Sinusoidal obstruction syndrome surgery: Difference between revisions

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liver transplant
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=== Patient evaluation prior to transplantation ===
Pre-transplant [[patient]] evaluation has the following objectives: 
* Assesment of ability of the [[patient]] to withstand [[surgery]]
* Assesment of ability of the [[patient]] to withstand [[immunosuppression]] 
* Assessment of [[Patient|patients]] demands of post-transplantation care
Pre-transplant evaluation is particularly aggressive in patients prior to [[Organ transplant|transplantation]] to minimize post operative morbidity and mortality due to effects of surgery and [[Immunosuppression|immunosuppressive therapy]].The following evaluations are required:
* Cardiopulmonary 
* Screening for [[Cancer of unknown primary origin|occult cancer]]
* Screening for occult [[infection]] 
* [[Psychosocial|Psychosocial evaluation]]
==== Laboratory investigations ====
Laboratory investigations essential for patient evaluation prior to liver transplantation are as follows: 
==== General investigations ====
* [[Liver function tests]]:
** [[Bilirubin]] levels
** [[Alanine transaminase|ALT]] levels
** [[Aspartate transaminase|AST]] levels
** [[Alkaline phosphatase|ALP]] levels
** [[Prothrombin time|International normalized ratio [INR]]]
* [[Blood typing|ABO-Rh blood typing]] 
* [[Calcium]] levels
* [[Vitamin D]] levels
* [[Complete blood count]] 
* [[Creatinine clearance]] 
==== Cause specific investigations ====
* Serum [[Sodium|Na]] levels
* Serum [[alpha-fetoprotein]] 
* [[Serology]]: 
** [[Hepatitis A]], [[Hepatitis B|B]] and [[Hepatitis C|C]] 
** [[Human Immunodeficiency Virus (HIV)|Human immunodeficiency virus]]
** [[Cytomegalovirus]]
** [[Epstein Barr virus|Epstein-Barr virus]] 
** [[Chickenpox|Varicella]] 
* [[Urine|Urinalysis]]
* Urine [[:Category:Drugs|drug]] screen
==== Cardiopulmonary evaluation ====
Cardiopulmonary evaluation helps in the evaluation of the [[patient]] for pathologies that need to be ruled out prior to transplantation:<ref name="pmid24716201">{{cite journal |vauthors=Martin P, DiMartini A, Feng S, Brown R, Fallon M |title=Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation |journal=Hepatology |volume=59 |issue=3 |pages=1144–65 |year=2014 |pmid=24716201 |doi= |url=}}</ref><ref name="pmid14583357">{{cite journal |vauthors=Zoghbi GJ, Patel AD, Ershadi RE, Heo J, Bynon JS, Iskandrian AE |title=Usefulness of preoperative stress perfusion imaging in predicting prognosis after liver transplantation |journal=Am. J. Cardiol. |volume=92 |issue=9 |pages=1066–71 |year=2003 |pmid=14583357 |doi= |url=}}</ref>
* [[Heart|Cardiac]] pathologies:<ref name="pmid16498651">{{cite journal |vauthors=Guckelberger O, Mutzke F, Glanemann M, Neumann UP, Jonas S, Neuhaus R, Neuhaus P, Langrehr JM |title=Validation of cardiovascular risk scores in a liver transplant population |journal=Liver Transpl. |volume=12 |issue=3 |pages=394–401 |year=2006 |pmid=16498651 |doi=10.1002/lt.20722 |url=}}</ref><ref name="pmid9346688">{{cite journal |vauthors=Plotkin JS, Scott VL, Pinna A, Dobsch BP, De Wolf AM, Kang Y |title=Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation |journal=Liver Transpl Surg |volume=2 |issue=6 |pages=426–30 |year=1996 |pmid=9346688 |doi= |url=}}</ref>
** [[Coronary heart disease|Coronary artery disease]] 
** [[Valvular heart disease]] 
** [[Cardiomyopathy]]
* [[Lung|Pulmonary]] pathologies:<ref name="pmid12540791">{{cite journal |vauthors=Colle IO, Moreau R, Godinho E, Belghiti J, Ettori F, Cohen-Solal A, Mal H, Bernuau J, Marty J, Lebrec D, Valla D, Durand F |title=Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study |journal=Hepatology |volume=37 |issue=2 |pages=401–9 |year=2003 |pmid=12540791 |doi=10.1053/jhep.2003.50060 |url=}}</ref><ref name="pmid14762853">{{cite journal |vauthors=Krowka MJ, Mandell MS, Ramsay MA, Kawut SM, Fallon MB, Manzarbeitia C, Pardo M, Marotta P, Uemoto S, Stoffel MP, Benson JT |title=Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database |journal=Liver Transpl. |volume=10 |issue=2 |pages=174–82 |year=2004 |pmid=14762853 |doi=10.1002/lt.20016 |url=}}</ref><ref name="pmid11965583">{{cite journal |vauthors=Starkel P, Vera A, Gunson B, Mutimer D |title=Outcome of liver transplantation for patients with pulmonary hypertension |journal=Liver Transpl. |volume=8 |issue=4 |pages=382–8 |year=2002 |pmid=11965583 |doi=10.1053/jlts.2002.31343 |url=}}</ref>
** [[Pulmonary hypertension]] 
** [[Hepatopulmonary syndrome]] 
** [[Restrictive lung disease]] 
** [[Chronic obstructive pulmonary disease|Obstructive lung disease]]
* The following tests are done for the cardiopulmonary evaluation of a patient:<ref name="pmid24716201" /><ref name="pmid22763103">{{cite journal |vauthors=Lentine KL, Costa SP, Weir MR, Robb JF, Fleisher LA, Kasiske BL, Carithers RL, Ragosta M, Bolton K, Auerbach AD, Eagle KA |title=Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation |journal=J. Am. Coll. Cardiol. |volume=60 |issue=5 |pages=434–80 |year=2012 |pmid=22763103 |doi=10.1016/j.jacc.2012.05.008 |url=}}</ref><ref name="pmid21737011">{{cite journal |vauthors=Raval Z, Harinstein ME, Skaro AI, Erdogan A, DeWolf AM, Shah SJ, Fix OK, Kay N, Abecassis MI, Gheorghiade M, Flaherty JD |title=Cardiovascular risk assessment of the liver transplant candidate |journal=J. Am. Coll. Cardiol. |volume=58 |issue=3 |pages=223–31 |year=2011 |pmid=21737011 |doi=10.1016/j.jacc.2011.03.026 |url=}}</ref> 
