Ryoichi Goto1, Yukiko Kosai-Fujimoto2, Shintaro Yagi3, Tsuyoshi Kobayashi4, Nobuhisa Akamatsu5, Tsuyoshi Shimamura6, Satoru Imura7, Satoshi Ogiso8, Shugo Mizuno9, Mitsuhisa Takatsuki10, Takasuke Fukuhara11, Tatsuya Kanto12, Susumu Eguchi10, Katsuhiko Yanaga13, Yasuhiro Ogura8, Takumi Fukumoto14, Mitsuo Shimada7, Kiyoshi Hasegawa5, Hideki Ohdan4, Shinji Uemoto3, Yuji Soejima15, Toru Ikegami2, Tomoharu Yoshizumi2, Akinobu Taketomi1, Yoshihiko Maehara2,16. 1. Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 4. Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 5. Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan. 6. Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan. 7. Department of Surgery, Tokushima University, Tokushima, Japan. 8. Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan. 9. Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Mie, Japan. 10. Department of Surgery, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan. 11. Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 12. National Center for Global Health and Medicine Research Center for Hepatitis and Immunology, Ichikawa, Japan. 13. Department of Surgery, Jikei University School of Medicine, Tokyo, Japan. 14. Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 15. Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. 16. Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan.
Abstract
AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.
AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.