Annual Report of the New Zealand Liver Transplant Unit

2003

Summary:

In the calendar year of 2003 the New Zealand Liver Transplant Unit (NZLTU) undertook 73 liver transplant assessments and performed 38 liver transplants in 37 patients (one re-transplant). Of these 37 patients, 2 have died (one of probable intracerebral infection and the other of metastatic hepatocellular carcinoma) and the remaining 35 are all at home (crude survival rate of 95%). Overall programme survival rates are still very acceptable with a one year actual and actuarial survival rate of 93.3% (the national average in the US is 86.6%). Allograft rejection continues to be common, occurring in 39% of patients in 2003, but has proven easy to treat in the majority of cases (with bolus steroids). Two patients required plasmapheresis and/or antilymphocyte antibody treatment for rejection. The paediatric programme continued in 2003 with 6 children receiving 6 liver allografts. It is pleasing to report that all children transplanted thus far (n=13 to date) are alive, out of hospital and well. Similarly, the live donor liver transplant programme continued with one further such transplant (adult-to-child) in 2003. Both donor and recipient are well. As in 2002, the commonest liver disease in recipients was hepatitis C (30%) followed closely by hepatitis B (24%). Waiting times for a liver transplant, on average, have not increased in 2003 (103 days in 2003 versus 124 days in 2002). However, the low cadaveric organ donor rate continues to be of concern given that 7 of the 54 patients (13%) listed for transplantation in 2003 had to be delisted for deterioration or died whilst waiting for a liver to become available. Once again, in 2003, NZLTU imported more Australian livers than were exported. NZLTU continues to be a strong proponent of changes in the organisation of organ donor services in New Zealand. There is a maldistribution of blood group O livers and a suggestion for this to be remedied is included.

Clinical Record:

The average waiting time for all 38 transplants was 103 days (a decrease over the average of 124 days in 2002). Those transplanted for acute liver failure or primary graft failure (n=5) waited an average of 2.2 days whereas those with chronic liver disease waited an average of 118 days (126 days for blood group O patients, 87 days for blood group A patients, 173 days for blood group B patients, and 187 days for blood group AB patients). Of importance in this distribution of waiting times is the fact that blood group O patients are potentially disadvantaged by the fact that blood group O livers can be, and are, used for non-O recipients (usually on the basis of urgency). In 2003, there were 17 blood group O livers used but only 8 of these (47%) were placed on blood group O recipients. This contrasts with blood group A livers which were placed in blood group A recipients on 17 of 18 occasions (94%). Over a 2 year period (2002 & 2003) blood group O recipients waited significantly longer, on average, than blood group A recipients (154 days versus 85 days, p = 0.006). A similar phenomenon occurred in North America and has been remedied by strict rules regarding the use of blood group O livers. This is discussed under the section of this report entitled “Overview of the Service” below.

Data Analysis:

The age distribution of the 37 patients transplanted in calendar year 2003 is shown in Figure 1. A bimodal distribution is evident.

The indications for liver transplantation were:

Hepatitis C virus related (with or without alcoholic liver disease) 11/38

Hepatitis B virus related 9/38

Alcoholic liver disease (without viral hepatitis) 5/38

Biliary atresia 4/38

Cryptogenic 3/38

Non A, non B hepatitis 2/38

Alpha-1 antitrypsin deficiency 1/38

Primary sclerosing cholangitis 1/38

Primary biliary cirrhosis 1/38

Other acute 1/38

Of the patients listed for the indications above, 9/38 (24%) also had hepatocellular carcinomata that fell within our predetermined criteria. Five patients had acute liver failure or a failed allograft as the indication for transplantation. Of these 5, 2 had non A, non B hepatitis, 2 had acute hepatitis B or a flare thereof, and one patient had arterial insufficiency of a liver allograft resulting in ischaemic cholangiopathy (in the absence of hepatic artery thrombosis).

