1
Allocation of Donor Livers in the People’s Republic of China
Wenshi JIANG1, Wen LI1, Haibo WANG2, Sheung Tat FAN2
1
2
China Liver Transplant Registry, Shenzhen, China and
Department of Surgery, The University of Hong Kong,
Queen Mary Hospital, Hong Kong, China
Keywords: Allocation, Liver transplantation
Word count: 2280
Number of tables: 2
Number of figures: 2
2
Footnotes
Corresponding author:
Professor Sheung Tat FAN
Department of Surgery
The University of Hong Kong
Queen Mary Hospital
102 Pok Fu Lam Road
Hong Kong
China
Tel: (852) 2255 4703
Fax: (852) 2986 5262
E-mail: stfan@hku.hk
Abbreviations: PRC, People’s Republic of China; OPO, organ procurement organization;
MELD, Model for End-stage Liver Disease; PELD, Pediatric End-stage Liver Disease; HCC,
hepatocellular carcinoma; COTRS, China Organ Transplant Response System
Declaration: All authors participated in the study design; data analysis, and interpretation of
data; drafting and critical review of the manuscript; and they have all seen and approved the
final version. There is no conflict of interests in this article.
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Abstract
Liver transplantation is the mainstream treatment for patients with end-stage liver
diseases saving thousands of lives each year in the People’s Republic of China (PRC). Since
the first clinical liver transplantation in 1978, new techniques and strategies to improve
patient survival have evolved in China. While patient survival after liver transplantation has
greatly improved in recent years, the shortage of donor organs has become the major issue
limiting the development of liver transplantation. Similar to the early experience in the
United States and the United Kingdom, the shortfall between the demand for and supply of
donor organs has given rise to an equitable organ allocation system. The Human Organ
Transplant Regulation promulgated by the State Council of the PRC in 2007 called for the
development of a fair and transparent organ allocation and sharing system in China.
In December 2010, the first national liver and kidney allocation policy of the PRC was
officially initiated by the Ministry of Health. The purpose wasto maximize the utilization of
organs for patients in need of transplantation and enhance public trust on the equitable and
transparent organ allocation and sharing system in China. The China Organ Transplant
Response System (COTRS) was launched nationwide in April 2011 to identify the best match
between donors and recipients, and to ensure the traceability of each donor organ. The first
successful organ allocation by the COTRS for controlled donation after cardiac death was
accomplished one week after the system launched and symbolized the establishment of a
national organ allocation and sharing network in China.
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Background
Liver transplantation is one of the greatest successes in medicine and is now saving
thousands of lives each year in the People’s Republic of China (PRC). The first clinical liver
transplantation in China was performed in 1978 (1). However, China then had a moratorium
period with total suspension of liver transplantation for more than 10 years until 1993, when
there was a remarkable growth in the number of liver transplants (1).
As of December 2009, the cumulative number of liver transplants in the PRC was 16089,
which was the second largest number of liver transplantations performed worldwide (Figure
1). Similar to the US and the UK, the disparity between donor organ demand and supply has
widened as organ transplantation has evolved from a high-risk experimental procedure to an
effective therapeutic modality for patients with end-stage liver diseases (2, 3). Such
imbalance has made an equitable organ allocation system inevitable and imperative (4, 5).
The Legal Framework
“The Human Organ Transplant Regulation” promulgated by the State Council of the
PRC in 2007 assigns the Ministry of Health and provincial public health authorities
governance over clinical
organ transplantation and
initiation of an equitable organ
allocation system in China(6). Having gone through a research phase conducted by the China
Liver Transplant Registry and an open comment period conducted by the national Organ
Transplant Committee, the first national liver and kidney allocation policy of the PRC was
enacted and announced by the Ministry of Health in December 2010.
The specific aims were:
optimize the availability of organs for patients in need of
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transplant and ensure that the allocation procedures are in compliance with the principles of
fairness, equality and transparency. The policy clearly states the objectives to be achieved
and the principle to be followed in the construction of an organ allocation and sharing
framework. It also provides guidelines for determining organ allocation to patients on the
liver and kidney transplant waiting list and the criteria of organ matching.
Allocation of Deceased Donor Livers
Principles of justice, fairness, equity and transparency have been acknowledged as the
golden criteria in allocating organ by the international transplant community (7, 8). Under
these rules, all allocation policies are evaluated by organ utility/wastage, waitlist mortality,
recipient post-transplant survival, transplant benefit, allocation efficiency and the extent to
which they can be achieved. What complicates the rationale in policy making are the
tradeoffs between these measures. To reach an approach in keeping with the national criteria
for organ allocation, the OTC reached a consensus on the following principles and objectives:

Ranking of organ transplant candidates should be based upon sound medical need that
adheres with the principles of fairness, equity and transparency.

