Adult-to-adult living donor liver transplantation for fulminant hepatic failure

Without liver transplantation, the prognosis for fulminant hepatic failure is extremely poor.¹ A shortage of cadaver donors has resulted in some patients dying while waiting for a suitable donor.² In Western Australia, our experience is that 60% of patients with fulminant hepatic failure die before a cadaver liver becomes available. Living donor liver transplantation was initially developed to circumvent waiting list deaths in children. The technique was subsequently expanded to include adult patients because of insufficient availability of cadaveric organs.³ While adult-to-child living donor liver transplantation is a relatively safe and accepted practice,⁴ adult-to-adult living donor liver transplantation is still controversial. The concern is that, because adult recipients require larger grafts, healthy adult donors may be at greater risk of death or complications.⁵

The world experience in adult-to-adult living donor liver transplantation is rapidly increasing, and many studies show recipient outcomes similar to those with whole-organ implants, as well as low donor risk.^2,3,6-9 To date, there have been no reports of adult-to-adult living donor liver transplantation in Australia. We report such a case. The Sir Charles Gairdner Hospital Human Ethics Committee approved an adult-to-adult living donor transplantation program.

Clinical record

Recipient details

The recipient was a previously well, 71 kg, 19-year-old mother of a 15-month-old son. She had acquired hepatitis B virus (HBV) infection. Her admission on 15 April 2000 was preceded by 2-3 weeks of worsening jaundice and constitutional symptoms. Physical examination revealed deep jaundice, but no signs of chronic liver disease.

At admission, the patient had a serum bilirubin level of 474 µmol/L (normal, < 20 µmol/L), serum alanine transferase (ALT) level > 300 U/L (normal, < 40 U/L), and an international normalised ratio of prothrombin time (INR) of 1.9. She tested positive for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), and negative for antibodies to hepatitis C and HIV.

On the fifth day (20 April 2000), there was a marked clinical deterioration, with the development of unresponsive coma requiring intubation and ventilation. The patient met three King's College Hospital criteria for poor prognosis in fulminant hepatic failure:

• a time interval of more than seven days between jaundice and the onset of encephalopathy;

• a major disturbance in coagulation; and

• a serum bilirubin level > 300 mmol/L.

The presence of these criteria suggested the likelihood of recovery without transplantation was less than 7%.¹⁰

On transfer to Sir Charles Gairdner Hospital, the patient fulfilled the Australasian and New Zealand liver group criteria for urgent listing for orthotopic cadaver liver transplantation. In the event of no cadaver liver becoming available, the possibility of a living donor liver transplant was discussed with the family.

The recipient's mother, grandmother and two sisters volunteered as donors. On blood typing, her grandmother and a sister were found to be ABO blood group compatible. The sister was the more suitable donor as the grandmother had cardiovascular comorbidities.

Donor details

The donor was a 64 kg, 24-year-old woman, with no significant medical history. She smoked four cigarettes a day, but drank no alcohol. Preoperative evaluation by an independent psychiatrist demonstrated no psychosocial impediment to liver donation. Serum electrolyte levels, liver function tests, full blood analysis, and coagulation studies were normal, and serology for HIV and hepatitis B and C viruses was negative. An abdominal computed tomography scan showed a normal liver with a total volume of 1512 mL. The right lobe volume was estimated at 1133 mL, giving an estimated graft-to-recipient body weight ratio of > 1.0%; this was adequate for transplantation.^11,12 Preoperative angiography showed the right hepatic artery arising from the superior mesenteric artery, and the left originating from the coeliac axis. Endoscopic retrograde cholangiopancreatography had to be abandoned because of patient intolerance. A magnetic resonance imaging cholangiogram showed conventional biliary anatomy, with the right anterior and posterior ducts joining 5 mm from the confluence of the right and left hepatic ducts.

Five counselling sessions were conducted over two days between medical staff and the donor (with and without members of her family). Informed consent was obtained from the donor, with the understanding that the donor or her family could stop the process at any time without giving a reason.

On the fifth day after referral to the transplant unit, the living donor liver transplantation from sister to sister proceeded concurrently in adjacent operating theatres.

Donor surgery

Donor surgery was performed as previously described through a right subcostal incision with a midline extension to the xiphoid process. ^6,13

Before the completion of the donor right lobectomy, the recipient hepatectomy was commenced. Final clamping of the donor right lobe vessels was undertaken when the recipient was ready to receive the graft. The donor's total estimated blood loss for the procedure was 2000 mL, replaced by two units of packed red blood cells and one unit of autologous blood perioperatively. The total procedure time was 6 h 15 min.

