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

Abstract

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.

This Is What Metabolic Dysfunction–Associated Steatotic Liver Disease Looks Like: Potential of a Multiparametric MRI Protocol

“…Additionally, MRI-PDFF is used in early clinical trials to assess treatment response [94][95][96] . On the other hand, lower liver fat in individuals with advanced fibrosis or cirrhosis was associated with worse outcome 97 . Therefore, MRE and gadoxetic acid-enhanced MRI may be more advisable for more advanced stages.…”

Epidemiology, natural history, and management of patients with CHB concurrent with MASLD

“…A cohort study from Hong Kong showed that reduced controlled attenuation parameter was an independent risk factor for HCC incidence, with a 10 dB/m lower controlled attenuation parameter increasing the risk of HCC by 6%. [9] Similarly, a meta-analysis of individual participants conducted by Lee SW et al [11] demonstrated that patients with NASH within low liver fat content group exhibited the highest incidence rate of decompensation and HCC compared to patients with NASH within the higher liver fat group. Low liver fat content was proved to be associated with the highest indication for the composite outcome of decompensation, HCC, and all-cause mortality.…”

Decreases in liver cT1 accurately reflect histological improvement induced by therapies in MASH: a multi-centre pooled cohort analysis

“…[23][24][25] MASH cirrhosis is characterised by progressive reduction in liver fat content as the fibrosis burden increases and consequently the development of cryptogenic cirrhosis. This is likely the main reason that liver fat content has not been shown to predict liverrelated outcomes 26,27 .…”