# Etiology of cirrhosis is associated with risk of hepatic decompensation and hepatocellular carcinoma

## TL;DR

This study finds that non-viral causes of cirrhosis are linked to a higher risk of liver complications but a lower risk of liver cancer compared to viral causes.

## Contribution

The study identifies how the shift from viral to non-viral cirrhosis etiologies affects liver-related complications and cancer risk.

## Key findings

- Metabolic and alcohol-related cirrhosis are associated with higher rates of liver decompensation.
- Non-viral cirrhosis is linked to lower hepatocellular carcinoma incidence compared to viral cirrhosis.
- The study predicts a rising burden of liver decompensation as non-viral causes become more common.

## Abstract

The impact of the changing epidemiology from viral to non-viral etiologies of cirrhosis on the burden of liver-related complications remains unclear.

We conducted a retrospective cohort study of adult patients with cirrhosis and an index outpatient visit between January and December 2015 at two U.S. health systems. We excluded patients with a history of hepatocellular carcinoma (HCC) or both prevalent ascites and hepatic encephalopathy. Fine-Gray sub-distribution hazard models were used to characterize time-to-incident hepatic decompensation and incident HCC through 2020, with liver transplantation and death as competing events, and multivariable Fine-Gray regression was used to identify associated factors.

We identified 1029 patients (median age 58 years, 54.9% male, 19.5% non-Hispanic White). Over a median follow-up of 84.7 months, 36.4% developed incident hepatic decompensation (46.7% ascites, 21.1% hepatic encephalopathy, and 32.3% ascites plus hepatic encephalopathy), 14.5% developed HCC, 2.0% underwent transplant, and 23.0% died. The cumulative 1-, 2-, and 3-year incidence of hepatic decompensation were 7.0%, 10.8%, and 16.3% and incidence of HCC were 3.0%, 5.0%, and 6.9%, respectively. Compared to viremic hepatitis C, higher risk of hepatic decompensation was associated with metabolic dysfunction-associated steatotic liver disease (MASLD) (sHR 1.52, 95% CI 0.94 - 2.45) and alcohol-associated cirrhosis (sHR 1.68, 95%CI 1.10 - 2.57), while incident HCC was inversely associated with MASLD (sHR 0.27; 95% CI 0.12–0.59) and alcohol-associated cirrhosis (sHR 0.45; 95% CI 0.23–0.84).

Increasing proportions of non-viral liver disease will likely lead to a greater burden of hepatic decompensation and reduced HCC in contemporary populations.

The online version contains supplementary material available at 10.1186/s12876-025-04538-y.