Wits Transplant Annual Data Report 2018 Adult and Paediatric Liver Transplantation

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INTRODUCTION

Wits Donald Gordon Medical Centre (WDGMC) is part of the University of Witwatersrand's Academic Teaching Hospital Complex, within the Faculty of Health Sciences, Johannesburg, South Africa. Wits Transplant, a transplantation unit at WDGMC, hosts the largest adult and paediatric liver transplant programme in the country. From the inception of the programme in 2004 to the end of 2018, liver transplants were performed in 410 adults and 174 children with acute or chronic end-stage liver disease (ESLD). To increase organ availability, routine splitting of suitable deceased donor livers where possible was implemented. This procedure splits a single deceased donor liver to produce two usable grafts. Moreover, in 2012 the first paediatric living donor liver transplant (LDLT) programme in South Africa was started. Both initiatives contribute substantially to increasing the number of transplants performed annually, and there is still further capacity within the programme for expansion. However, each year, waitlisted adults and children are lost due to organ shortages. Despite considerable challenges, Wits Transplant has created a model of equitable care that provides access to transplantation for any adult or child with ESLD, irrespective of payer status.(1–3) As the programme continues to expand and diversify, and in the absence of a national liver transplant registry, annual reporting of outcomes was implemented, which is mandatory in many international transplant centres. As such, this is the first annual report for Wits Transplant.

METHODS

Using REDcap, prospective databases for the paediatric and adult liver transplant programmes were established at WDGMC, with approval from the Wits Human Research Ethics Committee. While most data were previously collected and are available for year-on-year comparison, there are some additional variables collected for the first time in 2018, and these comprise the baseline comparator for future reports.

Paediatric and adult data collected

Recipient variables at time of transplant: age, sex, self-reported race, primary cause of ESLD, transplant history (first or re-transplant), blood type (ABO), referring health sector, height, weight, body mass index, mid-upper arm circumference (MUAC) z-scores (children <5 years), medical urgency [Status 1 score, paediatric ESLD (PELD) score, model for ESLD (MELD) score (adults)], presence or absence of diabetes mellitus (adults), time on the waitlist, transplant type (liver alone, liver and other organ), graft type (whole liver, split liver and reduced- size graft), days in hospital after transplant, biopsy-proven graft rejection within 90 days of transplant, 1-month, 1-year and 3-year recipient and graft survival. Status 1 score is given to patients who are high urgency, with 7 days or less life expectancy if not transplanted. This score is most applicable to acute liver failure patients. Donor variables: blood type (ABO), vital status (living or deceased donor) and donor risk index (DRI) for deceased donors (adults).(4)

Potential liver transplant recipients on the waitlist: numbers at the start and end of every year, reason for removal from the waitlist, age, sex, self-reported race, primary disease, medical urgency (PELD score) and wait time.

Outcomes

All survival estimates are for first transplants and all causes of ESLD. One-month, and 1-year patient and graft survival estimates, respectively, are based on transplants carried out in the 2.5 years before the last 12 months of follow-up, i.e. patients transplanted between 1 July 2015 and 31 December 2017. Three-year patient and graft survival estimates are based on transplants carried out in the 2.5 years before the last 3 years of follow-up, i.e. patients transplanted between 1 July 2013 and 31 December 2015. Risk-adjusted estimates are based on the observed vs estimated deaths (or graft failures) using a model based on transplant number, chronic vs acute liver failure, recipient age and sex.

RESULTS

Paediatric liver transplant report

Of 174 paediatric patients transplanted since inception, the majority (125) were performed between 1 January 2014 and 31 December 2018 (Figure 1). Of these 125 cases, 57 were living donor and 68 deceased donor transplants. In the deceased donor group, 37 were whole liver, 27 split liver and 4 reduced-size grafts.

