Genetic risk bolsters diet effects on hepatic steatosis, fibrosis

The effect of certain dietary patterns on liver fat content (LFC) and iron-controlled T1 time (cT1, a measure of liver inflammation and fibrosis) may be elevated among patients who are at greater genetic risk for steatotic liver disease (SLD), suggests a study. This indicates that dietary interventions can be of benefit in this population.

“Dietary patterns may influence [the] severity of hepatic steatosis and inflammation/fibrosis even more in people at increased genetic risk than in those at low or average risk, and thus those with elevated genetic risk for hepatic steatosis or inflammation/fibrosis may benefit more from following dietary recommendations,” the researchers said.

This study included 21,618 UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. Dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions served as the primary predictors. LFC was the primary outcome, while cT1 and liver-related events or mortality were secondary outcomes.

In noninteraction models, Mediterranean diet as well as intakes of fruits/vegetables/legumes and fish significantly correlated with a lower LFC, whereas higher consumption of red/processed meat and all genetic predictors correlated with a higher LFC. [J Hepatol 2024;81:379-388]

In interaction models, all genetic predictors were associated with Mediterranean diet and intakes of fruits/vegetables/legumes. Moreover, interactions were noted between steatosis polygenic risk score (PRS) and fish intake as well as the TM6SF2 genotype and red/processed meat intake to influence LFC.

The dietary effect on LFC were 3.8-fold higher in PNPLA3-rs738409-GG individuals than PNPLA3-rs738409-CC counterparts and 1.4‒3.0-fold higher in the top quartile of the steatosis PRS than the bottom quartile. Notably, gene-diet interactions were more robust among overweight individuals.

In addition, the steatosis PRS showed interactions with Mediterranean diet and intakes of fruits/vegetables/legumes to affect cT1, while most dietary and genetic predictors correlated with the risk of liver-related events or mortality by age 70 years.

“These results are relevant for patients and medical providers because they show that genetic risk is not fixed (ie, modifiable factors can mitigate or exacerbate this risk) and realistic dietary changes may result in meaningful improvement in liver steatosis and inflammation/fibrosis,” the researchers said.

Hepatic steatosis

Several studies observed the association of specific eating patterns, as measured by Mediterranean diet scales and the alternate healthy eating index, with decreased hepatic steatosis. [J Hepatol 2013;59:138-143; Gastroenterology 2018;155:107-117]

Other studies also reported that some dietary components such as high intake of red/processed meat, low dietary fibre intake, and sugar sweetened beverage consumption could increase hepatic steatosis. [Eur J Clin Nutr 2015;69:914-921; Hepatology 2020;71:1940-1952; Liver Int 2020;40:815-824; Nutrition 2019;62:32-38]

“Recent AASLD guidelines on the management of metabolic dysfunction-associated steatotic liver disease recommend weight loss but note that there is insufficient data to recommend any specific type of diet,” the investigators said. [Hepatology 2018;67:328-357]