Liver transplant remains a well-established treatment that can drastically improve the survival and quality of life for patients with end-stage liver disease and certain hepatic malignancies. It is crucial for the primary care provider (PCP) and/or general gastroenterologist to understand the basics of liver transplantation as they play an important role in the management of patients with liver disease. Timely identification and referral to a transplant center is key. We are providing the PCP with an overview of liver transplantation indications, evaluation process, and management factors to consider prior to transplant. We want to highlight the importance of identification of potential liver transplant candidates who may benefit from early referral as well as provide information on evolving trends and advances in the liver transplant process. By raising liver transplantation knowledge, we can improve patient outcomes, facilitate timely referral, and ensure comprehensive care for patients throughout the transplantation process.

Introduction 

Despite the advances in the management of chronic liver disease, liver transplantation remains a definitive life sustaining treatment for patients with severe acute or advanced chronic liver disease despite best medical therapy. It is important for the provider to be aware of the basics of the liver transplant process as they are often the gatekeepers to help screen patients requiring referral for liver transplantation. The process of liver transplantation is often both complex and multifaceted requiring a multidisciplinary approach between multiple healthcare professionals, including the PCP. This article aims to educate providers who treat patients with liver disease with an overview of the indications for liver transplantation, the evaluation process, and the pre-transplant management of patients during the waiting list period. Learning the principles of liver transplantation and management of patients with chronic liver disease can facilitate improved outcomes of patients. In addition, this paper serves to provide basic clinical updates within the last decade on liver transplantation for practitioners who manage cirrhosis. 

Liver Transplant Statistics

The first successful human liver transplant was performed in 1963 by Dr. Thomas Starzl. Since then, over 200,000 liver transplants have been performed in the United States (US) in the past 35 years. According to the Organ Procurement and Transplantation Network (OPTN), the liver is the second most transplanted organ. Between 2019-2022, the average number of liver transplants per year in the US was between 7,000-8,000 for deceased donors and 400-500 for living donors. Despite the COVID-19 pandemic, 8,906 liver transplants were performed in the United States in 2020, which was more than in any previous year.¹ The average wait time for liver transplant can range widely, from a few days to up to 5 years depending on the urgency. As of April 2023, there were approximately 10,000 patients listed for liver transplant. Liver transplant recipients had a five-year survival rate of >70%, compared to 15% for patients receiving medical therapy alone, emphasizing the life-saving impact of transplantation.²

Alcohol associated liver disease was the leading indication for transplant in 2020. Other common categories for adult liver transplantation are hepatitis C virus infection, hepatocellular carcinoma (HCC), acute liver failure, and non-alcoholic steatohepatitis (NASH) according to the 2019 OPTN.³

Research has revealed disparities in liver transplant access and outcomes based on ethnicity. A study published in the American Journal of Transplantation found that Hispanic and African American patients faced a higher risk of waitlist mortality and lower chances of receiving a liver transplant compared to Caucasian patients.⁴ A significant gender disparity also exists in the donor pool. In the United States, approximately 62% of deceased liver donors are male, while only 38% are female. 

Timing of Referral for Liver Transplant Evaluation

Who is a Candidate for Liver Transplantation?

Patients with severe acute or advanced chronic liver disease for which medical therapy has reached maximization should be evaluated for liver transplantation.⁵ The main population that the PCP should focus on referring for liver transplantation are patients with decompensated cirrhosis, cirrhotic patients with MELD (Model for End Stage Liver Disease) score ≥ 15, and patients with significant quality of life issues secondary to their end stage liver disease. Hepatic decompensation develops due to progressive portal hypertension from cirrhosis, with varying presentations, such as hepatic encephalopathy, ascites, variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension. Patients who develop hepatic decompensation in the form of variceal bleeding, hepatic encephalopathy, or ascites have significantly reduced survival compared to cirrhotic patients who are well-compensated. The median survival of persons with compensated cirrhosis is 9-12 years compared to 2 years in persons with decompensated forms of liver disease. In a patient with compensated cirrhosis, the rate of decompensation is 5-7% per year.⁶ Providers should be screening for hepatic decompensations in a routine and systematic fashion. 

