Journal of Hepatocellular Carcinoma (2021-03-01)

Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

  • Gül-Klein S,
  • Kästner A,
  • Haber PK,
  • Krenzien F,
  • Wabitsch S,
  • Krannich A,
  • Andreou A,
  • Eurich D,
  • Tacke F,
  • Horst D,
  • Pratschke J,
  • Schmelzle M

Journal volume & issue
Vol. Volume 8
pp. 133 – 143


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Safak Gül-Klein,1 Anika Kästner,1 Philipp Konstantin Haber,1 Felix Krenzien,1 Simon Wabitsch,1 Alexander Krannich,2 Andreas Andreou,3 Dennis Eurich,1 Frank Tacke,4 David Horst,5 Johann Pratschke,1 Moritz Schmelzle1 1Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany; 2Clinical Study Center, Clinical Trial Office, Charité—Universitätsmedizin Berlin, Berlin, Germany; 3Division of Acute Care Surgery, Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland; 4Department of Hepatology/Gastroenterology, Charité—Universitätsmedizin Berlin, Berlin, Germany; 5Institute of Pathology, Charité—Universitätsmedizin Berlin, Berlin, GermanyCorrespondence: Safak Gül-KleinDepartment of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, GermanyEmail [email protected]: The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival.Patients and Methods: Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence. Cox’s regression analysis was conducted revealing risk factors for HCC recurrence.Results: HCC recurred in 47 of 252 analyzed patients with a median time to recurrence of 20 months. Patients with AR (28.6%) had a significantly higher frequency of recurrence compared to patients without AR (13.0%, p=0.002). Multiple Cox regression analyses identified AR within 20 months to be an independent risk factor for HCC recurrence both as dichotomized (HR=2.91, 95%CI: 1.30– 6.53; p=0.009) and as a continuous variable (HR=1.81, 95%CI: 1.28– 2.54; p=0.001). HCC recurrence and AR were associated with higher grades of liver fibrosis one year after LT, when compared to patients without AR (p=0.019).Conclusion: Our results demonstrate an association of AR with HCC recurrence after LT with implications for intervals of monitoring in tumor surveillance. Graft fibrosis and immune mechanisms are potentially related and causal interactions are worth further investigation.Keywords: histology, protocol liver biopsy, graft fibrosis, immunological mechanisms, predictors of tumor relapse