# Progression to Decompensation of Severe Fibrosis Compared to Cirrhosis in MASLD: A Systematic Review and Meta‐Analysis

## TL;DR

This study finds that people with F3 fibrosis in MASLD can progress to severe liver issues, like cirrhosis and cancer, similar to those with F4 fibrosis, though it takes longer.

## Contribution

The study provides a meta-analysis showing that F3 fibrosis in MASLD carries significant risks of decompensation and HCC, comparable to F4 fibrosis.

## Key findings

- F3 fibrosis in MASLD can progress to cirrhosis and decompensation in a significant proportion of patients.
- Hepatocellular carcinoma (HCC) can develop in F3 MASLD, especially in men.
- Patients with F3 fibrosis take roughly double the time to reach decompensation compared to those with F4 fibrosis.

## Abstract

Metabolic associated steatotic liver disease (MASLD) is increasing in prevalence worldwide. Clinical practice is focused on identifying those with cirrhosis and monitoring for complications such as varices and hepatocellular carcinoma (HCC). Non‐invasive tests of fibrosis differentiate between F3 and F4 fibrosis poorly. People with F3 fibrosis may progress and develop decompensated liver disease. The aim of this review is to examine the progression to decompensated liver disease in patients with F3 fibrosis compared to those with F4 fibrosis.

Searches were carried out in four databases; articles were screened by two independent reviewers against pre‐specified inclusion and exclusion criteria.

Twenty‐nine studies were included in the review: 12 with paired liver biopsies, 2 progression to cirrhosis, 13 progression to decompensation, 2 portal hypertension in F3 fibrosis and 13 on HCC in F3 fibrosis. Rates of progression on paired biopsies were 16%–30% over varied follow‐up. Varices were found in 16% of patients with F3 fibrosis and rates of non‐cirrhotic HCC varied from 37%–75%. Pooled univariate HR for F3 progression and F4 progression to major adverse liver outcomes (MALO) were 8.15 (95% CI 3.42–19.43) and 38.16 (95% CI 11.58–125.76), respectively.

Progression to cirrhosis and decompensation events occurs in a significant proportion of patients with F3 fibrosis in MASLD. There is evidence of portal hypertension and HCC developing in F3 MASLD. Further work to identify risk groups, including those at risk of rapid progression to guide future clinical management is urgently required given the prognostic inflection of decompensated disease.

Progression to cirrhosis and decompensation occurs in a significant proportion of patients with MASLD and F3 fibrosis.There is a risk of developing HCC in F3 MASLD, particularly in men.Clinically significant portal hypertension can develop in F3 MASLD.It takes roughly double the time for patients with F3 fibrosis to develop a decompensating event compared with those with F4 fibrosis.

Progression to cirrhosis and decompensation occurs in a significant proportion of patients with MASLD and F3 fibrosis.

There is a risk of developing HCC in F3 MASLD, particularly in men.

Clinically significant portal hypertension can develop in F3 MASLD.

It takes roughly double the time for patients with F3 fibrosis to develop a decompensating event compared with those with F4 fibrosis.