Risk factors for post-hepatectomy liver failure following resection of primary hepatobiliary versus metastatic cancer

Abstract

Background: Post-hepatectomy liver failure (PHLF) is a significant source of morbidity and mortality following major hepatic resection. Prior studies evaluating risk factors for PHLF have focused on patients with primary liver malignancies, such as hepatocellular carcinoma (HCC), who often have associated underlying hepatic dysfunction. Hepatic dysfunction is less common in patients undergoing hepatectomy for metastatic disease and we hypothesized other risk factors may be associated with PHLF in this population. The aim of this study was to identify and compare pre-operative risk factors for PHLF between patients undergoing major hepatectomy for primary hepatobiliary (HPB) malignancy versus hepatic resection for metastatic disease. Methods: This study included patients who underwent elective major hepatectomy, defined as right-lobectomy or tri-segmentectomy, for primary HPB malignancy or metastatic disease from 2014–2016 from the National Surgical Quality Improvement Program (NSQIP) Hepatic database. The primary outcome was clinically significant PHLF (Grade B or C). Patient, disease, and pre-operative laboratory values were compared between patients with primary HPB malignancy or metastatic disease and their association with PHLF was evaluated. Separate multivariable logistic regression models for patients with primary HPB malignancy or metastatic disease were constructed to analyze risk factors for clinically significant PHLF and included all variables that were significant with an α less than 0.25 on univariate analysis. Results: From 2014–2016, 868 patients underwent major hepatectomy for primary HPB malignancy and 1,308 patients underwent major hepatectomy for metastatic cancer. Patients undergoing major hepatectomy for HPB malignancy were older (mean age 45.5 versus 40.5 years, p 10: 15.2% vs 4.7%, p < 0.001), and had lower pre-operative albumin levels (<3.5 g/dl: 18.6% vs 10.6%, p < 0.001) compared to those undergoing major hepatectomy for metastatic disease. PHLF occurred in 106 patients (12.2%) undergoing hepatectomy for HPB malignancy and in 71 patients (5.4%) undergoing hepatectomy for metastatic disease (p < 0.001). For patients with a primary HPB malignancy, low and high BMI (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.17-3.48 for <25 kg/m2, and OR, 2.49; 95% CI, 1.41-4.40 for ≥30 versus 25–29 kg/m2), cirrhotic liver texture (OR, 2.20; 95% CI, 1.15-4.24), MELD score ≥ 10 (OR, 1.86; 95% CI, 1.08-3.22), and diagnosis of gallbladder cancer and intrahepatic cholangiocarcinoma (IHC) (OR, 5.62; 95% CI, 2.01-15.71 for gallbladder cancer, and OR,1.85; 95% CI, 1.10-3.12 for IHC versus HCC) were associated with an increased odds of PHLF. For patients with metastatic disease, a diagnosis of diabetes (OR, 2.26; 95% CI, 1.22-4.18) and a pre-operative albumin <3.5 g/dl (OR, 2.51; 95% CI, 1.36-4.65) were associated with an increased odds of PHLF. Conclusion: Among patients who underwent major hepatectomy, the pre-operative risk factors for PHLF differ between patients with primary HPB malignancy and patients with metastatic cancer. While clinical factors such as a diagnosis of cirrhosis or an elevated MELD score are commonly used to identify patients at elevated risk for PHLF, neither MELD score nor cirrhosis are associated with PHLF in patients undergoing hepatectomy for metastatic disease as the incidence of these risk factors is very low in this population. In this study we identify diabetes and a low albumin level as independent factors strongly associated with an increased risk of PHLF in patients with metastatic cancer undergoing major hepatectomy, which should be considered in pre-operative planning and extent of hepatectomy for metastatic disease.