Recipient surgery

The recipient surgery was through a similar incision. The entire liver, which was atrophic, heavily bile stained and showed massive hepatic necrosis histopathologically, was removed. The donor right lobe was implanted, hepatic vein end-to-side to the inferior vena cava ("piggyback" style). The other vessels and the right hepatic bile duct were joined end-to-end to the recipient structures. The total operative time was 10 h 10 min and the total ischaemic time was 55 min. The recipient required six units of packed red blood cells, 18 units of platelets and 24 units of fresh frozen plasma perioperatively. Immunosuppression was initiated with cyclosporin and methylprednisolone, together with prophylaxis for hepatitis B virus infection with hepatitis B immunoglobulin infusions and lamivudine.

Postoperative details

The donor was extubated several hours after leaving the operating theatre and, after 24 hours in the intensive care unit, was transferred to the general ward. Recovery was complicated by right basal atelectasis, which was treated by intensive chest physiotherapy. All liver function tests were normal at discharge on Day 6. A staphylococcal infection in the drain wound required a two-day readmission, but responded to flucloxacillin treatment. The donor returned to normal full activities four weeks later.

The recipient made a slower postoperative recovery. There was an immediate improvement, and extubation occurred on the fifth day after surgery, with transfer to the general ward on Day 7. At this time her serum bilirubin level was 242 µmol/L, serum ALT level was 262 U/L, and INR was 1.2, improved from the pre-surgery values of 670 µmol/L, 1060 U/L and 5.1, respectively. Her serum lactate level was 8.1 mmol/L (normal, < 1.3 mmol/L). Complications included Staphylococcus aureus septicaemia, right middle and lower lobe consolidation, and an episode of severe acute graft rejection. On the 33rd day after surgery, the recipient was discharged. Two months after transplantation, her serum bilirubin level was 341 µmol/L, serum alkaline phosphatase level was 374 U/L (normal, 35-135 U/L), and serum ALT level was 80 U/L. A stricture of the biliary anastomosis was stented at this time.

Three months after transplantation, there was still no filling of the right posterior bile duct, necessitating laparotomy and reanastomosis of the duct. The patient made an uncomplicated recovery and was discharged on Day 7.

Persisting abnormal liver function tests at five and a half months led to a liver biopsy. Moderately severe chronic rejection was diagnosed, and the immunosuppressive medication was changed from cyclosporin to tacrolimus. At 12 months, results of liver function tests were normal and the recipient had returned to normal activities.

Discussion

This case represents the first adult-to-adult living donor liver transplantation in Australia. To date, there has been one reported adult-to-child living donor liver transplantation in Australia.¹⁴

The outcome of fulminant hepatic failure is extremely poor.¹⁰ Liver transplantation is the only effective treatment, but must be timely as delays result in sicker patients and higher mortality rates.¹⁵ In our patient, an urgent adult-to-adult living donor liver transplantation was undertaken because of the lack of availability of a cadaver graft.

The reported experience of living donor liver transplantation in the high-urgency or emergency setting is limited, but internationally the outcomes are reported to be similar to conventional cadaver liver transplantation. Emergency living donor liver transplantation in 15 adults with fulminant hepatic failure had an overall patient survival rate of 59%,⁹ which is in the range reported for urgent cadaver transplantation (50%-68% survival at one year).^1,16 In another series, adult patients with acute or chronic liver failure who were listed for high-urgency transplantation and received either living right lobe or extended living left lobe grafts had a one-year survival rate of 85%.²

As living donor liver transplantation exposes essentially healthy individuals to a life-threatening procedure, the processes of informed consent and patient selection must be strictly adhered to. Our donor volunteered early in the selection process. In accordance with the principle of self-selection or free voluntarism,² care was taken to ensure there was no undue pressure on the potential donor from other family members. All members of the family understood they could stop the process at any time. If a potential donor does decide to withdraw from the process, this should remain confidential, and a medical excuse should be made for the cancellation.¹⁷

In our case, the donor made a speedy and uneventful recovery, but the recipient's recovery was complicated by a stricture at the biliary anastomosis. Biliary complications occur in 10%-35% of whole-organ cadaver transplants.^17,18 Strictures are usually anastomotic and develop more than one month after surgery.¹⁹ Presently, there appears no clear benefit in using duct-to-duct biliary anastomoses or choledochojejunostomy.^17,19 Three months after transplantation, our patient had a stricture corrected surgically.

Recently, much attention has focused on a decline in the number of cadaveric organs available for emergency and elective transplantation. In Japan and Hong Kong, where there are critical shortages of cadaveric donors because of religious, cultural or legislative impediments, living donor liver transplantation has become an important adjunct to cadaveric transplantation.^2,3 Some transplant centres in Japan and the United States have also been successfully using living donor liver transplants in the non-emergency setting.⁶ In Australia, between 6% and 8% of patients waiting for cadaver liver transplantation die each year, compared with 10% in the United States.^20,21 Most of these patients are adults, as the number of children on the waiting list has been reduced significantly by the use of split liver cadaveric and living donor liver transplantation.^22,23 Following the worldwide experience with living donor liver transplantation, the Transplant Society of Australia and New Zealand²¹ has recently supported the use of living donor liver transplantation in emergency situations, but has questioned its elective role because of concerns about donor safety and inadequate data demonstrating a local need.