The PCP should be aware of the definition of fulminant or acute liver failure and recognize the need for expedited inpatient evaluation in a liver transplantation center. Fulminant liver failure is the rapid hepatic deterioration with development of hepatic encephalopathy and coagulopathy in patients who do not have underlying liver disease. If the adult patient has fulminant liver failure, and anticipated life expectancy of less than 7 days without liver transplant, in an intensive care unit, and acute onset of hepatic encephalopathy with one of the following criteria: (1) ventilator dependence (2) required dialysis or (3) INR >2, then the patient qualifies for Status 1A. When listed as Status 1A, the OPTN prioritizes the search for first available liver donors by expanding the criteria from regional to national. For the purposes of this paper, we would like to focus on recognition of indications for liver transplant referral for patients with chronic liver disease in the outpatient setting.

There are clinical considerations to help determine successful liver transplant candidacy. Oftentimes, the patient has to be sick enough, where transplant would increase survival odds, but not too ill where they would not be expected to survive the operation and the immediate postoperative period. Patients must be able to demonstrate the insight and willingness to comply with a complex medical regimen required post-transplantation, particularly the need to take chronic immunosuppressive medications to prevent allograft rejection and prophylactic antibiotics/antivirals to prevent infection. Patients cannot have other severe comorbid conditions that could potentially compromise the graft or patient survival. These evaluations will occur in the transplant center through a comprehensive multidisciplinary team approach. 

Understanding the Basics

Classification of Liver Disease Severity

The Child-Turcotte-Pugh Score and the MELD-3.0 scoring system help classify the liver disease severity and need for liver transplantation evaluation. The Child-Turcotte classification system was developed in 1964 to risk-stratify patients undergoing shunt surgery for portal hypertensive decompression. In 1972, Pugh modified the Child-Turcotte system, and it became known as the Child-Turcotte-Pugh (CTP) score. Components of the CTP score include the serum total bilirubin, serum albumin, INR, presence/quantity of ascites, and presence/grade of encephalopathy. CTP score has been shown to accurately predict surgical outcomes in patients with cirrhosis and portal hypertension. In addition, clinicians have widely used this tool to assess the risk of short-term mortality in cirrhotic patients. Overall, the 30-day post operative mortality following abdominal surgery of a cirrhotic patient with CTP score A is 10%, CTP score B is 30% and CTP score C is 76–82%. One year survival is 45% in CTP score C, compared to 95% and 80% in CTP score A and CTP score B, respectively.⁷ Patients with CTP-C scores are the sickest, and special attention should be focused on this group. 

Model of End Stage Liver Disease (MELD) Score is another prognostic scoring system which estimates the survival probability of a patient with end-stage liver disease. It is calculated using the serum bilirubin, serum creatinine, and INR. United Network for Organ Sharing (UNOS) manages the United States transplant allocation system and uses the MELD score for organ recipient priority. In 2002, the MELD score was adopted by UNOS for deceased liver organ allocation. The MELD scores range from 6 to 40, which correspond to 3-month survival odds of 90% and 7%, respectively. In January 2016, the MELD score was further modified to incorporate serum sodium to create the MELD-Na equation as hyponatremia in cirrhosis is a marker of increased liver transplant waitlist mortality.⁸ Further adaptations of the MELD score have been utilized to reduce wait time death of patients on the transplant list and make listing more equitable. In July 2023, the MELD 3.0 score was implemented to reduce liver transplant wait list mortality by accounting for female sex, serum albumin, and a lowered serum creatinine cut-off from 4.0 mg/dL to 3.0 mg/dL. The new scoring system addresses the disparity that females have had consistently lower transplant rates historically.⁹

The PCP should use prognostic score systems of CTP score and MELD-3.0 score to risk stratify cirrhotic patients. Patients with decompensated cirrhosis or MELD-3.0 ≥ 15 are recommended to be referred to a liver transplant center for evaluation due to their high risk of morbidity and mortality. 