** [[Pulse oximetry]]<ref name="pmid17392034">{{cite journal |vauthors=Arguedas MR, Singh H, Faulk DK, Fallon MB |title=Utility of pulse oximetry screening for hepatopulmonary syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=5 |issue=6 |pages=749–54 |year=2007 |pmid=17392034 |doi=10.1016/j.cgh.2006.12.003 |url=}}</ref> 
** Screening for [[hepatopulmonary syndrome]]:
*** Indicates worse prognosis in cirrhotic patients and qualifies patients for standard [[MELD Score|Model for End-stage Liver Disease (MELD) exception points]]
**** [[Hepatopulmonary syndrome]] is characterized by the following:
***** [[Liver]] disease 
***** Intrapulmonary vascular dilatations
***** Impaired [[oxygenation]]
** [[Arterial blood gas]] (ABGs):
*** ABGs are performed in patients with normal [[pulse oximetry]] in order to calculate age-adjusted [[alveolar-arterial gradient]]
** [[Chest X-ray|Chest imaging]]
** [[Spirometry|Pulmonary function testing]]
** [[Electrocardiogram]]:
*** Electrocardiogram helps detect the presence of the following conditions:
**** [[Cardiac arrhythmia|Cardiac arrhythmias]]
**** Conduction defects
** Signs of the following:
*** [[Hypertrophy (medical)|Hypertrophy]] of the [[Heart|cardiac]] chamber 
*** Prior cardiac [[ischemia]] 
** [[Cardiac stress test|Cardiac stress testing]]:<ref name="pmid21898768">{{cite journal |vauthors=Prentis JM, Manas DM, Trenell MI, Hudson M, Jones DJ, Snowden CP |title=Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation |journal=Liver Transpl. |volume=18 |issue=2 |pages=152–9 |year=2012 |pmid=21898768 |doi=10.1002/lt.22426 |url=}}</ref>
*** [[Cardiac stress testing|Noninvasive cardiac testing]] is performed in the following cases:
**** [[Patient|Patients]] older than 40 years of age 
**** [[Patient|Patients]] younger than forty years of age, with multiple risk factors for [[Coronary heart disease|coronary artery disease]]
** If abnormalities are noticed on [[Cardiac stress test|cardiac stress testing]], the [[patient]] undergoes [[cardiac catheterization]] 
** In case of presence of clinically significant [[Coronary heart disease|coronary artery stenosis]], [[revascularization]] before transplantation is considered
** [[Echocardiography]]:
*** [[Echocardiography|Transthoracic contrast-enhanced echocardiography]]:
**** [[Valvular heart disease]] 
**** Suspected cases of [[hepatopulmonary syndrome]]:
***** If the [[oxygen saturation]] on [[pulse oximetry]] is low (<96 percent) 
**** [[Portopulmonary hypertension]]:
***** [[Pulmonary arterial hypertension|Pulmonary arterial hypertension (PAH)]] associated with [[portal hypertension]]
==== Cancer screening ====
Prior to transplantation, screening for the following carcinomas is recommended:
* Hepatocellular carcinoma ([[Hepatocellular carcinoma|HCC]]): 
** Investigations for the staging of HCC include:
*** [[Computed tomography|Abdominal CT scan]] 
*** [[Magnetic resonance imaging|MRI]] 
** Investigations for the assessment of invasion of [[Circulatory system|vasculature]]: 
*** Multiphase contrast-enhanced [[Computed tomography|CT scanning]] 
*** [[Magnetic resonance imaging|Contrast-enhanced MRI]]
*** [[Ultrasound|Transabdominal ultrasonography]] with [[Doppler|Doppler imaging]] 
*** [[Contrast medium|Contrast]]-enhanced [[Medical ultrasonography|ultrasonography]] 
* [[Skin cancer]]: 
** Skin examination
** Biopsy incase of suspected lesions
* [[Colorectal cancer|Colon cancer]]:
** [[Colonoscopy]] for screening of colon cancer is done in case of:
*** Age of 50 years
*** History of [[Colorectal cancer|colon cancer]] in a first-degree relative
*** Patients with [[primary sclerosing cholangitis]]
* Screening is also done for the following:
** [[Cervical cancer]] 
** [[Breast cancer]] 
** [[Prostate cancer]]
==== Upper GI endoscopy ====
* To detect [[varices]]
==== Bone densitometry ====
* [[Screening (medicine)|Screening]] for [[osteoporosis]] 
* Osteoporotic patients are treated with [[Bisphosphonate|bisphosphonates]] before transplanatation
==== Vaccinations and evaluation for infection ====
* [[Virus|Viral]] [[Serology|serologies]]
* Workup for [[tuberculosis]]: 
** Skin testing 
** [[Interferon-gamma]] release assay 
* Screening in endemic areas for: 
** [[Strongyloidiasis|Strongyloides]]
** [[Coccidioidomycosis|Coccidiomycosis]] 
* [[Vaccination|Vaccinations]] recommended before liver transplantation include:
** [[Streptococcus pneumoniae|Pneumococcus]] 
** [[Tetanus]] 
** [[Pertussis]] 
** [[Diphtheria]] 
** [[Hepatitis A|Hepatitis A, B]] 
==== Psychosocial evaluation and education ====
* Discussion of risks and benefits of [[Organ transplant|transplantation]]
* Ensuring social support
* [[Substance abuse|Substance use disorders]] eg [[alcohol]] must be treated prior to transplantation:
** [[Rehabilitation (neuropsychology)|Rehabilitation]]
** Abstinence program
* [[Education]] of the family
* [[Compliance|Patient compliance]] with elaborate behavioral and medical regimens
===Techniques===
* Before [[Organ transplant|transplantation]], [[liver]] support therapy might be indicated ( called bridging-to-[[Organ transplant|transplantation]]). 
* Artificial [[liver]] support like [[liver dialysis]] or bioartificial [[liver]] support concepts are currently under preclinical and clinical evaluation. 
* Virtually all liver transplants are done in an orthotopic fashion, that is the native [[liver]] is removed and the new [[liver]] is placed in the same anatomic location. 