To date, there have been three reported deaths in 2000 living liver donors, giving a mortality rate of 0.15%.^24,25 Case-series reports also indicate minimal donor morbidity, with minimal operative blood loss, and average lengths of stay of one week.^2,7,8 Donor morbidities include minor and major complications in 30%. Of these, biliary strictures and cholestasis are the more prevalent.²⁵

Adult living donor liver transplantation is likely to be extended to waiting list patients when death while waiting increases to the proportions reported from Europe and North America and after procedures are in place for recipient and potential donor to be fully informed at transplant listing. Donor mortality and morbidities are a serious issue, but can be minimised by adequate donor work-up and selection.

References

1. Bismuth H, Samuel D, Castaing D, et al. Orthotopic liver transplantation in fulminant and subfulminant hepatitis. Ann Surg 1995; 222: 109-119.
2. Lo CM, Fan ST, Liu CL, et al. Applicability of living donor liver transplantation to high-urgency patients. Transplantation 1999; 67: 73-77.
3. Inomata Y, Uemoto S, Asonuma K, et al. Right lobe graft in living donor liver transplantation. Transplantation 2000; 69: 258-264.
4. Grewal HP, Thistlethwaite JR, Loss GE, et al. Complications in 100 living-liver donors. Ann Surg 1998; 228: 214-219.
5. Strong RW. Whither living donor liver transplantation? Liver Transplant Surg 1999; 5: 536-538.
6. Marcos A, Fisher RA, Ham JM, et al. Right lobe living donor liver transplantation. Transplantation 1999; 68: 798-803.
7. Fan ST, Lo CM, Liu CL, et al. Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg 2000; 135: 336-340.
8. Marcos A, Fisher RA, Ham JM, et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation 2000 (a); 69: 2410-2415.
9. Uemoto S, Inomata Y, Sakuri T, et al. Living donor liver transplantation for fulminant hepatic failure. Transplantation 2000; 70: 152-157.
10. O'Grady JG, Alexander GJM, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1997; 97: 439-445.
11. Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999; 67: 321-327.
12. Marcos A, Fisher RA, Ham JM, et al. Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation. Transplantation 2000 (b); 69: 1375-1379.
13. Wachs ME, Bak TE, Karrer FM, et al. Adult living donor liver transplantation using a right hepatic lobe. Transplantation 1998; 66: 1313-1316.
14. Strong RW, Lynch SV, Ong TN, et al. Successful liver transplantation from a living donor to her son. N Engl J Med 1990; 322: 1505-1507.
15. Shakil AO, Mazariegos GV, Kramer DJ. Fulminant hepatic failure. Surg Clin North America 1999; 79: 77-108.
16. Washburn WK, Bradley J, Cosimi AB, et al. A regional experience with emergency liver transplantation. Transplantation 2000; 61: 235-239.
17. Marcos A. Right lobe living donor liver transplantation: A review. Liver transplantation 2000; 6: 3-20.
18. Jeffrey GP, Brind AM, Ormonde DG, et al. Management of biliary tract complications following liver transplantation. Aust N Z J Surg 1999; 69: 717-722.
19. Mazariegos GV, Molmenti EP, Kramer DJ. Early complications after orthotopic liver transplantation. Surg Clin North America 1999; 79: 109-129.
20. Kam I. Anatomical variations of the liver. Technical issues with Donors and Outcomes. The Second International Symposium Dedicated to Expanding the Donor Pool, Living Donor and Split Liver Transplantation; XVIII International Congress of the Transplantation Society 2000.
21. Transplant Society of Australia and New Zealand (TSANZ). Live donor liver transplantation in Australia: Current recommendations. Liver Transplant Standing Committee. April 2000: Canberra, Australia.
22. Rogier X, Broering DC, Mueller L, Living-donor liver transplantation in children. Langenbecks Arch Surg 1999; 384(6): 528-535.
23. Reding R, de Goyet J de V, Delbeke I, et al. Paediatric liver transplantation with cadaveric or living related donors. Comparative results in 90 elective recipients of primary grafts. J Paediatr 1999; 134(3): 280-286.
24. Schiano TD, Kim-Schluger L, Gondolesi G, Miller CM. Adult living donor transplantation. The hepatologist's perspective. Hepatology 2001; 33: 3-8.
25. Renz JF, Roberts JP. Long-term complications of living donor liver transplantation. Liver Transpl 2000; 6 Suppl 2: 73-76.

Authors' details

Reprints will not be available from the authors.
Correspondence: Professor A K House, University Department of Surgery, QEII Medical Centre, M Block, Verdun Road, Nedlands, WA 6907.
akhouseATcyllene.uwa.edu.au

Make a comment