The GP's role in the care spectrum for kidney and liver transplant patients, from initial identification to post-transplant, is crucial. The SingHealth Duke-NUS Transplant Centre shares practical guidance for primary care physicians.
The general practitioner’s role in the care spectrum for kidney and liver transplant patients, from initial identification to post-transplant, is crucial. We share practical guidance for screening, identifying at-risk patients and determining appropriate timing for referrals to a specialist or transplant centre.
INTRODUCTION
As general practitioners (GPs) on the frontlines of healthcare in Singapore, you play a pivotal role in identifying and managing patients who may eventually require organ transplantation.
The landscape of organ transplantation, particularly for liver and kidney diseases, presents unique challenges in our Southeast Asian context. With Singapore ranking fifth globally in the incidence of treated end-stage kidney disease, and liver cirrhosis being the ninth leading cause of death in Southeast Asia, early identification and intervention are crucial.
Kidney Transplantation:
Improving Outcomes for End-Stage Kidney Disease
PREVALENCE OF END-STAGE KIDNEY DISEASE IN SINGAPORE
Singapore faces a significant healthcare challenge with end-stage kidney disease (ESKD). According to the United States Renal Data System Annual Report 2023, Singapore ranks fifth globally in treated ESKD incidence. This high prevalence is primarily driven by diabetes, affecting over 60% of ESKD patients who are above 60 years of age.
The Singapore Renal Registry presents concerning statistics: more than 1,000 patients annually require long-term dialysis, with 7,745 patients on dialysis as of December 2022. These numbers underscore the urgent need for effective management strategies and treatment options.
Understanding the impact of ESKD and transplantation
ESKD carries a sobering prognosis, with only 29.6% of patients surviving 10 years, primarily due to cardiovascular complications and infections. However, kidney transplantation has emerged as a transformative intervention that dramatically improves these outcomes.
BENEFITS OF KIDNEY TRANSPLANTATION
In Singapore, transplant recipients show an impressive 84.8% 10-year survival rate, demonstrating that transplantation can reduce premature mortality by over 50%.
Beyond survival benefits, transplantation significantly improves quality of life and proves more cost-effective for both patients and the healthcare system. Recipients can return to work, continue their education, support their families and actively contribute to society.
IMPORTANCE OF TIMING AND PATIENT SELECTION
Medical professionals should initiate discussions about transplantation when a patient’s glomerular filtration rate falls below 20 ml/min.
While some patients may be ineligible due to conditions such as dementia, limited life expectancy or poor functional status, most can be considered for transplantation if their medical conditions are properly managed.
Key concerns that need addressing include active infections, malignancies, cardiac conditions and psychiatric disorders.
TRANSPLANT OPTIONS
Deceased donor transplantation
Singapore’s deceased donor programme faces significant challenges. Currently, approximately 400 patients are on the waiting list, but with only 28 transplants performed annually, the waiting time can extend to eight years.
Despite legislative changes to expand the donor pool through amendments to the Human Organ Transplant Act, including provisions for older donors and those with circulatory death, up to 80% of potential deceased donors remain unsuitable for donation.
The eligibility criteria for deceased donor recipients are particularly strict, reflecting the scarcity of organs. Patients must be free from malignancy (except for incidental small renal cell carcinoma), coronary artery disease, cerebrovascular stroke or major peripheral vascular disease. This stringent selection process aims to ensure optimal outcomes given the limited organ availability.
Living donor transplantation: The preferred choice
Living donor transplantation consistently demonstrates superior outcomes, with recipient survival rates of 89% at 10 years compared to 81% for deceased donor recipients. The transplanted kidney survival rate also shows significant advantages: 83% at 10 years for living donors versus 68% for deceased donors.
This option offers several crucial benefits, including:
Planned surgery timing for optimal preparation
Selection flexibility when multiple donors are available
The possibility of paired kidney exchange for incompatible pairs
Singapore General Hospital (SGH) has achieved remarkable success with innovative transplant approaches, including ABO incompatible transplantations, which have shown impressive results with 100% patient and 97% graft survival rates at one year. The hospital also offers options for human leukocyte antigen (HLA) incompatible transplantation after appropriate desensitisation protocols.
THE ADVANTAGE OF PRE-EMPTIVE TRANSPLANTATION WITH LIVING DONOR TRANSPLANT
Up to 20% of kidney transplants performed at SGH are pre-emptive kidney donor transplants. A significant benefit of living donor transplantation is the possibility of pre-emptive transplantation before dialysis becomes necessary.
Research demonstrates that this approach reduces transplant failure risk by 27% and mortality by 31% compared to post-dialysis transplantation. These improvements stem from avoiding prolonged exposure to malnutrition, chronic inflammation and uremic toxins. The evaluation process typically takes three to six months, making early discussion of living donation crucial for optimal timing.
