Liver transplantation: Difference between revisions

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{{SI}}
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{{CMG}}; {{AE}} {{Cherry}}




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==Overview==
==Overview==


'''Liver transplantation''' or '''hepatic transplantation''' is the replacement of a diseased [[liver]] with a healthy liver [[allograft]]. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and the donor organ is placed in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure.
When a healthy [[liver]] [[allograft]] is used in place of damaged [[liver]] tissue, it is termed as [[liver transplantation]]. Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in the 1960s. In 1963, the first liver transplant in humans was attempted by Dr. [[Thomas Starzl]] of Colorado, United States. The most common indications for liver transplantation in the United States are [[hepatitis C virus]], [[alcoholic liver disease]], autoimmune [[liver]] disease, [[primary biliary cirrhosis]], [[primary sclerosing cholangitis]], [[hepatitis B virus]], [[liver]] disease due to inborn errors of [[metabolism]], [[cancer]], [[biliary atresia]] and [[acute liver failure]]. On the other hand, absolute contraindications to liver transplantation include [[hepatocellular carcinoma]] with [[metastasis]], [[acute liver failure]] with persistently elevated [[intracranial pressure]] [[Intracranial pressure|ICP]] >50mmHg, [[Angiosarcoma|hemangiosarcoma]], hilar [[cholangiocarcinoma]], [[sepsis]], and active [[alcohol]] or [[drug abuse]]. Pretransplant measures such as cardiopulmonary evaluation, screening for [[Cancer of unknown primary origin|occult cancer]], [[infection]], and [[psychosocial]] evaluation must be performed prior to surgery. The most commonly used technique employed in patients is orthotopic transplantation. This involves removal of the native [[liver]] and placement of the donor organ in the same anatomic location as the original [[liver]]. [[Immunosuppressive agents]] used after transplantation include [[cyclosporine]], [[everolimus]], [[mycophenolate]], [[Corticosteroid|corticosteroids]], [[azathioprine]], and [[tacrolimus]] in different combinations. The most common causes of death in liver transplant patients are [[infection]], [[Cancer|malignancy]], and [[Transplant rejection|rejection]]. It is necessary to monitor [[Patient|patients]] for signs of complications and treat them effectively.


