RT Journal Article
SR Electronic
T1 Higher activity of alcohol dehydrogenase is correlated with hepatic fibrogenesis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.118.249425
DO 10.1124/jpet.118.249425
A1 Na Gao
A1 Jing Li
A1 Ming-rui Li
A1 Bing Qi
A1 Zhao Wang
A1 Gao-ju Wang
A1 Jie Gao
A1 Hai-ling Qiao
YR 2018
UL http://jpet.aspetjournals.org/content/early/2018/09/18/jpet.118.249425.abstract
AB Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC). Prevention, stabilization and reversal disease progression is vital for patients with hepatofibrosis, and identifying risk factors for hepatofibrosis is urgently needed. This study examines the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers from HCC patients (n=88) with comparison to the activities found in patients with normal livers (n=74). A fibrosis-carcinoma rat model was used to study activity of ADH in fibrosis and HCC, and relationship between innate ADH activity and extent of hepatofibrosis or HCC. There was substantial inter-individual variation in the activities of ADH and ALDH in normal livers. The activities of total ADH, ADHI and ADHII in fibrotic livers were significantly higher than that in normal liver (P < 0.001), while the activity of ALDH was slightly higher. The positive rates of ADHI and ADHII were 84.1% and 77.3%; the area under the receiver operator characteristics (ROC) curve was 0.943 and 0.912, respectively. For the rat model as compared to the control, ADH activity in liver was significantly increased at the fibrotic and HCC stages and there was no significant difference between ADH activity in liver at these two stages. The innate activity of ADH in serum was well correlated with the extent of hepatofibrosis as indicated by Masson area%, Ki67+%, PCNA+%, and GST-p average density at fibrotic stage but not at HCC stage. Higher activity of ADH is a risk factor for hepatofibrogenesis and it might be a prevention target for hepatofibrosis.