title: A Mechanistic Assessment of the Discordance between Normal Serum Alanine Aminotransferase Levels and Altered Liver Histology in Chronic Hepatitis B.
abstract: To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Xianqiong
authors.initials: X
authors.lastname: Gong
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Jiaen
authors.initials: J
authors.lastname: Yang
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Jinmo
authors.initials: J
authors.lastname: Tang
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Gu
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Huang
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liang
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Manying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Lab for Endogenous Infection, Shenzhen Nanshan Hospital, Shenzhen, Guangdong, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Qianguo
authors.initials: Q
authors.lastname: Mao
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D005260:Female; D019694:Hepatitis B, Chronic / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male
chemical_list: D000410:Alanine Transaminase