* The [[Organ transplant|transplant]] operation may be conceptualized as consisting of:<ref name="pmid16035067">{{cite journal |vauthors=Eghtesad B, Kadry Z, Fung J |title=Technical considerations in liver transplantation: what a hepatologist needs to know (and every surgeon should practice) |journal=Liver Transpl. |volume=11 |issue=8 |pages=861–71 |year=2005 |pmid=16035067 |doi=10.1002/lt.20529 |url=}}</ref><ref name="pmid15859440">{{cite journal |vauthors=Tuttle-Newhall JE, Collins BH, Desai DM, Kuo PC, Heneghan MA |title=The current status of living donor liver transplantation |journal=Curr Probl Surg |volume=42 |issue=3 |pages=144–83 |year=2005 |pmid=15859440 |doi= |url=}}</ref><ref name="pmid15541931">{{cite journal |vauthors=Steadman RH |title=Anesthesia for liver transplant surgery |journal=Anesthesiol Clin North America |volume=22 |issue=4 |pages=687–711 |year=2004 |pmid=15541931 |doi=10.1016/j.atc.2004.06.009 |url=}}</ref><ref name="pmid26449392">{{cite journal |vauthors=Park JI, Kim KH, Lee SG |title=Laparoscopic living donor hepatectomy: a review of current status |journal=J Hepatobiliary Pancreat Sci |volume=22 |issue=11 |pages=779–88 |year=2015 |pmid=26449392 |doi=10.1002/jhbp.288 |url=}}</ref><ref name="pmid24716201">{{cite journal |vauthors=Martin P, DiMartini A, Feng S, Brown R, Fallon M |title=Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation |journal=Hepatology |volume=59 |issue=3 |pages=1144–65 |year=2014 |pmid=24716201 |doi= |url=}}</ref>
** [[Hepatectomy]] (liver removal) phase   
** Anhepatic (no [[liver]]) phase   
** Postimplantation phase 
* The surgery is done through a large [[incision]] in the upper [[abdomen]]. 
* The [[hepatectomy]] involves the division of:<ref name="pmid14625822">{{cite journal |vauthors=Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, Neuhaus P, Lerut J, Salizzoni M, Pollard S, Muhlbacher F, Rogiers X, Garcia Valdecasas JC, Berenguer J, Jaeck D, Moreno Gonzalez E |title=Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry |journal=Liver Transpl. |volume=9 |issue=12 |pages=1231–43 |year=2003 |pmid=14625822 |doi=10.1016/j.lts.2003.09.018 |url=}}</ref><ref name="pmid16691300">{{cite journal |vauthors=Shah SA, Levy GA, Adcock LD, Gallagher G, Grant DR |title=Adult-to-adult living donor liver transplantation |journal=Can. J. Gastroenterol. |volume=20 |issue=5 |pages=339–43 |year=2006 |pmid=16691300 |pmc=2659892 |doi= |url=}}</ref>
** All [[Ligamentous laxity|ligamentous]] attachments to the [[liver]] 
** [[Common bile duct]] 
** [[Hepatic artery]] 
** [[Portal vein]] 
* Usually, the retrohepatic portion of the [[inferior vena cava]] is removed along with the [[liver]], although an alternative technique preserves the recipient's [[Vena cavae|vena cava]] ("piggyback" technique). 
* The donor's [[blood]] in the [[liver]] is replaced by an ice-cold organ storage solution, such as UW ([[Viaspan]]) or  [[Histidine-tryptophan-ketoglutarate|HTK]] until the [[allograft]] [[liver]] is implanted. 
* Implantation involves [[Anastomosis|anastomoses]] (connections) of the [[inferior vena cava]], [[portal vein]], and [[hepatic artery]]. 
* After [[blood]] flow is restored to the new [[liver]], the [[Bile duct|biliary]] ([[bile duct]]) [[anastomosis]] is constructed, either to the recipient's own [[bile duct]] or to the [[small intestine]]. 
* The [[surgery]] usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the [[surgeon]]. 
* The large majority of liver transplants use the entire [[liver]] from a non-living donor for the [[Organ transplant|transplant]], particularly for adult recipients.<ref name="pmid15376341">{{cite journal |vauthors=Reddy S, Zilvetti M, Brockmann J, McLaren A, Friend P |title=Liver transplantation from non-heart-beating donors: current status and future prospects |journal=Liver Transpl. |volume=10 |issue=10 |pages=1223–32 |year=2004 |pmid=15376341 |doi=10.1002/lt.20268 |url=}}</ref><ref name="pmid15776458">{{cite journal |vauthors=Martinez OM, Rosen HR |title=Basic concepts in transplant immunology |journal=Liver Transpl. |volume=11 |issue=4 |pages=370–81 |year=2005 |pmid=15776458 |doi=10.1002/lt.20406 |url=}}</ref> 
* A major advance in [[Pediatrics|pediatric]] liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult [[liver]] is used for an infant or child. 
* Further developments in this area included split liver transplantation in which one [[liver]] is used for transplants for two recipients and [[living donor liver transplantation]], in which a portion of the liver of a healthy person is removed and used as the [[allograft]]. 
* Living [[Blood donation|donor]] liver transplantation for [[Pediatrics|pediatric]] recipients involves removal of approximately 20% of the [[liver]] ([[Couinaud]] segments 2 and 3).
{{#ev:youtube|v=hquWw4rRHh8}}
===Orthotopic Liver Transplantation===
* Donor selection based on [[Cardiac biomarkers|biomarkers]] and risk indices is a crucial aspect of orthotopic liver transplantation and involves:
** Preference of younger over older donors 
** Appropriate selection of recipients 
** Age based matching of donors and recipients
* [[Surgery]] for liver transplantation involves the following steps:<ref name="pmid9290801">{{cite journal |vauthors=Friend PJ |title=Liver transplantation |journal=Transplant. Proc. |volume=29 |issue=6 |pages=2716–8 |year=1997 |pmid=9290801 |doi= |url=}}</ref><ref name="pmid9448876">{{cite journal |vauthors=McCaughan GW, Koorey DJ |title=Liver transplantation |journal=Aust N Z J Med |volume=27 |issue=4 |pages=371–8 |year=1997 |pmid=9448876 |doi= |url=}}</ref><ref name="pmid16498709">{{cite journal |vauthors=Middleton PF, Duffield M, Lynch SV, Padbury RT, House T, Stanton P, Verran D, Maddern G |title=Living donor liver transplantation--adult donor outcomes: a systematic review |journal=Liver Transpl. |volume=12 |issue=1 |pages=24–30 |year=2006 |pmid=16498709 |doi= |url=}}</ref>
