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Han JW, Park SH. Advancing immunosuppression in liver transplantation: the role of regulatory T cells in immune modulation and graft tolerance. CLINICAL TRANSPLANTATION AND RESEARCH 2024; 38:257-272. [PMID: 39696994 PMCID: PMC11732766 DOI: 10.4285/ctr.24.0059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 11/23/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024]
Abstract
Prolonged immunosuppressive therapy in liver transplantation (LT) is associated with significant adverse effects, such as nephrotoxicity, metabolic complications, and heightened risk of infection or malignancy. Regulatory T cells (Tregs) represent a promising target for inducing immune tolerance in LT, with the potential to reduce or eliminate the need for life-long immunosuppression. This review summarizes current knowledge on the roles of Tregs in LT, highlighting their mechanisms and the impact of various immunosuppressive agents on Treg stability and function. The liver's distinct immunological microenvironment, characterized by tolerogenic antigen-presenting cells and high levels of interleukin (IL)-10 and transforming growth factor-β, positions this organ as an ideal setting for Treg-mediated tolerance. We discuss Treg dynamics in LT, their association with rejection risk, and their utility as biomarkers of transplant outcomes. Emerging strategies, including the use of low-dose calcineurin inhibitors with mammalian target of rapamycin inhibitors, adoptive Treg therapy, and low-dose IL-2, aim to enhance Treg function while providing sufficient immunosuppression. Thus, the future of LT involves precision medicine approaches that integrate Treg monitoring with tailored immunosuppressive protocols to optimize long-term outcomes for LT recipients.
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Affiliation(s)
- Ji Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Su-Hyung Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
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Schmidt K, Spann A, Khan MQ, Izzy M, Watt KD. Minimizing Metabolic and Cardiac Risk Factors to Maximize Outcomes After Liver Transplantation. Transplantation 2024; 108:1689-1699. [PMID: 38060378 DOI: 10.1097/tp.0000000000004875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients' outcomes posttransplant. The major risk factors for post-liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.
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Affiliation(s)
- Kathryn Schmidt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Ashley Spann
- Division of Gastroenterology and Hepatology, Vanderbilit University, Nashville, TN
| | - Mohammad Qasim Khan
- Division of Gastroenterology and Hepatology, University of Western Ontario, London, ON, Canada
| | - Manhal Izzy
- Division of Gastroenterology and Hepatology, Vanderbilit University, Nashville, TN
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Liu D, Bonwick WMW, Sumithran P, Grace JA, Sinclair M. Budesonide in Liver Immunology: A Therapeutic Opportunity in Liver Transplantation. CURRENT TRANSPLANTATION REPORTS 2024; 11:197-206. [DOI: 10.1007/s40472-024-00441-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 09/06/2024]
Abstract
Abstract
Purpose of Review
A major remaining challenge in liver transplantation is achieving the balance between adequate immunosuppression to prevent allograft rejection and minimising immunosuppression-related side effects. Systemic corticosteroids contribute to the development of multi-system adverse effects that increase recipient morbidity and mortality. Oral budesonide undergoes significant first-pass hepatic metabolism, thereby minimising systemic availability, but maintains a similar immunosuppressive impact on the liver and gastrointestinal tract as systemic corticosteroids. This review aims to explore the rationale for oral budesonide as an alternative immunosuppressant to conventional corticosteroids following liver transplantation.
Recent findings
Despite increasing evidence of efficacy and safety in other gastrointestinal conditions, research on the role of budesonide as an alternative immunosuppressant to conventional corticosteroids in the liver transplant setting remains scarce. However, existing literature suggests efficacy in the treatment and prevention of acute rejection after liver transplantation, with minimal toxicity.
Summary
The unique pharmacokinetic profile of oral budesonide may address the unmet need for a medical therapy that has efficacy but with a better safety profile compared to conventional corticosteroids in the liver transplant setting.
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Kim J, Joh JW, Lee KW, Choi DL, Wang HJ. Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial. Ann Hepatobiliary Pancreat Surg 2024; 28:238-247. [PMID: 38484785 PMCID: PMC11128783 DOI: 10.14701/ahbps.23-129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/04/2024] [Accepted: 02/04/2024] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.
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Affiliation(s)
- Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Korea
| | - Hee-Jung Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
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Shimada S, Miyake K, Venkat D, Gonzalez H, Moonka D, Yoshida A, Abouljoud M, Nagai S. Clinical characteristics of new-onset diabetes after liver transplantation and outcomes. Ann Gastroenterol Surg 2024; 8:383-393. [PMID: 38707230 PMCID: PMC11066488 DOI: 10.1002/ags3.12775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/21/2023] [Accepted: 12/24/2023] [Indexed: 05/07/2024] Open
Abstract
Background We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.
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Affiliation(s)
- Shingo Shimada
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Katsunori Miyake
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Deepak Venkat
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Humberto Gonzalez
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Dilip Moonka
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
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Zhou J, Sun H, Wang Z, Cong W, Zeng M, Zhou W, Bie P, Liu L, Wen T, Kuang M, Han G, Yan Z, Wang M, Liu R, Lu L, Ren Z, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Hou J, Ji Y, Yun J, Bai X, Cai D, Chen W, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Guo Y, Hua B, Huang X, Jia W, Li Q, Li T, Li X, Li Y, Li Y, Liang J, Ling C, Liu T, Liu X, Lu S, Lv G, Mao Y, Meng Z, Peng T, Ren W, Shi H, Shi G, Shi M, Song T, Tao K, Wang J, Wang K, Wang L, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zeng Y, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhang Y, Zhao M, Zhao Y, Zheng H, Zhou L, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Zhang L, Yang C, Wu Z, Dai Z, Chen M, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Teng G, et alZhou J, Sun H, Wang Z, Cong W, Zeng M, Zhou W, Bie P, Liu L, Wen T, Kuang M, Han G, Yan Z, Wang M, Liu R, Lu L, Ren Z, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Hou J, Ji Y, Yun J, Bai X, Cai D, Chen W, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Guo Y, Hua B, Huang X, Jia W, Li Q, Li T, Li X, Li Y, Li Y, Liang J, Ling C, Liu T, Liu X, Lu S, Lv G, Mao Y, Meng Z, Peng T, Ren W, Shi H, Shi G, Shi M, Song T, Tao K, Wang J, Wang K, Wang L, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zeng Y, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhang Y, Zhao M, Zhao Y, Zheng H, Zhou L, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Zhang L, Yang C, Wu Z, Dai Z, Chen M, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Teng G, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). Liver Cancer 2023; 12:405-444. [PMID: 37901768 PMCID: PMC10601883 DOI: 10.1159/000530495] [Show More Authors] [Citation(s) in RCA: 142] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 01/24/2023] [Indexed: 10/31/2023] Open
Abstract
Background Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."
