Abstract
Background and aimsFibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD). We evaluate the association between baseline insulin resistance and future fibrosis progression in patients with NAFLD without diabetes.Approach and resultsThis retrospective longitudinal study with 8-year follow-up period included 32,606 (men, 83%) participants aged >20 years (average age, 38.0 years) without diabetes at baseline who completed at least two comprehensive health checkups from January 1, 2010 to December 31, 2018. NAFLD was diagnosed based on ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate baseline insulin resistance. Fibrosis progression was assessed using the aspartate aminotransferase to platelet ratio index (APRI). The advanced liver fibrosis with an APRI value above the intermediate fibrosis probability (≥0.5) developed in a total of 2,897 participants during 136,108 person-years. 114 participants progressed to a high fibrosis probability stage (APRI >1.5) during 141,064 person-years. Using the lowest baseline HOMA-IR quartile group (Q1) as a reference, the multivariate-adjusted hazard ratio (HR) for development of advanced liver fibrosis (APRI ≥0.5) in the highest baseline HOMA-IR quartile group (Q4) was 1.95 (95% confidence interval [CI] 1.74–2.19; Model 4). And the HR for development of advanced liver fibrosis with high fibrosis probability was 1.95 (95% CI 1.10–3.46; Model 4). The positive association was maintained throughout the entire follow-up period. The baseline HOMA-IR model was superior to the baseline body mass index (BMI) model in predicting the progression of fibrosis probability.ConclusionsIn this longitudinal study, we found that the degree of baseline insulin resistance, assessed by HOMA-IR values, was positively associated with future fibrosis progression in patients with NAFLD without diabetes.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common liver-related disease worldwide and is increasing in proportion to the growing population with obesity and metabolic syndrome [1]
We found that the degree of baseline insulin resistance, assessed by homeostasis model assessment of insulin resistance (HOMA-IR) values, was positively associated with future fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) without diabetes
As baseline HOMA-IR quartile increased, the levels of baseline metabolic parameters and lifestyle conditions associated with increased IR or NAFLD progression were increasingly unfavorable except for smoking status (Table 1) [2, 4, 7]
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common liver-related disease worldwide and is increasing in proportion to the growing population with obesity and metabolic syndrome [1]. Given that there is currently no established medical treatment for biopsy-proven NASH and liver fibrosis other than lifestyle modification, it is very important to prevent progression in the early stages of NAFLD [2, 7]. From this point of view, finding a simple and reliable metabolic factor capable of predicting the progression of fibrosis in patients with NAFLD is a major concern for clinicians. Fibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD).
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