Serum Nutritional Markers as Prognostic Factors for Hepatic and Extrahepatic Carcinogenesis in Japanese Patients with Nonalcoholic Fatty Liver Disease

Serum zinc (Zn) levels and the branched chain amino acid/tyrosine molar ratio (BTR) were reported to decrease with the progression of various chronic liver diseases. We investigated the impact of BTR and Zn on the incidence of malignancies in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). A total of 179 Japanese NAFLD patients who underwent liver biopsy were enrolled. Hepatocellular carcinoma (HCC) and extrahepatic malignancies developed in 7 (3.9%) and 10 (5.6%) patients, respectively, during the follow-up period (median 7.9 years). Patients with low BTR levels (<5.0) and Zn deficiency (<70 μg/dL) had significantly higher incidences of HCC and extrahepatic malignancies (P < 0.001 and 0.026), respectively. Multiple logistic regression analyses revealed the following risk factors: liver fibrosis (F3–4) (hazard ratio [HR] 24.292, 95% confidence interval [CI] 2.802–210.621, P = 0.004) and BTR < 5.0 (HR 5.462, 95% CI 1.095–27.253, P = 0.038) for HCC, and serum Zn level <70 μg/dL (HR 3.504, 95% CI 1.010–12.157, P = 0.048) and liver inflammation (A2–3) (HR 3.445, 95% CI 0.886–13.395, P = 0.074) for extra-hepatic malignancies. In conclusion, serum BTR and Zn levels were useful for predicting HCC and extrahepatic malignancies in NAFLD, respectively.