Liver Transplantation

Liver Transplantation

Author Dilip Chakravarty K Division of HPB Surgery and Liver Transplantation Department of General Surgery Chang Gung Memorial Hospital (Linkou) Taipei, Taiwan (ROC)

Co-authors WC Lee YY Jan Professor and Chief Professor and Chairman Department of Liver and Transplantation Surgery Department of General Surgery Chang Gung Transplantation Institute (Linkou) Chang Gung Memorial Hospital (Linkou) Chang Gung University Chang Gung University Taipei, Taiwan (ROC) Taipei, Taiwan (ROC)

Po-Huang Lee YC Chen Professor of Surgery and Chairman Department of Nephrology Department of Surgery and Chang Gung Memorial Hospital (Linkou) Liver Transplantation Program Chang Gung University National Taiwan University Hospital Taipei, Taiwan (ROC) Taipei, Taiwan (ROC)

Foreword Sir Roy Calne

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—Thomas E Starzl

Contributors

Sir Roy Yorke Calne FRS Miin-Fu Chen MD Arianeb Mehrabi Emeritus Professor of Surgery Professor of Surgery and Department of General, Visceral University of Cambridge and Superintendent, Chang Gung and Transplantation Surgery National University of Singapore Memorial Hospital (Linkou) University of Heidelberg, Im Cambridge, United Kingdom Chang Gung University Neuenheimer Feld 110, 69120 Taipei, Taiwan (ROC) Heidelberg, Germany Masatoshi Makuuchi MD PhD President, Japanese Red Cross Medical Carl-Gustav Groth MD Chao-Long Chen MD Center, 4-1-22 Hiro-o, Shibuya-ku Professor Emeritus Superintendent and Chief Tokyo 150-8935, Japan Transplantation Surgery Department of Liver transplantation Karolinska Institute Chang Gung Memorial Hospital Burckhardt Ringe Fogdevreten 2A SE- 171 77 Kaohsiung Medical Center Department of Surgery Stockholm, Sweden Kaohsiung, Taiwan (ROC) Center for Liver, Biliary and Constantino Fondevila Pancreas Diseases Assistant Professor of Surgery Drexel University College of Medicine Hironori Haga MD Liver Surgery and Liver Transplant Philadelphia, Pennsylvania Associate Professor Department of Surgical Pathology Unit, Institute of Digestive Diseases Pav. 4, 3rd floor, office 19 Sung Gyu Lee Hokkaido University Hospital Hospital Clinic, University of Department of Surgery North 14, West 5, Kita-ku Barcelona, Villarroel 170 Asan Medical Center, Ulsan University Sapporo, 060-8648, Japan Barcelona 08036, Spain 388-1 Poong-Nap Dong Song-Pa Ku, Seoul 138-736, Korea Jordi Bruix Laura Llado Barcelona Clínic Liver Cancer Group Department of Surgery and Hiroto Egawa MD Liver Unit, Hospital Clinic Gastroenterology Organ Transplant Unit Liver Transplant Unit, Hospital U. Kyoto University Hospital CIBERehd, Institute for Biomedical Investigations, August Pi Sunyer Bellvitge, University of Barcelona, 54 Kawara-cho, Sakyo-ku Barcelona, Spain Kyoto-606-8507, Japan Villarroel 170, 08036, Barcelona Catalonia, Spain C/Feixa Llarga s/n, 08907 Hospitalet Ll, Barcelona, Spain Hiroshi Imamura MD Department of Hepatobiliary Nai-Jen Liu MD Jia Fan MD PhD FACS Pancreatic Surgery Chief Liver Cancer Institute Juntendo School of Medicine Division of Therapeutic Endoscopy Zhongshan Hospital, Fudan 2-1-1, Hongo, Bunkyo-ku Department of Hepatogastroenterology University Tokyo 113-8421, Japan Chang Gung Memorial Hospital 180 Feng Lin Road, Shanghai, 200032 Taipei, Taiwan China Seiji Kawasaki MD Department of Hepatobiliary- James Neuberger Pancreatic Surgery, Juntendo Christian S Kuhr MD FACS Liver Unit University, 2-1-1 Director of Transplantation Queen Elizabeth Hospital Hongo Bunkyo-ku, Tokyo 113-8421 Virginia Mason Medical Center Birmingham B15 2TH Japan Seattle, Washington, USA United Kingdom viii Liver Transplantation