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Affiliation(s)
- Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenming Cong
- Department of Pathology, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Lianxin Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Ming Kuang
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Zhiping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Maoqiang Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China
| | - Ruibao Liu
- Department of Interventional Radiology, The Tumor Hospital of Harbin Medical University, Harbin, China
| | - Ligong Lu
- Department of Interventional Oncology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Changhong Liang
- Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Chen
- Editorial Department of Chinese Journal of Digestive Surgery, Chongqing, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jinlin Hou
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingping Yun
- Department of Pathology, Tumor Prevention and Treatment Center, Sun Yat-sen University, Guangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Dingfang Cai
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weixia Chen
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Yongjun Chen
- Department of Hematology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenwu Cheng
- Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shuqun Cheng
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China
| | - Wengzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yabing Guo
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Baojin Hua
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaowu Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weidong Jia
- Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China
| | - Qiu Li
- Department of Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Xun Li
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Yaming Li
- Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Changquan Ling
- Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai, China
| | - Tianshu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiufeng Liu
- Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China
| | - Shichun Lu
- Institute and Hospital of Hepatobiliary Surgery of Chinese PLA, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, China
| | - Guoyue Lv
- Department of General Surgery, The First Hospital of Jilin University, Jilin, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Zhiqiang Meng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Weixin Ren
- Department of Interventional Radiology the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guoming Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Shi
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jianhua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kui Wang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lu Wang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoying Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiming Wang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Baocai Xing
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China
| | - Jiamei Yang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianyong Yang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yefa Yang
- Department of Hepatic Surgery and Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yunke Yang
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shenglong Ye
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhenyu Yin
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Yong Zeng
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bixiang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Boheng Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Ti Zhang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
| | - Ming Zhao
- Minimally Invasive Interventional Division, Liver Cancer Group, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yongfu Zhao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Honggang Zheng
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ledu Zhou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinghong Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongsheng Xiao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lan Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhifeng Wu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi Dai
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Minshan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jianqiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiujun Cai
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Feng Shen
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shukui Qin
- Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China
| | - Gaojun Teng
- Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jiahong Dong
- Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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7
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Nunez M, Praglin CR, Torres AM, Agudelo EZ, Braun HJ, Huang CY, Syed S, Roberts JP, Roll GR. Steroid Avoidance After Adult Living Donor Liver Transplant: A Cohort Analysis. Transplant Direct 2023; 9:e1488. [PMID: 37250489 PMCID: PMC10212610 DOI: 10.1097/txd.0000000000001488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/14/2023] [Accepted: 04/04/2023] [Indexed: 05/31/2023] Open
Abstract
Although steroid avoidance (SA) has been studied in deceased donor liver transplant, little is known about SA in living donor liver transplant (LDLT). We report the characteristics and outcomes, including the incidence of early acute rejection (AR) and complications of steroid use, in 2 cohorts of LDLT recipients. Methods Routine steroid maintenance (SM) after LDLT was stopped in December 2017. Our single-center retrospective cohort study spans 2 eras. Two hundred forty-two adult recipients underwent LDLT with SM (January 2000-December 2017), and 83 adult recipients (December 2017-August 2021) underwent LDLT with SA. Early AR was defined as a biopsy showing pathologic characteristics within 6 mo after LDLT. Univariate and multivariate logistic regressions were performed to evaluate the effects of relevant recipient and donor characteristics on the incidence of early AR in our cohort. Results Neither the difference in early AR rate between cohorts (SA 19/83 [22.9%] versus SM 41/242 [17%]; P = 0.46) nor a subset analysis of patients with autoimmune disease (SA 5/17 [29.4%] versus SM 19/58 [22.4%]; P = 0.71) reached statistical significance. Univariate and multivariate logistic regressions for early AR identified recipient age to be a statistically significant risk factor (P < 0.001). Of the patients without diabetes before LDLT, 3 of 56 (5.4%) on SA versus 26 of 200 (13%) on SM needed medications prescribed for glucose control at the time of discharge (P = 0.11). Patient survival was similar between SA and SM cohorts (SA 94% versus SM 91%, P = 0.34) 3 y after transplant. Conclusions LDLT recipients treated with SA do not exhibit significantly higher rates of rejection or increased mortality than patients treated with SM. Notably, this result is similar for recipients with autoimmune disease.
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Affiliation(s)
- Miguel Nunez
- School of Medicine, University of California San Francisco, San Francisco, CA
| | - Claudia R. Praglin
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Ana M. Torres
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Eliana Z. Agudelo
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Hillary J. Braun
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA
| | - Shareef Syed
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Garrett R. Roll
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA
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8
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Idalsoaga F, Ayares G, Díaz LA, Arnold J, Ayala-Valverde M, Hudson D, Arrese M, Arab JP. Current and emerging therapies for alcohol-associated hepatitis. LIVER RESEARCH (BEIJING, CHINA) 2023; 7:35-46. [PMID: 39959695 PMCID: PMC11792060 DOI: 10.1016/j.livres.2023.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/16/2023] [Accepted: 03/07/2023] [Indexed: 03/17/2023]
Abstract
Alcohol-related liver disease (ALD) encompasses a spectrum of diseases caused by excessive alcohol consumption. ALD includes hepatic steatosis, steatohepatitis, variable degrees of fibrosis, cirrhosis, and alcohol-associated hepatitis (AH), the latter being the most severe acute form of the disease. Severe AH is associated with high mortality (reaching up to 30%-50%) at 90 days. The cornerstone of ALD, and particularly AH, treatment continues to be abstinence, accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome (AWS). In severe AH with model for end-stage liver disease (MELD) score ≥21, corticosteroids can be used, especially MELD score between 25 and 39, where the highest benefit is achieved. Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation. The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway. This includes the modulation and management of the innate immune response, gut dysbiosis, bacterial translocation, and bacteria-derived products from the intestine. These hold promise for the future of AH treatment.
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Affiliation(s)
- Francisco Idalsoaga
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gustavo Ayares
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Díaz
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jorge Arnold
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - María Ayala-Valverde
- Internal Medicine Service, Hospital El Pino, Critical Patient Unit, Clinica Davila, Santiago, Chile
| | - David Hudson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Marco Arrese
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
- Alimentiv, London, Ontario, Canada
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9
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De Martin E, Londoño MC, Emamaullee J, Lerut J, Potts J, Aluvihare V, Spiro M, Raptis DA, McCaughan G. The optimal immunosuppression management to prevent early rejection after liver transplantation: A systematic review of the literature and expert panel recommendations. Clin Transplant 2022; 36:e14614. [PMID: 35143096 DOI: 10.1111/ctr.14614] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 02/06/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND The optimal immunosuppression protocol to prevent early acute cellular rejection (ACR) after liver transplantation (LT) avoiding prolonged hospitalization and early hospital readmission is undefined. OBJECTIVES To identify the most suitable immunosuppression regimen for inclusion in ERAS programs in order to minimize early ACR after LT and to provide expert panel recommendations DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies from January 2000 onward focusing on early ACR were included. Rates of early renal dysfunction and infection were evaluated. CRD42021245586 RESULTS: Thirty-seven studies met inclusion criteria; 23 randomized controlled trials, 14 retrospective or prospective observational comparative or noncomparative studies. Several sources of biases which potentially confound conclusions were identified: heterogeneity in immunosuppression protocols, higher serum tacrolimus levels than currently used in clinical practice, differences in the definition of ACR. CONCLUSIONS Tacrolimus is the standard immunosuppression after LT and can be used in combination with other drugs such as corticosteroids and MMF, and in association with anti-IL2 receptor antibody (IL2Ra) induction. (Quality of Evidence; Low | Grade of Recommendation; Strong). Low dose or delayed introduction of tacrolimus in association with corticosteroids and MMF and/or anti-IL2Ra induction can be used to reduce acute kidney injury. (Quality of Evidence; Low | Grade of Recommendation; Strong). Use of tacrolimus in association with corticosteroids and MMF and/or anti-IL2Ra induction does not lead to increased infection rates. (Quality of Evidence; Low | Grade of Recommendation; Weak).
