Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study.

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60-80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60-80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.