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Obesity increases risk for fibrosis progression in fatty liver disease

Obesity and weight gain correlated with an increased risk for fibrosis progression based on aspartate aminotransferase-to-platelet ratio in a large cohort study of adults with nonalcoholic fatty liver disease.

“Weight gain during adulthood is associated with higher leptin and lower adiponectin levels, possibly leading to the development of NASH,” Yejin Kim, MD, from the Kangbuk Samsung Hospital in South Korea, and colleagues wrote. “The protective effect of weight loss against fibrosis progression may relate to fat loss, by which the adverse impacts of excess adiposity may be diminished.”

Among a cohort of 40,700 Korean patients with NAFLD and low APRI, factors positively associated with weight change categories were male sex, current smoking, alcohol use and education level.

In contrast, factors inversely associated with weight change categories included hypertension, diabetes, history of cardiovascular disease, systolic and diastolic blood pressure, glucose, total cholesterol, triglycerides and homeostatic model assessment of insulin resistance (HOMA-IR).

In a multivariate analysis for APRI progression, the researchers compared weight loss and weight gain with weight stability through weight change quintiles. Researchers observed less APRI progression among patients in the first (HR = 0.68; 95% CI, 0.62-0.74) and second quintiles (HR = 0.86; 95% CI, 0.78-0.94) than in the fourth (HR = 1.17; 95% CI, 1.07-1.28) and fifth quintiles (HR = 1.71; 95% CI, 1.58-1.85). The significance did not change after adjusting for high sensitive C-reactive protein (hsCRP) and HOMA-IR.

Additionally, the researchers found that other metabolic factors such as increasing quintiles of triglyceride, uric acid and HOMA-IR, as well as decreasing quintiles of HDL cholesterol correlated with an increased risk for worsening APRI in a dose-response manner (P < .001).

“Although the mechanisms underlying the association between excessive adiposity or fat gain and the fibrosis progression are not yet fully understood, insulin resistance and inflammation are thought to be involved,” the researchers wrote. “However, after adjustment for HOMA-IR and hsCRP, the association between obesity, weight gain and fibrosis progression remained significant.”

Kim and colleagues also noted that weight change reflects a patient’s muscle structure and that sarcopenia has been shown to correlate with significant liver fibrosis in NAFLD. Therefore, they advise that other factors besides BMI should be considered in NAFLD cases, such as fat distribution and body composition. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.