Study Highlights Efficacy of ALT/HDL-C Ratio as Biomarker for NAFLD

Credit: PixaBay

The alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) ratio is positively associated with nonalcoholic fatty liver disease (NAFLD) and may be an effective biomarker for identifying NAFLD, according to a new study.

Using cross-sectional data from the NAGALA project, which contains data related to more than 20,000 people with risk factors for chronic diseases such as diabetes and NAFLD, the retrospective analysis showed a stronger association between the ALT/HDL-C ratio and NAFLD in subgroups based on age, sex, and abdominal obesity, also identifying the ALT/HDL-C ratio as an effective indicator of NAFLD risk with a suggested threshold of 15.97.¹

“Considering the current global pandemic of NAFLD which has caused a serious disease burden to society and individuals, in addition to making a breakthrough in the pathogenesis of NAFLD as soon as possible, we also need to develop simple indicators that can efficiently and quickly identify high-risk groups of NAFLD. These efforts are crucial for the prevention, management and treatment of NAFLD,” wrote investigators.¹

NAFLD affects up to 25% of people worldwide.² Imaging tests may reveal fat in the liver, although further evaluation with a biopsy is often needed to better assess fat, inflammation, and scarring. There are noninvasive alternatives to a liver biopsy, but a combination of tests are often recommended and liver biopsy may still eventually be necessary.³

To assess the association between the ALT/HDL-C ratio and NAFLD, Yang Zou, PhD, of the Jiangxi Provincial People's Hospital in China, and a team of investigators used data from 20,944 individuals from the NAGALA project undergoing health screenings at the Murakami Memorial Hospital Health Examination Center in Japan. The current study excluded participants who were diagnosed with liver diseases other than fatty liver at baseline, consumed alcohol at a rate of ≥210g/week for males or ≥140g/week for females at baseline, were diagnosed with diabetes or a fasting plasma glucose level exceeding 6.1mmol/L at baseline, had incomplete baseline data, were taking oral medication at baseline, or withdrew from the study for unknown reasons.¹

In total, investigators identified 14,251 participants for data analysis. Among the cohort, the average age was 43.53 years, 7402 (51.94%) participants were male, the mean ALT/HDL-C ratio was 15.43, and 2507 (17.59%) participants had NAFLD. Participants with ALT/HDL-C ratios >18.08 were more likely to be male (89.30%), smokers and drinkers, have MetS (19.54%), and have NAFLD (48.40%).¹

Logistic regression analysis showed a significant positive association between the ALT/HDL-C ratio and NAFLD when the ALT/HDL-C ratio was treated as a continuous variable in an unadjusted model (odds ratio [OR], 8.61; 95% confidence interval [CI], 7.80-9.51), stepwise adjusted models (OR, 3.30; 95% CI, 2.96-3.67; OR, 3.23; 95% CI, 2.90-3.60), and fully adjusted model (OR, 3.05; 95% CI: 2.63-3.53). Investigators noted when the ALT/HDL-C ratio was treated as a categorical variable, the OR gradually increased for NAFLD with increasing ALT/HDL-C ratio quartiles in both adjusted and unadjusted models, indicating a positive trend (All P-trend < .0001).¹

In subgroups stratified by gender, age, and waist circumference, investigators noted an increased prevalence of NAFLD among patients aged 44-59 years (20.35%), males (27.41%), and those with abdominal obesity (48.73%). After adjusting for variables across all subgroups, a stronger association between the ALT/HDL-C ratio and NAFLD was observed in the subgroup of individuals aged 45 years and above (OR 4.09; 95% CI, 3.29-5.09), males (OR 3.56; 95% CI, 3.05-4.16), and abdominal obesity (OR, 1.06; 95% CI, 1.05-1.08). Likelihood ratio tests showed significant interactions between these subgroups and the association (All P-interactions < .05).¹

Investigators performed receiver operating characteristic analysis to determine and compare the effectiveness of different ratios for identifying NAFLD. Results indicated ALT/HDL-C ratio had the highest area under the curve (0.8553) and specificity (0.7872), also significantly improving the discriminatory performance for NAFLD at a statistical level (P < .001) compared to ALT, HDL-C, the aspartate aminotransferase to HDL-C ratio, and the gamma-glutamyl transferase to HDL-C ratio. Based on these findings, investigators suggested an ALT/HDL-C ratio of 15.97 as a screening threshold for identifying NAFLD.¹

“The current study demonstrated for the first time the potential utility of the ALT/HDL-C ratio in identifying NAFLD,” investigators concluded.¹ “Future research could focus more on the association between the ALT/HDL-C ratio and IR, metabolic disorders, and obesity-related diseases to further validate its applicability in other conditions.”

References:

1. Qiu J, Kuang M, Yang R, et al. The newly proposed alanine aminotransferase to high-density lipoprotein cholesterol ratio has shown effectiveness in identifying non-alcoholic fatty liver disease. Front. Endocrinol. 14:1239398. doi:10.3389/fendo.2023.1239398
2. Cleveland Clinic. Non-Alcohol Related Fatty Liver Disease. Diseases & Conditions. Accessed September 21, 2023. https://my.clevelandclinic.org/health/diseases/22437-non-alcoholic-fatty-liver-disease
3. American College of Gastroenterology. Non-alcoholic fatty liver disease (NAFLD). Patients. Accessed September 21, 2023. https://gi.org/topics/fatty-liver-disease-nafld/