==Liver Transplantation==
==Liver Transplantation==
===History===
===History===
* In the 1960s, Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in Boston and Chicago.
* In the 1960s, Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in Boston and Chicago.
* In 1963, the first liver transplant in humans was attempted by a surgical team led by Dr. [[Thomas Starzl]]<ref>{{cite journal |author=STARZL T, MARCHIORO T, VONKAULLA K, HERMANN G, BRITTAIN R, WADDELL W |title=HOMOTRANSPLANTATION OF THE LIVER IN HUMANS |journal=Surg Gynecol Obstet |volume=117 |issue= |pages=659-76 |year= |pmid=14100514}}</ref> of Denver, Colorado, United States.
* In 1963, the first liver transplant in humans was attempted by a surgical team led by Dr. [[Thomas Starzl]] of Denver, Colorado, United States.<ref>{{cite journal |author=STARZL T, MARCHIORO T, VONKAULLA K, HERMANN G, BRITTAIN R, WADDELL W |title=HOMOTRANSPLANTATION OF THE LIVER IN HUMANS |journal=Surg Gynecol Obstet |volume=117 |issue= |pages=659-76 |year= |pmid=14100514}}</ref>
* Dr. Starzl performed several additional [[Organ transplant|transplants]] over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post-transplantation.
* Dr. Starzl performed many additional [[Organ transplant|transplants]] until he was successful in 1967 with the first one-year survival post-transplantation.
* In 1970, the regimen for [[Immunosuppression|immunosuppressive therapy]] following [[Organ transplant|transplant]] was introduced, but [[azathioprine]] and [[Steroid|steroids]] did not improve survival rates of patients.
* In 1970, the regimen for [[Immunosuppression|immunosuppressive therapy]] following [[Organ transplant|transplant]] was introduced, but [[azathioprine]] and [[Steroid|steroids]] did not improve survival rates of patients.
* In the 1980s, with the introduction of [[cyclosporine]] by Sir [[Roy Calne]], there was an improvement in [[Transplant rejection|rejection]] rates.
* In the 1980s, with the introduction of [[cyclosporine]] by Sir [[Roy Calne]], there was an improvement in [[Transplant rejection|rejection]] rates.
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* In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.   
* In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.   
* Recently, the introduction of newer [[immunosuppressive agents]] such as [[IL-2 receptor]] blockers and [[tacrolimus]], have drastically increased patient [[Survival rate|survival rates]] to 1 and 5-year rates of approximately 85 and 70 percent respectively.<ref name="pmid15679767">{{cite journal |vauthors=Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM |title=A comparison of liver transplantation outcomes in the pre- vs. post-MELD eras |journal=Aliment. Pharmacol. Ther. |volume=21 |issue=2 |pages=169–77 |year=2005 |pmid=15679767 |doi=10.1111/j.1365-2036.2005.02321.x |url=}}</ref>   
* Recently, the introduction of newer [[immunosuppressive agents]] such as [[IL-2 receptor]] blockers and [[tacrolimus]], have drastically increased patient [[Survival rate|survival rates]] to 1 and 5-year rates of approximately 85 and 70 percent respectively.<ref name="pmid15679767">{{cite journal |vauthors=Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM |title=A comparison of liver transplantation outcomes in the pre- vs. post-MELD eras |journal=Aliment. Pharmacol. Ther. |volume=21 |issue=2 |pages=169–77 |year=2005 |pmid=15679767 |doi=10.1111/j.1365-2036.2005.02321.x |url=}}</ref>   
* Liver transplantation is now performed at over one hundred centers in the [[USA]], as well as numerous centers in Europe and elsewhere.  One year [[patient]] [[Survival analysis|survival]] is 85-90%, and outcomes continue to improve, although liver transplantation remains a formidable [[Surgery|procedure]] with frequent complications. 
* Unfortunately, the supply of [[liver]] [[allograft]]s from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of [[#Living donor transplantation|living donor liver transplantation]].
* In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.
* In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.
===Indications===
===Indications===
* Liver transplantation is applicable to any acute or chronic condition resulting in irreversible [[liver]] dysfunction, provided that the recipient does not have other conditions that will preclude a successful [[Organ transplant|transplant]].
Liver transplantation is applicable to any acute or chronic condition resulting in irreversible [[liver]] dysfunction, provided that the recipient does not have other conditions that will preclude a successful [[Organ transplant|transplant]]. Most liver transplants are performed for [[Chronic liver disease|chronic liver diseases]] that lead to irreversible scarring of the [[liver]], or [[cirrhosis]].
* Most liver transplants are performed for [[Chronic liver disease|chronic liver diseases]] that lead to irreversible scarring of the [[liver]], or [[cirrhosis]].
* The most common indications for liver transplantation in the United States are:
* The most common indications for liver transplantation in the United States are:
** [[Hepatitis C virus]]  
** [[Hepatitis C]]
** [[Alcoholic liver disease]]  
** [[Alcoholic liver disease]]  
** Idiopathic/autoimmune liver disease  
** Idiopathic or autoimmune liver disease  
** [[Primary biliary cirrhosis]]
** [[Primary biliary cirrhosis]]
** [[Primary sclerosing cholangitis]]  
** [[Primary sclerosing cholangitis]]  
** [[Hepatitis B virus]]  
** [[Hepatitis B]]
** Metabolic [[liver]] disease (eg, inborn errors of [[metabolism]])  
** Metabolic [[liver]] disease (e.g. inborn errors of [[metabolism]])  
** [[Cancer]]  
** [[Carcinoma]]  
** [[Biliary atresia]]
** [[Biliary atresia]]
** [[Acute liver failure]] :  
** [[Acute liver failure]]:  
*** Severe acute [[liver]] injury with impaired synthetic function of the [[liver]](INR ≥1.5) and [[encephalopathy]] in the absence of pre existing [[liver]] disease or cirrhosis.
*** Severe acute [[liver]] injury with impaired synthetic function of the [[liver]] (INR ≥1.5) and [[encephalopathy]] in the absence of pre existing [[liver]] disease or cirrhosis
*** Common causes:
*** Common causes:
**** [[Virus|Viral]]
**** [[Virus|Viral]]
**** Drug-induced
**** Drug-induced
*** [[Acute liver failure]] has the highest priority for liver transplantation, and warrants immediate referral to [[Organ transplant|transplantation]] centre  
*** [[Acute liver failure]] has the highest priority for liver transplantation and warrants immediate referral to [[Organ transplant|transplantation]] centre  
*** In the absence of [[Organ transplant|transplantation]], [[Patient|patients]] may recover or die  
*** In the absence of [[Organ transplant|transplantation]], [[Patient|patients]] may recover or die  
** [[Cirrhosis]]:
** [[Cirrhosis]]:
*** Only in cases of complications such as [[portal hypertension]], or compromised [[Liver|hepatic]] function (marker for impaired survival)
*** Cirrhosis is an indication only in the presence of complications such as [[portal hypertension]] or compromised [[Liver|hepatic]] function (marker for impaired survival)
*** Signs of decompensated [[cirrhosis]] include:
*** Signs of decompensated [[cirrhosis]] include:
**** [[Ascites]]
**** [[Ascites]]
**** [[Encephalopathy]]
**** [[Encephalopathy]]
**** [[Esophageal varices|Variceal]] [[Bleeding|hemorrhage]]
**** [[Esophageal varices|Variceal hemorrhage]]
**** [[Hepatorenal syndrome]]
**** [[Hepatorenal syndrome]]
*** Transplantation evaluation is commenced in patients with [[MELD Score|MELD score]] >10:
*** Transplantation evaluation is commenced in patients with [[MELD Score|MELD score]] >10:
*** This gives the [[patient]] time for pretransplantation evaluation
*** This gives the [[patient]] time for pre transplantation evaluation (as a [[MELD Score|MELD score]] ≥15 is an indication for transplantation)
*** [[Patient]] has ample time for education, before the development of symptoms of [[hepatic encephalopathy]] that may impair cognition  
*** [[Patient]] has ample time for education, before the development of symptoms of [[hepatic encephalopathy]] that may impair cognition  
*** [[Patient|Patients]] with [[cirrhosis]] are candidates for liver transplantation in the following scenarios:
*** [[Patient|Patients]] with [[cirrhosis]] are candidates for liver transplantation in the following scenarios:
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**** Cases of Child B cirrhosis with [[portal hypertension]] but a low [[MELD Score|MELD score]]  
**** Cases of Child B cirrhosis with [[portal hypertension]] but a low [[MELD Score|MELD score]]  
**** [[MELD Score|MELD]] exception points are given to patients with pathologies that may impair survival without impacting the [[MELD Score|MELD score]] such as:
**** [[MELD Score|MELD]] exception points are given to patients with pathologies that may impair survival without impacting the [[MELD Score|MELD score]] such as:
***** [[Cancer]]: [[Hepatocellular carcinoma|HCC]], [[Cholangiocarcinoma|Hilar cholangiocarcinoma]]  
***** [[Cancer]]:  
****** [[Hepatocellular carcinoma|HCC]]  
****** [[Cholangiocarcinoma|Hilar cholangiocarcinoma]]  
***** Complications of [[cirrhosis]]:
***** Complications of [[cirrhosis]]:
****** [[Hepatopulmonary syndrome]]
****** [[Hepatopulmonary syndrome]]
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****** [[Hepatic artery]] [[thrombosis]]  
****** [[Hepatic artery]] [[thrombosis]]  
***** [[Cystic fibrosis]]:
***** [[Cystic fibrosis]]:
****** [[Primary hyperoxaluria]]
***** [[Primary hyperoxaluria]]
****** [[Familial amyloid polyneuropathy]]
***** [[Familial amyloid polyneuropathy]]
***** Other conditions that may also be indications for transplantation that do not qualify for [[MELD Score|MELD]] or [[MELD Score|MELD]] exception points include:
***** Other indications for transplantation that do not qualify for [[MELD Score|MELD]] or [[MELD Score|MELD]] exception points include:
****** Intractable [[Itch|pruritus]] in case of [[primary biliary cirrhosis]]
****** Intractable [[Itch|pruritus]] in case of [[primary biliary cirrhosis]]
****** Refractory [[Esophageal varices|variceal]] [[Bleeding|hemorrhage]]
****** Refractory [[Esophageal varices|variceal hemorrhage]]
****** Refractory [[ascites]]
****** Refractory [[ascites]]
****** Refractory [[hepatic encephalopathy]]
****** Refractory [[hepatic encephalopathy]]
****** [[Portal hypertensive gastropathy]] leading to chronic [[blood]] loss
****** [[Portal hypertensive gastropathy]] leading to chronic [[blood]] loss
****** Recurrent [[cholangitis]] in patients with [[Primary sclerosing cholangitis|PSC]]  
****** Recurrent [[cholangitis]] in patients with [[Primary sclerosing cholangitis|PSC]]  
****** [[Hepatocellular carcinoma|HCC]]: a single lesion ≤5 cm or up to three separate [[Lesion|lesions]] all <3 cm, no evidence of gross [[vascular]] invasion, and no regional [[Lymph node|nodal]] or distant [[metastasis]].
****** [[Hepatocellular carcinoma|HCC]]:  
******* A single lesion ≤5 cm or up to three separate [[Lesion|lesions]] all <3 cm
******* No evidence of gross [[vascular]] invasion, and
******* No regional [[Lymph node|nodal]] or distant [[metastasis]]
****** [[Neuroendocrine tumors]] that have metastasized to the [[liver]]  
****** [[Neuroendocrine tumors]] that have metastasized to the [[liver]]  
****** [[Hepatocellular carcinoma|HCC]] (including fibrolamellar [[Hepatocellular carcinoma|HCC]])  
****** [[Hepatocellular carcinoma|HCC]] (including fibrolamellar [[Hepatocellular carcinoma|HCC]])  
****** Large [[Hepatocellular adenoma|hepatic adenomas]]  
****** Large [[Hepatocellular adenoma|hepatic adenomas]]  
****** Epithelioid hemangioendothelioma  
****** [[Hemangioendothelioma|Epithelioid hemangioendothelioma]]
****** [[Metabolic disorder|Metabolic disorders]]:  
****** [[Metabolic disorder|Metabolic disorders]]:  
******* [[Alpha 1-antitrypsin deficiency|Alpha-1 antitrypsin deficiency]]
******* [[Alpha 1-antitrypsin deficiency|Alpha-1 antitrypsin deficiency]]
******* [[Wilson's disease|Wilson disease]]
******* [[Wilson's disease|Wilson disease]]
******* [[Acute intermittent porphyria]]
******* [[Acute intermittent porphyria]]
******* [[Glycogen storage disease]] (type I and type IV)  
******* [[Glycogen storage disease]] ([[Glycogen storage disease type I|type I]] and type IV)  
******* [[Tyrosinemia]]  
******* [[Tyrosinemia]]  
******* [[Hemochromatosis]]
******* [[Hemochromatosis]]
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=== Contraindications ===
=== Contraindications ===


