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REVIEW The Liver Transplant Operation Charles Miller, Teresa Diago Uso The first liver transplantation was performed by Thomas Starzl in Denver, Colorado, in 1963. 1 Over the past 50 years, the field has experienced tremendous medical and surgical advancement, with 1- and 5-year survival approaching 90% and 75%, respectively, in most series. Successful transplantation involves a fascinating complex of donor and recipient factors, which represent the focus of this review. Donor Factors Donor quality is one of the most important determinants of peritransplantation and posttransplantation organ func- tion. Donors can be defined as standard criteria donors (i.e., good quality donors) or extended criteria donors, which may include steatotic livers, older donors, donors with positive serology, split livers, and donors after cardiac death (DCD). Other factors that affect organ quality are mechanism of death, hemodynamic instability that requires pressor support, and electrolyte derangement (sodium level at procurement >160 mmol/L). All of these factors along with predicted ischemia times are among the important var- iables that can help with the initial decision of whether or not to pursue the procurement of a liver. Ischemia time can be divided into cold ischemia time (CIT) and warm ische- mia time (WIT). CIT begins when the liver is cooled with cold perfusion solution during organ procurement and ends when the organ is placed in the transplant field for implan- tation. The time from removal of the liver from ice until vascular reperfusion represents the WIT. During this period, the liver warms slowly to a temperature of 12.5 C while the caval and portal vein anastomoses are performed. 2 CIT and WIT of 6 to 12 hours and 30 to 60 minutes, respectively, are acceptable, with shorter times being necessary when transplanting marginal donors to maximize early graft func- tion. Matching donor and recipient characteristics is another important aspect of preoperative planning. For instance, older donors (>60 years) transplanted to hepatitis C virus recipients are associated with more aggressive posttrans- plantation hepatitis C virus recurrence, 3 and a suboptimal organ (fatty livers, old grafts, or DCD organs) transplanted to a very sick patient often results in poor transplantation outcome. 4 DCDs are donors who do not meet the criteria for brain death and must be pronounced dead after life support has been terminated and after a variable agonal phase (which should not exceed 30 minutes) and ultimately irreversible cessation of circulation. Livers procured from DCDs are more susceptible to primary nonfunction and chronic bili- ary complications, probably due to the hypoperfusion dur- ing the agonal phase. These are all important concepts when considering donor and recipient factors in the delicate phase of organ acceptance and transplantation. Recipient Factors Recipient Hepatectomy and Preparation for Implanta- tion. Hepatectomy of the native liver is the first step of the operation. This can be a challenging procedure due to the intimate anatomical relationship of the liver with the retrohepatic inferior vena cava (IVC) in the setting of coa- gulopathy and portal hypertension. A history of previous upper abdominal surgery can make the operation even more hazardous. Hepatectomy can be performed using one of two techni- ques: the conventional technique or the piggyback tech- nique. In the conventional technique, the native retrohepatic IVC is removed en bloc with the liver. The donor vena cava (always procured along with the liver) is anastomosed in an end-to-end fashion to both the suprahe- patic and infrahepatic IVC to recreate the original anatomi- cal situation (Fig. 1.A,B). In the piggyback technique, the Abbreviations: CIT, cold ischemia time; DCD, donors after cardiac death; IVC, inferior vena cava; WIT, warm ischemia time. From the Cleveland Clinic, Liver Transplant Program, Department of General Surgery Cleveland, OH. Potential conflict of interest: Nothing to report. View this article online at wileyonlinelibrary.com V C 2013 by the American Association for the Study of Liver Diseases doi: 10.1002/cld.232 192 Clinical Liver Disease, Vol 2, No 4, August 2013 An Official Learning Resource of AASLD

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Page 1: The liver transplant operation

REVIEW

The Liver Transplant Operation

Charles Miller, Teresa Diago Uso

The first liver transplantation was performed by ThomasStarzl in Denver, Colorado, in 1963.1 Over the past 50years, the field has experienced tremendous medical andsurgical advancement, with 1- and 5-year survivalapproaching 90% and 75%, respectively, in most series.Successful transplantation involves a fascinating complex ofdonor and recipient factors, which represent the focus ofthis review.

