Abstract

Background: Patients with decompensated cirrhosis are frequently hospitalized and often undergo multiple invasive procedures. We aimed to define the incidence of procedural-related bleeding in patients with acute on chronic liver failure (ACLF) and to compare it with that of patients without ACLF.

Methods: Prospective, multi-center, international cohort study of hospitalized patients with cirrhosis undergoing non-surgical procedures. Patients were followed until 28 days from admission, death, liver transplantation, and/or undergoing surgery. Procedural bleeding was defined according to ISTH definitions and defined as major, clinically relevant non-major (CRNMB), and other. The risk of the procedure was judged to be low or high risk based on recent AASLD guidelines. ACLF at admission was defined according to European Foundation for the Study of Chronic Liver Failure.

Results: A total of 1,051 patients undergoing 2,688 non-surgical procedures were enrolled from 20 centers in North and South America. 224 (21.3%) of the patients enrolled had ACLF on admission versus 827 patients without ACLF on admission. At admission patients with ACLF more commonly had ascites, AKI and infection. Length of stay was longer in patients with ACLF (mean 17.4 days ACLF vs. 11.9 days non-ACLF) and they underwent more procedures while hospitalized (mean 3.3 ACLF vs. 2.3 non-ACLF). Proportion of high risk procedures in patients with ACLF was lower compared to patients without ACLF (4.9% ACLF vs. 10.5% non-ACLF, p <0.001). Prior to procedures coagulation parameters were significantly different in patients with ACLF ((platelets (k/uL) 100 ACLF vs. 116 non-ACLF p<0.001; INR 2.1 ACLF vs. 1.7 non-ACLF, p<0.001; fibrinogen (mg/dL) 181 ACLF vs 201 non-ACLF, p=0.005). Patients with ACLF were more likely to receive pre-procedure prophylaxis with platelet and plasma transfusion. A total of 76 procedural related bleeding events were identified in this cohort (25 major, 30 clinically relevant non-major, and 21 other bleeds). Bleeding was more prevalent in patients with ACLF compared to patients without ACLF (14.2% ACLF vs. 5.3%, p<0.001) with a relative risk of bleeding for patients of 2.69 [95% CI 1.74, 4.13] (See Table). Non-procedural related bleeding while hospitalized occurred more frequently in patients with ACLF (21% ACLF vs. 15% non-ACLF, p=0.035). Patients with ACLF had higher mortality and more commonly underwent liver transplantation during 28-day follow up.

Conclusion: Prior studies have demonstrated patients with ACLF have unique hemostatic profiles compared to patients with decompensated cirrhosis. Patients with ACLF are more likely to develop procedural related bleeding despite undergoing lower risk procedures more commonly compared to patients with decompensated cirrhosis without ACLF. Factors which may explain this observation include increased number of procedures, comorbidities, and severity of liver disease.