Absolute contraindications: <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>
Absolute contraindications for liver transplantation include:<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>
* [[Metastasis]] outside the [[liver]], past the curative stage
* [[Metastasis]] outside the [[liver]], past the curative stage
* [[Hepatocellular carcinoma]] with [[metastasis]] (Stage 1V)
* [[Hepatocellular carcinoma]] with [[metastasis]] (Stage 1V)
* [[Acute liver failure|Acute Liver Failure]] with persistently elevated [[intracranial pressure]] [[Intracranial pressure|ICP]] >50mmHg( due to [[hepatic encephalopathy]])
* [[Acute liver failure|Acute Liver Failure]] with persistently elevated [[intracranial pressure]] [[Intracranial pressure|ICP]] > 50 mmHg (due to [[hepatic encephalopathy]])
* [[Angiosarcoma|Hemangiosarcoma]]
* [[Angiosarcoma|Hemangiosarcoma]]
* Hilar [[cholangiocarcinoma]] with [[liver]] involvement
* [[cholangiocarcinoma|Hilar cholangiocarcinoma]] with [[liver]] involvement
* [[Sepsis]]
* [[Sepsis]]
* Active [[alcohol]] or [[drug abuse]]
* Active [[alcohol]] or [[drug abuse]]
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* Absence of social support
* Absence of social support