Donor FactorsDonor quality is one of the most important determinants

of peritransplantation and posttransplantation organ func-tion. Donors can be defined as standard criteria donors(i.e., good quality donors) or extended criteria donors,which may include steatotic livers, older donors, donorswith positive serology, split livers, and donors after cardiacdeath (DCD). Other factors that affect organ quality aremechanism of death, hemodynamic instability that requirespressor support, and electrolyte derangement (sodium levelat procurement >160 mmol/L). All of these factors alongwith predicted ischemia times are among the important var-iables that can help with the initial decision of whether ornot to pursue the procurement of a liver. Ischemia time canbe divided into cold ischemia time (CIT) and warm ische-mia time (WIT). CIT begins when the liver is cooled withcold perfusion solution during organ procurement and endswhen the organ is placed in the transplant field for implan-tation. The time from removal of the liver from ice untilvascular reperfusion represents the WIT. During this period,the liver warms slowly to a temperature of 12.5�C while thecaval and portal vein anastomoses are performed.2 CIT andWIT of 6 to 12 hours and 30 to 60 minutes, respectively,are acceptable, with shorter times being necessary whentransplanting marginal donors to maximize early graft func-tion. Matching donor and recipient characteristics is another

important aspect of preoperative planning. For instance,older donors (>60 years) transplanted to hepatitis C virusrecipients are associated with more aggressive posttrans-plantation hepatitis C virus recurrence,3 and a suboptimalorgan (fatty livers, old grafts, or DCD organs) transplantedto a very sick patient often results in poor transplantationoutcome.4

DCDs are donors who do not meet the criteria for braindeath and must be pronounced dead after life support hasbeen terminated and after a variable agonal phase (whichshould not exceed 30 minutes) and ultimately irreversiblecessation of circulation. Livers procured from DCDs aremore susceptible to primary nonfunction and chronic bili-ary complications, probably due to the hypoperfusion dur-ing the agonal phase. These are all important conceptswhen considering donor and recipient factors in the delicatephase of organ acceptance and transplantation.

Recipient FactorsRecipient Hepatectomy and Preparation for Implanta-

tion. Hepatectomy of the native liver is the first step ofthe operation. This can be a challenging procedure due tothe intimate anatomical relationship of the liver with theretrohepatic inferior vena cava (IVC) in the setting of coa-gulopathy and portal hypertension. A history of previousupper abdominal surgery can make the operation evenmore hazardous.

Hepatectomy can be performed using one of two techni-ques: the conventional technique or the piggyback tech-nique. In the conventional technique, the nativeretrohepatic IVC is removed en bloc with the liver. Thedonor vena cava (always procured along with the liver) isanastomosed in an end-to-end fashion to both the suprahe-patic and infrahepatic IVC to recreate the original anatomi-cal situation (Fig. 1.A,B). In the piggyback technique, the

Abbreviations: CIT, cold ischemia time; DCD, donors after cardiac death; IVC, inferior vena cava; WIT, warm ischemia time.From the Cleveland Clinic, Liver Transplant Program, Department of General Surgery Cleveland, OH.

Potential conflict of interest: Nothing to report.View this article online at wileyonlinelibrary.comVC 2013 by the American Association for the Study of Liver Diseases

doi: 10.1002/cld.232

192 Clinical Liver Disease, Vol 2, No 4, August 2013 An Official Learning Resource of AASLD

Page 2: The liver transplant operation

liver is completely dissected from the IVC, which is there-fore preserved and only partially clamped at completion ofthe hepatectomy. A common cuff is created by joining thethree hepatic vein orifices together, and the donor suprahe-patic cava is anastomosed in an end-to-side fashion to thecommon cuff of recipient hepatic veins (Fig. 2.). The retro-hepatic donor vena cava (i.e., the cul-de-sac) is ligated. Oneof the major advantages of this technique is that the venousreturn is preserved during the anhepatic phase. Further-more, only one IVC anastomosis is performed, shorteningthe anhepatic phase time. This is the only technique possi-ble when the IVC is not present in the graft (i.e., in livingdonors and split livers).

The conventional technique requires complete occlusionof the vena cava. Consequently, some surgeons prefer touse a veno-venous bypass during the anhepatic phase toavoid hemodynamic instability caused by total caval occlu-sion. Many other surgeons rarely if ever use the bypass tech-nique, however, and rely on advanced anesthesia techniquesand a more rapid implantation to achieve the same results.The conventional technique does not require the sometimestedious dissection of the caudate lobe from the vena cava,making the hepatectomy easier and faster. The decisionbetween the conventional technique or the piggyback tech-nique is most often made according to a surgeon’s experienceand personal preference.5,6 In our program, we use the con-ventional technique in 40% to 50% of cases, mostly withoutthe use of veno-venous bypass. No study in the literature hasproven superiority of one technique over the other.

