Natural history of patients with NAFLD-associated compensated advanced chronic liver disease stratified according to severity of portal hypertension

Background and Aims  NAFLD is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG). In NAFLD-ACLD decompensation may occur at lower HVPG thresholds than in other ACLD etiologies. Here we investigate the clinical course of strictly compensated NAFLD-ACLD patients according to severity of PH.

Method  In this European multicentre study, NAFLD-cACLD patients were characterized by HVPG at baseline. Patients with any previous decompensation, hepatocellular carcinoma and portal vein thrombosis were excluded. First occurrence of hepatic decompensation or liver-related death defined the composite study endpoint.

Results  342 patients with NAFLD-cACLD (median MELD 8, median HVPG 11 mmHg) were included. CSPH (HVPG≥10 mmHg) was present in 210 patients (61.4%) including 71 patients with severe PH (HVPG ≥16mmHg; PH16; 20.8%). Median BMI was 31.7, with a significantly lower BMI in the CSPH group (p=0.011). During a median follow-up of 41.5 months, 85 (24.9%) patients developed liver-related events: 36 (10.5%) ascites, 23 (6.7%) hepatic encephalopathy, 16 (4.7%) variceal bleeding and 10 (2.9%) liver-related death.CSPH (SHR: 4.81, p<0.001) and PH16 (SHR: 6.44, p<0.001) represented significant risk factors for developing decompensation or liver-related death. Importantly, NAFLD-cACLD patients developed decompensation even without CSPH with a rate of 1.5% within the first year (Y1) and 3.3% within Y2. Variceal bleeding did not occur in patients without CSPH. With increasing severity of PH (HVPG 10-15 / ≥16 mmHg) the cumulative incidence rates for developing first hepatic decompensation gradually increased: Y1: 2.2% / 8.7%, Y2: 10.7% / 13.5%, Y5 36.3% / 50.3%.

Conclusion  CSPH is strongly linked to the incidence of hepatic decompensation in NAFLD-cACLD. Decompensation, however, may also occur, albeit at low rates, at HVPG<10mmHg, suggesting an underestimation of PH severity by HVPG. Nevertheless, HVPG represents an important risk stratification tool in NAFLD-cACLD patients.

Publication History

Article published online:
24 May 2023