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Summary: Background: There are limited data on the prevalence and treatment of at‐risk metabolic dysfunction‐associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States. Aim: To estimate the prevalence of at‐risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies. Methods: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023. Metabolic dysfunction‐associated steatotic liver disease (MASLD) was defined by an magnetic resonance imaging proton density fat fraction ≥5% and at least one metabolic risk factor without any other chronic liver disease or secondary cause for hepatic steatosis. Results: We included 530 adult patients with T2DM. The mean (±SD) age and body mass index (BMI) were 64.4 (±8.1) years and 31.5 (±6.1) kg/m2, respectively. Among patients with T2DM, the prevalence of MASLD, at‐risk MASH and cirrhosis was 69.6%, 13.6% and 6.8%, respectively. Among patients with co‐existing T2DM and obesity, the prevalence of MASLD, at‐risk MASH and cirrhosis was 77.8%, 15.9% and 9.0%, respectively, and was higher than in participants without obesity (p < 0.0001, 0.0543 and 0.0128, respectively). Conclusion: Among adults aged ≥50 years with T2DM, the prevalence of MASLD, at‐risk MASH and cirrhosis is high, posing a significant risk for liver‐related morbidity and mortality. Approximately 14% of patients with T2DM may be candidates for pharmacologic therapies specific to MASH‐related fibrosis. [ABSTRACT FROM AUTHOR]

Summary Background Aims Methods Results Conclusions Genetic factors contribute to the risk and severity of metabolic dysfunction‐associated steatotic liver disease (MASLD). However, the utility of genetic testing in risk stratification remains poorly characterised.To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines.We prospectively enrolled adults aged ≥50 years with T2DM recruited from clinics. PRS was the sum of risk alleles in PNPLA3, TM6SF2 and SERPINA1 minus the protective variant in HSD17B13. We performed magnetic resonance elastography and vibration‐controlled transient elastography to assess for advanced fibrosis and cirrhosis.Of 382 included patients, the mean age and BMI were 64.8 (±8.4) years and 31.7 (±6.2) kg/m2 respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, p = 0.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis‐4 index (FIB‐4) index <1.3 (9.6% vs. 2.3%, p = 0.036) but was not significantly different in other FIB‐4 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk.Utilising a well‐phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at‐risk populations may improve risk prediction. [ABSTRACT FROM AUTHOR]

Summary: Background: Magnetic resonance imaging‐proton density fat fraction (MRI‐PDFF) is an excellent biomarker for the non‐invasive quantification of hepatic steatosis. Aim: To examine clinical and histologic factors associated with discordance between steatosis grade determined by histology and MRI‐PDFF in patients with non‐alcoholic fatty liver disease (NAFLD) Methods: We included 728 patients with biopsy‐proven NAFLD from UC San Diego (n = 414) and Yokohama City University (n = 314) who underwent MRI‐PDFF and liver biopsy. Patients were stratified by steatosis, and matched with MRI‐PDFF cut‐points for each steatosis grade: 0 (MRI‐PDFF < 6.4%), 1 (MRI‐PDFF: 6.4%–17.4%), 2 (MRI‐PDFF: 17.4%–22.1%), 3 (MRI‐PDFF ≥ 22.1%). Primary outcome was major discordance defined as ≥2 steatosis grade difference determined by histology and MRI‐PDFF. Results: Mean (±SD) age and BMI were 55.3 (±13.8) years and 29.9 (±4.9) kg/m2, respectively. The distributions of histology and MRI‐PDFF‐determined steatosis were 5.5% grade 0 (n = 40), 44.8% 1 (n = 326, 44.8%), 33.9% 2 (n = 247), and 15.8% 3 (n = 115) vs. 23.5% grade 0 (n = 171), 49.7% 1 (n = 362), 12.9% 2 (n = 94), and 13.9% 3 (n = 101). Major discordance rate was 6.6% (n = 48). Most cases with major discordance had greater histology‐determined steatosis grade (n = 40, 88.3%), higher serum AST and liver stiffness, and greater likelihood of fibrosis ≥2, ballooning ≥1 and lobular inflammation ≥2 (all p < 0.05). Conclusion: Histology overestimates steatosis grade compared to MRI‐PDFF. Patients with advanced NASH are likely to be upgraded on steatosis grade by histology. These data have important implications for steatosis estimation and reporting on histology in clinical practice and trials, especially in patients with stage 2 fibrosis. [ABSTRACT FROM AUTHOR]

Summary: Background: Variants in multiple genetic loci modify the risk of non‐alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis. Aim: To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis. Methods: This is a cross‐sectional analysis derived from a well‐characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE. Results: Two hundred sixty‐four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1‐8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2‐18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19‐0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype‐age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a −0.41 kPa (95% CI: −0.76 to −0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis. Conclusion: Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non‐invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk. [ABSTRACT FROM AUTHOR]