First and further liver decompensation in patients with metabolic-dysfunction associated steatotic liver disease: what clinical impact?

Background/Aims We investigated the incidence of first and further decompensation and their impact on mortality in patients with compensated advanced chronic liver disease (cACLD) due to metabolic-dysfunction associated steatotic liver disease (MASLD). Methods Data from Italian patients at the first diagnosis of MASLD-related cACLD (that is, F3-F4 fibrosis at histology and/or liver stiffness measurement >10 KPa) were retrospectively reviewed and analyzed. The cumulative incidence of first decompensation, further decompensation (development or recurrence of a second decompensating event), and death was assessed. Clinical events of first decompensation were discriminated as acute or non-acute according to a recent, not yet validated, proposal of decompensated cirrhosis classification. Results 1,140 patients with MAFLD-related cACLD were enrolled (56.7% males, mean age 43 years, 56.3% obese, 64.5% diabetic). In a mean follow-up of 108 months 844 patients did not develop decompensation and 6.3% of them died; among the 296 patients (25.9%) who experienced first decompensation the raw rate of mortality was 25.9% (p<0.001). First decompensation was acute in 48.9% and non-acute in 51.1% of cases. Overall, in this group the mortality rate was slightly higher, but not statistically significant, in patients with further decompensation compared to those without (40.3% vs 35.3%, p=0.38). After patient stratification for the type of first decompensation, further decompensation increased the risk of mortality in patients with non-acute first decompensation (46.8% vs 36.7% in those without further decompensation), but not in those with acute first decompensation (33.8% vs 33.7% in those without further decompensation). The present analysis will be refined by including data about 4,000 other patients from international cohorts and by considering hepatic and extrahepatic competing risks. Conclusion In MAFLD-related cACLD with non-acute first decompensation, a significant increase in mortality is associated to the development of further decompensation.