Relative contraindications:<ref name="pmid24716201" /><ref name="pmid22070476">{{cite journal |vauthors=Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC |title=Early liver transplantation for severe alcoholic hepatitis |journal=N. Engl. J. Med. |volume=365 |issue=19 |pages=1790–800 |year=2011 |pmid=22070476 |doi=10.1056/NEJMoa1105703 |url=}}</ref><ref name="pmid21412058">{{cite journal |vauthors=Cooper C, Kanters S, Klein M, Chaudhury P, Marotta P, Wong P, Kneteman N, Mills EJ |title=Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort |journal=AIDS |volume=25 |issue=6 |pages=777–86 |year=2011 |pmid=21412058 |doi=10.1097/QAD.0b013e328344febb |url=}}</ref><ref name="pmid18301332">{{cite journal |vauthors=Mindikoglu AL, Regev A, Magder LS |title=Impact of human immunodeficiency virus on survival after liver transplantation: analysis of United Network for Organ Sharing database |journal=Transplantation |volume=85 |issue=3 |pages=359–68 |year=2008 |pmid=18301332 |doi=10.1097/TP.0b013e3181605fda |url=}}</ref><ref name="pmid22328294">{{cite journal |vauthors=Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG |title=Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection |journal=Liver Transpl. |volume=18 |issue=6 |pages=716–26 |year=2012 |pmid=22328294 |pmc=3358510 |doi=10.1002/lt.23411 |url=}}</ref><ref name="pmid17902123">{{cite journal |vauthors=Cross TJ, Antoniades CG, Muiesan P, Al-Chalabi T, Aluvihare V, Agarwal K, Portmann BC, Rela M, Heaton ND, O'Grady JG, Heneghan MA |title=Liver transplantation in patients over 60 and 65 years: an evaluation of long-term outcomes and survival |journal=Liver Transpl. |volume=13 |issue=10 |pages=1382–8 |year=2007 |pmid=17902123 |doi=10.1002/lt.21181 |url=}}</ref><ref name="pmid11726833">{{cite journal |vauthors=Prachalias AA, Pozniak A, Taylor C, Srinivasan P, Muiesan P, Wendon J, Cramp M, Williams R, O'Grady J, Rela M, Heaton ND |title=Liver transplantation in adults coinfected with HIV |journal=Transplantation |volume=72 |issue=10 |pages=1684–8 |year=2001 |pmid=11726833 |doi= |url=}}</ref><ref name="pmid11726816">{{cite journal |vauthors=Wreghitt T |title=Liver Transplantation in Adults Coinfected With HIV. Transplantation 2001; 72: 1684 |journal=Transplantation |volume=72 |issue=10 |pages=1594–5 |year=2001 |pmid=11726816 |doi= |url=}}</ref><ref name="pmid11750549">{{cite journal |vauthors=Stock P, Roland M, Carlson L, Freise C, Hirose R, Terrault N, Frassetto L, Coates T, Roberts J, Ascher N |title=Solid organ transplantation in HIV-positive patients |journal=Transplant. Proc. |volume=33 |issue=7-8 |pages=3646–8 |year=2001 |pmid=11750549 |doi= |url=}}</ref><ref name="pmid12883195">{{cite journal |vauthors=Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, Terrault NA, Frassetto LA, Palefsky JM, Tomlanovich SJ, Ascher NL |title=Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study |journal=Transplantation |volume=76 |issue=2 |pages=370–5 |year=2003 |pmid=12883195 |doi=10.1097/01.TP.0000075973.73064.A6 |url=}}</ref><ref name="pmid12619020">{{cite journal |vauthors=Neff GW, Bonham A, Tzakis AG, Ragni M, Jayaweera D, Schiff ER, Shakil O, Fung JJ |title=Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease |journal=Liver Transpl. |volume=9 |issue=3 |pages=239–47 |year=2003 |pmid=12619020 |doi=10.1053/jlts.2003.50054 |url=}}</ref>
Relative contraindications for liver transplantation include:<ref name="pmid24716201" /><ref name="pmid22070476">{{cite journal |vauthors=Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC |title=Early liver transplantation for severe alcoholic hepatitis |journal=N. Engl. J. Med. |volume=365 |issue=19 |pages=1790–800 |year=2011 |pmid=22070476 |doi=10.1056/NEJMoa1105703 |url=}}</ref><ref name="pmid21412058">{{cite journal |vauthors=Cooper C, Kanters S, Klein M, Chaudhury P, Marotta P, Wong P, Kneteman N, Mills EJ |title=Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort |journal=AIDS |volume=25 |issue=6 |pages=777–86 |year=2011 |pmid=21412058 |doi=10.1097/QAD.0b013e328344febb |url=}}</ref><ref name="pmid18301332">{{cite journal |vauthors=Mindikoglu AL, Regev A, Magder LS |title=Impact of human immunodeficiency virus on survival after liver transplantation: analysis of United Network for Organ Sharing database |journal=Transplantation |volume=85 |issue=3 |pages=359–68 |year=2008 |pmid=18301332 |doi=10.1097/TP.0b013e3181605fda |url=}}</ref><ref name="pmid22328294">{{cite journal |vauthors=Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG |title=Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection |journal=Liver Transpl. |volume=18 |issue=6 |pages=716–26 |year=2012 |pmid=22328294 |pmc=3358510 |doi=10.1002/lt.23411 |url=}}</ref><ref name="pmid17902123">{{cite journal |vauthors=Cross TJ, Antoniades CG, Muiesan P, Al-Chalabi T, Aluvihare V, Agarwal K, Portmann BC, Rela M, Heaton ND, O'Grady JG, Heneghan MA |title=Liver transplantation in patients over 60 and 65 years: an evaluation of long-term outcomes and survival |journal=Liver Transpl. |volume=13 |issue=10 |pages=1382–8 |year=2007 |pmid=17902123 |doi=10.1002/lt.21181 |url=}}</ref><ref name="pmid11726833">{{cite journal |vauthors=Prachalias AA, Pozniak A, Taylor C, Srinivasan P, Muiesan P, Wendon J, Cramp M, Williams R, O'Grady J, Rela M, Heaton ND |title=Liver transplantation in adults coinfected with HIV |journal=Transplantation |volume=72 |issue=10 |pages=1684–8 |year=2001 |pmid=11726833 |doi= |url=}}</ref><ref name="pmid11726816">{{cite journal |vauthors=Wreghitt T |title=Liver Transplantation in Adults Coinfected With HIV. Transplantation 2001; 72: 1684 |journal=Transplantation |volume=72 |issue=10 |pages=1594–5 |year=2001 |pmid=11726816 |doi= |url=}}</ref><ref name="pmid11750549">{{cite journal |vauthors=Stock P, Roland M, Carlson L, Freise C, Hirose R, Terrault N, Frassetto L, Coates T, Roberts J, Ascher N |title=Solid organ transplantation in HIV-positive patients |journal=Transplant. Proc. |volume=33 |issue=7-8 |pages=3646–8 |year=2001 |pmid=11750549 |doi= |url=}}</ref><ref name="pmid12883195">{{cite journal |vauthors=Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, Terrault NA, Frassetto LA, Palefsky JM, Tomlanovich SJ, Ascher NL |title=Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study |journal=Transplantation |volume=76 |issue=2 |pages=370–5 |year=2003 |pmid=12883195 |doi=10.1097/01.TP.0000075973.73064.A6 |url=}}</ref><ref name="pmid12619020">{{cite journal |vauthors=Neff GW, Bonham A, Tzakis AG, Ragni M, Jayaweera D, Schiff ER, Shakil O, Fung JJ |title=Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease |journal=Liver Transpl. |volume=9 |issue=3 |pages=239–47 |year=2003 |pmid=12619020 |doi=10.1053/jlts.2003.50054 |url=}}</ref>
* Infection with [[Human Immunodeficiency Virus (HIV)|HIV]] ([[HIV AIDS|AIDS]])
* Infection with [[Human Immunodeficiency Virus (HIV)|HIV]] ([[HIV AIDS|AIDS]])
* Age >65 years
* Age > 65 years
* Any serious [[Pathology|pathologies]] of the [[lung]] or [[heart]] that cannot be corrected
* Serious [[Pathology|pathologies]] of the [[lung]] or [[heart]] that cannot be corrected
* [[Body mass index|BMI]] ≥40
* [[Body mass index|BMI]] ≥ 40
* [[Alcoholic liver disease]]:Only performed if abstinent for ≥ 6 months
* [[Alcoholic liver disease]] (only performed if abstinent for ≥ 6 months)
* Presence of social support
* Presence of social support
* Participation in an [[Alcohol, Drug Abuse, and Mental Health Services Block Grant|alcohol abstinence]] and [[Rehabilitation counseling|rehabilitation program]]
* Participation in an [[Alcohol, Drug Abuse, and Mental Health Services Block Grant|alcohol abstinence]] and [[Rehabilitation counseling|rehabilitation program]]