SAFETY OF LIVING DONATION
The safety of living donation is well-documented through comprehensive data. The Singapore Donor Care Registry reports no donor deaths or kidney failure at two-year follow-up, and SGH studies show well-preserved kidney function, with 43.1% of donors regaining 75% or more of their pre-donation function after five years. International data further supports the safety profile: the 15-year risk of kidney failure is less than 1%, perioperative death risk is below 0.03%, and complications remain manageable, with minor issues affecting 10-20% and major complications occurring in less than 3% of cases.
KIDNEY TRANSPLANT SERVICES AT SGH
Since its first kidney transplant in 1970, SGH has established itself as a leader in transplantation, performing over 1,700 procedures and holding 49% of Singapore’s market share. As the national referral centre receiving patients from 70% of all hospitals in Singapore, SGH offers comprehensive services including ABO and HLA incompatible transplants, paired kidney exchange and innovative programmes such as hepatitis B and HIV donor transplantation. The hospital’s multidisciplinary outpatient transplant centre ensures holistic, coordinated care for all recipients.
The successful management of ESKD in Singapore requires coordinated effort between primary care and specialist services. As kidney donors remain scarce, emphasis on prevention and early intervention becomes increasingly important. GPs are crucial in the transplant ecosystem, serving as the first line of defence against ESKD progression. Their long-term relationship with patients uniquely positions them to detect chronic kidney disease early, monitor disease progression, identify complications early and advocate for living kidney donation when appropriate.
Other responsibilities include initiation of renal-protective therapies and ongoing patient support throughout the transplant journey.
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Liver Transplantation:
The Only Definitive Treatment for Certain Liver Complications
WHEN IS LIVER TRANSPLANT NEEDED?
Indications
Patients with acute liver failure or complications of liver disease may require liver transplantation as curative therapy.
In Singapore, the most common indications for liver transplantation are chronic hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) / liver cancer, followed closely by metabolic dysfunction-associated steatotic liver disease (MASLD).
Liver disease in Singapore
Cirrhosis is the ninth leading cause of death in Southeast Asia. 75% of all liver cancers occur in Asia, mostly due to viral hepatitis, with a high burden of hepatitis B in Southeast Asia. In Singapore, the prevalence of MASLD in the population is 40%, and is projected to increase even further by the year 2030.
Fortunately, both viral hepatitis and MASLD can be managed to prevent disease progression.
For patients who meet treatment criteria, effective antiviral therapy with minimal side effects (e.g., entecavir and tenofovir) can slow down the progression of fibrosis and decrease the risk of developing HCC.
For MASLD, diet, exercise and management of metabolic complications remain the cornerstone of treatment.
Acute liver failure is a different entity which can be caused by acetaminophen toxicity, drug-induced liver injury or flare of pre-existing liver disease (usually hepatitis B or autoimmune hepatitis). There is currently no acute liver failure data registry in Asia, but many cases of the condition in Singapore are due to reactivation of the hepatitis B virus.
Screening and risk management
Unfortunately, patients with chronic liver disease and even cirrhosis can have no symptoms. Once patients begin to show symptoms, their liver disease is already quite advanced.
For patients with chronic hepatitis B, even for patients who have been told that they are carriers, it is essential to do regular liver cancer screening with ultrasound imaging. If patients have a family history of liver cancer, they should consider antiviral therapy to reduce their risk of HCC.
LIVER TRANSPLANTATION AS CURATIVE THERAPY
Liver transplantation is the only definitive management for complications due to end-stage liver disease including HCC, and for acute liver failure. Without transplantation, most patients will not survive. While a major surgery, long-term patient outcomes for liver transplant at SGH are excellent and comparable with international benchmarks.
LIVER TRANSPLANTATION AT SGH
In Singapore, there is a limited number of deceased donors. As a result, both deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) are performed locally.
SGH performed its first DDLT in February 2006 and first LDLT in May 2006. Since then, the hospital has performed a total of 187 liver transplants – 130 DDLT and 57 LDLT.
For donors, SGH has pioneered laparoscopic donor hepatectomy since 2019. Living donor safety and outcomes are of critical importance, and since its programme’s inception, SGH has had zero living donor mortalities.
Abnormal laboratory/imaging findings
Splenomegaly: This could be a sign of underlying portal hypertension Thrombocytopaenia: This could also be a sign of underlying portal hypertension
Abnormal liver enzymes: This could signify underlying inflammation Elevated alpha-fetoprotein: This should be investigated to exclude HCC Low albumin: This could represent abnormal liver function and inadequate nutrition
Abnormal clinical findings
Presence of ascites
Spider angioma
Jaundice, yellowing of skin or the eyes Palmar erythema Swelling in the legs, feet or ankles
| Referral to a specialist Patients should be referred to a specialist if they have:
Cirrhosis or clinical signs and symptoms of portal hypertension An abnormal Fibrosis-4 (FIB-4) score (calculated using age, AST, ALT, and platelet count), for consideration of Fibroscan to further stage liver disease. A FIB-4 score <1.3 is low risk for having significant liver disease.