Patient and graft survival:

Of the 37 patients transplanted in 2003, 35 are currently alive and well, giving a crude survival of 95%. 2 patients died, one of metastatic hepatocellular carcinoma (HCC) at 4 months post transplant and one of presumed intracerebral infection at 6 months post transplant. Both of these patients had received combined liver and kidney transplants but for somewhat different indications. The patient with the HCC had pre-existing renal insufficiency but was not dialysis dependent. He received a combined transplant because he had insufficient renal reserve to tolerate a liver transplant and the concomitant calcineurin inhibitor medication required. The other patient was on dialysis and had end stage liver disease secondary to hepatitis C infection. This patient had aggressive rejection of the renal allograft and required antibody therapy. She developed a rapidly growing lesion in her brain which was most likely fungal in origin and died as a result of this. An autopsy was not permitted by her family. Since the inception of the programme there have been 194 transplants in 186 patients giving a crude retransplant rate of 4.3% which is low by international standards (a more typical figure being around 10%). Overall actuarial patient survival is illustrated in Figure 2. It should be noted that patient numbers at 6 years are small. Numbers are now sufficiently large overall that one year actuarial and actual patient survival figures are the same (93%). These figures compare very favourable with up-to-date figures from the US Transplant Registry Data Base where the national average one-year patient survival rate was 87%.

Figure 2

Assessed patients:

There were 73 patients assessed for liver transplantation in 2003. This puts the ratio of assessments to transplants at 1.9 which is higher than in previous years (for example, in 2002 the ratio was 1.5). The funding formula provides for an average ratio of around 1.6. The outcome of these assessments is summarised in Figure 3.

Figure 3

Liver donors:

From the 40 deceased NZ donors utilised in 2003 there were 34 livers retrieved, 3 of which were discarded because they were deemed unsuitable (too fatty). 26 livers were used whole a 3 were split with the smaller segment being transplanted into a child and the larger segment being exported to Australia (2 to Brisbane and 1 to Sydney). 2 additional whole livers were exported to Australia for urgent patients (both to Sydney). We imported 8 livers from Australia, a number of which had been declined by all Australian centres as unsuitable. The number of deceased donors per million of population in 2003 was 10 in New Zealand and 9 in Australia. These figures are low by international standards. One liver segment came from a live donor.

Demographics of transplanted patients:

The mean age of those transplanted in 2003 was 42 years (range 6 months to 69 years) similar to that in 2002. There were 26 males and 15 females transplanted. The mean hospital stay post-transplant was 15.2 days, including a mean ICU stay of 2.5 days (range of 1-29 days with a median of 1 day). The racial mix of patients transplanted in 2003 was compared to population demographics (see Figure 4). As expected, there is a slight over-representation of Pacific Island and Asian ethnicities in keeping with the high prevalence of hepatitis B infection in these groups.

Figure 4

Rejection:

Episodes of rejection were experienced by 39% of patients in 2003, slightly less than that in 2002 (50%, difference not significant). These patients were treated with bolus corticosteroids but two patients did not respond. One had plasmapheresis and antilymphocyte antibody and a further patient had antilymphocyte antibody. No grafts were lost because of rejection. In the entire programme, only two liver allografts have been lost to rejection (out of 194) giving a very low likelihood of a patient experiencing graft loss from this cause (around 1%).

Surgical details:

The mean surgical time for liver transplant operations in 2003 was 6.3 hours (range 3.9 – 10.4 hours). The mean number of units of red cells used during the transplants was 3.8 units (range 0 – 15 units) with a median of 3 units. Figure 5 shows the trend of average intra-operative red cell use over the years. In 8 of 38 cases (21%) no units of red cells were required during the transplant.

Personnel

In early 2003 Justine Kime joined our staff as a recipient co-ordinator. Justine and our senior recipient co-ordinator, Margaret Johnston, have distinguished themselves by sitting and passing the North American Transplant Co-ordinators credentialling examination. This is a major achievement on both a personal level (the examination is substantial and includes questions about all solid organ transplants) and for the liver unit which seeks to promote self-development and high professional standards.

The longstanding temporary secretary in the unit, Alexandra Jamieson, is no longer resident in the NZLTU office area but nevertheless provides excellent ongoing transcription services for the unit by remaining responsible for liver unit typing whilst being a member of the transcription unit on the Greenlane site. This was part of the restructuring of all support services at ADHB. In this regard, our unit secretary, Kathy Oliver is now officially “Team Support” for Abdominal Organ Transplantation Services.

We were fortunate, in 2003, to have the services of Dr Michelle Zuckerman, recently arrived from the busy paediatric liver transplant programme in Birmingham, who acted as a locum paediatric gastroenterologist/hepatologist. We greatly appreciated her enthusiasm for the care of transplanted patients and great attention to detail. Michelle has subsequently returned to her homeland of South Africa.