Sergio Mies MD PhD Ta Sen Yeh MD PhD. Rei Ping Tang MD Associate Professor of Surgery Professor of surgery Chief of Division of Colorectal Sao Paulo Medical School - USP Chang Gung Memorial Hospital Surgery, Department of Surgery Liver Unit, Instituto Dante Pazzanese Director of Surgical Laboratory Chang Gung Memorial Hospital de Cardiologia, São Paulo - SP Chang Gung University Chang Gung University Brazil Taipei, Taiwan Taipei, Taiwan

Nicolas Jabbour MD FACS Yao-Ming Wu MD Director Chun-Yen Lin MD DPhil (Oxon) Assistant Professor Nazih Zuhdi Transplant Institute Associate Professor Division of Hepatobiliary surgery INTEGRIS Baptist Medical Center Department of Gastroenterology and Transplantation surgery 3300 NW Expressway, 100-3444 Chang-Gung Memorial Hospital and Department of Surgery Oklahoma City, OK 73112-4481 College of Medicine National Taiwan University Hospital USA Chang-Gung University Taipei, Taiwan Taipei, Taiwan Jaime Bosch MD PhD Chun Nan Yeh MD Liver Unit Chih Chung Lin MD Assistant Professor Institut d’Investigacions Biomediques Division of Liver transplantation Department of General Surgery August Pi i Sunyer (IDIBAPS) Anesthesia Chang Gung Memorial Hospital University of Barcelona Department of Anesthesia Chang Gung University Hospital Clýnic, C.Villarroel 170, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan 08036, Barcelona, Spain Chang Gung University Linkou, Taoyuan Taiwan Sung-Yu Chu MD H Ramesh MS MCh FACS FRCS Department of Medical Imaging and Director of Surgical Gastroenterology Interventional Radiology and Liver Transplantation Surgery Ching Sung Lee MD Chang Gung memorial hospital Lakeshore Hospital and Research Division of Therapeutic Endoscopy Linkou, Taoyuan, Taiwan Center, Nettoor, Cochin 682304, Department of Hepatogastroenterology Kerala, India Chang Gung Memorial Hospital Chang Gung University Akshay Kumar Mishra MD Kyu-Bo Sung MD Taipei, Taiwan Deputy Director Department of Radiology (Monitoring and Evaluation/ Asan Medical Center Tsann Long Hwang MD Surveillance) University of Ulsan College of Vice President and Dean AP State AIDS Control Society, Medicine, 388-1, Pungnap-2dong, Department of General Surgery DM and HS Campus Songpa-gu, Seoul 138-736 Chang Gung Memorial Hospital Hyderabad-500095, India Republic of Korea and School of Medicine Chang Gung University SP Samantaray MS Pere Ginès MD Taipei, Taiwan Department of Cardiothoracic and Liver Unit, 7-3 Vascular Surgery, MKCG Medical Institut de Malalties Digestives Hirotaka Tashiro MD College, Berhampur, India Hospital Clinic, IDIBAPS Hiroshima University University of Barcelona 1-2-3 Kasumi, Minami-ku Chin Hsin Chen Villaroel 170, 08036 Hiroshima 734-8551, Japan Department of Proctology Barcelona, Spain Chang Gung Memorial Hospital Rey Hung Hu MD PhD Taoyuan, Taiwan Yuji Soejima Associate Professor Assistant Professor Division of Hepatobiliary Surgery Piyush Joshi MD Department of Surgery and Science and Transplantation Surgery Surgeon Commander Kyushu University, 3-1-1 Maidashi Department of Surgery Classified Specialist Radiology Higashi-Ku, Fukuoka 812-8582 National Taiwan University Hospital Command Hospital Japan Taipei, Taiwan Pune, India Contributors ix

