Published online Nov 21, 2019. doi: 10.3748/wjg.v25.i43.6440
Peer-review started: June 26, 2019
First decision: August 28, 2019
Revised: September 23, 2019
Accepted: November 7, 2019
Article in press: November 7, 2019
Published online: November 21, 2019
Processing time: 151 Days and 23.1 Hours
Serum amyloid A (SAA) is an acute phase protein mainly synthesized by the liver. SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells, the major scar forming cells in the liver. However, few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases.
To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B (CHB) patients.
Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study. The patients included 205 with CHB, 22 with active autoimmune liver disease (AILD), 21 with nonalcoholic steatohepatitis (NASH), 14 with drug-induced liver injury (DILI), and 16 with pyogenic liver abscess. Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level. Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls. Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error (alpha = 0.05/6 = 0.008). For statistical tests of other variables, P < 0.05 was considered statistically significant. Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis.
All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients, with the highest SAA level found in patients with pyogenic liver abscess (398.4 ± 246.8 mg/L). Patients with active AILD (19.73 ± 24.81 mg/L) or DILI (8.036 ± 5.685 mg/L) showed higher SAA levels than those with active CHB (6.621 ± 6.776 mg/L) and NASH (6.624 ± 4.891 mg/L). Single (P < 0.001) and multivariate logistic regression analyses (P = 0.039) for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L. Serum levels of SAA and CRP (C-reactive protein) were positively correlated in patients with CHB (P < 0.001), pyogenic liver abscess (P = 0.045), and active AILD (P = 0.02). Serum levels of SAA (0.80-871.0 mg/L) had a broader fluctuation range than CRP (0.30-271.3 mg/L).
Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess. It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.
Core tip: Serum amyloid A (SAA) is an acute phase protein known to have diagnostic and prognostic value in many diseases. However, the SAA level and its clinical significance in various liver diseases have not been reported. Our study found that serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess, and to a less extent, to reflect mild inflammatory status in autoimmune liver diseases, drug-induced liver injury, chronic active hepatitis B, and nonalcoholic steatohepatitis. Serum level of SAA can be confounded by various inflammatory diseases, thus it is not a specific indicator for certain diseases.