=== Pretransplant evaluation ===
=== 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===
===Techniques===
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* Artificial [[liver]] support like [[liver dialysis]] or bioartificial [[liver]] support concepts are currently under preclinical and clinical evaluation.   
* 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.   
* 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:
* 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     
** [[Hepatectomy]] (liver removal) phase     
** Anhepatic (no [[liver]]) phase     
** Anhepatic (no [[liver]]) phase     
** Postimplantation phase   
** Postimplantation phase   
* The operation is done through a large [[incision]] in the upper [[abdomen]].   
* The surgery is done through a large [[incision]] in the upper [[abdomen]].   
* The [[hepatectomy]] involves division of:
* 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]]   
** All [[Ligamentous laxity|ligamentous]] attachments to the [[liver]]   
** [[Common bile duct]]   
** [[Common bile duct]]   
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* 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]].   
* 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 [[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.   
* 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 small child.   
* 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 healthy person's [[liver]] is removed and used as the [[allograft]].   
* 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).
* 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===
===Orthotopic Liver Transplantation===
* Donor selection based on [[Cardiac biomarkers|biomarkers]] and risk indices is a crucial aspect of orthotopic liver transplantation and involves:
* Donor selection based on [[Cardiac biomarkers|biomarkers]] and risk indices is a crucial aspect of orthotopic liver transplantation and involves:
** Preference of younger to older donors   
** Preference of younger over older donors   
** Appropriate selection of recipients   
** Appropriate selection of recipients   
** Age based matching of donors and recipients  
** Age based matching of donors and recipients  
* [[Surgery]] 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>
* [[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  
** Excision of the [[liver]] of the recipient  
** Separation of:
** Separation of:
Line 151: Line 296:
*** [[Hepatic artery]]
*** [[Hepatic artery]]
*** [[Portal vein]]  
*** [[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).
** 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 done.
** In order to maintain [[blood]] flow of the [[hepatic artery]], anastomosis of donor [[liver]] at vascular sites is performed
** [[Anastomosis]] of the [[Bile duct|bile ducts]] of the [[graft]] and recipient is performed.
** Then, [[anastomosis]] of the [[Bile duct|bile ducts]] of the [[graft]] and recipient is performed
** In addition, choledochojejunostomy may also be 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:
** Postoperatively, stenting of the [[bile duct]] using a T-tube may help monitor:
*** Production of [[bile]]
*** Production of [[bile]]
Line 160: Line 305:


===Immunosuppressive management===
===Immunosuppressive management===
* Postimplant [[immunosuppression]] ensures survival of the [[patient]] and [[allograft]].
* 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>
* [[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]]
** [[Cyclosporine]]
Line 181: Line 326:
** [[Azathioprine]]  
** [[Azathioprine]]  
** [[Prednisone]]
** [[Prednisone]]
* The risk of [[Rejection|chronic rejection]] in [[Patient|patients]] with liver transplantation decreases with time,although recipients may need to take [[Immunosuppresive drug|immunosuppresive therapy]] for the rest of their lives.
* 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===
===Results===
* [[Prognosis]] is quite good:
* 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%  
** 1-year survival is 83%  
** 5-year survival is 76%  
** 5-year survival is 76%  
** 10-year survival is 66%
** 10-year survival is 66%
* Majority of deaths happen during the first three months after [[Organ transplant|transplantation]].
* Majority of deaths occur during the first three months after [[Organ transplant|transplantation]]