** Excision of the [[liver]] of the recipient
** Separation of:
*** [[Common bile duct]]
*** [[Superior vena cava]]
*** [[Inferior vena cava]]
*** [[Hepatic artery]]
*** [[Portal vein]]
** During [[surgery]], venovenous bypass helps in diversion of flow from disrupted [[Inferior vena cava|Inferior Vena Cava]] ([[Inferior vena cava|IVC]]) and [[portal vein]] to Superior Vena Cava (SVC)
** In order to maintain [[blood]] flow of the [[hepatic artery]], anastomosis of donor [[liver]] at vascular sites is performed
** Then, [[anastomosis]] of the [[Bile duct|bile ducts]] of the [[graft]] and recipient is performed
** In addition, choledochojejunostomy may also be performed incase of bile duct pathology
** Postoperatively, stenting of the [[bile duct]] using a T-tube may help monitor:
*** Production of [[bile]]
*** Postoperative function of the [[Liver|hepatic]] [[graft]]
===Immunosuppressive management===
* Postimplant [[immunosuppression]] ensures survival of the [[patient]] and [[allograft]]
* [[Immunosuppressive agents]] used in patients receiving a liver transplant include the following:<ref name="pmid15606606">{{cite journal |vauthors=Perry I, Neuberger J |title=Immunosuppression: towards a logical approach in liver transplantation |journal=Clin. Exp. Immunol. |volume=139 |issue=1 |pages=2–10 |year=2005 |pmid=15606606 |pmc=1809260 |doi=10.1111/j.1365-2249.2005.02662.x |url=}}</ref><ref name="pmid25208324">{{cite journal |vauthors=Papadopoulos-Köhn A, Achterfeld A, Paul A, Canbay A, Timm J, Jochum C, Gerken G, Herzer K |title=Daily low-dose tacrolimus is a safe and effective immunosuppressive regimen during telaprevir-based triple therapy for hepatitis C virus recurrence after liver transplant |journal=Transplantation |volume=99 |issue=4 |pages=841–7 |year=2015 |pmid=25208324 |doi=10.1097/TP.0000000000000399 |url=}}</ref>
** [[Cyclosporine]]
** [[Everolimus]]
** [[Mycophenolate]]
** [[Corticosteroid|Corticosteroids]]
** [[Azathioprine]]
** [[Tacrolimus]]
** [[Sirolimus]]
* Agents used for induction therapy include:
** High-dose [[Corticosteroid|corticosteroids]]
** Antithymocyte globulin
** [[Monoclonal antibodies|Monoclonal antibody]]
** [[Azathioprine]]
** [[Cyclosporine]]/[[Tacrolimus]] ([[Immunosuppressive drug|calcineurin inhibitors]])
** Antiproliferative agents
* Agents for long-term [[immunosuppression]]:
** [[Cyclosporine]] or [[Mycophenolate|Mycophenolate Mofetil]]
** [[Tacrolimus]]
** [[Azathioprine]]
** [[Prednisone]]
* The risk of [[Rejection|chronic rejection]] in [[Patient|patients]] with liver transplantation decreases with time, although recipients may need to take lifelong [[Immunosuppresive drug|immunosuppresive therapy]]
===Results===
* The [[prognosis]] of liver transplantation is good:<ref name="pmid24686540">{{cite journal |vauthors=Chen XB, Xu MQ |title=Primary graft dysfunction after liver transplantation |journal=HBPD INT |volume=13 |issue=2 |pages=125–37 |year=2014 |pmid=24686540 |doi= |url=}}</ref><ref name="pmid25644567">{{cite journal |vauthors=Liu JH, Yan S, Zheng SS |title=[Application of transient elastography in early prognosis after liver transplantation] |language=Chinese |journal=Zhejiang Da Xue Xue Bao Yi Xue Ban |volume=43 |issue=6 |pages=678–82 |year=2014 |pmid=25644567 |doi= |url=}}</ref><ref name="pmid29301479">{{cite journal |vauthors=Lindström L, Jørgensen KK, Boberg KM, Castedal M, Rasmussen A, Rostved AA, Isoniemi H, Bottai M, Bergquist A |title=Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study |journal=Scand. J. Gastroenterol. |volume= |issue= |pages=1–8 |year=2018 |pmid=29301479 |doi=10.1080/00365521.2017.1421705 |url=}}</ref><ref name="pmid29249127">{{cite journal |vauthors=Germani G, Becchetti C |title=Liver transplantation for non-alcoholic fatty liver disease |journal=Minerva Gastroenterol Dietol |volume= |issue= |pages= |year=2017 |pmid=29249127 |doi=10.23736/S1121-421X.17.02467-9 |url=}}</ref><ref name="pmid29237362">{{cite journal |vauthors=Egeli T, Unek T, Ozbilgin M, Agalar C, Derici S, Akarsu M, Unek IT, Aysin M, Bacakoglu A, Astarcıoglu I |title=De Novo Malignancies After Liver Transplantation: A Single Institution Experience |journal=Exp Clin Transplant |volume= |issue= |pages= |year=2017 |pmid=29237362 |doi=10.6002/ect.2017.0111 |url=}}</ref>
** 1-year survival is 83%
** 5-year survival is 76%
** 10-year survival is 66%
* Majority of deaths occur during the first three months after [[Organ transplant|transplantation]]
===Living donor transplantation===
* Living donor liver transplantation (LDLT) has emerged in recent decades as a critical [[Surgery|surgical]] option for patients with end stage liver disease, such as [[cirrhosis]] and/or [[hepatocellular carcinoma]] often attributable to one or more of the following:<ref name="pmid16691300" /><ref name="pmid27115011">{{cite journal |vauthors=Nadalin S, Capobianco I, Panaro F, Di Francesco F, Troisi R, Sainz-Barriga M, Muiesan P, Königsrainer A, Testa G |title=Living donor liver transplantation in Europe |journal=Hepatobiliary Surg Nutr |volume=5 |issue=2 |pages=159–75 |year=2016 |pmid=27115011 |pmc=4824742 |doi=10.3978/j.issn.2304-3881.2015.10.04 |url=}}</ref><ref name="pmid12606737">{{cite journal |vauthors=Brown RS, Russo MW, Lai M, Shiffman ML, Richardson MC, Everhart JE, Hoofnagle JH |title=A survey of liver transplantation from living adult donors in the United States |journal=N. Engl. J. Med. |volume=348 |issue=9 |pages=818–25 |year=2003 |pmid=12606737 |doi=10.1056/NEJMsa021345 |url=}}</ref>