Portal Vein Anastomosis. After completing the IVC anas-tomosis, portal vein anastomosis is performed in an end-to-end fashion and the liver is reperfused. Reperfusion is oneof the most critical parts of transplantation. This can becharacterized by profound hemodynamical instability (bra-dycardia and hypotension) and is the result of the suddenintroduction in the systemic circulation of cold andcytokine-rich graft effluent. To avoid profound reperfusionsyndrome, the liver is flushed with room temperature salineand then with systemic blood from either the portal vein orthe IVC to wash and warm the graft just prior to formalreperfusion.

Some degree of portal vein thrombosis may be present inup to 13% of transplants.7 This must be dealt with via sim-ple portal thrombectomy or secondarily with portal vein

FIGURE 1. Liver transplantation: the conventional technique. (A) The native retrohepatic vena cava is removed en bloc with the liver. (B) The donor IVC is anasto-mosed in an end-to-end fashion to the recipient suprahepatic and infrahepatic IVC.

FIGURE 2. Liver transplantation: the piggyback technique. The donorsuprahepatic IVC is anastomosed in an end-to-side fashion to the commoncuff of the recipient hepatic veins. The retrohepatic donor vena cava is ligated.

R E V I E W The Liver Transplant Operation Miller and Diago Uso

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replacement with venous grafts (typically the donor iliacvein is used as a conduit) interposed between the donorportal vein and a recipient splanchnic vein (portal vein,superior mesenteric vein, coronary vein, or a large porto-systemic collateral). In selected cases, especially when thereis a well-developed spleno-renal shunt, the left renal veincan be used as an excellent source of portal inflow.

Hepatic Artery Anastomosis. The most common anddurable approach to hepatic artery reconstruction is an end-to-end anastomosis between the donor’s celiac axis and therecipient’s common hepatic artery just at the confluencewith the gastroduodenal artery (Fig. 3.A). Depending onsurgeon preference and anatomical factors (e.g., arterial var-iants, vessel diameter, living donor grafts), the level of thereconstruction may vary.

The most common deceased donor arterial anatomicalvariant is the presence of a right arterial branch originatingfrom the superior mesenteric artery (�15% of cases) (Fig.3.B).8 Different back table techniques are used to recon-struct this variant; the focus of the reconstruction is toallow for only one simple anastomosis in the recipient. Theeasiest and most common reconstruction technique is theanastomosis of the separate right hepatic branch to thestump of the donor gastroduodenal artery.

In the case of a left accessory hepatic artery (�10% ofcases),8 this branch takes off from the donor’s left gastricartery (Fig. 3.C). This is preserved during donor surgery,and the arterial anastomosis is performed as describedabove between the donor’s celiac axis (therefore proximal tothe accessory artery) and the recipient’s common hepaticartery. The use of running versus interrupted suture in thearterial anastomosis is usually subject to the diameter of thevessel (interrupted used for smaller vessels).

During procurement, these accessory arteries may gounrecognized and become injured. Most injuries can be

identified and reconstructed at the back table. For severeinjuries that defy attempts at reconstruction, it is good toremember that the replaced left hepatic artery is usually anaccessory artery, and ligation or thrombosis should not cre-ate drastic consequences, as there are rich collaterals withinthe umbilical fissure. The replaced right hepatic artery isusually the only arterial supply to the right lobe and proxi-mal bile duct, and lack of patency can have far more severemanifestations of biliary leak, biliary stricture, and rightlobe ischemia with abscess.

In case of poor recipient arterial inflow that may becaused by celiac stenosis or inadvertent damage to the com-mon hepatic artery during hepatectomy, an interpositional

FIGURE 3. Hepatic artery anatomy. (A) Anatomy of the standard hepatic artery. (B) Replaced (accessory) right hepatic artery from the superior mesenteric artery.(C) Replaced (accessory) left hepatic artery from the left gastric artery.

FIGURE 4. Hepatico-jejunostomy with a defunctionalizated Roux-en-Yintestinal loop.

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arterial graft (usually the iliac artery of the donor) is placedbetween the infrarenal or supraceliac aorta and the donorceliac axis.