===Living donor 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:
* 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 [[Alcoholism|alcohol]] abuse   
** Long-term untreated [[Hepatitis C]] infection
** Long-term untreated [[Hepatitis C|Hepatitis C infection]]  
** Long-term untreated [[Hepatitis B]] infection
** Long-term untreated [[Hepatitis B|Hepatitis B infection]]  
* The concept of LDLT is based on:
* The concept of LDLT is based on:
** Remarkable regenerative capacities of the human [[liver]]   
** Remarkable regenerative capacities of the human [[liver]]   
** Widespread shortage of [[cadaver]]ic livers for patients awaiting [[Organ transplant|transplant]]   
** 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 recipient’s diseased [[liver]] has been entirely removed.  
* 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.
* 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]].  
* 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  
* More technically demanding than standard, cadaveric donor liver transplantation  
* Has faced several [[Ethics committee (disambiguation)|ethical]] problems  
* 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 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>  
* 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 rejection of the [[graft]]  
** Acute [[Transplant rejection|rejection]] of the [[graft]]  
** Adverse effects of [[Immunosuppression|immunosuppressive therapy]]  
** Adverse effects of [[Immunosuppression|immunosuppressive therapy]]  
** [[Bile duct|Biliary]] [[Stenosis|stricture]]  
** [[Bile duct|Biliary]] [[Stenosis|stricture]]  
Line 221: Line 367:
** [[Infection]]  
** [[Infection]]  
** [[Cancer|Malignancy]]  
** [[Cancer|Malignancy]]  
** [[Transplant rejection|Rejection]]   
** [[Transplant rejection]]   
* To monitor the [[patient]] for complications, the following investigations are used:  
* To monitor the [[patient]] for complications, the following investigations are used:  


==== Laboratory investigations ====
** 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]]
*** 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:  
** Electrolyte panel
**** [[Complete blood count|CBC]]
** [[Liver function tests]]
**** Electrolyte panel
** [[Blood urea nitrogen|Kidney function tests]] (KFTs)
**** [[Liver function tests]]
*** [[Blood urea nitrogen|Blood urea nitrogen (BUN)]]  
**** [[Renal function tests]] (RFTs)
*** [[Creatinine|Creatinine levels]]  
***** [[Blood urea nitrogen|Blood urea nitrogen (BUN)]]  
** Drug levels in case of altered [[BUN|Kidney Function Tests]], or suspected [[Transplant rejection|rejection]]:
***** [[Creatinine|Creatinine levels]]  
*** [[Cyclosporine]] levels
**** Drug levels in case of altered [[renal function tests]] or suspected [[Transplant rejection|rejection]]:
*** [[Tacrolimus]] levels
***** [[Cyclosporine]] levels
** In case of suspected [[infection]]:
***** [[Tacrolimus]] levels
*** [[Blood culture]]
**** In case of suspected [[infection]]:
*** [[Urine culture]]
***** [[Blood culture]]
*** Pharyngeal culture
***** [[Urine culture]]
*** [[Sputum culture]]
***** [[Pharynx|Pharyngeal]] culture
***** [[Sputum culture]]


==== Imaging studies ====
==== Imaging studies ====
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==== Acute and chronic graft rejection ====
==== 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>
[[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
* Occurrence: roughly 20-70 percent patients
* Timing: 1-2 weeks post- transplantation
* Timing: 1-2 weeks post- transplantation, within first three months of [[Organ transplant|transplantation]]
* Outcome: [[Graft]] dysfunction
* Outcome: [[Graft]] dysfunction
* Clinical presentation:  
* Clinical presentation:  
** [[Jaundice]]
** [[Jaundice]]
** [[Fever]]  
** [[Fever]]  
** Liver [[tenderness]]
** Right-upper-quadrant [[tenderness]]
** Generalized abdominal tenderness
** [[Eosinophilia]]
** [[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:  
* Laboratory evidence:  
** Abnormal [[liver function tests]]
** Abnormal [[liver function tests]]
Line 269: Line 423:
*** [[Alanine transaminase|Alanine aminotransferase]] ([[Alanine transaminase|ALT]])  
*** [[Alanine transaminase|Alanine aminotransferase]] ([[Alanine transaminase|ALT]])  
*** [[Aspartate transaminase|Aspartate aminotransferase]] ([[Aspartate transaminase|AST]])  
*** [[Aspartate transaminase|Aspartate aminotransferase]] ([[Aspartate transaminase|AST]])  
* Treatment of [[Acute (medicine)|acute]] [[Transplant rejection|rejection]]:  
* 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]]:
** High-dose [[Steroid|steroids]]:
*** [[Prednisolone]] 200 mg  
*** [[Prednisolone]] 200 mg  
*** [[Methylprednisolone]] 1 g for 3 days)
*** [[Methylprednisolone]] 1 g for 3 days  
*** High-dose [[steroid]] bolus followed by a rapid taper over 1 week
*** High-dose [[steroid]] bolus followed by a rapid taper over 1 week


Line 294: Line 448:


==== Infection ====
==== 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:
* <1 month : Common conditions developing in [[Patient|patients]] in the early posttransplant period include intra-[[Abdomen|abdominal]] [[Infection|infections]] such as:
** [[Cholangitis]]
** [[Cholangitis]]
Line 303: Line 458:
** Opportunistic [[Organism|organisms]]
** Opportunistic [[Organism|organisms]]


* After the first 6 months, risk of [[infection]] in transplant patients is equal to that of the population.
* 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:   
* [[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):  
** [[Bacteria|Bacterial]] (most common):  
*** [[Enterococcus|Enterococci]]  
*** [[Enterococcus|Enterococci]]  
Line 311: Line 466:
*** Gram-negative aerobes  
*** Gram-negative aerobes  
*** [[Anaerobic organism|Anaerobes]]  
*** [[Anaerobic organism|Anaerobes]]  
** Fungal: [[Candidiasis|Candida]] (75% of fungal infections)   
** Fungal: [[Candidiasis|Candida]] (75% of [[fungal infections]])   
** Presenting symptoms:  
** 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]]  
*** [[Fever]] (absent or low grade) 
*** [[Abdominal pain]]   
*** [[Abdominal pain]]   
*** [[Jaundice]]  
*** [[Jaundice]]  
*** Masking of [[Symptom|symptoms]] may occur due to [[immunosuppression]] 
*** Minimal [[pain]] at [[infection]] site