Baiju Senadhipan MS Mch Aratatran Nahak MS Mch Manesh Senan MS MCh MNAMS FRCS Chief of Gastrointestinal Surgery Consultant Cadiothoracic surgeon Consultant Plastic Surgeon Holicross Hospital, Kottiyam, Fortis Hospital, Mohali, Chandigarh KIMS Hospital , Anamugham PO, Kollam, Kerala, India India Anayara, Trivandrum, India

Santosh K Shau MS Ramendrapati Pandey Chih-chi Wang MD Surgeon Commander Institute of Biomedical Science Director Classified Specialist Surgery Chang Gung University Department of General Surgery INHS Jeevanti, Vasco-Da-Gama Taipei, Taiwan Chang Gung Memorial Hospital Goa, India Kaohsiung Medical Center Kaohsiung, Taiwan (ROC) Chai Chiah Yang MD M Jayashri PhD Department of Surgery Department of Molecular Virology Vani Chakravarty MS MRCOG Taipei Medical University Hospital Chung Gung University Consultant Gynecologist Taipei, Taiwan Taipei, Taiwan Bangalore, India

Foreword

The book Liver Transplantation is the result of an enormous amount of work and scholarship, and to put so many different aspects of liver transplantation into one volume is a significant achievement. Dr Dilip and his colleagues have produced a comprehensive text on liver transplantation covering all aspects of this very complicated subject, starting with the history, the relevant anatomy of the liver, clinical and ethical aspects of liver transplantation with particular emphasis on the ethics of adult liver donors. The text is well illustrated with particularly good photographs and details of surgical techniques. The complications and short- and long-term results are discussed, including the morbidity and mortality of living donation. The medical and anesthetic aspects of liver transplantation and pediatric liver transplantation are also described and the individual details of special diseases. As liver transplantation has no geographical boundaries, the book will be welcomed by the transplant units. It provides a very fulsome handbook of the subject, suitable for surgeons and physicians and especially young surgeons in training, to give them a readily available and practical “hands-on” account of liver transplantation. The authors are to be congratulated on this up-to-date and authoritative review of liver transplantation, which should be available in all medical libraries and the offices of doctors, nurses and other health care personnel involved in the complicated aspects of liver transplantation.

Sir Roy Calne FRS Emeritus Professor of Surgery; University of Cambridge Visiting Professor to Department of Surgery; National University of Singapore Cambridge, United Kingdom

Preface

Hepatitis B virus is the most common cause of cirrhosis and hepatocellular carcinoma since many decades in Taiwan and rest of Asia, whereas hepatitis C virus is the leading cause in the Western countries. In Taiwan even though the first hepatic surgery program was started in 1954 by Dr TY Lin, and first experimental auxiliary liver transplantation was attempted by Dr CJ Lee in 1960; clinically first successful deceased donor liver transplantation was performed by Dr CL Chen in 1984. In present transplantation scenario, very good results can be achieved after liver transplantation due to the advances in surgical techniques and better postoperative care. Evolution of living donor liver transplantation has reduced the number of patients on waiting list and increased the number of transplants all over the world. This book “Liver Transplantation” is a complete book on liver transplantation which comprehensively describes almost every aspect of the liver transplantation including donor selection, surgical techniques practised in different types of transplantation, postoperative management, long-term complications and the management of complications of end stage liver disease. I believe this book is very helpful for the fellows who visit any liver transplantation unit. Most authors write their own experience and protocols followed at their transplant units. But this book includes not only our experience but also describes an overall comprehensive review of transplantation techniques and principles practiced in both east and west. The book is completed by the contribution of professionals from three different medical universities in Taiwan and many pioneers from across the world. We are very thankful to all the contributors for making this project successful. I appreciate the initiative taken by Dr Dilip and his interest and motivation in involving Chang Gung Memorial Hospital (Linkou and Kaohsiung branches) and National Taiwan University Hospital together along with many professionals from across the world to complete this project.