** Long-term [[Alcoholism|alcohol]] abuse 
** Long-term untreated [[Hepatitis C|Hepatitis C infection]]
** Long-term untreated [[Hepatitis B|Hepatitis B infection]]
* The concept of LDLT is based on:
** Remarkable regenerative capacities of the human [[liver]] 
** Widespread shortage of [[cadaver]]ic livers for patients awaiting [[Organ transplant|transplant]] 
* In LDLT, a piece of healthy [[liver]] is surgically removed from a living person and transplanted into a recipient, immediately after the diseased [[liver]] of the recipient has been entirely removed 
* Historically, LDLT was used as a means for parents of children with severe [[liver]] disease to donate a portion of their healthy [[liver]] to replace the damaged [[liver]] of their children
* In 1986, the first successful LDLT was performed at the Universidade de São Paulo (USP) Medical School, by Dr. [[Silvano Raia]].
* More technically demanding than standard, cadaveric donor liver transplantation
* Has faced several [[Ethics committee (disambiguation)|ethical]] problems<ref name="pmid16184540">{{cite journal |vauthors=Krahn LE, DiMartini A |title=Psychiatric and psychosocial aspects of liver transplantation |journal=Liver Transpl. |volume=11 |issue=10 |pages=1157–68 |year=2005 |pmid=16184540 |doi=10.1002/lt.20578 |url=}}</ref>
===Complications of Liver Transplantation===
* Complications that may develop in [[Organ transplant|transplant]] recipients include the following:<ref name="pmid9546022">{{cite journal |vauthors=Savitsky EA, Uner AB, Votey SR |title=Evaluation of orthotopic liver transplant recipients presenting to the emergency department |journal=Ann Emerg Med |volume=31 |issue=4 |pages=507–17 |year=1998 |pmid=9546022 |doi= |url=}}</ref>
** Acute [[Transplant rejection|rejection]] of the [[graft]]
** Adverse effects of [[Immunosuppression|immunosuppressive therapy]]
** [[Bile duct|Biliary]] [[Stenosis|stricture]]
** [[Bile duct|Biliary]] leak
** [[Vascular]] [[thrombosis]]
** [[Sepsis]]
** [[Cancer|Malignancy]]
* Immediate postoperative complications of liver transplantation include:
** Acute [[Transplant rejection|rejection]]
** Early [[graft]] failure
** [[Bile duct|Biliary]] complications
** [[Vascular]] complications
* The most common causes of death in liver transplant patients are as follows:
** [[Infection]]
** [[Cancer|Malignancy]]
** [[Transplant rejection]] 
* To monitor the [[patient]] for complications, the following investigations are used:
** Laboratory investigations
*** The following laboratory investigations help in providing evidence of [[Transplant rejection|rejection]], and also help in the assessment of [[:Category:Drugs|drugs]]( [[Azathioprine]], [[Cyclosporine]] and [[Tacrolimus]]) along with their effect on [[bone marrow]] and [[Kidney|renal]] function:
**** [[Complete blood count|CBC]]
**** Electrolyte panel
**** [[Liver function tests]]
**** [[Renal function tests]] (RFTs)
***** [[Blood urea nitrogen|Blood urea nitrogen (BUN)]]
***** [[Creatinine|Creatinine levels]]
**** Drug levels in case of altered [[renal function tests]] or suspected [[Transplant rejection|rejection]]:
***** [[Cyclosporine]] levels
***** [[Tacrolimus]] levels
**** In case of suspected [[infection]]:
***** [[Blood culture]]
***** [[Urine culture]]
***** [[Pharynx|Pharyngeal]] culture
***** [[Sputum culture]]
==== Imaging studies ====
* Chest radiography:
** May be done if the [[patient]] has any of the following cardinal signs of [[respiratory disease]] such as:
*** [[Fever]]
*** [[Cough]]
*** [[Dyspnea]]
*** Abnormal findings on [[chest]] examination
* [[Medical ultrasonography|Abdominal ultrasonography]]
* [[Computed tomography|Computed tomography scan]]
* [[Endoscopic retrograde cholangiopancreatography|Endoscopic retrograde cholangiopancreatography (ERCP)]]
==== Acute and chronic graft rejection ====
[[Acute (medicine)|Acute]] [[graft]] [[Transplant rejection|rejection]]:<ref name="pmid9546022">{{cite journal |vauthors=Savitsky EA, Uner AB, Votey SR |title=Evaluation of orthotopic liver transplant recipients presenting to the emergency department |journal=Ann Emerg Med |volume=31 |issue=4 |pages=507–17 |year=1998 |pmid=9546022 |doi= |url=}}</ref>
* Vigilance is required for detection of [[Transplant rejection|rejection]] due to subtle presentations
* Occurrence: roughly 20-70 percent patients
* Timing: 1-2 weeks post- transplantation, within first three months of [[Organ transplant|transplantation]]
* Outcome: [[Graft]] dysfunction
* Clinical presentation:
** [[Jaundice]]
** [[Fever]]
** Right-upper-quadrant [[tenderness]]
** Generalized abdominal tenderness
** [[Eosinophilia]]
* In case of mild [[Transplant rejection|rejection]], symptoms may be nonspecific and include:
** Low-grade [[fever]]
** [[Fatigue]]
** [[Malaise]]
** Generalized [[Muscle weakness|weakness]]
* Laboratory evidence:
** Abnormal [[liver function tests]]
** Elevated [[Bilirubin]]
** Elevated [[alkaline phosphatase]] levels
** Elevation of hepatocellular enzymes:
*** [[Alanine transaminase|Alanine aminotransferase]] ([[Alanine transaminase|ALT]])
*** [[Aspartate transaminase|Aspartate aminotransferase]] ([[Aspartate transaminase|AST]])
* Treatment of [[Acute (medicine)|acute]] [[Transplant rejection|rejection]]:<ref name="pmid16451781">{{cite journal |vauthors=Levitsky J, Cohen SM |title=The liver transplant recipient: what you need to know for long-term care |journal=J Fam Pract |volume=55 |issue=2 |pages=136–44 |year=2006 |pmid=16451781 |doi= |url=}}</ref>