* Laboratory investigations:  
* Laboratory investigations:  
Line 334: Line 491:
** [[Liver biopsy]]  
** [[Liver biopsy]]  


* Treatment of [[infection]]:  
* 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]]  
** [[Antimicrobials]] prescribed for non-[[Immunosuppression|immunosuppressed]] [[Patient|patients]]


==== Cytomegalovirus (CMV) ====
==== Cytomegalovirus (CMV) ====
Line 346: Line 503:
* Clinical presentation:
* Clinical presentation:
** [[Fever]]
** [[Fever]]
** Malaise  
** [[Malaise]]
** [[Arthralgia|Arthralgias]]
** [[Arthralgia|Arthralgias]]


Line 352: Line 509:
** [[Reactive lymphocyte|Atypical lymphocytes]]  
** [[Reactive lymphocyte|Atypical lymphocytes]]  
** [[Thrombocytopenia]]  
** [[Thrombocytopenia]]  
** Mildly elevated transaminase levels
** Mildly elevated [[transaminase]] levels


* Imaging findings:  
* Imaging findings:  
Line 371: Line 528:
* [[Hepatitis B|Hepatitis B infection]]
* [[Hepatitis B|Hepatitis B infection]]
* [[Cancer|Malignancy]]:
* [[Cancer|Malignancy]]:
** In [[Organ transplant|transplant]] [[Patient|patients]], [[Cancer|malignancy]] is the second leading cause of late mortality.
** 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:
** Common [[Cancer|malignancies]] occuring in [[Patient|patients]] after transplantation include:
*** [[Lymphoma|Lymphomas]]  
*** [[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
*** [[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]]
*** Posttransplant [[Lymphoproliferative disorders|lymphoproliferative disorder]]


Line 400: Line 557:
[[Category:Pediatrics]]
[[Category:Pediatrics]]
[[Category:Needs content]]
[[Category:Needs content]]
* {{cite journal | author=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 | year=2005 | pages=861-71 | volume=11 | issue=8  | id=PMID 16035067}}
* {{cite journal | author=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 | year=2003 | pages=1231-43 | volume=9 | issue=12  | id=PMID 14625822}}
* {{cite journal | author=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 | year=2004 | pages=1223-32 | volume=10 | issue=10  | id=PMID 15376341}}
* {{cite journal | author=Tuttle-Newhall JE, Collins BH, Desai DM, Kuo PC, Heneghan MA | title=The current status of living donor liver transplantation | journal=Curr Probl Surg | year=2005 | pages=144-83 | volume=42 | issue=3  | id=PMID 15859440}}
* {{cite journal | author=Martinez OM, Rosen HR | title=Basic concepts in transplant immunology | journal=Liver Transpl | year=2005 | pages=370-81 | volume=11 | issue=4  | id=PMID 15776458}}
* {{cite journal | author=Krahn LE, DiMartini A | title=Psychiatric and psychosocial aspects of liver transplantation | journal=Liver Transpl | year=2005 | pages=1157-68 | volume=11 | issue=10  | id=PMID 16184540}}
* Nadalin S, Malagò M, et al. Current trends in live liver donation. ''Transpl. Int.'' 2007;20:312-30.
* Vohra V. Liver transplantation in India. ''Int Anesthesiol Clin.'' 2006;44:137-49.
* Strong RW. Living-donor liver transplantation: an overview. ''J Hepatobiliary Pancreat Surg.'' 2006;13:370-7.
* Fan ST. Live donor liver transplantation in adults. ''Transplantation.'' 2006;82:723-32.




Latest revision as of 20:49, 25 January 2018


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]


Overview

When a healthy liver allograft is used in place of damaged liver tissue, it is termed as liver transplantation. Thomas Starzl used dogs as the first animals for research on liver transplantation in the 1960s. In 1963, the first liver transplant in humans was attempted by Dr. Thomas Starzl of Colorado, United States. The most common indications for liver transplantation in the United States are hepatitis C virus, alcoholic liver disease, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, hepatitis B virus, liver disease due to inborn errors of metabolism, cancer, biliary atresia and acute liver failure. On the other hand, absolute contraindications to liver transplantation include hepatocellular carcinoma with metastasis, acute liver failure with persistently elevated intracranial pressure ICP >50mmHg, hemangiosarcoma, hilar cholangiocarcinoma, sepsis, and active alcohol or drug abuse. Pretransplant measures such as cardiopulmonary evaluation, screening for occult cancer, infection, and psychosocial evaluation must be performed prior to surgery. The most commonly used technique employed in patients is orthotopic transplantation. This involves removal of the native liver and placement of the donor organ in the same anatomic location as the original liver. Immunosuppressive agents used after transplantation include cyclosporine, everolimus, mycophenolate, corticosteroids, azathioprine, and tacrolimus in different combinations. The most common causes of death in liver transplant patients are infection, malignancy, and rejection. It is necessary to monitor patients for signs of complications and treat them effectively.