Additional resources have been found for a second hepatologist and additional, part-time, transplant surgical fellow. While permanent appointments are being determined for these positions we have been fortunate in having Dr Rachael Harry, formerly of Kings College Hospital in London, as a locum for the hepatology position. Rachael has bought with her a wealth of experience and endless good humour.

Liaison

Interaction with our Australian colleagues continues to be important to the viability of our unit. We once again imported more livers in 2003 than we exported but were able to maintain goodwill in the transactions by offering back to Australian units trisegments that resulted from split livers (where we had used only the left lateral segment for a paediatric recipient). We had 3 meetings with our Australian counterparts, the clinical and research meetings of the Australian and New Zealand Liver Transplant Group and the liver transplant standing committee meeting of the Transplantation Society of Australia and New Zealand. The clinical meeting was in fact hosted by our unit at the Hilton Hotel in Auckland. Feedback from the meeting was very positive and participants were keen to come again.

Close liaison continued with the Donor Co-ordinator Office in 2003 and this was greatly helped by media attention surrounding a Select Committee inquiry into organ donation stimulated by a petition by one Andy Tookey, the parent of a child with biliary atresia who will likely one day require a liver transplant. One of our live liver donors, through political contacts and the help of Associate Professor John McCall, was able to stimulate further support at the highest level such that the government recommended strongly that a newly revamped donor service be developed with additional resources. This organisation is to be called “Organ Donation New Zealand” and is expected to take shape in the year 2004/05. With a medical director and additional resource, it seems reasonable to expect that organ donor rates might improve.

Most members of the NZLTU staff are actively engaged in education. This takes a variety of forms but includes audiences of nurses, doctors, medical students, patients, non-medical professional societies, the general public, community fund raising groups, radio listeners and television viewers.

Quality requirements

The method of NZLTU audit was changed in 2003 to be systematic rather than responsive to sentinel events (such as morbidity or mortality). Subjects that were audited included both technical subjects (bile leaks, vascular complications) and medical issues (rejection rates, recurrent hepatitis). Protocol adjustments were made on the basis of these reviews. Total unit audit continued by way of looking at the whole of our practice (assessments, listing, death on the waiting list, delisting, transplantation) on an annual basis.

There were no formal complaints regarding assessed or transplanted patients in 2003.

The New Zealand Liver Transplant Advisory Group continues to convene for paediatric recipient candidate appraisal purposes. This has been most valuable and we appreciate the input of the members of this committee.

Preparations were made for a credentialling exercise for all surgeons on the NZLTU staff. This credentialling review was completed in early 2004 and will be part of next year’s annual report. Suffice to say it was a very favourable review.

Overview of the service

The annual liver transplant volume has stabilised (see Figure 6). However, this is not because of a levelling off of demand. Rather it is a consequence of a limited number of deceased donor livers. More patients were assessed and listed in 2003 than in 2002 and more recipients died on the waiting list or were delisted because of deterioration. This indicates that had there been more donors, more transplants would have been completed. The assigned volume maximum by the MOH is 45 per annum, a readily achievable target if there were more deceased donors.

Outcomes have continued to be pleasing in general with patient and graft survival rates at a very acceptable level. The low retransplant rate is especially pleasing in a financially constrained environment (liver retransplantation is notoriously expensive). There have also been isolated cases that have been outstanding. Associate Professor McCall transplanted an adult Jehovah’s Witness patient knowing that blood and blood products were not allowed. This patient had an excellent outcome.

The issues of blood group O recipient waiting times and the allocation of blood group O livers have been under much discussion in North America. The resolution in many organ procurement regions has been to confine the use of blood group O livers to blood group O recipients and those blood group B patients with a MELD score of >25 (MELD is a disease severity score that predicts the order in which patients with end stage liver disease are likely to die). This solution will be actively discussed during 2004.

Associate Professor Gane continues his busy schedule of clinical trials and in 2003 received permission to recruit a full time research nurse at Auckland City Hospital to compliment those he already directs at Middlemore Hospital. These trials involve both immunosuppressive agents and treatment trials in hepatitis patients.

The in-patient service has moved to Auckland City Hospital. This is a well-designed and visually pleasant environment that patients enjoy being in. The operating room facilities are very well appointed and most infrastructural supports are functioning well. There are still difficulties, on occasion, in getting non-transplant patients into the hospital but thus far we have never had to decline deceased donor organs because of a shortage of beds.