Clinical Efficacy and Safety of Anticoagulation Therapy for Pyrrolizidine Alkaloids-Induced Hepatic Sinusoidal Obstruction Syndrome: A Retrospective Multicenter Cohort Study

Objectives: Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) has been reported to have high mortality. Limited data were available about the outcomes of anticoagulation therapy in PA-HSOS. We aimed to evaluate the efficacy and safety of anticoagulation therapy for the patients with PA-HSOS and also to explore the possible predictors for anticoagulation efficacy. Methods: We collected clinical data on a total of 249 PA-HSOS patients from January 2012 to December 2017 at 4 tertiary care hospitals in China. 151 patients received anticoagulation therapy plus symptomatic treatment, and 98 patients received symptomatic treatment. The efficacy and safety outcomes were analyzed using Fine and Gray competing risk analysis method and Cox regression model. The predictors for complete response to anticoagulation therapy in PA-HSOS patients were investigated using clinical data. Results: The cumulative complete response rate was higher in the anticoagulation group than in the supportive group (60.9% vs36.7%, adjusted HR, 4.51; p<0.0001). The cumulative mortality was 12.6% in the anticoagulation group compared with 43.9% in the supportive group (adjusted HR, 0.07; p<0.0001). In subgroup analysis, for mild, moderate, severe, and very severe groups, the adjusted HRs (95% CI) for complete response rates were 7.05 (3.00-16.59), 5.26 (2.31-12.42), 2.59 (0.85- 7.87), and 2.05 (0.61-6.92), respectively; and the adjusted HRs (95% CI) for mortalities were 0.02 (0.01-0.09), 0.04 (0.01-0.14), 0.19 (0.01- 3.98), and 0.07 (0.02-1.27), respectively (p<0.0001 for the interaction test). Lower total bilirubin level (HR 0.98) and longer treatment duration (HR 1.27) predicted higher complete response rates of anticoagulation therapy. Conclusions: Anticoagulation therapy improves clinical remission and the survival in selected patients with mild or moderate PA-HSOS. Anticoagulation therapy has a similar safety profile to supportive therapy. Trial Registration: The study was registered in the chictr.Org database (ChiCTR1800017775). Funding Statement: National Natural Science Foundation of China (No. 8157040652) and Nanjing Medical Science and technique Development Foundation (No. QRX17037). Declaration of Interests: All authors report no relevant financial or personal conflicts of interest. Ethics Approval Statement: This is a retrospective, multicenter cohort study conducted at four Chinese tertiary care hospitals. This study was approved by local ethic committees.