Allocation and sharing of organs should serve medical purposes. The transplant team
has the rights to decline an unsuitable organ for a specific candidate based upon rational
medical judgments.

The allocation policy should minimize waiting list mortality as its first priority. On the
premise that waiting list mortality is kept to the lowest level, the best patient and graft
survival is considered the second priority of the
allocation policy .
6

As far as organ utility is concerned, the allocation policy should minimize organ wastage
and maximize the efficiency of organ allocation.

To promote equity, the allocation policy should take into account the disparity in
medical/demographic characteristics among candidates. Those with biological or
medical disadvantages should be given an equitable opportunity to receive a
transplantable organ.

The allocation policy should be periodically reviewed and revised.
Geographic Distribution of Donor Organs
The organ distribution area is expanded using the
following approach until a suitable
candidate is found.

Distribution within a transplant center: When the donor’s host hospital is one of the
certified liver transplant centers in the PRC, the waiting list of the donor’s host hospital
is considered first.

Distribution within transplant centers serviced by the host organ procurement
organization (OPO) of the donor liver: The distribution area includes
the waiting lists
of all transplant hospitals within the service area of a specific OPO (this is also the
minimal distribution area when the host hospital of the donor is not one of the certified
transplant centers in the PRC).

Distribution within a region where the donor’s host hospital is located: The distribution
area includes the waiting lists of all the transplant hospitals within the province where
the host hospital is located.
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
Distribution within the country: The distribution area refers to the national waiting list.
Organ Allocation Ranking Criteria
Disease Severity
The ranking system is designed to accommodate three groups of patients under three
main diagnosis categories. Ranking priorities are given to candidates in the same geographic
distribution area based primarily on their urgency for a transplant with little regard to the
waiting time. Candidates with fulminant hepatic failure are granted the first priority on the
waitlist and are labeled as super urgent candidates (Table1). The definitions of super urgent
candidates are similar to those for 1A candidates currently adopted by the United Network for
Organ Sharing(9). The Model for End-stage Liver Disease (MELD) and Pediatric End-stage
Liver Disease (PELD) scoring systems have been adopted for allocation of deceased donor
livers to those with chronic liver disease(10).
An exception system promoted by Wiesner,et al is incorporated into the MELD scoring
system for candidates diagnosed with hepatocellular carcinoma (HCC)(11). However, the T1
tumor(12) will not earn additional points when applying the HCC exception under the
current policy. The issue will be reconsidered afterl sufficient data has been collected to
address its necessity. The status of active candidates on the waiting list requires timely
updating according to their current MELD/PELD scores.
HCC Candidates
The effect of the MELD scoring system in predicting the 3-month waitlist mortality has
8
been reported in several previous studies (13-15). Nevertheless, the MELD exception scoring
system is imperfect.
It places HCC candidates with lower MELD scores
to preferentially
receive a donor organ (Figure 2) yet, does not consider the risk of drop-out due to progression
of HCC. Data from the US suggested similar results (11, 16). HCC recipients accounted for
almost 50% of the liver transplant recipients pool in the PRC(17). This finding urges the need
to incorporate an exception system for HCC candidates into the MELD-based system in order
to eliminate the inequality.
The Milan criteria (18)(a single lesion 5 cm in diameter or three lesions 3 cm diameter
each) was employed although the expansion of this criteria is under debate. HCC candidates
meeting the Milan criteria but exceeding T1 stage (Table 2) will be assigned a mortality risk
of 30% if their MELD score computed from the laboratory data is less than this. Application
of the HCC exception system should be accompanied by a report of the alpha-fetoprotein
level. Re-certification is required every 3 months. An increase of 10% in the mortality score
will be assigned to those who have been successfully granted extension upon each
re-certification.
ABO Blood Type Compatibility
Candidates with blood type incompatible to the donor are not considered in the
donor-recipient matching unless they are of the super urgent status or have MELD/PELD
scores equal or higher than 30.
Waiting Time
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Calculation of waiting time for a liver candidate is initiated at the time of listing. In
principle, the waiting time for a candidate is calculated as the sum of the waiting time
accrued at the current MELD/PELD score and the waiting time accrued at any previous
higher scores. For a super urgent candidate, the waiting time is the cumulative length of time
he/she is/was currently and previously at this status registered on the liver waiting list. For a
candidate with a particular MELD/PELD score, his/her time of waiting is the length of time
he/she remains at the current level plus those days he/she accrued at any previous higher (or