Prof Po-Huang Lee MD, PhD Professor of Surgery and Chairman Department of Surgery and Liver Transplantation Program National Taiwan University Hospital Taipei, Taiwan (ROC)

Acknowledgments

Liver transplantation as a whole is a challenging procedure in the field of surgery. Even though four decades have passed ever since the first successful liver transplantation, new innovative techniques are emerging each and every day. Evolution of living donor liver transplantation has changed the concept of liver transplantation. Keeping in view of changing trends in approach to the management of a patient with end stage liver disease and recent advances in the field of liver transplantation, it is essential to have a book which narrates everything about liver transplantation starting from the management of complications in a cirrhosis patient to long-term outcomes in liver transplantation. Every new fellow who enters a liver transplantation unit finds it difficult to understand the principles and techniques of liver transplantation. Each center designs its own protocols based on available resources. It takes time for a new comer to get acquainted with the transplantation procedures, postoperative management, immunosuppression and management of early and late complications of liver transplantation. The purpose of writing the book is to give information briefly and lucidly about the various surgical techniques followed at different institutions with a comparative analysis of the long-term results. This book describes different types of liver transplantations including their technical aspects, pre- and postoperative management, early and late complications and long-term outcome both in the Eastern and Western countries. We tried to narrate all the recent innovations in surgical techniques and management in the field of liver transplantation in depth. I am extremely obliged to chief editors of all the journals we referred, all the contributors across the globe who cooperated in contributing material in the form of script, illustrations and tables, and made this one and half year long project successful. My sincere thanks to liver transplant teams of CGMH (Linkou), CGMH- Kaohsiung Medical Center and National Taiwan University Hospital. I am thankful to Prof. Miin-Fu Chen, Prof. Yi-Yin Jan, Prof. Chao-Long Chen, Prof. Po-Huang Lee, Prof. Wei-Chen Lee, Prof. Tsann-Long Hwang, Prof. Rei-Ping Tang, Prof. Ta-Sen Yeh and Dr. Yung-Chang Chen for their motivation, support and contribution to this project. I am very grateful to Sir Roy Calne for his timely guidance and suggestions in improving the quality of this book to meet the international standards. My wholehearted thanks to Ariel for her continuous selfless support and cooperation during the entire course of this project. She is closely involved in every aspect of this book starting from manuscript writing, to the final editing process. Such a challenging project would not have been possible without her cooperation. The people who made this book reader friendly and attractive by their graphic designing skills and hard work are Shu Fang Huang, Stone, Yueh Chia He, Stacey Hsu, Ming yu Lin and Ivy Cheng. I personally remain indebted to them. My sincere thanks to Dr. Hitesh Gopalan for his inspiration and timely suggestions. The people behind my success are my parents, my family Dr Vani, Navisha and Anushka. My sincere thanks to Shri Jitendar P Vij (Chairman and Managing Director), Mr Tarun Duneja (Director-Publishing) and Staff of Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India, who made my dreams, come true.

Dilip Chakravarty K Division of HPB Surgery and Liver Transplantation Department of General Surgery Chang Gung Memorial Hospital (Linkou) Taipei, Taiwan (ROC)

Contents

Abbreviations ...... xix 1. History of Liver Transplantation ...... 1 2. Anatomy of Liver ...... 8 3. UNOS, Organ Allocation Policy and MELD Score ...... 24 4. Indications and Contraindications of Liver Transplantation ...... 32 5. Liver Transplantation Team ...... 39 6. Evaluation of Live Donor ...... 41 7. Graft Volume Estimation and Donor with Fatty Liver ...... 54 8. Liver Donation after Brain Death and Cardiac Death ...... 58 (A) Heart-beating Donors/Donation After Brain Death (B) Donation after Cardiac Death (DCD) 9. Marginal Donor and Donor Risk Index ...... 67 10. Donor Surgery ...... 70 (A) Right Lobe Graft (B) Left Lateral Segment (C) Right Posterior Segment or Right Lateral Sector Graft (D) Left Lobes Graft (E) Deceased Donor Hepatectomy 11. Graft Preservation and Bench Procedure...... 90 12. Recipient Surgery ...... 97 (A) Live Donor Liver Transplantation: Recipient Hepatectomy (B) Right Lobe Graft (C) Left Lobe Graft (D) Left Lateral Segment Graft (E) Recipient Surgery for Deceased Donor Liver Transplantation 13. Reperfusion Syndrome and Preservation Injury ...... 118 14. Technical Modifications in Recipient Surgery...... 120 15. Small for Size Syndrome ...... 127 16. Split Liver Transplantation ...... 131 17. Dual Grafts ...... 140 18. Auxiliary Partial Orthotopic Liver Transplantation (APOLT) ...... 144 19. Domino Liver Transplantation ...... 149 20. Postoperative Care and Immunosuppression ...... 155 21. Immunosuppression Drugs ...... 166 xviii Liver Transplantation