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Affiliation(s)
- Eleonora De Martin
- APHP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM Unit 1193, FHU Hepatinov, Villejuif, France
| | - Maria-Carlota Londoño
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer and Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Catalonia, Spain
| | - Juliet Emamaullee
- Department of Surgery, University of Southern California, Los Angeles, USA
| | - Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université catholique Louvain (UCL), Brussels, Belgium
| | - Jonathan Potts
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK
| | - Varuna Aluvihare
- Transplant Hepatology Lead Institute of Liver Studies, King's College Hospital, London, UK
| | - Michael Spiro
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK.,Department of Anesthesia and Intensive Care Medicine, Royal Free Hospital, London, UK
| | - Dimitri Aristotle Raptis
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Geoffrey McCaughan
- A.W. Morrow Gastroenterolgy and Liver Center, Sydney Medical School, Centenary Institute, Australian National Liver Transplant Unit, University of Sydney, Sydney, Australia
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- APHP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM Unit 1193, FHU Hepatinov, Villejuif, France
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10
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Ayares G, Idalsoaga F, Díaz LA, Arnold J, Arab JP. Current Medical Treatment for Alcohol-Associated Liver Disease. J Clin Exp Hepatol 2022; 12:1333-1348. [PMID: 36157148 PMCID: PMC9499849 DOI: 10.1016/j.jceh.2022.02.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/06/2022] [Indexed: 12/12/2022] Open
Abstract
Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.
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Key Words
- AC, Amoxicillin/clavulanate
- ACLF, Acute-on-Chronic Liver Failure
- ADLs, Activities of Daily Living
- AH, Alcohol-Associated Hepatitis
- AKI-HRS, Acute Kidney Injury - Hepatorenal Syndrome
- ALD
- ALD, Alcohol-Associated Liver Disease
- ASH, Alcoholic Steatohepatitis
- AUD, Alcohol Use Disorder
- AWS, Alcohol Withdrawal Syndrome
- BCAAs, Branched-Chain Amino Acids
- CDC, Center for Disease Control
- CI, Confidence Interval
- COVID-19, Coronavirus Disease 2019
- CT, Computerized Tomography
- GABA, gamma-aminobutyric acid agonist
- HBV, Hepatitis B Virus
- HCC, Hepatocellular Carcinoma
- HCV, Hepatitis C Virus
- HE, Hepatic Encephalopathy
- HIV, Human Immunodeficiency Virus
- HR, Hazard Ratio
- IBW, Ideal Body Weight
- ICA, International Club of Ascites
- IL-1β, Interleukin-1β
- IL-22, Interleukin-22
- KPS, Karnofsky Performance Status
- LB, Liver Biopsy
- LPS, Lipopolysaccharide
- LSM, Liver Stiffness Measurement
- LT, Liver Transplantation
- MDF, Maddrey’s Discriminant Function
- MELD, Model of End-Stage Liver Disease
- MRI, Magnetic Resonance Imaging
- MUST, Malnutrition Universal Screening Tool
- NIAAA, National Institute on Alcohol Abuse and Alcoholism
- NRS-2002, Nutritional Risk Screening-2002
- OR, Odds Ratio
- PAMPs, Pathogen-Activated Molecular Patterns
- PMI, Psoas Muscle Index
- PTX, Pentoxifylline
- RAI, Relative Adrenal Insufficiency
- RCT, Randomized Clinical Trials
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- ROS, Reactive Oxygen Species
- RR, Relative Risk
- SIRS, Systemic Inflammatory Response Syndrome
- TNF, Tumor Necrosis Factor
- WKS, Wernicke-Korsakoff Syndrome
- alcohol
- alcohol use disorders
- alcohol-associated hepatitis
- cirrhosis
- fatty liver disease
- steatosis
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Affiliation(s)
- Gustavo Ayares
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis A. Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jorge Arnold
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan P. Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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11
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Kniepeiss D, Rosenkranz AR, Fickert P, Schemmer P. [Update: Immunosuppression in organ transplantation]. Dtsch Med Wochenschr 2022; 147:1199-1212. [PMID: 36070738 DOI: 10.1055/a-1716-8031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Immunosuppression is an essential prerequisite for successful transplantation. In order to reduce the sometimes-considerable side effects, combination therapies with different agents are used. This article aims to provide an up-to-date overview of immunosuppression after liver and kidney transplantation.
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12
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Zhang X, Lichvar A, Chan C, Choi D. Evaluating the Incidence and Risk Factors for Acute Cellular Rejection in a Steroid Sparing Liver Transplant Center. Ann Pharmacother 2022; 57:553-559. [PMID: 36004388 DOI: 10.1177/10600280221120059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Corticosteroids has been the mainstay of immunosuppression (IMS) following liver transplant (LT). With the advent of more potent IMS, complete steroid withdrawal has become possible after LT. However, there is limited data regarding the incidence and risk factors for acute cellular rejection (ACR) in LT recipients on steroid sparing regimens. OBJECTIVE To identify the incidence and risk factors of ACR in LT recipients at an urban LT center utilizing a steroid-sparing IMS regimen. METHODS This was a single center retrospective study evaluating incidence of ACR in adults (>18 years) who received a LT between 01/01/2008 and 6/30/2019 at a steroid-sparing liver transplant center. Data between patients who had ACR and patients who did not were compared and risk factors were identified by multivariate logistic linear regression. RESULTS A total of 266 patients were included in this analysis, of which 18.4% experienced ACR within the first year of LT. Median time to first ACR was 134 (interquartile range [IQR]: 34-246) days. Black race (odds ratio [OR]: 4.39, P < 0.001), continued need for prednisone (OR: 2.80, P = 0.015) and cytomegalovirus (CMV) viremia (OR: 6.27, P < 0.001)) were independent risk factors for ACR. Tacrolimus use was associated with less ACR (OR: 0.33, P = 0.013). CONCLUSION AND RELEVANCE Steroid sparing regimens for IMS post-LT were not associated with an increased incidence of ACR when compared to reported ACR rates in literature. Potential risk factors for ACR include Black race, the use of prednisone maintenance IMS therapy, and CMV viremia.
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Affiliation(s)
- Xunjie Zhang
- University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA
| | - Alicia Lichvar
- Center for Transplantation, University of California San Diego Health, San Diego, CA, USA
| | - Christine Chan
- Division of Gastroenterology and Hepatology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA
| | - David Choi
- Department of Pharmacy, Division of Gastroenterology and Hepatology, University of Chicago Medicine, Chicago, IL, USA
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13
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[Kidney failure after liver transplantation]. Nephrol Ther 2022; 18:89-103. [PMID: 35151596 DOI: 10.1016/j.nephro.2021.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 05/11/2021] [Accepted: 11/06/2021] [Indexed: 02/06/2023]
Abstract
One third of cirrhotic patients present impaired kidney function. It has multifactorial causes and has a harmful effect on patients' morbi-mortality before and after liver transplant. Kidney function does not improve in all patients after liver transplantation and liver-transplant recipients are at high risk of developing chronic kidney disease. Causes for renal dysfunction can be divided in three groups: preoperative, peroperative and postoperative factors. To date, there is no consensus for the modality of evaluation the risk for chronic kidney disease after liver transplantation, and for its prevention. In the present review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease to determine a risk stratification for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this setting, and highlight the indications of combined liver-kidney transplantation.
