Low liver fat in non‐alcoholic steatohepatitis‐related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality

• Published in: Alimentary pharmacology & therapeutics Vol. 59; no. 1; pp. 80 - 88
• Main Authors: Lee, Sung Won, Huang, Daniel Q., Bettencourt, Ricki, Ajmera, Veeral, Tincopa, Monica, Noureddin, Nabil, Amangurbanova, Maral, Siddiqi, Harris, Madamba, Egbert, Majzoub, Abdul M., Nayfeh, Tarek, Tamaki, Nobuharu, Izumi, Namiki, Nakajima, Atsushi, Yoneda, Masato, Idilman, Ramzan, Gumussoy, Mesut, Oz, Digdem Kuru, Erden, Ayse, Loomba, Rohit
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2024
• Subjects: Carcinoma, Hepatocellular - pathology; Cirrhosis; Elasticity Imaging Techniques; Fibrosis; Hepatocellular carcinoma; Humans; Liver; Liver - diagnostic imaging; Liver - pathology; Liver cancer; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - pathology; Magnetic Resonance Imaging; Mortality; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - pathology; Sensitivity analysis
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.17783

Summary Background Progression 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. Aim To investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH‐related significant fibrosis and cirrhosis. Methods In 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. Results The 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. Conclusions Low 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. Low 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.