Parental Non-alcoholic Fatty Liver Disease Increases Risk of Non-alcoholic Fatty Liver Disease in Offspring

Michelle T. Long; Ellen B. Gurary; Joseph M. Massaro; Jiantao Ma; Udo Hoffmann; Raymond T. Chung; Emelia J. Benjamin; Rohit Loomba

Disclosures

Liver International. 2019;39(4):740-747. 

In This Article

Abstract and Introduction

Abstract

Background & Aims: Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography.

Methods: We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ≥30 kg/m2). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included.

Results: Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78).

Conclusions: Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.

Introduction

Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, is characterized by hepatic steatosis in the absence of excess alcohol intake or other causes.[1,2] In a minority of individuals, hepatic steatosis can progress to steatohepatitis and fibrosis though it is not fully understood why some people develop liver fibrosis and others have a relatively benign disease course.[3] Hepatic steatosis is associated with features of the metabolic syndrome, including obesity, insulin resistance, hypertension, and dyslipidemia; however, these traits alone are not sufficient to produce hepatic steatosis.[4] Recent genetic association studies have suggested an association between the patatin-like phospholipase domain-containing 3 (PNPLA3) genotype, among others, and hepatic steatosis.[5–11] However, the PNPLA3 genotype explains only 10-12% of the variance in the trait;[9] therefore, there remains much to be discovered regarding the genetic susceptibility to hepatic steatosis.

To date, there has been limited investigation regarding the risk of hepatic steatosis among children of affected parents. Prior studies utilizing twin cohorts suggest hepatic steatosis is heritable; however, these studies have been limited by relatively small sample sizes or the use of serum aminotransferase levels as a surrogate for hepatic steatosis.[12–14]

We examined the association between parental hepatic steatosis and risk of hepatic steatosis in offspring by utilizing the multigenerational Framingham Heart Study cohorts which characterized hepatic steatosis using computed tomography. We hypothesized that offspring with one or more parents with hepatic steatosis will have an increased odds of hepatic steatosis. Further, we hypothesized that this relationship would be maintained after adjusting for potential confounding factors including body mass index (BMI).

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