Liver Transplantation

History

  • In the 1960s, Thomas Starzl used dogs as the first animals for research on liver transplantation in Boston and Chicago.
  • In 1963, the first liver transplant in humans was attempted by a surgical team led by Dr. Thomas Starzl of Denver, Colorado, United States.[1]
  • Dr. Starzl performed many additional transplants until he was successful in 1967 with the first one-year survival post-transplantation.
  • In 1970, the regimen for immunosuppressive therapy following transplant was introduced, but azathioprine and steroids did not improve survival rates of patients.
  • In the 1980s, with the introduction of cyclosporine by Sir Roy Calne, there was an improvement in rejection rates.
  • In 1983, liver transplantation was no longer an experimental modality, but a clinically acceptable form of therapy for both adult and pediatric patients with appropriate indications.
  • In 1986, the introduction of monoclonal antibodies such as muromonab-CD3 [OKT3] further contributed to improvement of quality of immunosuppressive therapy used in patients, with significant decline in rejection rates.
  • In 1988, University of Wisconsin (UW) solution was developed, which ensured a smooth surgery and longer preservation period.
  • In 1992, the concept of xenotransplantation and cloning techniques were introduced by Starzl.
  • In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.
  • Recently, the introduction of newer immunosuppressive agents such as IL-2 receptor blockers and tacrolimus, have drastically increased patient survival rates to 1 and 5-year rates of approximately 85 and 70 percent respectively.[2]
  • In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.

Indications

Liver transplantation is applicable to any acute or chronic condition resulting in irreversible liver dysfunction, provided that the recipient does not have other conditions that will preclude a successful transplant. Most liver transplants are performed for chronic liver diseases that lead to irreversible scarring of the liver, or cirrhosis.

Contraindications

Absolute contraindications for liver transplantation include:[3]

Relative contraindications for liver transplantation include:[3][4][5][6][7][8][9][10][11][12][13]

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:[3][14]

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:[29][42][43]
  • 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[44]

Complications of Liver Transplantation

    • Laboratory investigations

Imaging studies

Acute and chronic graft rejection

Acute graft rejection:[45]

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:

External Links


References

  1. ↑ STARZL T, MARCHIORO T, VONKAULLA K, HERMANN G, BRITTAIN R, WADDELL W. "HOMOTRANSPLANTATION OF THE LIVER IN HUMANS". Surg Gynecol Obstet. 117: 659–76. PMID 14100514.
  2. ↑ Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM (2005). "A comparison of liver transplantation outcomes in the pre- vs. post-MELD eras". Aliment. Pharmacol. Ther. 21 (2): 169–77. doi:10.1111/j.1365-2036.2005.02321.x. PMID 15679767.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 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.
  4. ↑ Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC (2011). "Early liver transplantation for severe alcoholic hepatitis". N. Engl. J. Med. 365 (19): 1790–800. doi:10.1056/NEJMoa1105703. PMID 22070476.
  5. ↑ Cooper C, Kanters S, Klein M, Chaudhury P, Marotta P, Wong P, Kneteman N, Mills EJ (2011). "Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort". AIDS. 25 (6): 777–86. doi:10.1097/QAD.0b013e328344febb. PMID 21412058.
  6. ↑ Mindikoglu AL, Regev A, Magder LS (2008). "Impact of human immunodeficiency virus on survival after liver transplantation: analysis of United Network for Organ Sharing database". Transplantation. 85 (3): 359–68. doi:10.1097/TP.0b013e3181605fda. PMID 18301332.
  7. ↑ Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG (2012). "Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection". Liver Transpl. 18 (6): 716–26. doi:10.1002/lt.23411. PMC 3358510. PMID 22328294.
  8. ↑ Cross TJ, Antoniades CG, Muiesan P, Al-Chalabi T, Aluvihare V, Agarwal K, Portmann BC, Rela M, Heaton ND, O'Grady JG, Heneghan MA (2007). "Liver transplantation in patients over 60 and 65 years: an evaluation of long-term outcomes and survival". Liver Transpl. 13 (10): 1382–8. doi:10.1002/lt.21181. PMID 17902123.
  9. ↑ Prachalias AA, Pozniak A, Taylor C, Srinivasan P, Muiesan P, Wendon J, Cramp M, Williams R, O'Grady J, Rela M, Heaton ND (2001). "Liver transplantation in adults coinfected with HIV". Transplantation. 72 (10): 1684–8. PMID 11726833.
  10. ↑ Wreghitt T (2001). "Liver Transplantation in Adults Coinfected With HIV. Transplantation 2001; 72: 1684". Transplantation. 72 (10): 1594–5. PMID 11726816.
  11. ↑ Stock P, Roland M, Carlson L, Freise C, Hirose R, Terrault N, Frassetto L, Coates T, Roberts J, Ascher N (2001). "Solid organ transplantation in HIV-positive patients". Transplant. Proc. 33 (7–8): 3646–8. PMID 11750549.
  12. ↑ Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, Terrault NA, Frassetto LA, Palefsky JM, Tomlanovich SJ, Ascher NL (2003). "Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study". Transplantation. 76 (2): 370–5. doi:10.1097/01.TP.0000075973.73064.A6. PMID 12883195.
  13. ↑ Neff GW, Bonham A, Tzakis AG, Ragni M, Jayaweera D, Schiff ER, Shakil O, Fung JJ (2003). "Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease". Liver Transpl. 9 (3): 239–47. doi:10.1053/jlts.2003.50054. PMID 12619020.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 29.0 29.1 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.
  30. ↑ 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.
  31. ↑ Martinez OM, Rosen HR (2005). "Basic concepts in transplant immunology". Liver Transpl. 11 (4): 370–81. doi:10.1002/lt.20406. PMID 15776458.
  32. ↑ Friend PJ (1997). "Liver transplantation". Transplant. Proc. 29 (6): 2716–8. PMID 9290801.
  33. ↑ McCaughan GW, Koorey DJ (1997). "Liver transplantation". Aust N Z J Med. 27 (4): 371–8. PMID 9448876.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 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.
  37. ↑ Chen XB, Xu MQ (2014). "Primary graft dysfunction after liver transplantation". HBPD INT. 13 (2): 125–37. PMID 24686540.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ 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.
  42. ↑ 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.
  43. ↑ 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.
  44. ↑ 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.
  45. ↑ 45.0 45.1 45.2 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.
  46. ↑ 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.
  47. ↑ 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.
  48. ↑ 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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