Fig 1:

Number of transplants per year

Overall, most paediatric recipients were female (61.6%), younger than 5 years of age at the time of transplant (73.6%) and just over half (53.6%) were transplanted for cholestatic liver disease, predominantly biliary atresia (Table 1). Between 2014 and 2018, there was a threefold increase (15%–47%) in referrals from the public sector and a fivefold increase (5%–26%) in referrals for acute liver failure.

Table 1:

Recipient characteristics.

	2014	2015	2016	2017	2018
Number of transplants	20	26	23	22	34
Age (%)
<1 year	10	15	13	9	9
1–5 years	75	54	57	68	62
6–10 years	0	8	17	9	3
11–17 years	15	23	13	14	26
Sex (%)
Male	35	38	26	41	44
Female	65	62	74	59	56
Self-reported race (%)
Black	70	62	57	68	76
White	20	23	39	18	6
Indian	10	4	4	0	6
Mixed	0	12	0	14	12
Primary disease (%)
Acute liver failure	5	23	9	14	26
Choleostatic disease	45	58	57	64	47
Budd–Chiari/Veno-occlusive disease	25	0	4	9	3
Metabolic disease	0	12	4	5	3
Malignancy	10	0	4	0	0
Other	15	4	22	9	21
Transplant history (%)
First	90	92	91	95	91
Re-transplant	10	8	9	5	9
Blood type (%)
A	35	15	48	45	29
B	25	23	9	9	29
AB	0	0	9	5	3
O	40	62	35	41	38
Health-care sector (%)
Funded	85	92	65	41	53
Public	15	8	35	59	47
Wait time (%)
<31 days	30	35	17	27	44
31–60 days	10	0	4	5	12
61–90 days	10	23	13	9	3
3–<6 months	30	19	39	32	20
6–<12 months	15	15	13	18	6
1–<2 years	5	8	13	9	9
2–<3 years	0	0	0	0	3
3 years or longer	0	0	0	0	3

As nutritional status is an important predictor of outcome in paediatric patients, to assess nutritional status in children younger than 5 years, z-scores for height, weight and MUAC were calculated (Supplementary Data: Table 1 and Figure 1).

Medical urgency for transplantation was determined by the PELD score, with a trend towards transplanting sicker children with higher PELD scores, which is in keeping with increased referrals of children with acute liver failure (Table 2).

Table 2:

Recipient medical urgency.

	2014	2015	2016	2017	2018
Medical urgency (%)
Status 1	Not recorded				26
MELD/PELD ≥ 35	5	15	9	14	0
MELD/PELD 30–34	5	15	9	0	0
MELD/PELD 15–29	30	54	57	45	35
MELD/PELD < 15	55	8	26	41	35
Unknown	5	8	0	0	2

For the entire cohort, the incidence of biopsy-proven rejection within 90 days of transplant, and graft and recipient survival are depicted in Figure 2 and Table 3, respectively.

Fig 2:

Incidence of biopsy-proven acute graft rejection in the first 90 days after transplant

Table 3:

Survival.

	Patient		Graft
	Unadjusted	Risk-adjusted	Unadjusted	Risk-adjusted
1-month survival
Number of transplants	62		62
Survival estimate (%) (95% CI)	92 (82–97)	98 (88–99)	89 (78–94)	94 (82–99)
1-year survival
Number of transplants	62		62
Survival estimate (%) (95% CI)	79 (67–87)	82 (69–90)	77 (65–86)	80 (67–89)
3-year survival
Number of transplants	48		48
Survival estimate (%) (95% CI)	71 (56–82)	71 (56–82)	65 (49–76)	61 (46–71)

Complete waitlist data were only available for 2018 (Supplementary Data: Tables 2 and 3). Most children were transplanted within 6 months of being waitlisted (Table 1). Of 97 children waitlisted for transplant in 2018, 10 died while awaiting a transplant and 6 of these were listed for acute liver failure.

The number of donors for paediatric liver transplantation has increased largely due to the introduction of the LDLT programme, and by far the most common procedure performed is liver alone transplant (Tables 4 and 5). The median length of hospital stay post-transplant remained consistent, at approximately 1 month.

