Background: Nonalcoholic fatty liver disease (NAFLD), a complication frequently coexisting with diabetes, is at high risk of progression to nonalcoholic steatohepatitis (NASH), cirrhosis, liver failure, and hepatocellular carcinoma. Advanced NASH and advanced hepatitis C have poor prognoses, and therapeutic intervention is limited. In contrast, NAFLD may be related to serum lipoprotein(a) (Lp[a]) levels. However, the association between serum Lp(a) levels and progression of NAFLD to NASH remains unknown. We therefore investigated this issue among patients with biopsy-proven NAFLD.

Methods: We enrolled 136 patients with biopsy-proven NAFLD (nonalcoholic fatty liver [NAFL], 20 patients; stage 1, 29 patients; stage 2, 32 patients; stage 3, 26 patients; stage 4, 29 patients), and classified them into the advanced NASH group (stages 3 and 4) and the non-advanced group (NAFL, and stages 1 and 2). Serum Lp(a) levels were measured using the turbidimetric latex agglutination method, and data were divided into tertiles.

Results: In total, 76.5% and 47.2% of the patients were diabetic in the advanced NASH group and the non-advanced group, respectively. Serum Lp(a) levels in the advanced NASH group were significantly lower than those in the non-advanced group (P = 0.009). Multivariate analysis, adjusted for age, sex, body mass index, diabetes mellitus, dyslipidemia, and hypertension, showed that lower serum Lp(a) levels were significantly associated with a higher prevalence of advanced NASH; the adjusted odds ratios (95% confidence intervals) for advanced NASH in relation to serum Lp(a) levels of ≤6.1, 6.2-13, and ≥13.1 mg/dL were 1.00 (reference), 0.333 (0.14-0.791), and 0.341 (0.124-0.937), respectively (P for trend = 0.004).

Conclusions: It was concluded that lower levels of serum Lp(a) could be a significant risk factor for advanced NASH and that serum Lp(a) levels may be a useful tool for distinguishing between NASH and NAFL.


K. Konishi: None. T. Miyake: None. H. Senba: None. S. Yamamoto: None. S. Furukawa: None. T. Watanabe: None. Y. Koizumi: None. O. Yoshida: None. M. Hirooka: None. T. Kumagi: None. M. Abe: None. B. Matsuura: None. Y. Hiasa: None.

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