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14
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Chaitou AR, Valmiki S, Valmiki M, Zahid M, Aid MA, Fawzy P, Khan S. New-Onset Diabetes Mellitus (NODM) After Liver Transplantation (LT): The Ultimate Non-diabetogenic Immunosuppressive Therapy. Cureus 2022; 14:e23635. [PMID: 35510006 PMCID: PMC9057316 DOI: 10.7759/cureus.23635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 03/29/2022] [Indexed: 11/05/2022] Open
Abstract
New-onset diabetes mellitus (NODM) is a common long-term complication after liver transplantation (LT). It is thought to be drug-induced in most cases, no matter the underlying disease that cause liver failure and indicated transplantation. Standard post-transplantation (PT) immunosuppressive regimens include prolonged use of calcineurin inhibitors (CNIs), namely tacrolimus (TAC), alongside corticosteroids to avoid acute and chronic graft rejection. This combination is well known for its diabetogenicity. Significant differences between the applied regimens stand out concerning the duration and dosages to prevent the metabolic side effects of these drugs in the long run without compromising the graft's survival. Studies were collected after an extensive research of PubMed database for this very specific topic using the following MeSH keywords in multiple combinations: "Liver Transplantation," "Diabetes Mellitus," "NODM," "Tacrolimus," "Cyclosporine A," and "Steroids." In addition, we used the same keywords for regular searches in Google Scholar. Only the relevant English human studies between 2010 and 2020 were collected except for review articles. Duplicates were eliminated using Mendeley software. Twelve relevant studies directly related to the targeted topic were collected and discussed, including five retrospective cohorts, four prospective cohorts, one clinical trial, one prospective pilot, and one case report. Their topics included primarily the factors increasing the risk of new-onset diabetes mellitus after liver transplantation (NODALT), TAC-based immunosuppression and its relative blood levels affecting the possible development of NODALT, the role of cyclosporine in substituting TAC regimen, and the effect of different steroids-avoiding protocols on the prevention of NODALT. The reviewed studies suggested that lowering the serum concentration of tacrolimus (cTAC) throughout the PT period and eliminating the corticosteroids regimen as early as possible, among other measures, can significantly impact the rate of emergence of NODM. This traditional review tackles the most recent studies about NODALT to establish a comprehensive view on this issue and guide clinicians and researchers for the safest immunosuppressive regimen to date, while maintaining a balanced metabolic profile.
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15
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Singh N, Ma M, Montano-Loza AJ, Bhanji RA. Learning from a rare phenomenon — spontaneous clearance of chronic hepatitis C virus post-liver transplant: A case report. World J Hepatol 2022; 14:456-463. [PMID: 35317181 PMCID: PMC8891670 DOI: 10.4254/wjh.v14.i2.456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/26/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma. Spontaneous clearance of HCV has been documented after an acute infection in 20%-45% of individuals. However, spontaneously resolved chronic hepatitis C following liver transplant (LT) is rare and has been documented only in a few case reports. The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events, which are typically associated with significant changes in the host immunity.
CASE SUMMARY We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation. These patients either failed or had no HCV treatment prior to transplant, but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction (PCR). Diagnosis of HCV was based on viremia through PCR or liver biopsy. All three patients currently undergo surveillance and have no recurrence of HCV.
CONCLUSION Examining each patient’s clinical course, we learned about many viral, host and cellular-factors that may have enhanced the host’s immunity leading to spontaneous clearance of HCV. Though HCV treatment has excellent cure rates, understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.
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Affiliation(s)
- Noreen Singh
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Mang Ma
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Rahima A Bhanji
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
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16
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Zhang K, Zheng S. The need for deepened molecular mechanism exploration in new onset diabetes after transplantation (NODAT). Hepatobiliary Surg Nutr 2021; 10:896-898. [PMID: 35004966 PMCID: PMC8683927 DOI: 10.21037/hbsn-2021-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 10/21/2021] [Indexed: 08/30/2023]
Affiliation(s)
- Ke Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
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17
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Majumdar A, Verbeek J, Tsochatzis EA. Non-alcoholic fatty liver disease: Current therapeutic options. Curr Opin Pharmacol 2021; 61:98-105. [PMID: 34688168 DOI: 10.1016/j.coph.2021.09.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/13/2021] [Accepted: 09/20/2021] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and has an estimated global prevalence of 25%. NAFLD is found in up to 80% of people with obesity and over 60% of patients with diabetes. Cardiovascular disease is the main cause of mortality, followed by extra-hepatic cancers and then liver-specific complications of cirrhosis and hepatocellular carcinoma. Lifestyle modification remains the primary intervention in NAFLD. Weight loss achieved through dietary modification and exercise can lead to histologic improvement and reversal of metabolic complications. Current drug therapy is limited to pioglitazone and vitamin E; however, several agents are currently under phase III development. This review summarises the current treatment options in NAFLD.
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Affiliation(s)
- Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; Central Clinical School, The University of Sydney, Australia
| | - Jef Verbeek
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
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18
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Azhie A, Sheth P, Hammad A, Woo M, Bhat M. Metabolic Complications in Liver Transplantation Recipients: How We Can Optimize Long-Term Survival. Liver Transpl 2021; 27:1468-1478. [PMID: 34165872 DOI: 10.1002/lt.26219] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 06/14/2021] [Accepted: 06/17/2021] [Indexed: 12/27/2022]
Abstract
Liver transplantation (LT) recipients have experienced a significant improvement in short-term survival during the past 3 decades attributed to advancements in surgical techniques, perioperative management, and effective immunosuppressive regimens. However, long-term survival is affected by a high incidence of metabolic disorders and their consequences, including cardiovascular disease (CVD) and malignancies. Pretransplant metabolic impairments especially in those with nonalcoholic steatohepatitis cirrhosis are aggravated by the addition of posttransplant weight gain, physical inactivity, and reversal from catabolic to anabolic state. Moreover, although immunosuppressants are vital to avoid graft rejection, long-term exposure to these medications is implicated in metabolic impairments after LT. In this review, we summarize the molecular pathogenesis of different metabolic disorders after LT, including diabetes mellitus, dyslipidemia, and nonalcoholic fatty liver disease. Furthermore, CVD, malignancies, and graft rejections were provided as significant complications of post-LT metabolic conditions threatening both the patient and graft survival. Ultimately, emerging preventive and treatment strategies for posttransplant diabetes mellitus are summarized. This review highlights the significant need for more clinical trials of antihyperglycemic agents in LT recipients. Also, translational studies will help us to better understand the molecular and genetic factors underlying these metabolic complications and could lead to more personalized management in this high-risk population.
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Affiliation(s)
- Amirhossein Azhie
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Priya Sheth
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Ahmed Hammad
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of General Surgery, Mansoura University, Mansoura, Egypt
| | - Minna Woo
- Division of Endocrinology and Metabolism, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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19
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Czarnecka K, Czarnecka P, Tronina O, Bączkowska T, Durlik M. Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation. IMMUNITY INFLAMMATION AND DISEASE 2021; 10:3-21. [PMID: 34598315 PMCID: PMC8669703 DOI: 10.1002/iid3.538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/26/2021] [Accepted: 09/14/2021] [Indexed: 12/13/2022]
Abstract
The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient‐centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity‐related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre‐ and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long‐term survival rates.
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Affiliation(s)
- Kinga Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Paulina Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Olga Tronina
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Teresa Bączkowska
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
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20
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Abstract
One-third of patients with cirrhosis present kidney failure (AKI and CKD). It has multifactorial causes and a harmful effect on morbidity and mortality before and after liver transplantation. Kidney function does not improve in all patients after liver transplantation, and liver transplant recipients are at a high risk of developing chronic kidney disease. The causes of renal dysfunction can be divided into three groups: pre-operative, perioperative and post-operative factors. To date, there is no consensus on the modality to evaluate the risk of chronic kidney disease after liver transplantation, or for its prevention. In this narrative review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease in order to establish a risk categorization for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this context, and highlight the indications of combined liver–kidney transplantation.
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21
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Abstract
Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period.
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22
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Kathirvel M, Mallick S, Sethi P, Thillai M, Durairaj MS, Nair K, Sunny A, Mathew JS, Varghese CT, Chandran B, Pillai Thankamony Amma BS, Menon RN, Balakrishnan D, Gopalakrishnan U, Surendran S. Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT). HPB (Oxford) 2021; 23:666-674. [PMID: 33032883 DOI: 10.1016/j.hpb.2020.09.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.