Table 4:

Donor characteristics.

	2014	2015	2016	2017	2018
Number of transplants	20	26	23	22	34
Blood type (%)
A	25	8	35	36	35
B	15	19	4	9	18
AB	0	0	9	5	3
O	60	73	52	50	44

Table 5:

Transplant characteristics.

	2014	2015	2016	2017	2018
Number of transplants	20	26	23	22	34
Procedure type (%)
Liver alone	100	92	96	91	94
Liver and another organ	0	8	4	9	6
Median days in hospital after transplant (liver alone transplants)	29 Days	36 Days	34 Days	26 Days	29 Days

Adult liver transplant report

In total, 44 adult liver transplants were performed in 2018, which was similar to previous years (Figure 3). The static numbers of recipients transplanted annually reflect the deceased donor organ shortage and the need for LDLT in the adult population – a programme commenced in September 2019 and still in its infancy at Wits Transplant.

Fig 3:

Number of transplants per year

There was only one deceased donor organ that was split for use in adults in 2018, which is fewer than previous years (Table 6). More than likely, this reflects unsuitability of adult recipients for a split graft, because the right segment of the split liver is often too small to support a full-sized adult. It could also be explained by a natural variation from year to year.

Table 6:

Overview of transplants.

	2014	2015	2016	2017	2018
Number of transplants	32	43	36	46	44
Donor type (n)
Living donor transplants	0	0	1	0	0
Deceased donor transplants	32	43	35	46	44
Whole liver	25	41	33	40	43
Split liver	7	2	2	6	1

Overall, half of the recipients were between 50 and 64 years of age, and although there was a slight male predominance, the number of women transplanted is steadily increasing (Table 7). The two most common causes of chronic liver disease were steatohepatitis (alcoholic/non-alcoholic) and cholestasis. Chronic viral infection comprised the least common cause, and for the first time in 2018, there were no recipients transplanted for chronic hepatitis C infection. This most likely is attributable to new direct antiviral agents for hepatitis C, which are highly effective in patients with ESLD. The number of transplant prodecures performed for acute liver failure were more than double in 2018 when compared to 2017 (Table 7).

Table 7:

Adult recipient characteristics.

	2014	2015	2016	2017	2018
Number of transplants	32	43	36	46	44
Age (%)
18–34 years	9	16	22	22	16
35–49 years	44	30	28	19	21
50–64 years	41	47	36	48	52
65 years or older	6	7	14	11	11
Sex (%)
Male	75	65	64	65	59
Female	25	35	36	35	41
Self-reported race (%)
Black	28	19	25	29	14
White	53	63	69	61	73
Indian	16	16	6	4	9
Mixed	3	2	0	4	4
Unknown	0	0	0	2	0
Primary disease (%)
Acute liver failure	19	9	8	9	18
ASH/NASH	41	33	28	26	23
Cholestatic	22	35	28	33	23
Hepatitis B	6	5	3	4	5
Hepatitis C	3	5	3	2	0
Metabolic	3	2	6	15	5
Malignancy	6	2	22	4	9
Other	0	9	3	7	20
Transplant history (%)
First	97	95	94	93	98
Re-transplant	3	5	6	7	2
Blood type (%)
A	44	35	56	39	32
B	9	19	8	15	25
AB	0	0	6	4	7
O	47	46	30	41	36
Health-care sector (%)
Funded	87	88	84	89	89
Public	13	12	14	11	11
Wait time (%)
<31 days	41	30	33	33	45
31–60 days	19	21	11	13	21
61–90 days	3	5	11	17	11
3–<6 months	22	19	25	19	9
6–<12 months	12	18	14	11	7
1–<2 years	3	7	6	7	7
BMI (%)
<18.5 kg/m2	0	0	3	4	0
18.5–<25 kg/m2	38	40	53	22	36
25–<28 kg/m2	16	21	17	37	21
28–<30 kg/m2	22	12	14	11	9
30–<35 kg/m2	12	16	5	24	25
≥35 kg/m2	9	9	8	2	9
Unknown	3	2	0	0	0
Medical urgency (%)
Status 1	Not recorded			9	18
MELD ≥ 35	12	5	5	0	0
MELD 30–34	0	2	6	9	2
MELD 15–29	63	70	72	48	34
MELD < 15	25	23	17	35	45
Diabetes (%)	31	29	14	22	29

