-based models, including the more recent MELD 3.0 model, to investigate their predictive performance on 6-week mortality. Models were also recalibrated and externally validated using additional external centers. Results: All recalibrated MELD-based and CTP-based models had excellent discrimination to identify patients at higher risk for 6-week mortality on initial presentation. The recalibrated CTP score model maintained the best calibration and performance within the validation cohort. Patients with low CTP scores (Class A, score 5–6) were strongly associated with < 5% mortality, while high CTP score (Class C, score > 9) were associated with > 20% mortality. Conclusion: Use of liver severity index-based models accurately predict 6-week mortality risk for patients admitted to the hospital with acute variceal hemorrhage and supports the utilization of these models in future clinical trials as well as their use in clinical practice. Export