Administration of Antithrombin III Attenuates Posthepatectomy Liver Failure in Hepatocellular Carcinoma

Abstract

Background/Aims: Coagulopathy can cause disseminated intravascular coagulation and posthepatectomy liver failure. Posthepatectomy liver failure predicts a poor prognosis after hepatectomy for hepatocellular carcinoma. Although antithrombin III reduces hypercoagulation, the impact of postoperative antithrombin III administration remains unknown. The aim of this study was to determine whether postoperative antithrombin III administration protects against the development of coagulation disorders. Methods: Data from 164 patients who received antithrombin III and 169 who did following curative hepatectomy for hepatocellular carcinoma were retrospectively collected and analyzed. To overcome bias due to different distributions of covariates for the two groups, a one-to-one match was created using propensity score analysis. After matching, patient outcomes were analyzed. Results: A multivariate analysis of the whole group revealed that antithrombin III activity of <50% on postoperative day 1 was an independent risk factor for posthepatectomy liver failure. After one-to-one matching, the rate of posthepatectomy liver failure was significantly lower in the AT-III-treated group than in the non-AT-III-treated group (16.3% (7/43) vs. 44.2% (19/43), p < 0.01). Conclusions: Antithrombin III may attenuate posthepatectomy liver failure in hepatocellular carcinoma, possibly by suppressing coagulopathy.

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

“…As IGF-I is known to be centrally involved during liver regeneration[42] ATIII might potentially act as an inducer of hepatic regeneration. In this context, we would like to point out that recently clinical data on the beneficial effect of postoperative ATIII administration was reported by Kuroda et al[16]. Patients that received ATIII substitution after curative resection for HCC had a significantly lower risk of postoperative LD, suggesting a potential role of ATIII during liver regeneration.…”

“…Taken together, to our knowledge this study presents the first clinical evidence for a fundamental impact of ATIII-activity on postoperative risk stratification in a routine clinical setting of patients undergoing curative liver resection, while given clinical evidence primarily relays on HCC patients[14–16]. Postoperative ATIII-activity was found to be a valuable and independent predictor for postoperative LD and poor clinical outcome after hepatic resection.…”

“…However, this hypothesis needs further investigation. This is of specific clinical interest, as therapeutic efficiency of postoperative ATIII substitution might not be limited to HCC patients as reported previously[16], but be presumably beneficial in all patients undergoing liver resection independent of underlying liver disease.…”

“…Patients that received ATIII substitution after curative resection for HCC had a significantly lower risk of postoperative LD, suggesting a potential role of ATIII during liver regeneration. However, the authors hypothesized that ATIII might reduce incidences of LD through a suppression of coagulopathies[16]. Previously it was shown that ATIII reduces ischemia/reperfusion injury in a rodent model[40].…”

“…Furthermore, levels of ATIII have been shown to be altered in patients with liver disease[12, 13]. Recently, ATIII was reported to be a valuable marker for clinical outcome in hepatocellular carcinoma (HCC) patients undergoing curative intended liver resection[14–16]. In particular, ATIII has been proposed as a marker for overall and progression free survival in HCC patients[14].…”