Unadjusted recipient survival at 1 and 3 years was 83% (95% CI 74%–89%) and 75% (95% CI 65%–83%), respectively. Similarly, unadjusted graft survival at 1 and 3 years was 82% (95% CI 73%–88%) and 70% (95% CI 60%–79%), respectively (Table 8).

Table 8:

Survival.

	Patient		Graft
	Unadjusted	Risk-adjusted	Unadjusted	Risk-adjusted
1-month survival
Number of transplants	100		100
Survival estimate (%) (95% CI)	92 (85–96)	95 (88–99)	91 (83–95)	94 (86–98)
1-year survival
Number of transplants	100		100
Survival estimate (%) (95% CI)	83 (74–89)	87 (77–93)	82 (73–88)	86 (76–92)
3-year survival
Number of transplants	88		88
Survival estimate (%) (95% CI)	75 (65–83)	76 (66–84)	70 (60–79)	69 (59–78)

The highest rates of biopsy-proven acute rejection within the first 90 days of transplant occurred in the 18–34 age group (Figure 4), but this did not affect 1-year recipient survival when analysed by age group (Figure 5).

Fig 4:

Incidence of biopsy-proven acute graft rejection in the first 90 days after transplant

Fig 5:

One-year patient survival by age category* *The between group differences were not statistically significant.

Two-thirds of recipients waited for liver transplantation for less than 60 days in 2018, which is a substantial improvement from previous years (Supplementary Data: Table 4). At the start of 2018, there were 25 waitlisted patients, 63 were added during the year, 2 were removed for being too ill for transplant and 9 died without undergoing transplant (Supplementary Data: Table 5). Of the 13 Status 1 patients, 4 died without transplantation.

Two-thirds of donors had a DRI (4) of <2.00 (Table 9). This demonstrates the relatively young deceased donor pool where most deaths are attributable to traumatic injury or intracranial events. There were no living donors in 2018.

Table 9:

Donor characteristics.

	2014	2015	2016	2017	2018
Number of transplants	32	43	36	46	44
Blood type (%)
A	34	28	50	39	36
B	6	12	17	17	27
AB	3	0	5	2	5
O	56	60	28	41	32
Donor risk index (cadaver donors) (%)
≤1.00	3	0	0	4	0
1.01–1.40	19	35	23	11	23
1.41–1.60	3	19	17	24	21
1.61–1.80	16	16	11	18	12
1.81–2.00	16	12	17	11	14
>2.00	41	14	20	31	28
Unknown	3	4	11	–	2

In 2018, most transplants were ABO compatible, in keeping with trends from previous years (Supplementary Data: Table 6). However, because of the increase in the number of transplants for acute liver failure, the proportion of major ABO incompatible transplants also increased substantially (Supplementary Data: Table 6). In 2018, no simultaneous liver–kidney transplants were performed (Supplementary Data: Table 7).

The high rates of endemic CMV infection in South Africa are reflected in donor and recipient serological testing, where close to 60% of all donors and recipients are immune at the time of transplantation, with a subsequent low risk of CMV disease after transplant. Most donors and recipients were non-immune for hepatitis B infection, possibly due to the absence of a widespread vaccination before 1994. There were no donors or recipients with hepatitis C infection, and 7% of recipients were HIV positive (Supplementary Data: Table 8).

