Cholestatic pattern common in NAFLD, raises risk for adverse liver events

Patients with nonalcoholic fatty liver disease and liver-involved fibrosis frequently had a cholestatic pattern that increased the risk for liver-related events, according to a presentation at The Liver Meeting Digital Experience.

“While mild to moderate cytolysis with raised aminotransferase blood levels is a common feature of nonalcoholic fatty liver disease, an increase of [alkaline phosphatase] suggesting cholestasis is less frequently observed,” Grazia Pennisi, MD, of the section of gastroenterology and hepatology at University of Palermo, Italy, said during the presentation. “Prevalence and impact of a cholestatic pattern on the course of nonalcoholic fatty liver disease have not been assessed.”

In a multicenter cohort study, Pennisi and colleagues examined the prevalence of liver decompensation and hepatocellular carcinoma for up to 6 months in 582 patients with NAFLD, including 153 patients with a predominantly hepatocellular pattern (H), 157 patients with a predominantly cholestatic pattern (C) and 272 patients with a mixed pattern (M).

She noted F3 and F4 fibrosis were most common in patients with C pattern (55%) while only 26% of patients with H pattern and 37.5% of patients with M pattern had either stage. The C pattern group also had the most liver-related events with 51 patients; 15 patients with M pattern and only one with H pattern had any.

Age older than 55 years, low platelet count, low albumin, C pattern and F3 and F4 fibrosis were independently associated with liver-related events incidence. This remained true in the subgroup analysis of patients with F3 and F4 fibrosis.

Immunohistochemical analysis in 38 patients with F3 and F4 fibrosis revealed 58.3% of those with C pattern and 11.5% of those with H pattern had moderate- to high-grade ductular metaplasia with low-grade ductular proliferation.

In 14 patients whose gene expressions were analyzed, expression differed for NR1H3, RXRA and VCAM1 between the three patterns.

“In patients with nonalcoholic fatty liver disease, the presence of a cholestatic pattern, associated with specific changes of haptic morphology, predicts a higher risk of liver-related events,” Pennisi said. “Gene expression and immunohistochemical analysis, if externally validated, could contribute to identify new pathogenic mechanisms and potential target for therapeutic strategies of nonalcoholic fatty liver disease.”