Increased thrombin generation is linked to first hepatic decompensation in patients with compensated cirrhosis

Background: Coagulation alterations may contribute to cirrhosis progression. We explored whether increased thrombomodulin-modified thrombin generation (TM-TG) was associated with first hepatic decompensation in compensated cirrhosis. Methods: We retrospectively analyzed a prospectively collected cohort of 171 patients with compensated cirrhosis. TM-TG was measured at enrolment. The primary endpoint was the first hepatic decompensation. Time-to-event analyses were performed using cause-specific Cox models, with Fine-Gray models as a complementary competing risk approach. Results: Median age was 66 years, 66.7% were male, and 90.1% were Child-Pugh A; 70 (40.9%) patients had large varices. During a median follow-up of 3.3 years, 37 patients (21.6%) developed first hepatic decompensation. The 1-year, 2-year, 3-year, and 5-year cumulative incidences were 4.7%, 11.5%, 17.8%, and 31.5%, respectively. Compared with patients who remained compensated, those who developed first hepatic decompensation had lower platelet count (56 vs. 111 × 109/L), higher MELD score (9.97 vs. 8.93), more frequent large varices (73% vs. 36%), higher ETP-TM (822 vs. 752 nM min), and more often an ETP ratio >0.80 (70.3% vs. 44.0%) (all p<0.05). In multivariable analyses, higher ETP-TM remained independently associated with first hepatic decompensation in models including MELD (HR 1.27; sHR 1.30), large varices (HR 1.24; sHR 1.30), and platelet count (HR 1.29; sHR 1.31) (all p<0.05). Similarly, an ETP ratio >0.80 was independently associated with first hepatic decompensation in models including MELD (HR 2.81; sHR 2.9), large varices (HR 2.96; sHR 2.7), and platelet count (HR 3.41; sHR 3.32) (all p<0.05). Conclusion: In compensated cirrhosis, increased TM-TG is associated with the first hepatic decompensation, although confirmation in prospective studies is warranted.