22. Hepatic Hemodynamics and Role of Doppler Ultrasonography ...... 181 (A) Hepatic Hemodynamics (B) Doppler Ultrasonography in Liver Transplantation 23. ABO-Incompatible Liver Transplantation ...... 191 24. Electrolyte Abnormalities in ESLD ...... 197 25. Immunology of Transplantation ...... 204 26. Early Complications of Liver Transplantation ...... 213 (A) Primary Nonfunction (B) Allograft Rejection (C) Biliary Complications (D) Vascular Complications (E) Post-transplant Infections 27. Role of Liver Biopsy in Transplantation ...... 275 28. Renal Dysfunction in Liver Transplantation ...... 282 29. Long-term Care of Recipient...... 288 30. Pregnancy after Liver Transplantation ...... 298 31. Recurrent Diseases after Liver Transplantation ...... 301 32. Retransplantation ...... 310 33. Pediatric Liver Transplantation ...... 312 34. Anesthesia in Liver Transplantation ...... 320 35. Extracorporeal Liver Supporting Systems ...... 329 36. Health-related Quality of Life ...... 335 37. Liver Transplantation in Asia and Western Countries ...... 340 38. Hepatocellular Carcinoma and Liver Transplantation ...... 347 39. Hepatitis B Virus and Liver Transplantation ...... 358 40. Hepatitis C Virus and Liver Transplantation...... 370 41. Alcoholism and Liver Transplantation ...... 378 42. Autoimmune Liver Diseases ...... 383 43. Acute Liver Failure ...... 388 44. Metabolic Liver Diseases ...... 397 45. Non-alcoholic Fatty Liver Disease ...... 402 46. Wilson’s Disease ...... 407 47. Budd-Chiari Syndrome ...... 411 48. Recent Advances in Liver Transplantation ...... 415 (A) Hepatocyte Transplantation (B) Xenotransplantation (C) Stem Cell Transplantation 49. Complications of ESLD ...... 429 (A) Ascites (B) Portal Hypertension and Vericeal Bleeding (C) Hepatorenal Syndrome (D) Hepatic Encephalopathy (E) Hepatopulmonary Syndrome (F) Spontaneous Bacterial Peritonitis (G) Hyponatremia