Referral for liver transplant evaluation Patients should be referred for a liver transplant evaluation if they have: Decompensated liver disease (history of variceal bleeding, portal hypertension, ascites, hepatic encephalopathy), Liver cancer, or A Model for End-Stage Liver Disease (MELD) score >15
Patients who present with symptoms of acute liver failure (coagulopathy and new-onset encephalopathy) should be referred for urgent liver transplant evaluation.
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THE GP’S ROLE IN IDENTIFYING AT-RISK PATIENTS
Identifying patients at risk for hepatitis B
GPs play a critical role in identifying patients at risk for complications from liver disease. The leading cause of liver transplantation in Singapore is hepatitis B and its complications, including liver cancer. It is important for GPs to screen patients at risk for the disease, and to enrol those with the disease in a screening programme to check for abnormal liver enzymes and liver cancer.
Emphasising compliance to antiviral therapy
For those who are already on antiviral therapy, it is essential to emphasise compliance to prevent a hepatitis B flare. Patients who are hepatitis B core antibody-positive (even patients who are hepatitis B surface antigen-negative and surface antibody-positive) are at risk for hepatitis B flare in the setting of immunosuppression or chemotherapy.
Risk-stratifying patients with MASLD
MASLD / metabolic dysfunction-associated steatohepatitis (MASH) is another leading cause of liver disease and liver transplantation in Singapore. GPs also play a critical role in risk-stratifying patients with MASLD.
Patients with diabetes are at higher risk of developing MASLD and liver-related complications. As a result, we recommend that GPs perform FIB-4 screening in patients with fatty liver, especially for those with diabetes, to identify patients at risk for fibrosis.
Those with a FIB-4 value greater than 1.3 should be considered for Fibroscan to help stage their liver disease. Patients with Fibroscan scores >9.6 kPa should be referred to a hepatologist.
PREVENTING AND MANAGING LIVER DISEASE TOGETHER
We hope that with adequate preventative measures, together we can prevent the progression and complications of liver disease. Public health education is crucial for educating patients and families on the importance of vaccination, screening for viral hepatitis and the role of a healthy lifestyle for liver health.
For patients who require advanced therapies including liver transplantation, SGH has an experienced team of multidisciplinary specialists that provide high-quality patient-centred care.
KEY TAKEAWAYS FOR GPs
The success of organ transplantation in Singapore relies heavily on the collaborative effort between GPs and specialist centres. Your role as a GP extends beyond initial identification – you are essential partners in preventing disease progression, ensuring timely specialist referrals and supporting post-transplant care. Whether it is identifying patients with MASLD, monitoring those with hepatitis B, or managing ESKD, your interventions can significantly impact patient outcomes. While organ donation remains a challenge in Singapore, with both liver and kidney transplant waiting lists growing, SingHealth’s transplant programmes continue to achieve excellent outcomes comparable to international standards. Through our combined efforts in early detection, prevention and patient education, we can work together to optimise the care pathway for patients requiring organ transplantation.
We encourage you to maintain a high index of suspicion for organ dysfunction and to engage early with transplant centres when concerns arise. Your proactive involvement in identifying and referring suitable candidates for transplantation can make a crucial difference in patient survival and quality of life.
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REFERENCES
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Professor Terence Kee is Director of the Kidney Transplant Programme, and Senior Consultant at the Department of Renal Medicine in Singapore General Hospital. He is also President of the College of Physicians and Chair of the Asian Solid Organ Transplant Registry. Additionally, Prof Kee is a council member of the Singapore Society of Nephrology and the Asian Society of Transplantation. His interests are in clinical immunosuppression, BK virus, novel biomarkers and biologics for transplantation.
Dr Chanda Ho is a Senior Consultant at Singapore General Hospital in the Department of Gastroenterology & Hepatology. She completed her gastroenterology and transplant hepatology fellowships at the University of California, San Francisco. Dr Ho is active in the liver transplant community in Singapore. She is currently on the SingHealth Executive Committee for the Liver Transplant Programme, and the Director of Digital Transformation for the SingHealth Duke-NUS Transplant Centre. She also serves on the subcommittee on Liver Transplant for the National Organ Transplant Unit.
To find out more about our transplant programmes, GPs can contact the SingHealth Duke-NUS Transplant Centre or visit the website here.
Tel: 6312 2720
Email: [email protected]