** High-dose [[Steroid|steroids]]:
*** [[Prednisolone]] 200 mg
*** [[Methylprednisolone]] 1 g for 3 days
*** High-dose [[steroid]] bolus followed by a rapid taper over 1 week
* Alternative therapies include:
** [[Antibody]] treatments:
*** [[Monoclonal antibodies|Monoclonal]] therapy (OKT3 )
*** Antithymocyte [[globulin]]
[[Chronic (medical)|Chronic]] [[graft]] [[Transplant rejection|rejection]]: 
* Occurence: 5% of [[Patient|patients]]
* Main cause of late stage [[graft]] failure
* Features of [[Chronic (medical)|chronic]] [[Transplant rejection|graft rejection]] include:
** Gradual obliteration of small [[Bile duct|bile ducts]]
** Microvascular changes
* Symptoms:
** [[Jaundice]]
** [[Itch|Pruritus]]
* Laboratory investigations:
** Elevated serum [[alkaline phosphatase]]
** Elevated [[bilirubin]] levels
* Gold standard diagnostic modality: [[Liver biopsy]]
==== Infection ====
[[Infection|Infections]] may be classified based on the duration post [[Organ transplant|transplantation]].
* <1 month : Common conditions developing in [[Patient|patients]] in the early posttransplant period include intra-[[Abdomen|abdominal]] [[Infection|infections]] such as:
** [[Cholangitis]]
** [[Liver abscess]]
** [[Abscess|Abdominal abscess]]
* 1-6 months: [[Infection|Infections]] commonly occur due to:
** [[Virus|Viruses]]
** Opportunistic [[Organism|organisms]]
* After the first 6 months, risk of [[infection]] in transplant patients is equal to that of the population
* [[Infection]] is primarily [[Nosocomial infection|nosocomial]]. Common [[Organism|organisms]] responsible for causing [[infection]] post-transplant are as follows:<ref name="pmid27095647">{{cite journal |vauthors=Greendyke WG, Pereira MR |title=Infectious Complications and Vaccinations in the Posttransplant Population |journal=Med. Clin. North Am. |volume=100 |issue=3 |pages=587–98 |year=2016 |pmid=27095647 |doi=10.1016/j.mcna.2016.01.008 |url=}}</ref> 
** [[Bacteria|Bacterial]] (most common):
*** [[Enterococcus|Enterococci]]
*** [[Staphylococcus aureus|Staphylococci]]
*** Gram-negative aerobes
*** [[Anaerobic organism|Anaerobes]]
** Fungal: [[Candidiasis|Candida]] (75% of [[fungal infections]]) 
** Presenting symptoms: May be non-specific<ref name="pmid9546022">{{cite journal |vauthors=Savitsky EA, Uner AB, Votey SR |title=Evaluation of orthotopic liver transplant recipients presenting to the emergency department |journal=Ann Emerg Med |volume=31 |issue=4 |pages=507–17 |year=1998 |pmid=9546022 |doi= |url=}}</ref>
*** [[Fever]] (absent or low grade) 
*** [[Abdominal pain]] 
*** [[Jaundice]]
*** Masking of [[Symptom|symptoms]] may occur due to [[immunosuppression]] 
*** Minimal [[pain]] at [[infection]] site
* Laboratory investigations:
** Complete blood count (CBC)
** Serum chemistries 
** [[Liver function tests]]
** Coagulation panel 
** [[Urine|Urinalysis]]
** [[Urine culture]] 
** [[Blood culture]] 
* Imaging: 
** [[Abdominal X-ray|Abdominal radiographs]] 
** [[Chest X-ray|Chest radiographs]] 
** [[Computed tomography|Computed tomography (CT)]]
** Abdominal ultrasonography
** T-tube cholangiography
** [[Endoscopic retrograde cholangiopancreatography|Endoscopic retrogrande cholangiopancreatography (ERCP)]]
** [[Liver biopsy]]
* Treatment of [[infection]]:<ref name="pmid8804376">{{cite journal |vauthors=Muñoz SJ |title=Long-term management of the liver transplant recipient |journal=Med. Clin. North Am. |volume=80 |issue=5 |pages=1103–20 |year=1996 |pmid=8804376 |doi= |url=}}</ref>
** [[Antimicrobials]] prescribed for non-[[Immunosuppression|immunosuppressed]] [[Patient|patients]]
==== Cytomegalovirus (CMV) ====
* Most common [[Infection|viral infection]] (affects 25-85% patients)
* Occurrence: Between posttransplant months 1 and 3
* [[Infection]] may be:
** Primary
** Reactivated
* Clinical presentation:
** [[Fever]]
** [[Malaise]]
** [[Arthralgia|Arthralgias]]
* Laboratory investigations:
** [[Reactive lymphocyte|Atypical lymphocytes]]
** [[Thrombocytopenia]]
** Mildly elevated [[transaminase]] levels
* Imaging findings:
** [[Chest X-ray|CXR]]: [[CMV pneumonitis]] [[Patient|patients]] may have bilateral infiltrates on [[Chest X-ray|CXR]] 
* Serology: Indirect [[immunofluorescence]] testing method 
* Treatment: [[Ganciclovir]] intravenously for 2-4 weeks
==== Pneumocystis carinii pneumonia (PCP) ====
* May occur along with [[Cytomegalovirus infection|CMV infection]] or alone
* Diagnosis: Bronchoalveolar biopsy
* Treatment: [[Sulfamethoxazole-Trimethoprim|Trimethoprim-sulfamethoxazole]]
Other less common [[Organism|organisms]] causing [[infection]] include:
* [[Fungus|Fungi]] (especially [[Candidiasis|Candida]] species)
* [[Herpes simplex]]
* [[Herpes zoster]]
* [[Toxoplasma gondii|Toxoplasma]]
* [[Hepatitis C virus]] ([[Hepatitis C|HCV]])
* [[Hepatitis B|Hepatitis B infection]]
* [[Cancer|Malignancy]]:
** In [[Organ transplant|transplant]] [[Patient|patients]], [[Cancer|malignancy]] is the second leading cause of late mortality
** Common [[Cancer|malignancies]] occuring in [[Patient|patients]] after transplantation include:
*** [[Lymphoma|Lymphomas]]
*** [[Squamous cell carcinoma clinical features|Squamous cell carcinoma]]: [[Squamous cell carcinoma|SCC]] of [[skin]] is the most common [[Cancer|malignancy]] that occurs pos-tranplantation
*** Posttransplant [[Lymphoproliferative disorders|lymphoproliferative disorder]]


