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, which participates in the pathological process of a variety of inflammatory diseases. Immune and inflammatory responses participate in chronic liver injuries and fibrogenesis of various liver diseases including chronic hepatitis B (CHB) via activating hepatic stellate cells (HSCs), the key fibrogenic cells in the liver. It has been demonstrated that SAA induces inflammatory phenotype and promotes cell proliferation in activated HSCs. However, few studies have been reported on the serum levels of SAA in human liver diseases. It is of interest to investigate the diagnostic value and clinical significance of serum SAA level in patients with inflammatory liver diseases.
Few studies have been reported on the serum level of SAA and its clinical significance in human liver diseases. Yet many studies have demonstrated that the increase of serum SAA level is not only a consequence of inflammation or tissue injury, but also a promoting factor by itself to intensify the disease process. It has been reported that the transcription of SAA in the liver was significantly elevated in mouse models of liver fibrogenesis. SAA induces inflammatory phenotype and promotes cell proliferation in activated HSCs. The present study aimed at investigating the clinical significance of serum SAA levels in various liver diseases. The results will help to delineate whether SAA level may serve as an indicator of liver inflammation and fibrogenesis, and the potential impact of SAA on the diseases’ progression. The upstream regulation of SAA expression in various liver diseases will also be of great interest.
The main objective of this study was to investigate the serum levels of SAA in patients with various liver diseases, especially chronic hepatitis B, and analyze the factors associated with the alteration of SAA levels.
Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were enrolled in this study. The patients included 205 with chronic hepatitis B (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. The Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases and those of healthy controls. Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error. Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA levels. The 205 patients with CHB (59 active hepatitis and 146 inactive hepatitis) were divided into SAA ≥ 6.4 mg/L and SAA < 6.4 mg/L groups. The t-test or Chi-square test was used to perform single factor analysis of serum levels of SAA in patients with CHB. Then multivariate analysis was used to determine the independent risk factors for high serum levels of SAA in patients with CHB. Finally, the Spearman’s rank correlation test was used to determine correlation of SAA levels and CRP among patients with different liver diseases.
All patients except those with inactive CHB had higher serum SAA levels than healthy controls. Specifically, patients with pyogenic liver abscess had the highest SAA level (mean value: 398.4 ± 246.8 mg/L; median value: 413.5 mg/L). The serum SAA levels in patients with AILD, DILI, and pyogenic liver abscess were higher than those in patients with active CHB. Active CHB (χ2 = 16.78, P < 0.001, OR = 5.881), ALP ≥ 135 U/L (χ2 = 4.592, P = 0.032, OR = 4.093), and CRP ≥ 3 mg/L (χ2 = 17.01, P < 0.001, OR = 6.993) were associated with SAA levels higher than 6.4 mg/L. Active CHB (P = 0.039, OR = 6.222) was the independent factor associated with SAA serum levels higher than 6.4 mg/L by binary multivariate logistic regression analysis. Serum levels of SAA and CRP were positively correlated in patients with CHB (r = 0.620, P < 0.001), AILD (r = 0.504, P = 0.020), and pyogenic liver abscess (r = 0.508, P = 0.045). Serum levels of SAA (0.80-871.0 mg/L) displayed a broader fluctuation range than CRP (0.30-271.3 mg/L).
It was found in the present study that serum level of SAA is a sensitive biomarker for the inflammatory activity of pyogenic liver abscess, and to a lesser extent can reflect the mild inflammatory status of AILD, DILI, CHB, and NASH. SAA lacks specificity in the judgment of inflammatory diseases. It is therefore necessary to comprehensively consider the patient's systemic status before making judgment.
Previous studies and our data have showed that SAA participates in inflammatory response in human liver diseases. It may own an additional property to stimulate HSC activities during chronic liver injury and hepatitis. We speculate that SAA may be a potential fibrogenic factor that dynamically changes during liver fibrogenesis. The value of SAA detection in monitoring the prognosis of liver abscess and other liver diseases, the potential impact and underlying mechanisms of SAA on liver diseases’ progression, the upstream regulation of SAA expression in various liver diseases, and whether SAA may become a treatment target for inflammatory liver diseases warrant further investigation.