DISCUSSION

Compared to international transplant programmes, the overall annual number of paediatric and adult liver transplants at Wits Transplant is relatively small, despite being the largest volume liver transplant programme in South Africa. Transplant statistics are published annually in the USA as part of the OPTN/SRTR Annual Data Report. When compared with outcomes in the USA, adult patient survival after deceased donor liver transplantation at Wits Transplant compares favourably with 90% vs 87% at 1 year and 83% vs 76% at 3 years post-transplant, respectively. Paediatric liver transplantation at Wits Transplant also appears to be following similar trends to those in the USA, with more children being transplanted at higher acuity as assessed by MELD/PELD scores and Status 1 designation at the time of listing. Types of liver transplant procedures in pediatric recipients changed little over the past decade in the USA; 62.8% of patients received a whole liver in 2015–2017, 21.2% received a partial liver (either living donor or reduced deceased donor liver), and 16.0% received a split liver. This situation is completely reversed in South Africa where, because of the donor shortage, the vast majority (>60%) of our children receive a partial or split liver transplant. This may account for the better 1- and 3-year patient survival in the USA of 87% vs 82% and 82% vs 71%, respectively.(5)

The transplantation services at Wits Transplant are accessible to those with ESLD who require liver transplantation, irrespective of payer status, and our referral base is from any health facility in South Africa.

While this annual report is a comprehensive summary of our progress, we would like to emphasise the importance of pre-transplant nutritional status in children younger than 5 years. Our data demonstrate a shift to better nutritional status from 2014 to 2018, which resulted from a concerted effort to improve survival. To achieve this, transplantation was delayed in children with MUAC z-scores below –2, and we commenced a proactive nutritional rehabilitation programme, led by dieticians in the unit. Some instances required hospital admission for continuous enteral and parenteral nutrition and once optimised, the transplant proceeded. Female children, children with poor socio-economic circumstances, and those with congenital causes of liver failure are especially vulnerable to increased mortality post-transplant.

Within the discipline of transplantation, Wits Transplant has the expertise and capacity to perform many more transplants annually, but systemic challenges persist. These include limited awareness of indications for referral of patients with acute liver failure or ESLD among health practitioners. Often, referring facilities, especially those from the public sector, have few resources to support ill patients and their families during the referral process. While severe organ shortages continue to restrict the number of transplants performed annually, there is little commitment from the national government to support solid organ transplantation, which perpetuates the health systems failure that occurs at multiple levels. With paediatric LDLT steadily growing, expanding living donation into our adult programme remains one of our future goals to expand the organ donor pool for adults with ESLD.

CONCLUSION

Through the publication of this annual report for paediatric and adult liver transplantation from the Wits Transplant, we commit to making our data publicly accessible for citizens and fellow health-care professionals. Ultimately, we hope this annual report will become part of a national liver transplant registry, and that transplantation will become standard of care with equitable access for adults and children with ESLD in South Africa.

ACKNOWLEDGEMENT

Wits Donald Gordon Medical Centre funded the data collection and analysis.

Conflicts of interest

The authors have none to declare.

References

1. J Loveland, T Govender, J Botha, R Britz. Paediatric liver transplantation in Johannesburg: initial 29 cases and prospects for the future. S Afr Med J. 2012; 102(4):233–236.

2. J Loveland, R Britz, C Joseph, et al. Paediatric liver transplantation in Johannesburg revisited: 59 transplants and challenges met. S Afr Med J. 2014; 104(11):799–802.

3. S Tager, H Etheredge, J Fabian, J Botha. Reimagining liver transplantation in South Africa: a model for justice, equity and capacity building – the Wits Donald Gordon Medical Centre experience. S Afr Med J. 2019; 109(2):84–88.

4. S Feng, N Goodrich, J Bragg-Gresham, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006; 6(4):783–790.

5. WR Kim, JR Lake, JM Smith, et al. OPTN/SRTR annual data report liver. Am J Transplant. 2019; 19 Suppl 2:184–283.

Section

Supplementary data is available in the online version of this article (https://journals.co.za/content/journal/10520/EJC-1932c05c51)