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Objective We aimed to explore the discrepancies in clinical features and outcomes between damp-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods We performed an analysis including 111 HBV-ACLF patients recruited from December 2017 to December 2021 in the Fifth Medical Center of Chinese PLA General Hospital. According to traditional Chinese medicine syndromes, these patients were divided into the dampness-heat stasis jaundice syndrome group (n = 90) and the qi- deficiency stasis jaundice syndrome group (n = 21). All patients adopt the standard internal medicine treatment plan. Baseline data, laboratory indicators, complications, and disease scores, including the model for end-stage liver disease (MELD), MELD-Na, and Acute-on-Chronic Liver Failure (ACLF) Research Consortium (AARC) scores, were recorded. All patients were followed up to 90 days after enrollment. We compared the baseline demographic characteristics, 90 d mortality, and complications of HBV-ACLF patients with different syndromes. The confounding factors were adjusted through Cox analysis to evaluate the impact of dampness-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome on the prognosis and the development of complications. Results There were differences in age, clinical indicators, and outcomes between HBV-ACLF patients with dampness-heat stasis jaundice syndrome group and the qi-deficiency stasis jaundice syndrome group. The patients with qi-deficiency stasis jaundice syndrome group had higher MELD scores, MELD-Na scores, and AARC scores. Compared to patients with dampness-heat stasis jaundice syndrome group, patients with qi- deficiency stasis jaundice syndrome group were older, had worse liver synthesis and reserve function of the liver, and had a milder inflammatory response, and the proportion of patients with cirrhosis was higher (P<0. 05). Patients with qi-deficiency stasis jaundice syndrome group had a higher cumulative mortality rate within 90 days than patients with dampness-heat stasis jaundice syndrome group (P = 0. 013). Qi-deficiency stasis jaundice syndrome was dependently associated with a higher mortality risk than dampness-heat stasis jaundice syndrome (HR = 1.57, P = 0. 014). Multivariate analysis showed that older age (HR = 1. 06, P = 0. 006), elevated total bilirubin levels (HR =1.11, P = 0. 003), hyponatremia (HR = 1. 86, P = 0. 004), renal dysfunction (HR = 3. 27, P = 0. 027), and a basis of cirrhosis (HR = 2. 12, P = 0.024) were risk factors for 90-day mortality, and elevated prothrombin activity (HR = 0.94, P = 0.007) was a protective factor for 90-day mortality in HBV-ACLF patients. Additionally, patients with qi-deficiency stasis jaundice syndrome group had higher rates of new-onset spontaneous bacterial peritonitis, hepatic encephalopathy, and renal insufficiency than those with dampness-heat stasis jaundice syndrome group within 90 days (P < 0.05). Conclusion Our study suggested that qi-deficiency stasis jaundice syndrome is more serious than damp-heat stasis jaundice syndrome. Our multivariate analysis indicated that patients with qi-deficiency stasis jaundice syndrome had higher rates of mortality, new-onset spontaneous bacterial peritonitis, hepatic encephalopathy, and kidney dysfunction than patients with damp-heat stasis jaundice syndrome. This study preliminarily demonstrated that dampness-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome may hold significant value for disease conditions and prognosis prediction for HBV-ACLF patients. [ABSTRACT FROM AUTHOR]