Every effort should be made during the operation toassure early and late hepatic artery patency. Early hepaticartery thrombosis necessitates thrombectomy and recon-struction if it is identified before hepatic necrosis ensues; ifnot, and the liver is severely damaged, it may require earlyretransplantation. When hepatic artery thrombosis occurslater, it may be first recognized when the patient presentswith fever and hepatic abscess. Although this may also ulti-mately require retransplantation, many grafts can be sal-vaged with conservative supportive therapy aimed at takingadvantage of the development of collaterals that can supplyadequate perfusion and oxygenation to allow for hepaticparenchymal healing. Careful study of triphasic computedtomography scans and duplex ultrasound images oftenreveal patent intrahepatic arterial branches despite the pres-ence of a main hepatic artery thrombosis.

Biliary Anastomosis. Following the vascular anastomosisand the establishment of good hemostasis is the donor chole-cystectomy and biliary reconstruction. The preferred anasto-mosis is duct-to-duct between the donor and recipientcommon bile ducts. When there is unacceptable duct sizemismatch or the recipient bile duct is unusable (primarysclerosing cholangitis), a hepatico-jejunostomy with a defunc-tionalizated Roux-en-Y intestinal loop is performed (Fig. 4.).

The duct-to-duct anastomosis is usually performed withoutthe use of a T-tube. Although once very popular, removal ofT-tubes was found to be associated with a high rate of mor-bidity due to insertion site leak that often required emergenthospitalization and endoscopic retrograde cholangiopancrea-tography and stenting. As anastomotic techniques becamemore refined, internal stents and T-tubes fell into disfavor.9

Living Donor FactorsThe imbalance between organ supply and demand has

pushed the transplant community to look at ways to expandthe donor pool. Living donor liver transplantation is oneoption, despite its indisputable ethical and surgical chal-lenges (Fig. 5.A,B). This type of transplantation can be per-formed between an adult donor and either a pediatric oradult recipient. Because donor safety is of paramountimportance, only healthy donors in which the future liverremnant will be more than 35% are candidates for this pro-cedure. The technical challenges of the donor and recipientoperation are beyond the scope of this review; suffice it tosay, however, that the basis of the techniques have evolvedand have been refined from those used in deceased donortransplantation described above.10

CORRESPONDENCECharles Miller, M.D., Liver Transplant Program, Department of GeneralSurgery, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195.E-mail: [email protected]

References

1. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, WaddellWR. Homotransplantation of the liver in humans. Surg Gynecol Obstet1963;117:659–676.

2. Cursio R, Gugenheim J. Ischemia-reperfusion injury and ischemic-type bili-ary lesions following liver transplantation. J Transplant 2012;2012:164329.

3. Pratschke S, Loehe F, Graeb C, Jauch KW, Angele MK. Usage of marginalorgans for liver transplantation: a way around the critical organ shortage?Zentralbl Chir 2009;134:107–112.

FIGURE 5. Living donor liver transplantation. (A) Right lobe graft. (B) Left lobe remnant.

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4. Johnson SR, Alexopoulos S, Curry M, Hanto DW. Primary nonfunction(PNF) in the MELD era: an SRTR database analysis. Am J Transplant 2007;7:1003–1009.

5. Eghtesad B, Kadry Z, Fung J. Technical considerations in liver transplanta-tion: what a hepatologist needs to know (and every surgeon should practice).Liver Transpl 2005;11:861–871.

6. Hosein Shokouh-Amiri, M, Osama Gaber, A, Bagous WA, Grewal HP,Hathaway DK, et al. Choice of surgical technique influences perioperativeoutcomes in liver transplantation. Ann Surg 2000;231:814–823.

7. Werner KT, Sando S, Carey EJ, Vargas HE, Byrne TJ, Douglas DD, et al.Portal vein thrombosis in patients with end stage liver disease awaiting

liver transplantation: outcome of anticoagulation. Dig Dis Sci 2013;58:1776–1780.

8. Hiatt JR, Gabbay J, Busuttil RW. Surgical anatomy of the hepatic arteries in1000 cases. Ann Surg 1994;220:50–52.

9. Sotiropoulos GC, Sgourakis G, Radtke A, Molmenti EP, Goumas K,Mylona S, et al. Orthotopic liver transplantation: T-tube or not T-tube?Systematic review and meta-analysis of results. Transplantation 2009;87:1672–1680.

10. Quintini C, Hashimoto K, Uso TD, Miller C. Is there an advantage of liv-ing over deceased donation in liver transplantation? Transpl Int 2013;26:11–19.

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