Index ...... 465 Abbreviations

A ECG Electrocardiogram ABO-I ABO-Incompatibility EDV End diastolic volume ACR Acute cellular rejection EHBA Extrahepatic biliary atresia AD/ADV Adefovir dipivoxil ELTR European liver transplant registry AFP Alfa-fetoprotein ENBD Endoscopic nasobiliary drainage ALDLT Adult living donor liver transplantation ERCP Endoscopic retrograde cholangiopancreatography ALT Alanine amintransferase ESLV Estimated standard liver volume AMR Antibody mediated rejection ESLD End stage liver disease APOLT Auxiliary partial orthotopic liver transplantation ESRD End stage renal disease AZA Azathioprine EVR Early viral response APTT Activated partial thromboplastin time F AS Ananstomotic stricture FFP Fresh frozen plasma AST Aspartate amino transferase FHF Fulminant hepatic failure AVT Antiviral therapy G B GDA Gastroduodenal artery BD Bile duct GFR Glomerular filtration rate BMI Body mass index GRWR Graft recipient weight ratio C GV Graft volume γ CAH Chronic active hepatitis GGT -Glutamyl transpeptidase CBD Common bile duct H CBF Cerebral blood flow HAART Highly active antiretroviral therapy CC Choledocho-choledochostomy HAF Hepatic arterial flow CCO Continuous cardiac output CHA Common hepatic artery HA Hepatic artery CHB Chronic hepatitis B HAI Hepatic artery infusion CIN/CNI Calcineurin inhibitor HAT Hepatic artery thrombosis CIT Cold ischemic time HAV Hepatitis A virus CMV Cytomegalovirus HBV Hepatitis B virus CPHT Cavoportal hemitransposition HCC Hepatocellular carcinoma CPP Cerebral perfusion pressure HCV Hepatitis C virus CR Chronic rejection HDV Hepatitis D virus Cs A Cyclosporine A HIDA scan Hepato-iminodiacetic acid scan CT Scan Computerized tomography scan HLT Heterotopic liver transplantation CTP Child-Turcotte-Pugh score HPCS Hemiportocaval shunt CVVHD Continuous venovenous hemodialysis HRQL Health-related quality of life HRS Hepatorenal syndrome D HSV Herpes simplex virus DDLT Deceased donor liver transplantation HTK Histidine-Tryptophan-Ketoglutarate DRI Donor risk index I DUS Doppler ultrasonography IJV Internal jugular vein E IL Interleukin EBV Epstein-Barr virus IMV Inferior mesenteric vein xx Liver Transplantation

INR International normalized ratio PTCD Percutaneous transhepatic cholangiographic IRHV Inferior right hepatic vein drainage IUGR Intrauterine growth retardation PTLD Post-transplant lymphoproliferative disease ICP Infracranial pressure PT Prothrombin time IVC Inferior vena cava PTT Partial thromboplastin time IVIG Intravenous immunoglobulin PVBF Portal vein blood flow PVF Portal vein flow L PVI Portal vein infusion LAM Lamivudine PVP Portal venous pressure LDLT Living donor liver transplantation PV Portal vein LGA Left gastric artery PVT Portal vein thrombosis LHA Left hepatic artery LHV Left hepatic vein R LLG Left lobe graft RHA Right hepatic artery LPV Left portal vein RHV Right hepatic vein LT/LTX Liver transplantation RI Resistive index RLG Right lobe graft M RLV Residual liver volume MARS Molecular adsorbent recirculating system RPA Renoportal anastomosis MDCT Multi-detector computer tomography RPV Right portal vein MELD Model for end-stage liver disease RRT Renal replacement therapy MHA Middle hepatic artery RVR Rapid viral response MHV Middle hepatic vein MMF Mycophenolate mofetil S MPA Mycophenolic acid SAL Splenic artery ligation MPV Main portal vein SAT Systolic acceleration time MRCP Magnetic resonance cholangiopancreatography SBP Subacute bacterial peritonitis MRHV Middle right hepatic vein SFSG Small for size graft MRI Magnetic resonance imaging SFSS Small for size syndrome SI Situs inversus N SLT Split liver transplantation SMA Superior mesenteric artery NAS Non-anastomotic stricture SMV Superior mesenteric vein NASH Nonalcoholic steatohepatitis SPSS Splenic artery steal syndrome SRR Steroid resistant rejection O SVR Sustained viral response OLT Orthotopic liver transplantation SVR Systemic vascular resistance OPO Organ procurement organization OPTN Organ procurement transplant network T TACE Transarterial catheter embolisation P TNF Tumor necrotic factor TPA/tPA Tissue plasminogen activator PAH Pulmonary arterial hypertension TTFM Transient time flow meter PAP Pulmonary arterial pressure PBC Primary biliary cirrhosis U PCP Pneumocystis Carinii pneumonia ULN Upper normal limit PCR Polymerase chain reaction UNOS United Network for Organ Sharing PE Plasma exchange or plasmapheresis USG/US Ultrasonography PELD Pediatric end stage liver disease UW University of Wisconsin PGB Piggyback PI Pulsatility index V PNF Primary nonfunction VB Venovenous bypass PPH Portopulmonary hypertension VZV Varicella zoster virus PSC Primary sclerosing cholangitis PSV Peak systolic velocity W PT Prothrombin time WIT Warm ischemia time