Hepatic Resection for Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of 7226 Patients

Michele Molinari; Christof Kaltenmeier; Patrick-Bou Samra; Hao Liu; Charles Wessel; Mary Lou Klem; Stalin Dharmayan; Bishoy Emmanuel; Hasan Al Harakeh; Samer Tohme; David Geller; Amit Tevar; Christopher B Hughes; Abhinav Humar; Ramon Bataller; Jaideep Behari

doi:10.1097/AS9.0000000000000065

Hepatic Resection for Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of 7226 Patients

Ann Surg Open. 2021 May 3;2(2):e065. doi: 10.1097/AS9.0000000000000065. eCollection 2021 Jun.

Authors

Michele Molinari¹, Christof Kaltenmeier¹, Patrick-Bou Samra², Hao Liu¹, Charles Wessel³, Mary Lou Klem³, Stalin Dharmayan⁴, Bishoy Emmanuel¹, Hasan Al Harakeh¹, Samer Tohme¹, David Geller¹, Amit Tevar¹, Christopher B Hughes¹, Abhinav Humar¹, Ramon Bataller⁵, Jaideep Behari⁵

Affiliations

¹ From the Department of Surgery, Division of Transplant Surgery, University of Pittsburgh, Pittsburgh, PA.
² Department of Surgery, Division of General Surgery, Johns Hopkins University, Baltimore, MD.
³ Medical Health Library Services, University of Pittsburgh, Pittsburgh, PA.
⁴ Department of Surgery, Division of Transplant Surgery, University of Leeds, Leeds, United Kingdom.
⁵ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA.

Abstract

Objective: To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors.

Background: Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies.

Methods: Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed.

Results: Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05).

Conclusion: After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.

Keywords: alcoholic cirrhosis; cryptogenic cirrhosis; disease-free survival; hepatic resection; hepatocellular carcinoma; hepatoma; meta-analysis; meta-regression; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; overall survival; systematic review; viral hepatitis B; viral hepatitis C.