Elevated homocysteine level tied to higher NAFLD risk

Circulating homocysteine and folate concentrations appear to play a significant role in the development of nonalcoholic fatty liver disease (NAFLD), a study has shown.

A meta-analysis was performed on observational studies identified from three databases from inception to 7 April 2022 to examine the associations of serum homocysteine and folate concentrations with NAFLD. The researchers conducted Mendelian randomization (MR) analyses to strengthen the causal inference in these associations.

Subsequently, independent single-nucleotide polymorphisms with no linkage disequilibrium that had a robust association with serum homocysteine (n=13) and folate (n=2) concentrations were taken as instrumental variables from two meta-analyses of genome-wide association studies (GWAS) of 44,147 and 37,645 individuals of European ancestry, respectively.

The researchers then obtained data on NAFLD from a GWAS of 8,434 NAFLD patients and 770,180 controls of European ancestry. In addition, they included four liver enzyme as secondary outcomes from a GWAS of 361,194 individuals with European descent.

Twenty-two observational studies, including a total of 30,368 participants, met the eligibility criteria for the meta-analysis. A positive association was observed between serum homocysteine and NAFLD risk (n=20; odds ratio [OR], 1.96, 95 percent confidence interval [CI], 1.57‒2.45), while serum folate showed an inverse association with NAFLD risk (n=12; OR, 0.75, 95 percent CI, 0.58‒0.99).

MR analysis revealed ORs of 1.17 (95 percent CI, 1.01‒1.36) and 0.75 (95 percent CI, 0.55‒1.02) for every 1-standard deviation (SD) increase of genetically predicted circulating concentrations of homocysteine and folate, respectively.

Moreover, each 1-SD increment of genetically predicted circulating homocysteine and folate resulted in a change in alanine transaminase concentrations of 0.62 U/L (95 percent CI, 0.20‒1.04) and ‒0.84 U/L (95 percent CI, ‒0.14 to ‒1.54).

The findings of this study suggest for “future clinical exploration of the possibility of lowering homocysteine concentrations to prevent NAFLD,” the authors said.