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Affiliation(s)
- Manikandan Kathirvel
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India.
| | - Shweta Mallick
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Pulkit Sethi
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Manoj Thillai
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Madhu S Durairaj
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Krishnanunni Nair
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Aleena Sunny
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Johns S Mathew
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Christi T Varghese
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Biju Chandran
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Binoj S Pillai Thankamony Amma
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Ramachandran N Menon
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Dinesh Balakrishnan
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Unnikrishnan Gopalakrishnan
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Sudhindran Surendran
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
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23
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Choudhary NS, Saraf N, Saigal S, Soin AS. Long-term Management of the Adult Liver Transplantation Recipients. J Clin Exp Hepatol 2021; 11:239-253. [PMID: 33746450 PMCID: PMC7953009 DOI: 10.1016/j.jceh.2020.06.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/14/2020] [Indexed: 12/12/2022] Open
Abstract
The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients.
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Key Words
- AIH, autoimmune hepatitis
- BMI, body mass index
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- CVD, cardiovascular disease
- DDLT, deceased donor liver transplantation
- DM, diabetes mellitus
- DNM, de novo malignancy
- HCV, hepatitis C virus
- HR, hazard ratio
- IUCD, Intrauterine contraceptive devices
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MDRD, Modification of Diet in Renal Disease
- MMF, mycophenolate
- MS, metabolic syndrome
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- PTDM, posttransplantation diabetes mellitus
- PTMS, posttransplantation metabolic syndrome
- SVR, sustained virological response
- cardiovascular disease
- de novo malignancy
- eGFR, estimated glomerular filtration rate
- mTORi, Mammalian target of rapamycin inhibitors
- osteoporosis
- pregnancy
- recurrence
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
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24
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Gill MG, Majumdar A. Metabolic associated fatty liver disease: Addressing a new era in liver transplantation. World J Hepatol 2020; 12:1168-1181. [PMID: 33442446 PMCID: PMC7772736 DOI: 10.4254/wjh.v12.i12.1168] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/08/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease, is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation. The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management, including in the setting of liver transplantation. Patients with MAFLD present significant challenges in the pre-, peri- and post-transplant settings, largely due to the presence of medical comorbidities that include obesity, metabolic syndrome and cardiovascular risk factors. As the community prevalence of MAFLD increases concurrently with the obesity epidemic, donor liver steatosis is also a current and future concern. This review outlines current epidemiology, nomenclature, management issues and outcomes of liver transplantation in patients with MAFLD.
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Affiliation(s)
- Madeleine G Gill
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
| | - Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
- Central Clinical School, The University of Sydney, Sydney 2050, New South Wales, Australia
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25
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Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer 2020; 9:682-720. [PMID: 33442540 PMCID: PMC7768108 DOI: 10.1159/000509424] [Citation(s) in RCA: 527] [Impact Index Per Article: 105.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 06/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. SUMMARY Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. KEY MESSAGES Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019.
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Affiliation(s)
- Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenming Cong
- Department of Pathology, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianhua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Lianxin Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Maoqiang Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China
| | - Ruibao Liu
- Department of Interventional Radiology, The Tumor Hospital of Harbin Medical University, Harbin, China
| | - Ligong Lu
- Department of Interventional Oncology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhengang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Minshan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Changhong Liang
- Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Chen
- Editorial Department of Chinese Journal of Digestive Surgery, Chongqing, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingping Yun
- Department of Pathology, Tumor Prevention and Treatment Center, Sun Yat-sen University, Guangzhou, China
| | - Dingfang Cai
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongjun Chen
- Department of Hematology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenwu Cheng
- Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shuqun Cheng
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baojin Hua
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaowu Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weidong Jia
- Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China
| | - Yaming Li
- Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Tianshu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guoyue Lv
- Department of General Surgery, The First Hospital of Jilin University, Jilin, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Weixin Ren
- Department of Interventional Radiology The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guoming Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoying Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiming Wang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Baocai Xing
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China
| | - Jiamei Yang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianyong Yang
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yefa Yang
- Department of Hepatic Surgery & Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yunke Yang
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shenglong Ye
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengyu Yin
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Hubing South Road, Xiamen, China
| | - Bixiang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Boheng Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yongfu Zhao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Honggang Zheng
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinghong Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongsheng Xiao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi Dai
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gaojun Teng
- Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jianqiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Feng Shen
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shukui Qin
- Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China
| | - Jiahong Dong
- Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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26
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Kniepeiss D, Rosenkranz AR, Fickert P, Schemmer P. Update: Immunsuppression bei Organtransplantationen. TRANSFUSIONSMEDIZIN 2020. [DOI: 10.1055/a-1238-3285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
ZusammenfassungDie Immunsuppression ist eine wesentliche Grundvoraussetzung für eine erfolgreiche Transplantation. Zur Reduktion der teils beträchtlichen Nebenwirkungen werden Kombinationstherapien mit unterschiedlichen Wirkstoffen durchgeführt. Dieser Beitrag soll einen aktuellen Überblick zur Immunsuppression nach Leber- und Nierentransplantation geben.
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27
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Bari K, Shah SA, Kaiser TE, Cohen RM, Anwar N, Kleesattel D, Sherman KE. Safety and Efficacy of Budesonide for Liver Transplant Immune Suppression: Results of a Pilot Phase 2a Trial. Liver Transpl 2020; 26:1430-1440. [PMID: 32602616 PMCID: PMC7606621 DOI: 10.1002/lt.25837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/04/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023]
Abstract
Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.
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Affiliation(s)
- Khurram Bari
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Shimul A. Shah
- University of Cincinnati, Division of Transplant Surgery, Department of Surgery, Cincinnati, Ohio
| | - Tiffany E. Kaiser
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Robert M Cohen
- University of Cincinnati, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cincinnati, Ohio
| | - Nadeem Anwar
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - David Kleesattel
- University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio
| | - Kenneth E. Sherman
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
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28
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Sharma P, Arora A. Approach to prevention of non-alcoholic fatty liver disease after liver transplantation. Transl Gastroenterol Hepatol 2020; 5:51. [PMID: 33073046 DOI: 10.21037/tgh.2020.03.02] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 10/15/2019] [Indexed: 12/22/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease and non-alcoholic steatohepatitis (NASH) related cirrhosis is third common indication for liver transplantation (LT). Patients who have NASH related cirrhosis and are candidates for LT often have multiple comorbidities. These comorbidities need to be addressed before and after transplantation as it affects overall survival. Like hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis which recurs after transplantation, NASH also recurs after transplant however the impact of the recurrence on allograft and patient outcomes is unclear. Limited data suggests that it does not affect graft and patient survival. De novo NAFLD which is defined as occurrence of fatty liver in a patient who did not have fatty liver prior to LT can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Obesity, hyperlipidemia, diabetes as well as steroid dose and duration after LT are common predictors of recurrence of NAFLD after transplantation. Studies on prevention and treatment of NASH in post-transplant patients are lacking. Prevention of weight gain, regular exercises, weight reducing surgery, limited steroid use or steroid free regimen have been tried with varying success. Future studies for the prevention of NAFLD/NASH are required especially in post liver transplant patient.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
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29
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Majumdar A, Tsochatzis EA. Changing trends of liver transplantation and mortality from non-alcoholic fatty liver disease. Metabolism 2020; 111S:154291. [PMID: 32531295 DOI: 10.1016/j.metabol.2020.154291] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/18/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major international health concern. NAFLD is the leading global cause of liver disease with an estimated prevalence of 25% and is the fastest growing indication for liver transplantation (LT). The presence and severity of liver fibrosis is the only histologic predictor of clinical outcomes in this group. NAFLD poses several challenges in the peri-transplant setting including the management of multiple metabolic co-morbidities, post-transplant obesity and cardiovascular risk. However, post-LT outcomes in well-selected NAFLD patients appear similar to non-NAFLD indications, including in the setting of hepatocellular carcinoma (HCC). The rising prevalence of NAFLD may impact potential liver graft donors, which may in-turn adversely affect post-LT outcomes. This review outlines the current epidemiology, natural history and outcomes of NAFLD with a focus on pre- and post-liver transplant settings.
