Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease

Abstract

Background & aims: Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change.

Methods: Our study included 1521 participants who attended the seventh and eighth examinations (1998-2001 and 2005-2008) of the second-generation cohort or attended the first and second examinations (2002-2005 and 2008-2011) of the third-generation cohort in the Framingham Heart Study. The self-administered semiquantitative 126-item Harvard food frequency questionnaire was used to determine dietary intake in the year leading up to an examination. We assessed levels of liver fat using liver-phantom ratio (LPR) on computed tomography images from 2002 through 2005 and again from 2008 through 2011. LPR values are inversely related to liver fat: increased LPR indicates decreased liver fat. We examined associations of changes in 2 diet scores, the Mediterranean-style diet score (MDS) and Alternative Healthy Eating Index (AHEI), with changes in liver fat and new-onset fatty liver. We evaluated interactions between diet score change and a weighted genetic risk score for NAFLD, determined based on multiple single-nucleotide polymorphisms identified in genome-wide association studies of NAFLD. The primary outcome was change in LPR between baseline and follow-up measurement.

Results: For each 1 standard deviation increase in MDS, the LPR increased (meaning liver fat decreased) by 0.57 (95% confidence interval [CI] 0.27-0.86; P < .001) and the odds for incident fatty liver decreased by 26% (95% CI 10%-39%; P = .002). For each 1 standard deviation increase in AHEI, LPR increased by 0.56 (95% CI 0.29-0.84; P < .001) and the odds for incident fatty liver decreased by 21% (95% CI 5%-35%; P = .02). Increased diet scores were also associated with reduced odds of developing more-advanced fatty liver. Higher genetic risk scores were associated with increased liver fat accumulation in participants who had decreased MDS (P < .001) or AHEI scores (P = .001), but not in those with stable or improved diet scores (P for gene-diet interaction <.001).

Conclusions: In an analysis of participants in the Framingham Heart Study, increasing diet quality, determined based on MDS and AHEI scores, is associated with less liver fat accumulation and reduced risk for new-onset fatty liver. An improved diet is particularly important for individuals with a high genetic risk for NAFLD.

Keywords: Diet Quality; Fatty Liver; Prevention; Steatosis.

Figure 1

Association of change in Mediterranean-style diet (ΔMDS) and change in alternative healthy eating index (ΔAHEI) and incident fatty liver. Symbols and bars are odds ratios and 95% confidence interval. 1A is for ΔMDS and 1B is for ΔAHEI. Model adjusted for sex, age, baseline MDS or AHEI, baseline liver-phantom ratio, baseline AST/ALT ratio, energy intake, smoking, physical activity level, BMI, as well as change in smoking status, physical activity, and energy intake.

Figure 2

Predicted probability of incident fatty liver with elevated AST/ALT ratio (advanced NAFL) and incident fatty liver without elevated AST/ALT ratio (isolated NAFL) according to the change of diet quality. 2A for the Mediterranean-style dietary score (MDS) and 2B for the alternative healthy eating index (AHEI). Sample size was 1092, no fatty liver (N=912), isolated NAFL (N=122), and advanced NAFL (N=58). Model adjusted for sex, age, baseline MDS or AHEI, baseline liver-phantom ratio, baseline AST/ALT ratio, and baseline values of energy intake, smoking, physical activity level, BMI, as well as change in smoking status, physical activity, and energy intake.

Figure 3

Association between genetic risk score (GRS; tertile categories) and change in liver-phantom ratio across tertile categories of dietary score change. A is for Mediterranean-style dietary score (MDS) and B is for alternative healthy eating index (AHEI). Values of y-axis are mean change and 95% confidence interval in liver-phantom ratio (a lower value represent increase in liver fat accumulation). P-interaction and P-trend were calculated with adjustment for sex, age, and baseline values of liver-phantom ratio, dietary score (MDS or AHEI), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, smoking status, physical activity level, energy intake, BMI, as well as change in smoking status, physical activity, and energy intake.