equal) scores except the super urgent status. Within a distribution area, candidates under the
same MELD score level are ranked based upon their waiting time and blood compatibility.
Other Priorities
Candidates below 12 years old have a priority to receive livers recovered from donors
under 12 years old. To encourage organ donation, ranking priority is also granted to those
who were living donors or any of the immediate family members was a deceased donor.
The Allocation Program
A computer program named the China Organ Transplant Response System (COTRS)
was launched in April 2011 for implementation of organ allocation. Patient MELD/PELD
scoring, donor-recipient matching and organ allocation and sharing are processed
automatically by the computer system in compliance with the national organ allocation policy.
This ensures the equality of the organ allocation process and the traceability of each donor
organ. One week after the launch of COTRS, with a growing national waiting list, the first
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successful organ allocation and sharing of a controlled donation after cardiac death utilizing
COTRS was accomplished in the General Hospital of Guangzhou Military Command PLA
and the First Affiliated Hospital of Sun Yat-Sen University, China. The liver and kidneys
recovered from a 29-year-old blood type O donor were transplanted into three recipients on
the waiting list. This milestone transplant marked the initiation of the national organ
allocation and sharing network in the hope of promoting effective and efficient national organ
allocation and sharing in China.
For supervision purpose, the Ministry of Health and provincial public health authorities
can monitor each allocation procedure effectively by logging into the monitoring platform of
the system. Cases that do not follow the allocation rules will be captured and recorded in a
real-time fashion by the system. COTRS also serves to collect scientific data for evaluation of
the current policies.
The Road Map of COTRS
Establishment of Donor/Transplant Candidates Screening Modules
No uniform definition for donor acceptance criteria or the patient selection criteria for
listing/removal from waiting list has been reached at the national level. In order to understand
the clinical behavior of these selection and listing/delisting procedures, two corresponding
screening modules will be established in COTRS to capture detailed raw data bundled with
the process of screening. The donor screening module will serve as a decision making
support system to facilitate OPO navigation through the complex process of donor screening,
11
as well as an evaluation tool to assess the performance of the OPO system in China. The
patient screening module introduces convenience in patient listing and removal from waiting
list. The impact of these selection procedures on the donation rate and waiting list mortality
can be analyzed through the scientific data collected in the processes.
Minimum Standards for OPO
Recently, the national Organ Transplant Committee
announced the first hospital-based
OPO to be founded in the 163 certified transplant centers around the country. As far as the
organ allocation and sharing is concerned, the service area of each OPO should be defined in
order to optimize the availability of organs and eliminate inequities in geographical organ
distribution. For the purpose of regulating practices of the OPO, minimum standards need to
be established for improving the quality and protecting the safety of both donors and
recipients. What followed is the establishment of the certificate authority and performance
assessment system for OPO based on empirical evidence and measurement indexes.
Periodical Scientific Review on Allocation Policies
The lack of historical waitlist data in the planning phase of the allocation schema may
result in an imperfect solution for liver allocation in China. In the early research phase of
policy development, the research team from the China Liver Transplant Registry extensively
reviewed allocation policies of 15 countries worldwide. Due to the similarity of geographic
distribution and population census, many organ allocation polices and algorithms developed
in the US were considered suitable for adoption by the China organ allocation system.
12
Although the ranking criteria in use are widely recognized by the international transplant
community, the suitability of these criteria for use in
a different population of patients
remains unclear.
Issues such as the effect of HCC patient selection criteria on the scoring system,
incorporation of donor factor or post-transplant benefit, and the extent to which organ sharing
is compulsory for the super urgent candidates should be addressed and brought to further
investigation. Independent and multidisciplinary scientific reviews of the allocation policy
will be scheduled regularly for ensuring that the allocation system is as equitable as possible.
Conclusion
Organ shortage is one of the main hindrances to the healthy development of liver
transplantation in the PRC(1). Although different surgical strategies, such as living donor
liver transplantation and split-liver transplantation, have been promoted to expand the organ
pool(19), an allocation system that distributes organs in a fair, unbiased way is highly
desirable. The organ allocation and sharing network in the PRC is built upon a firm legal
framework that is derived from evidence-based practices. The Ministry of Health of the PRC
is responsible for governing the clinical application of organ transplantation including organ