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Affiliation(s)
- Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; Central Clinical School, The University of Sydney, Australia
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
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30
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Weeks SR, Luo X, Toman L, Gurakar AO, Naqvi FF, Alqahtani SA, Philosophe B, Cameron AM, Desai NM, Ottmann SE, Segev DL, Garonzik-Wang J. Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation. Clin Transplant 2020; 34:e14036. [PMID: 32652700 DOI: 10.1111/ctr.14036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/23/2020] [Accepted: 06/28/2020] [Indexed: 12/25/2022]
Abstract
Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.
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Affiliation(s)
- Sharon R Weeks
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Xun Luo
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Lindsey Toman
- Department of Pharmacy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ahmet O Gurakar
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Fizza F Naqvi
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Saleh A Alqahtani
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Niraj M Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Shane E Ottmann
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.,Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA
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31
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Man Kim J, Hwang S, Lee KW, Lee JG, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Choi IS, Yu HC, Choi D, Kim MS. New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study. Hepatobiliary Surg Nutr 2020; 9:425-439. [PMID: 32832494 PMCID: PMC7423540 DOI: 10.21037/hbsn.2019.10.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. RESULTS NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. CONCLUSIONS Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae-Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Geun Hong
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
| | - In Seok Choi
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - The Korean Organ Transplantation Registry Study Group
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
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32
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Samji NS, Verma R, Keri KC, Singal AK, Ahmed A, Rinella M, Bernstein D, Abdelmalek MF, Satapathy SK. Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges. Dig Dis Sci 2019; 64:3413-3430. [PMID: 31312990 DOI: 10.1007/s10620-019-05716-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 07/02/2019] [Indexed: 02/08/2023]
Abstract
Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | | | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine, Avera Transplant Institute, S. Cliff Ave, Sioux Falls, SD, 57105, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Mary Rinella
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology/Hepatology, Duke University, 40 Duke Medicine Cir, Durham, NC, USA
| | - Sanjaya K Satapathy
- Division of Hepatology at Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY, 11030, USA.
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Yang J, Yang L, Wu L, Zhao Q, Chen M, He X. Efficacy and Safety of Steroid Therapy for Posttransplant Hyperbilirubinemia Caused by Early Allograft Dysfunction: A Randomized Controlled Trial. Med Sci Monit 2019; 25:1936-1944. [PMID: 30870403 PMCID: PMC6429985 DOI: 10.12659/msm.915128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Hyperbilirubinemia is a common event that occurs after liver transplantation. Hyperbilirubinemia is usually caused by early allograft dysfunction. Glucocorticoid is widely used for immunosuppression, but few studies have analyzed the effects of steroid therapy on posttransplantation hyperbilirubinemia. The aim of this study was to assess whether glucocorticoid was beneficial in treating hyperbilirubinemia caused by early allograft dysfunction. MATERIAL AND METHODS Patients with postoperative hyperbilirubinemia (those with conditions such as biliary complications and rejections were excluded) were randomly assigned, in a 2: 1 ratio, to the steroid and control groups. Patients in the steroid group were treated with glucocorticoid combined with ursodeoxycholic acid, whereas patients in the control group were only treated with ursodeoxycholic acid. The primary endpoint was decrease in bilirubin and the secondary endpoint was safety. RESULTS From 1st June 2016 to 30th April 2018, 40 patients were enrolled into the steroid group, and 20 were enrolled into the control group. Donor, recipient, and operative data were similar between the 2 groups. The decrease in bilirubin levels in the steroid group was significantly greater than that in the control group on the first day after the intervention was finished (9.25±1.30 mg/dL vs. 3.11±1.45 mg/dL, p=0.005), and after 2 weeks (15.01±1.20 mg/dL vs. 8.88±1.98 mg/dL, p=0.007). The steroid group did not have a higher complication rate but it did have a shorter postoperative hospital stay than in the control group. CONCLUSIONS Low-dose steroid therapy was effective and safe for treating hyperbilirubinemia caused by early graft dysfunction, and it improved liver function.
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Affiliation(s)
- Jie Yang
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Lei Yang
- Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Linwei Wu
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Qiang Zhao
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Maogen Chen
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Xiaoshun He
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
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34
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Choudhary NS, Saigal S. Preventive Strategies for Nonalcoholic Fatty Liver Disease After Liver Transplantation. J Clin Exp Hepatol 2019; 9:619-624. [PMID: 31695252 PMCID: PMC6823688 DOI: 10.1016/j.jceh.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Sanjiv Saigal, Director, Hepatology & Liver Transplant, Medanta Institute of Digestive & Hepatobiliary Sciences &Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, PIN 122001, India.
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35
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Cillo U, Bechstein WO, Berlakovich G, Dutkowski P, Lehner F, Nadalin S, Saliba F, Schlitt HJ, Pratschke J. Identifying risk profiles in liver transplant candidates and implications for induction immunosuppression. Transplant Rev (Orlando) 2018; 32:142-150. [DOI: 10.1016/j.trre.2018.04.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 04/03/2018] [Accepted: 04/05/2018] [Indexed: 12/16/2022]
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36
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Zhu A, Leto A, Shaked A, Keating B. Immunologic Monitoring to Personalize Immunosuppression After Liver Transplant. Gastroenterol Clin North Am 2018; 47:281-296. [PMID: 29735024 DOI: 10.1016/j.gtc.2018.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Although immunosuppressive drugs have enhanced patient outcomes in transplantation, the liver transplant community has made significant research efforts into the discovery of more accurate and precise methods of posttransplant monitoring and diagnosing. Current research in biomarkers reveals many promising approaches.
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Affiliation(s)
- Andrew Zhu
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
| | - Alexandra Leto
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
| | - Abraham Shaked
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA.
| | - Brendan Keating
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
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37
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Castedal M, Skoglund C, Axelson C, Bennet W. Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation. Scand J Gastroenterol 2018; 53:741-747. [PMID: 29688072 DOI: 10.1080/00365521.2018.1463390] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Corticosteroids (CS) are traditionally used as part of the basal immunosuppression (IS) following liver transplantation (LT) but are known to be associated with an increased risk of new-onset diabetes mellitus (NODM), cardiovascular morbidity and mortality. The aim of this study was to retrospectively compare the incidence of transient as well as persistent NODM, rejection rate and patient- and graft survival between patients receiving steroid-based and steroid-free maintenance IS. MATERIALS AND METHODS A total of 238 patients liver transplanted (2008-2011) with deceased donor livers were divided into two groups, one group that received steroid-based IS (tacrolimus (TAC), corticosteroids (CS), ± mycophenolate mofetil (MMF); n = 155) (2008-2011) and another group of non-autoimmune recipients that received steroid-free IS (TAC, MMF; n = 83) according to our new maintenance IS-protocol starting January 2010. The primary and secondary end-points were patient- and graft survival, rejection rates and the incidence of NODM. The median follow-up times were 1248 days and 681 days, respectively. RESULTS The one-year patient- and graft survival in the steroid-based and steroid-free group was 92.7% and 93.3% (ns) and 87.6% and 84.9% (ns), respectively. The incidence of biopsy proven acute rejection (BPAR) was 27.7% in both groups (ns) during follow-up. The overall incidence of persistent NODM in the two groups were 16.8% and 2.9%, respectively (p < .01). CONCLUSIONS The results show that steroid-free low-dose tacrolimus-based IS following LT is safe and decreases the incidence of NODM significantly.