==References==
==References==

Revision as of 06:37, 5 February 2018

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Overview

Surgery

tips liver transplant




Patient evaluation prior to transplantation

Pre-transplant patient evaluation has the following objectives:

Pre-transplant evaluation is particularly aggressive in patients prior to transplantation to minimize post operative morbidity and mortality due to effects of surgery and immunosuppressive therapy.The following evaluations are required:

Laboratory investigations

Laboratory investigations essential for patient evaluation prior to liver transplantation are as follows:

General investigations

Cause specific investigations

Cardiopulmonary evaluation

Cardiopulmonary evaluation helps in the evaluation of the patient for pathologies that need to be ruled out prior to transplantation:[1][2]

Cancer screening

Prior to transplantation, screening for the following carcinomas is recommended:

Upper GI endoscopy

Bone densitometry

Vaccinations and evaluation for infection

Psychosocial evaluation and education

Techniques

{{#ev:youtube|v=hquWw4rRHh8}}

Orthotopic Liver Transplantation

Immunosuppressive management

Results

Living donor transplantation

  • Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma often attributable to one or more of the following:[17][30][31]
  • The concept of LDLT is based on:
    • Remarkable regenerative capacities of the human liver
    • Widespread shortage of cadaveric livers for patients awaiting transplant
  • In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the diseased liver of the recipient has been entirely removed
  • Historically, LDLT was used as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace the damaged liver of their children
  • In 1986, the first successful LDLT was performed at the Universidade de São Paulo (USP) Medical School, by Dr. Silvano Raia.
  • More technically demanding than standard, cadaveric donor liver transplantation
  • Has faced several ethical problems[32]

Complications of Liver Transplantation

    • Laboratory investigations

Imaging studies

Acute and chronic graft rejection

Acute graft rejection:[33]

Chronic graft rejection:

Infection

Infections may be classified based on the duration post transplantation.

  • After the first 6 months, risk of infection in transplant patients is equal to that of the population

Cytomegalovirus (CMV)

  • Most common viral infection (affects 25-85% patients)
  • Occurrence: Between posttransplant months 1 and 3
  • Infection may be:
    • Primary
    • Reactivated

Pneumocystis carinii pneumonia (PCP)

Other less common organisms causing infection include:

