Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence Following Transplantation

Liver Transpl. 2018 Sep;24(9):1233-1242. doi: 10.1002/lt.25194.

Abstract

Orthotopic liver transplantation (OLT) and resection are effective treatments for hepatocellular carcinoma (HCC). However, optimizing OLT and limiting HCC recurrence remains a vexing problem. New HCC Model for End-Stage Liver Disease and allocation algorithms provide greater observation of HCC patients, many while receiving local-regional treatments. Potential benefits of local-regional treatment for limiting HCC recurrence after OLT remain incompletely understood. Therefore, we aimed to define HCC-specific prognostic factors affecting recurrence in a contemporary, multicenter cohort of HCC patients undergoing OLT and specifically whether local-regional therapies limited recurrence. We identified 441 patients undergoing OLT for HCC at 3 major transplant centers from 2008 to 2013. Cox regression was used to analyze covariate-adjusted recurrence and mortality rates after OLT. "Bridging" or "downstaging" therapy was used in 238 (54%) patients with transarterial chemoembolization (TACE) being used in 170 (71%) of treated patients. The survival rate after OLT was 88% and 78% at 1 and 3 years, respectively, with HCC recurrence (28% of deaths) significantly increasing the mortality rate (hazard ratio [HR], 19.87; P < 0.001). Tumor size, not tumor number, either at presentation or on explant independently predicted HCC recurrence (HR, 1.36 and 1.73, respectively; P < 0.05) with a threshold effect noted at 4.0-cm size. Local-regional therapy (TACE) reduced HCC recurrence by 64% when adjusting for presenting tumor size (HR, 0.36; P < 0.05). Explant tumor size and microvascular invasion predicted mortality (HR, 1.19 and 1.51, respectively; P < 0.05) and pathologic response to therapy (TACE or radiofrequency ablation) significantly decreased explant tumor size (0.56-1.62 cm diameter reduction; P < 0.05). In conclusion, HCC tumor size at presentation or explant is the most important predictor for HCC recurrence after OLT. Local-regional therapy to achieve a pathologic response (decreasing tumor size) can limit HCC recurrences after OLT. Liver Transplantation 00 000-000 2018 AASLD.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / secondary
  • Carcinoma, Hepatocellular / surgery*
  • Disease Progression
  • Female
  • Humans
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / mortality
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Neoplasm Staging
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
  • United States