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Affiliation(s)
- M Castedal
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Skoglund
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Axelson
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - W Bennet
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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38
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Fairfield C, Penninga L, Powell J, Harrison EM, Wigmore SJ. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients. Cochrane Database Syst Rev 2018; 4:CD007606. [PMID: 29630730 PMCID: PMC6494590 DOI: 10.1002/14651858.cd007606.pub4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. OBJECTIVES To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017. SELECTION CRITERIA Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. DATA COLLECTION AND ANALYSIS We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed-effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table. MAIN RESULTS We included 17 completed randomised clinical trials, but only 16 studies with 1347 participants provided data for the meta-analyses. Ten of the 16 trials assessed complete postoperative glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids (782 participants) and six trials assessed short-term glucocorticosteroids versus long-term glucocorticosteroids (565 participants). One additional study assessed complete post-operative glucocorticosteroid avoidance but could only be incorporated into qualitative analysis of the results due to limited data published in an abstract. All trials were at high risk of bias. Only eight trials reported on the type of donor used. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low-quality evidence), graft loss including death (RR 1.15, 95% CI 0.90 to 1.46; low-quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; very low-quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression. Acute rejection and glucocorticosteroid-resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; low-quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low-quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low-quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low-quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta-analyses. AUTHORS' CONCLUSIONS Many of the benefits and harms of glucocorticosteroid avoidance or withdrawal remain uncertain because of the limited number of published randomised clinical trials, limited numbers of participants and outcomes, and high risk of bias in the trials. Glucocorticosteroid avoidance or withdrawal appears to reduce diabetes mellitus and hypertension whilst increasing acute rejection, glucocorticosteroid-resistant rejection, and renal impairment. We could identify no other benefits or harms of glucocorticosteroid avoidance or withdrawal. Glucocorticosteroid avoidance or withdrawal may be of benefit in selected patients, especially those at low risk of rejection and high risk of hypertension or diabetes mellitus. The optimal duration of glucocorticosteroid administration remains unclear. More randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal are needed. These should be large, high-quality trials that minimise the risk of random and systematic error.
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Affiliation(s)
- Cameron Fairfield
- Royal Infirmary Edinburgh ‐ NHS Lothian, Royal Infirmary EdinburghHepatobiliary‐Pancreatic Surgical Services and Edinburgh Transplant Unit51 Little France CrescentEdinburghMidlothianUKEH16 4SA
| | - Luit Penninga
- Rigshospitalet, Copenhagen University HospitalDepartment of Surgery and Transplantation C2122Blegdamsvej 9CopenhagenDenmarkDK‐2100
| | - James Powell
- NHS LothianScottish Liver Transplant UnitRoyal Infirmary of Edinburgh, 51 Little France CrescentEdinburghUKEH16 4SA
| | - Ewen M Harrison
- University of EdinburghClinical Surgery53 Little France CrescentEdinburghMidlothianUKEH16 4SA
| | - Stephen J Wigmore
- Royal Infirmary Edinburgh ‐ NHS Lothian, Royal Infirmary EdinburghHepatobiliary‐Pancreatic Surgical Services and Edinburgh Transplant Unit51 Little France CrescentEdinburghMidlothianUKEH16 4SA
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Chitturi S, Wong VWS, Chan WK, Wong GLH, Wong SKH, Sollano J, Ni YH, Liu CJ, Lin YC, Lesmana LA, Kim SU, Hashimoto E, Hamaguchi M, Goh KL, Fan J, Duseja A, Dan YY, Chawla Y, Farrell G, Chan HLY. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups. J Gastroenterol Hepatol 2018; 33:86-98. [PMID: 28692197 DOI: 10.1111/jgh.13856] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 05/31/2017] [Accepted: 06/25/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Shiv Chitturi
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Simon Kin-Hung Wong
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | | | - Yen-Hsuan Ni
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Hepatitis Research Center, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yu-Cheng Lin
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | | | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Etsuko Hashimoto
- Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | | | - Khean-Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Jiangao Fan
- Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Geoff Farrell
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Fairfield CJ, Harrison EM, Wigmore SJ. Duplicate publication bias weakens the validity of meta-analysis of immunosuppression after transplantation. World J Gastroenterol 2017; 23:7198-7200. [PMID: 29093629 PMCID: PMC5656468 DOI: 10.3748/wjg.v23.i39.7198] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 09/15/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023] Open
Abstract
Duplicate publication can introduce significant bias into a meta-analysis if studies are inadvertently included more than once. Many studies are published in more than one journal to maximize readership and impact of the study findings. Inclusion of multiple publications of the same study within a meta-analysis affords inappropriate weight to the duplicated data if reports of the same study are not linked together. As studies which have positive findings are more likely to be published in multiple journals this leads to a potential overestimate of the benefits of an intervention. Recent advances in immunosuppression strategies following liver transplantation have led to many studies investigating immunosuppressive regimes including immunosuppression monotherapy. In this letter we focus on a recently published meta-analysis by Lan et al investigating studies assessing immunosuppression monotherapy for liver transplantation. The authors claim to have identified fourteen separate randomised studies investigating immunosuppression monotherapy. Seven of the references appear to relate to only three studies which have been subject to duplicate publication. Several similarities can be identified in each of the duplicate publications including similar authorship, identical immunosuppression regimes, identical dates of enrolment and citation of the original publication in the subsequent manuscripts. We discuss the evidence of the duplicate publication inclusion in the meta-analysis.
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Affiliation(s)
- Cameron J Fairfield
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
| | - Ewen M Harrison
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
| | - Stephen J Wigmore
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
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Khan RS, Newsome PN. Non-alcoholic fatty liver disease and liver transplantation. Metabolism 2016; 65:1208-23. [PMID: 26997540 DOI: 10.1016/j.metabol.2016.02.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 02/01/2016] [Accepted: 02/23/2016] [Indexed: 02/07/2023]
Abstract
Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk.
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Affiliation(s)
- Reenam S Khan
- Gastroenterology and Hepatology, NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK, B15 2TH.
| | - Philip N Newsome
- Hepatology, NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK, B15 2TH.
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Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus. Transplantation 2016; 100:1705-13. [DOI: 10.1097/tp.0000000000001228] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Management of post liver transplantation recurrent hepatitis C infection with directly acting antiviral drugs: a review. Hepatol Int 2016; 10:749-61. [PMID: 27337961 DOI: 10.1007/s12072-016-9744-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 05/17/2016] [Indexed: 12/20/2022]
Abstract
Recurrent HCV infection (rHCV) of the liver allograft following transplantation is universal and is associated with poor graft and patient survival in comparison with other indications. Treatment of rHCV infection in the previous era with pegylated interferon and ribavirin was associated with low sustained virological response (SVR) due to poor tolerability, adverse events and graft rejection. Recently, directly acting antiviral drugs (DAA) have been approved for the treatment of hepatitis C infection and a number of clinical trials have been conducted across various centers in the management of rHCV infection of the graft. In this review we discuss about recent studies that have emerged on the use of NS5b polymerase inhibitor, sofosbuvir in combination with second generation protease inhibitor, simeprevir, fixed dose ledipasvir or daclatasvir with or without ribavirin in the treatment of post transplant rHCV infection.
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Siddiqui MS, Charlton M. Liver Transplantation for Alcoholic and Nonalcoholic Fatty Liver Disease: Pretransplant Selection and Posttransplant Management. Gastroenterology 2016; 150:1849-62. [PMID: 26971826 DOI: 10.1053/j.gastro.2016.02.077] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 02/12/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia. Lifestyle contributes to the development and progression of both diseases. Although alcohol abstinence can cause regression of ALD, and weight loss can cause regression of NAFLD, many patients with these diseases develop cirrhosis. ALD and NAFLD account for nearly 30% of liver transplants performed in the United States. Patients receiving liver transplants for ALD or NAFLD have similar survival times as patients receiving transplants for other liver disorders. Although ALD and NAFLD recur frequently after liver transplantation, graft loss from disease recurrence after transplantation is uncommon. Cardiovascular disease and de novo malignancy are leading causes of long-term mortality in liver transplant recipients with ALD or NAFLD.
