NAFLD progression may raise ESLD risk

Histological disease progression in patients with nonalcoholic fatty liver disease (NAFLD) is significantly associated with a higher rate of developing incident end-stage liver disease (ESLD) but not with all-cause mortality, a study has shown.

Swedish adults with biopsy-confirmed noncirrhotic NAFLD and two or more liver biopsies >6 months apart (1969‒2017; n=718) were included in this study.

NAFLD was categorized at initial biopsy as simple steatosis, nonfibrotic steatohepatitis (NASH), or noncirrhotic fibrosis. NAFLD progression was characterized by histological changes between biopsies (ie, incident NASH, incident fibrosis, fibrosis progression, cirrhosis).

The investigators calculated the multivariable adjusted hazard ratios (aHRs) for incident ESLD (ie, hospitalization for decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation) and mortality, according to NAFLD progression vs stable/regressed disease, using Cox regression.

A total of 497 patients (69.2 percent) had simple steatosis, 90 (12.5 percent) had nonfibrotic NASH, and 131 (18.2 percent) had noncirrhotic fibrosis at initial biopsy. Over a median of 3.4 years between biopsies, 30.4 percent (218/718) had NAFLD progression, including 12.5 percent (62/497) with incident nonfibrotic NASH, 24.0 percent (141/587) with incident fibrosis, and 5.6 percent (40/718) with cirrhosis.

NAFLD progression, compared with stable or regressed disease, resulted in significantly higher rates of developing incident ESLD (23.8 vs 11.4/1,000 person-years; difference, 12.4/1,000 person-years; aHR, 1.65, 95 percent confidence interval [CI], 1.17‒2.32).

The highest incidence of ESLD occurred with progression to cirrhosis (difference vs stable/regressed disease, 56.3/1,000 person-years), but a significantly increased risk was observed with earlier transitions, including from simple steatosis to incident fibrosis (difference vs stable/regressed disease, 18.9/1,000 person-years)

On the other hand, all-cause mortality rates appeared to show no significant difference when comparing NAFLD progression with stable/regressed disease (difference, 4.7/1,000 person-years; aHR, 0.99, 95 percent CI, 0.78‒1.24).

“[T]he results from this study can help inform the optimal design of future NAFLD therapeutic trials, while also providing the necessary evidence base for public health policies focused on preventing the development and progression of NAFLD,” the investigators said.