De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience
Ryoichi Goto
Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Search for more papers by this authorYukiko Kosai-Fujimoto
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorShintaro Yagi
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTsuyoshi Kobayashi
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorNobuhisa Akamatsu
Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
Search for more papers by this authorTsuyoshi Shimamura
Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
Search for more papers by this authorSatoru Imura
Department of Surgery, Tokushima University, Tokushima, Japan
Search for more papers by this authorSatoshi Ogiso
Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorShugo Mizuno
Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Mie, Japan
Search for more papers by this authorMitsuhisa Takatsuki
Department of Surgery, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorTakasuke Fukuhara
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Search for more papers by this authorTatsuya Kanto
National Center for Global Health and Medicine Research Center for Hepatitis and Immunology, Ichikawa, Japan
Search for more papers by this authorSusumu Eguchi
Department of Surgery, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorKatsuhiko Yanaga
Department of Surgery, Jikei University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasuhiro Ogura
Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorTakumi Fukumoto
Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorMitsuo Shimada
Department of Surgery, Tokushima University, Tokushima, Japan
Search for more papers by this authorKiyoshi Hasegawa
Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
Search for more papers by this authorHideki Ohdan
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorShinji Uemoto
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYuji Soejima
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
Search for more papers by this authorToru Ikegami
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorTomoharu Yoshizumi
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorCorresponding Author
Akinobu Taketomi
Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Correspondence: Dr Akinobu Taketomi, Department of Gastroenterological Surgery I, Hokkaido University Hospital, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan. Email: [email protected]Search for more papers by this authorYoshihiko Maehara
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan
Search for more papers by this authorRyoichi Goto
Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Search for more papers by this authorYukiko Kosai-Fujimoto
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorShintaro Yagi
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTsuyoshi Kobayashi
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorNobuhisa Akamatsu
Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
Search for more papers by this authorTsuyoshi Shimamura
Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
Search for more papers by this authorSatoru Imura
Department of Surgery, Tokushima University, Tokushima, Japan
Search for more papers by this authorSatoshi Ogiso
Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorShugo Mizuno
Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Mie, Japan
Search for more papers by this authorMitsuhisa Takatsuki
Department of Surgery, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorTakasuke Fukuhara
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Search for more papers by this authorTatsuya Kanto
National Center for Global Health and Medicine Research Center for Hepatitis and Immunology, Ichikawa, Japan
Search for more papers by this authorSusumu Eguchi
Department of Surgery, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorKatsuhiko Yanaga
Department of Surgery, Jikei University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasuhiro Ogura
Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorTakumi Fukumoto
Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorMitsuo Shimada
Department of Surgery, Tokushima University, Tokushima, Japan
Search for more papers by this authorKiyoshi Hasegawa
Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
Search for more papers by this authorHideki Ohdan
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorShinji Uemoto
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYuji Soejima
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
Search for more papers by this authorToru Ikegami
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorTomoharu Yoshizumi
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorCorresponding Author
Akinobu Taketomi
Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Correspondence: Dr Akinobu Taketomi, Department of Gastroenterological Surgery I, Hokkaido University Hospital, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan. Email: [email protected]Search for more papers by this authorYoshihiko Maehara
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan
Search for more papers by this authorConflict of interest: The authors have no conflict of interest.
Financial support: This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare of Japan (17fk0210107h0001).
Received 4 December 2019; revision 29 July 2020; accepted 14 August 2020.
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.
Supporting Information
| Filename | Description |
|---|---|
| hepr13565-sup-0001-Table_1_Suppinfo.docxWord 2007 document , 14.1 KB |
Table S1. Surveillance protocol for recipient with hepatocellular carcinoma post-liver transplantation in each institute. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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