References

  1. ↑ 1.0 1.1 1.2 Martin P, DiMartini A, Feng S, Brown R, Fallon M (2014). "Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation". Hepatology. 59 (3): 1144–65. PMID 24716201.
  2. ↑ Zoghbi GJ, Patel AD, Ershadi RE, Heo J, Bynon JS, Iskandrian AE (2003). "Usefulness of preoperative stress perfusion imaging in predicting prognosis after liver transplantation". Am. J. Cardiol. 92 (9): 1066–71. PMID 14583357.
  3. ↑ Guckelberger O, Mutzke F, Glanemann M, Neumann UP, Jonas S, Neuhaus R, Neuhaus P, Langrehr JM (2006). "Validation of cardiovascular risk scores in a liver transplant population". Liver Transpl. 12 (3): 394–401. doi:10.1002/lt.20722. PMID 16498651.
  4. ↑ Plotkin JS, Scott VL, Pinna A, Dobsch BP, De Wolf AM, Kang Y (1996). "Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation". Liver Transpl Surg. 2 (6): 426–30. PMID 9346688.
  5. ↑ Colle IO, Moreau R, Godinho E, Belghiti J, Ettori F, Cohen-Solal A, Mal H, Bernuau J, Marty J, Lebrec D, Valla D, Durand F (2003). "Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study". Hepatology. 37 (2): 401–9. doi:10.1053/jhep.2003.50060. PMID 12540791.
  6. ↑ Krowka MJ, Mandell MS, Ramsay MA, Kawut SM, Fallon MB, Manzarbeitia C, Pardo M, Marotta P, Uemoto S, Stoffel MP, Benson JT (2004). "Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database". Liver Transpl. 10 (2): 174–82. doi:10.1002/lt.20016. PMID 14762853.
  7. ↑ Starkel P, Vera A, Gunson B, Mutimer D (2002). "Outcome of liver transplantation for patients with pulmonary hypertension". Liver Transpl. 8 (4): 382–8. doi:10.1053/jlts.2002.31343. PMID 11965583.
  8. ↑ Lentine KL, Costa SP, Weir MR, Robb JF, Fleisher LA, Kasiske BL, Carithers RL, Ragosta M, Bolton K, Auerbach AD, Eagle KA (2012). "Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation". J. Am. Coll. Cardiol. 60 (5): 434–80. doi:10.1016/j.jacc.2012.05.008. PMID 22763103.
  9. ↑ Raval Z, Harinstein ME, Skaro AI, Erdogan A, DeWolf AM, Shah SJ, Fix OK, Kay N, Abecassis MI, Gheorghiade M, Flaherty JD (2011). "Cardiovascular risk assessment of the liver transplant candidate". J. Am. Coll. Cardiol. 58 (3): 223–31. doi:10.1016/j.jacc.2011.03.026. PMID 21737011.
  10. ↑ Arguedas MR, Singh H, Faulk DK, Fallon MB (2007). "Utility of pulse oximetry screening for hepatopulmonary syndrome". Clin. Gastroenterol. Hepatol. 5 (6): 749–54. doi:10.1016/j.cgh.2006.12.003. PMID 17392034.
  11. ↑ Prentis JM, Manas DM, Trenell MI, Hudson M, Jones DJ, Snowden CP (2012). "Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation". Liver Transpl. 18 (2): 152–9. doi:10.1002/lt.22426. PMID 21898768.
  12. ↑ Eghtesad B, Kadry Z, Fung J (2005). "Technical considerations in liver transplantation: what a hepatologist needs to know (and every surgeon should practice)". Liver Transpl. 11 (8): 861–71. doi:10.1002/lt.20529. PMID 16035067.
  13. ↑ Tuttle-Newhall JE, Collins BH, Desai DM, Kuo PC, Heneghan MA (2005). "The current status of living donor liver transplantation". Curr Probl Surg. 42 (3): 144–83. PMID 15859440.
  14. ↑ Steadman RH (2004). "Anesthesia for liver transplant surgery". Anesthesiol Clin North America. 22 (4): 687–711. doi:10.1016/j.atc.2004.06.009. PMID 15541931.
  15. ↑ Park JI, Kim KH, Lee SG (2015). "Laparoscopic living donor hepatectomy: a review of current status". J Hepatobiliary Pancreat Sci. 22 (11): 779–88. doi:10.1002/jhbp.288. PMID 26449392.
  16. ↑ Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, Neuhaus P, Lerut J, Salizzoni M, Pollard S, Muhlbacher F, Rogiers X, Garcia Valdecasas JC, Berenguer J, Jaeck D, Moreno Gonzalez E (2003). "Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry". Liver Transpl. 9 (12): 1231–43. doi:10.1016/j.lts.2003.09.018. PMID 14625822.
  17. ↑ 17.0 17.1 Shah SA, Levy GA, Adcock LD, Gallagher G, Grant DR (2006). "Adult-to-adult living donor liver transplantation". Can. J. Gastroenterol. 20 (5): 339–43. PMC 2659892. PMID 16691300.
  18. ↑ Reddy S, Zilvetti M, Brockmann J, McLaren A, Friend P (2004). "Liver transplantation from non-heart-beating donors: current status and future prospects". Liver Transpl. 10 (10): 1223–32. doi:10.1002/lt.20268. PMID 15376341.
  19. ↑ Martinez OM, Rosen HR (2005). "Basic concepts in transplant immunology". Liver Transpl. 11 (4): 370–81. doi:10.1002/lt.20406. PMID 15776458.
  20. ↑ Friend PJ (1997). "Liver transplantation". Transplant. Proc. 29 (6): 2716–8. PMID 9290801.
  21. ↑ McCaughan GW, Koorey DJ (1997). "Liver transplantation". Aust N Z J Med. 27 (4): 371–8. PMID 9448876.
  22. ↑ Middleton PF, Duffield M, Lynch SV, Padbury RT, House T, Stanton P, Verran D, Maddern G (2006). "Living donor liver transplantation--adult donor outcomes: a systematic review". Liver Transpl. 12 (1): 24–30. PMID 16498709.
  23. ↑ Perry I, Neuberger J (2005). "Immunosuppression: towards a logical approach in liver transplantation". Clin. Exp. Immunol. 139 (1): 2–10. doi:10.1111/j.1365-2249.2005.02662.x. PMC 1809260. PMID 15606606.
  24. ↑ Papadopoulos-Köhn A, Achterfeld A, Paul A, Canbay A, Timm J, Jochum C, Gerken G, Herzer K (2015). "Daily low-dose tacrolimus is a safe and effective immunosuppressive regimen during telaprevir-based triple therapy for hepatitis C virus recurrence after liver transplant". Transplantation. 99 (4): 841–7. doi:10.1097/TP.0000000000000399. PMID 25208324.
  25. ↑ Chen XB, Xu MQ (2014). "Primary graft dysfunction after liver transplantation". HBPD INT. 13 (2): 125–37. PMID 24686540.
  26. ↑ Liu JH, Yan S, Zheng SS (2014). "[Application of transient elastography in early prognosis after liver transplantation]". Zhejiang Da Xue Xue Bao Yi Xue Ban (in Chinese). 43 (6): 678–82. PMID 25644567.
  27. ↑ Lindström L, Jørgensen KK, Boberg KM, Castedal M, Rasmussen A, Rostved AA, Isoniemi H, Bottai M, Bergquist A (2018). "Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study". Scand. J. Gastroenterol.: 1–8. doi:10.1080/00365521.2017.1421705. PMID 29301479.
  28. ↑ Germani G, Becchetti C (2017). "Liver transplantation for non-alcoholic fatty liver disease". Minerva Gastroenterol Dietol. doi:10.23736/S1121-421X.17.02467-9. PMID 29249127.
  29. ↑ Egeli T, Unek T, Ozbilgin M, Agalar C, Derici S, Akarsu M, Unek IT, Aysin M, Bacakoglu A, Astarcıoglu I (2017). "De Novo Malignancies After Liver Transplantation: A Single Institution Experience". Exp Clin Transplant. doi:10.6002/ect.2017.0111. PMID 29237362.
  30. ↑ Nadalin S, Capobianco I, Panaro F, Di Francesco F, Troisi R, Sainz-Barriga M, Muiesan P, Königsrainer A, Testa G (2016). "Living donor liver transplantation in Europe". Hepatobiliary Surg Nutr. 5 (2): 159–75. doi:10.3978/j.issn.2304-3881.2015.10.04. PMC 4824742. PMID 27115011.
  31. ↑ Brown RS, Russo MW, Lai M, Shiffman ML, Richardson MC, Everhart JE, Hoofnagle JH (2003). "A survey of liver transplantation from living adult donors in the United States". N. Engl. J. Med. 348 (9): 818–25. doi:10.1056/NEJMsa021345. PMID 12606737.
  32. ↑ Krahn LE, DiMartini A (2005). "Psychiatric and psychosocial aspects of liver transplantation". Liver Transpl. 11 (10): 1157–68. doi:10.1002/lt.20578. PMID 16184540.
  33. ↑ 33.0 33.1 33.2 Savitsky EA, Uner AB, Votey SR (1998). "Evaluation of orthotopic liver transplant recipients presenting to the emergency department". Ann Emerg Med. 31 (4): 507–17. PMID 9546022.
  34. ↑ Levitsky J, Cohen SM (2006). "The liver transplant recipient: what you need to know for long-term care". J Fam Pract. 55 (2): 136–44. PMID 16451781.
  35. ↑ Greendyke WG, Pereira MR (2016). "Infectious Complications and Vaccinations in the Posttransplant Population". Med. Clin. North Am. 100 (3): 587–98. doi:10.1016/j.mcna.2016.01.008. PMID 27095647.
  36. ↑ Muñoz SJ (1996). "Long-term management of the liver transplant recipient". Med. Clin. North Am. 80 (5): 1103–20. PMID 8804376.

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