Izumi, Namiki

SummaryBackground & AimsThe natural progression of hepatic decompensation in metabolic dysfunction‐associated steatotic liver disease (MASLD) is not well‐characterised. We aimed to describe it by conducting a retrospective analysis.MethodsThis longitudinal, retrospective analysis of well‐characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver‐related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured.ResultsOf the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow‐up of 3.2 years. Ascites was the most common first liver‐related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver‐related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy‐three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years.ConclusionThe most common first liver‐related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.

SummaryBackgroundProgression to cirrhosis in non‐alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH‐related significant fibrosis and cirrhosis is unclear.AimTo investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH‐related significant fibrosis and cirrhosis.MethodsIn this meta‐analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI‐derived protein density fat fraction (MRI‐PDFF) were enrolled, and 296 patients with longitudinal follow‐up were analysed. MRE combined with fibrosis‐4 (MEFIB‐index), and MRI‐PDFF were used to measure liver fibrosis and fat, respectively. MEFIB‐negative, MEFIB‐positive+ MRI‐PDFF ≥5% and MEFIB‐positive+ MRI‐PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death.ResultsThe rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB‐negative) group (0%, 1% and 2% respectively). In multivariable‐adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5–235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings.ConclusionsLow liver fat content in patients with burnt‐out NASH‐related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.

Summary Background There are limited data regarding the longitudinal association between MEFIB‐Index (MRE combined with FIB‐4) versus MAST‐Score (MRI‐aspartate aminotransferase) and hepatic decompensation. Aim To examine the longitudinal association between MEFIB‐Index versus MAST‐Score in predicting hepatic decompensation in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI‐PDFF and were followed for hepatic decompensation. Cox‐proportional hazard analyses were used to assess the association between MEFIB‐Index versus MAST‐Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. Results This meta‐analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB‐Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST‐Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow‐up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB‐Index [HR = 49.22 (95% CI: 6.23–388.64, p < 0.001)] and a positive MAST‐Score [HR = 3.86 (95% CI: 1.46–10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB‐Index ( c ‐statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST‐Score ( c ‐statistic: 0.81, SE = 0.03) ( p < 0.0001) in predicting hepatic decompensation. Conclusion A combination of MRI‐based biomarker and blood tests, MEFIB‐Index and MAST‐Score can predict the risk of hepatic decompensation in patients with MASLD.

Background and Aims: Magnetic resonance elastography (MRE) is an accurate, continuous biomarker of liver fibrosis; however, the optimal combination with clinical factors to predict the risk of incident hepatic decompensation is unknown. Therefore, we aimed to develop and validate an MRE-based prediction model for hepatic decompensation for patients with NAFLD. Approach and Results: This international multicenter cohort study included participants with NAFLD undergoing MRE from 6 hospitals. A total of 1254 participants were randomly assigned as training (n = 627) and validation (n = 627) cohorts. The primary end point was hepatic decompensation, defined as the first occurrence of variceal hemorrhage, ascites, or HE. Covariates associated with hepatic decompensation on Cox-regression were combined with MRE to construct a risk prediction model in the training cohort and then tested in the validation cohort. The median (IQR) age and MRE values were 61 (18) years and 3.5 (2.5) kPa in the training cohort and 60 (20) years and 3.4 (2.5) kPa in the validation cohort, respectively. The MRE-based multivariable model that included age, MRE, albumin, aspartate aminotransferase, and platelets had excellent discrimination for the 3- and 5-year risk of hepatic decompensation (c-statistic 0.912 and 0.891, respectively) in the training cohort. The diagnostic accuracy remained consistent in the validation cohort with a c-statistic of 0.871 and 0.876 for hepatic decompensation at 3 and 5 years, respectively, and was superior to Fibrosis-4 in both cohorts (p < 0.05). Conclusions: An MRE-based prediction model allows for accurate prediction of hepatic decompensation and assists in the risk stratification of patients with NAFLD.