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Affiliation(s)
- M Shadab Siddiqui
- Division of Gastroenterology & Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Michael Charlton
- Division of Transplant Hepatology, Intermountain Medical Center, Murry, Utah
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Herzer K, Strassburg CP, Braun F, Engelmann C, Guba M, Lehner F, Nadalin S, Pascher A, Scherer MN, Schnitzbauer AA, Zimmermann T, Nashan B, Sterneck M. Selection and use of immunosuppressive therapies after liver transplantation: current German practice. Clin Transplant 2016; 30:487-501. [PMID: 26855333 DOI: 10.1111/ctr.12708] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2016] [Indexed: 01/01/2023]
Abstract
In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus-based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3-6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult-to-treat patient subpopulations.
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Affiliation(s)
- Kerstin Herzer
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.,Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | | | - Felix Braun
- Department for Transplantation Surgery, University Hospital Kiel, Kiel, Germany
| | - Cornelius Engelmann
- Department for Gastroenterology and Rheumatology, Section Hepatology, University of Leipzig, Leipzig, Germany
| | - Markus Guba
- Department for Transplant Surgery, University Hospital Munich, Munich, Germany
| | - Frank Lehner
- Department for Transplant Surgery, University Hospital Hannover, Hannover, Germany
| | - Silvio Nadalin
- Department for General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Andreas Pascher
- Department of Visceral and Transplant Surgery, Charite-Universitätsmedizin Berlin, Berlin, Germany
| | - Marcus N Scherer
- Department for General-, Visceral- and Transplant Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Andreas A Schnitzbauer
- Clinic for General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany
| | - Tim Zimmermann
- Department for Gastroenterology and Hepatology, University Hospital Mainz, Mainz, Germany
| | - Björn Nashan
- Department for Hepatobiliary Surgery and Transplantation, University Hospital Hamburg, Hamburg, Germany
| | - Martina Sterneck
- University Transplant Center, University Hospital Hamburg, Hamburg, Germany
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Fairfield C, Penninga L, Powell J, Harrison EM, Wigmore SJ. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients. Cochrane Database Syst Rev 2015:CD007606. [PMID: 26666504 DOI: 10.1002/14651858.cd007606.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. OBJECTIVES To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Social Sciences Citation Index, The Transplant Library, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) until September 2014. SELECTION CRITERIA Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver-transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding the perioperative period and excluding the occurrence of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. DATA COLLECTION AND ANALYSIS We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed. We assessed the risk of systematic errors using risk of bias domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table. MAIN RESULTS We included 16 completed randomised clinical trials with a total of 1347 participants. We found 10 trials that assessed complete postoperative glucocorticosteroid avoidance (excluding intra-operative use and treatment of rejection) versus short-term glucocorticosteroids (782 participants) and six trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids (565 participants). We found one ongoing trial assessing complete postoperative glucocorticosteroid avoidance versus short-term glucocorticosteroids, which is expected to enrol 300 participants. All trials were at high risk of bias. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low-quality evidence), graft loss including death (RR 1.16, 95% CI 0.91 to 1.48; low-quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; low-quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression. Acute rejection and glucocorticosteroid-resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; moderate-quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low-quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low-quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low-quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta-analyses. AUTHORS' CONCLUSIONS Many of the benefits and harms of glucocorticosteroid avoidance or withdrawal remain uncertain because of the limited number of published randomised clinical trials, limited numbers of participants and outcomes, and high risk of bias in the trials. Glucocorticosteroid avoidance or withdrawal appears to reduce diabetes mellitus and hypertension whilst increasing acute rejection, glucocorticosteroid-resistant rejection, and renal impairment. We could identify no other benefits or harms of glucocorticosteroid avoidance or withdrawal. Glucocorticosteroid avoidance or withdrawal may be of benefit in selected patients, especially those at low risk of rejection and high risk of hypertension or diabetes mellitus. The optimal duration of glucocorticosteroid administration remains unclear. More randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal are needed. These should be large, high-quality trials that minimise the risk of random and systematic error.
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Affiliation(s)
- Cameron Fairfield
- Hepatobiliary-Pancreatic Surgical Services and Edinburgh Transplant Unit, Royal Infirmary Edinburgh - NHS Lothian, Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, Midlothian, UK, EH16 4SA
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Hibi T, Shinoda M, Itano O, Obara H, Kitago M, Abe Y, Yagi H, Tanaka M, Hoshino K, Fujino A, Kuroda T, Kawachi S, Tanabe M, Shimazu M, Kitagawa Y. Steroid minimization immunosuppression protocol using basiliximab in adult living donor liver transplantation for hepatitis C virus-related cirrhosis. Hepatol Res 2015; 45:1178-84. [PMID: 25594837 DOI: 10.1111/hepr.12486] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 01/05/2015] [Accepted: 01/10/2015] [Indexed: 12/24/2022]
Abstract
AIM Recent randomized trials have failed to prove the benefit of steroid-free immunosuppression in liver transplantation for hepatitis C virus (HCV)-related cirrhosis. Furthermore, there is a lack of data on the use of basiliximab in living donor liver transplantation (LDLT). This pilot study evaluated the safety and efficacy of a steroid minimization protocol using basiliximab compared with standard immunosuppression. METHODS A single center, prospective cohort analysis was conducted to compare two immunosuppression regimens in adult recipients who underwent LDLT for HCV since 2004: calcineurin inhibitor/mizoribine/basiliximab (the St- group) and calcineurin inhibitor/mizoribine/steroid (the St+ group). Study end-points were rejection rates, recurrent HCV, patient survival and other adverse events up to 2 years after transplantation. RESULTS A total of 27 consecutive patients were enrolled. Transplantation characteristics were similar between the two groups (14 St- and 13 St+) except ABO incompatible cases being more common in the St+ group. Rejection rates, recurrent HCV, patient survival, fibrosis stage and new-onset diabetes mellitus at 2 years were comparable between the two groups. ABO incompatibility did not affect short- and long-term outcomes. Nine St- and seven St+ recipients underwent interferon and ribavirin therapy for recurrent HCV, with a sustained virological response rate of 33% and 29%, respectively. CONCLUSION A steroid minimization protocol with basiliximab in adult LDLT for HCV is safe and affords equivalent rejection rates compared with standard immunosuppression. However, no significant differences are observed with respect to recurrent HCV, patient survival and metabolic complications.
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Affiliation(s)
- Taizo Hibi
- Department of Surgery, Keio University School of Medicine
| | | | - Osamu Itano
- Department of Surgery, Keio University School of Medicine
| | - Hideaki Obara
- Department of Surgery, Keio University School of Medicine
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine
| | | | - Ken Hoshino
- Department of Surgery, Keio University School of Medicine
| | - Akihiro Fujino
- Department of Surgery, Keio University School of Medicine
| | - Tatsuo Kuroda
- Department of Surgery, Keio University School of Medicine
| | - Shigeyuki Kawachi
- Division of Digestive Surgery and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Motohide Shimazu
- Division of Digestive Surgery and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine
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50
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Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, Wang T, Liang J, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes 2015; 7:881-90. [PMID: 25676209 DOI: 10.1111/1753-0407.12275] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 01/13/2015] [Accepted: 01/27/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.
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Affiliation(s)
- Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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