allocation. The allocation policy for deceased livers and kidneys has been developed to
promote equality and efficiency in organ distribution. Ranking guidelines have been
devised for those with fulminant hepatic failure, HCC and other chronic liver diseases.
The system has been designed in a way to assure that organs are equitably allocated to
patients with the most urgent medical need with little regard to the waiting time. The current
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allocation system is imperfect. Nevertheless, it is believed that the establishment of the organ
allocation and sharing network will lead organ transplantation in China towards its healthy
development.
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model to predict survival in patients with end-stage liver disease. Hepatology.
2001;33(2):464-70.
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HepatocellularCarcinoma. China Liver Transplant Registry; 2010.
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17
Figure1. Numbers of liver transplantation in the world (2000-2009)
U.S.A ( N=59600 )1
Australia&New Zealand ( N=1947 )
European ( N=14790 )
2
Scandia ( N=2608 )
4
5
China ( N=16089 ) 3
Number of Transplants
7,000
6,000
5,000
4,000
China
3,000
2,000
1,000
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Transplant Year
Source:
1. Based on OPTN data as of July 06, 2011.
http://optn.transplant.hrsa.gov/data/annualReport.asp
2. Anuanl Report 2010.Eurotransplant International Foundation.
http://www.eurotransplant.org
3. Based on CLTR data of June 1, 2011. China Liver Transplant Registry.
http://www.cltr.org
4. ANZLT Registry Report 2009. Australia & New Zealand Liver Transplant Registry.
http://www.anzltr.org
5. NLTR 2010 Annual Report. The Nordic Liver Transplant Registry.
http://www.scandiatransplant.org
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Figure 2. Distribution of MELD scores at liver transplantation in China (1980-2010)
Source: China Liver Transplant Registry analysis, June 2011
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Table 1. Definition of super urgent status on the liver transplant waiting list in China
An adult candidate (18 years old) in one of the following categories with a life expectancy without a
liver transplant of less than 7 days can be listed as a super urgent candidate.
Adult
Category 1
Fulminant hepatic failure:
Fulminant hepatic failure is defined as the onset of hepatic encephalopathy within 8
weeks of the first symptoms of liver disease. Besides staying in the intensive care unit,
one of the three criteria below must be met: (i) ventilator dependence; (ii) requiring
dialysis or continuous veno-venous hemofiltration or continuous veno-venous
hemodialysis; (iii) international normalized ratio >2.0.
Adult
Category 2
Primary non-function of the transplanted liver graft:
The diagnosis of primary non-function of a transplanted liver graft should be made
within 7 days of transplantation, meeting one of the following:
(i) aspartate aminotransferase ≥3,000 U/L as well as an international normalized ratio
≥2.5 and/or acidosis, defined as having an arterial pH≤7.30 or venous pH of 7.25 and/or
lactate≥ 4mMol/L; or (ii) anhepatic candidate.
All labs must be from the same blood drawn within 24 hours to 7 days following the
transplant.
Adult
Category 3
Hepatic artery thrombosis in a transplanted liver graft within 7 days of transplantation,
and meeting one of the conditions (i) (ii) in Adult Category 2.
Adult
Category 4
Acute decompensated Wilson disease
A pediatric candidate (<18 years old) in one of the following categories with a life expectancy without
a liver transplant of less than 7 days can be listed as a super urgent candidate.
Pediatric
Category 1
Fulminant hepatic failure:
Fulminant liver failure is defined as the onset of hepatic encephalopathy within 8
weeks of the first symptoms of liver disease. Besides staying in the intensive care unit,
one of three criteria below must be met: (i) ventilator dependence; (ii) requiring dialysis
or continuous veno-venous hemofiltration or continuous veno-venous hemodialysis;
(iii) international normalized ratio >2.0.
Pediatric
Category 2
Primary non-function of the transplanted graft:
The diagnosis is made within 7 days of transplantation; additional criteria to be met for
this indication must include two of the followings: (i) aspartate aminotransferase ≥2000
U/L; (ii) international normlized ratio ≥2.5; (iii) total bilirubin ≥10 mg/dl; (iv) acidosis,
defined as having an arterial pH≤ 7.30, venous pH of 7.25 or lactate ≥4mMol/L.
All labs must be from the same blood drawn within 24 hours to 7 days following the
transplant.
Pediatric
Category 3
Hepatic artery thrombosis:
The diagnosis must be made within 14 days of transplantation.
Pediatric
Category 4
Acute decompensated Wilson disease
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Table 2. Hepatocellular carcinoma (HCC) exception for candidates on the liver
transplant waiting list
Hepatocellular carcinoma exception
Candidates with HCC diagnosed on the basis of imaging results that meet both of the
following conditions are eligible for the HCC exception:
(i) a single lesion >=1.9 but <5 cm in diameter or three lesions <3 cm diameter each.
(ii) no extrahepatic metastasis or macrovascular involvement (portal or hepatic vain) has
been found.
Application for an HCC exception should be accompanied by the alpha-fetoprotein level.
Re-certification is required every 3 months. An increase of 10% in mortality score will be
assigned to those who have been successfully granted extension upon each re-certification.