Predictive role of hepatic venous pressure gradient in bleeding events among patients with cirrhosis undergoing orthotopic liver transplantation

Abstract

Background & aims: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis.

Methods: We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event.

Results: The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG <16 mmHg), high-risk (HVGP ≥16 mmHg), and very high-risk (HVPG ≥20 mmHg).

Conclusions: HVPG predicted major bleeding events in patients with cirrhosis undergoing OLT. Including HVPG as part of pre-transplant assessment might enable better anticipation of the intraoperative course.

Impact and implications: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes but the proportion of this risk related to portal hypertension is unclear. Our work shows that hepatic venous pressure gradient (HVPG), the gold standard for estimating portal hypertension, is a strong predictor of major bleeding events and blood loss volume in patients with cirrhosis undergoing OLT. Three groups of patients can be identified according to their risk of major bleeding events: low-risk patients with HVPG <16 mmHg, high-risk patients with HVPG ≥16 mmHg, and very high-risk patients with HVPG ≥20 mmHg. HVPG could be systematically included in the pre-transplant assessment to anticipate intraoperative course and tailor patient management.

Keywords: bleeding; cirrhosis; hepatic venous pressure gradient; liver transplantation; portal hypertension; pre-transplant assessment.

Graphical abstract

Fig. 1

Heatmap showing the prevalence of the primary endpoint according to the HVPG and MELD score thresholds. The color of the boxes represents the prevalence of the primary endpoint in each sub-population according to the threshold categories of HVPG and MELD. The number of patients in each sub-population according to HVPG and MELD threshold categories is indicated (n). The primary endpoint was the occurrence of an intraoperative major bleeding event defined by the association of (i) significant intraoperative bleeding, namely blood loss ≥1,000 ml and/or RBC transfusion >2 U; associated with (ii) significant hemodynamic failure, namely intraoperative maximum norepinephrine dose ≥0.6 μg kg^-1.min^-1. HVPG, hepatic venous pressure gradient (mmHg); MELD, model for end-stage liver disease.

Fig. 2

Effect of HVPG on the risk of major intraoperative bleeding event and on intraoperative blood loss volume. (A) Impact (odds ratio) of different HVPG cut-offs on the risk of major intraoperative bleeding events using logistic regression. Major intraoperative major bleeding event was defined by the association of (i) significant intraoperative bleeding, namely blood loss ≥1,000 ml and/or RBC transfusion >2 U; associated with (ii) significant hemodynamic failure, namely intraoperative maximum norepinephrine dose ≥0.6 μg kg^-1.min^-1. (B) Correlation between different HVPG cut-offs and intraoperative blood loss volume using a linear regression model. Red circles and bars represent mean (SEM). HVPG, hepatic venous pressure gradient; RBC, red blood cell.

Fig. 3

Effect (OR) of HVPG on the risk of major intraoperative bleeding event among different subpopulations. Logistic regression used. Results are presented as OR [95% CI]. Major intraoperative major bleeding event was defined by the association of (i) significant intraoperative bleeding, namely blood loss ≥1,000 ml and/or RBC transfusion >2 U; associated with (ii) significant hemodynamic failure, namely intraoperative maximum norepinephrine dose ≥0.6 μg kg^-1.min^-1. ACLF, acute-on-chronic liver failure; ALD, alcohol-related liver disease; HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease; Met-ALD, MASLD and increased alcohol intake; OR, odds ratio; RBC, red blood cell; SLD, steatotic liver disease., ,