Indications for Liver Transplant Evaluation

Liver transplantation can restore quality of life and prolong patient survival. Progressive advancements in care of liver transplant patients show favorable short and long term outcomes. Graft survival is 91.2% at 1 year, 76.5% at 5 years, and 56.4% at 10 years.¹⁰ The main indications for liver transplantation are decompensated liver disease, acute liver failure, primary unresectable hepatic malignancy, inherited metabolic liver disease, and retransplantation. Chart 1 provides an inclusive list of indications for liver transplantation. 

The Evolving Liver Transplantation Population

The most recent American Association of the Study of Liver Disease (AASLD) Guidelines has modified nomenclature to change “alcoholic” to “alcohol-associated” cirrhosis to help reduce the stigma associated with the disease faced by patients and family members.¹¹ Alcohol-associated liver disease is the most common indication for liver transplant in the United States at present. Alcohol-associated liver disease has surpassed hepatitis C as the leading indication for liver transplant in the United States in the last several years. Since the introduction of well tolerated direct acting antivirals with substantial rates of hepatitis C eradication, there is a reduction in the need for liver transplantation and development of hepatocellular carcinoma in this subset of patients.¹²

Alcohol-associated liver disease and metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH) are projected to be the leading indications for liver transplantation in the near-future.¹³ Obesity and metabolic syndrome are risk factors for development of metabolic dysfunction associated liver disease (MASLD), which can progress to MASH and cirrhosis. The rate of obesity has doubled in the last 30 years worldwide, with the growth rate within the United States being one of the highest. Patients added to the transplant wait list with NASH as an indication increased by 170% between 2004 and 2013.¹⁴ It is predicted that MASH will be the leading indication for liver transplant in the U.S. over the next 10 to 20 years.¹⁵ Up to 25% of patients with MASH will progress to cirrhosis with increased risk of hepatocellular carcinoma development, therefore early diagnosis and management may curb the need for liver transplantation. Patients with MASH-induced cirrhosis can be a challenging population to manage due to comorbid conditions such as severe cardiovascular disease, which can preclude transplantability. Metabolic clinics for weight loss and early referral for bariatric surgery may be an option to help reduce MASLD-associated fibrosis but is not recommended in decompensated liver disease. Potential pharmacologic treatments for MASH are being studied. Resmetirom, an oral liver-directed thyroid hormone receptor beta–selective agonist, has been recently FDA approved for patients with stage 2-3 fibrosis secondary to MASH, which has been shown to be helpful in hepatic fibrosis regression.¹⁶

Alcohol-induced hepatitis is one of the most severe manifestations of alcohol-associated liver disease, with high morbidity and mortality. Liver transplantation may be considered as a last option for patients with alcohol-induced hepatitis when medical treatment has failed or is contraindicated. Many liver transplant centers require six months of alcohol abstinence prior to evaluation for liver transplantation. Due to the risk of significant morbidity and mortality without transplantation during that 6-month period, predictors have been studied in the US and Europe to identify a subset of patients with low risk of recidivism. Select patients with severe alcohol-induced hepatitis who fail to respond to medical therapy should be considered for liver transplant.¹⁷ The most favorable factors associated with low risk of recidivism include: alcohol induced hepatitis as initial hepatic decompensating event, good social support, insight to severity of disease, absence of severe psychiatric disorders, recent life stressor, prolonged duration of abstinence prior to transplantation, stable employment, and a covenant to adhere to life-long alcohol abstinence.¹⁸ Although there are similar favorable one and three years survival outcomes in patients transplanted for alcohol induced hepatitis compared to other indications for liver transplant, the cumulative incidence of persistent alcohol use post-transplant was 10% in the first year and 17% by the third year, with increasing alcohol use associated with increased mortality over time, based on recent studies.¹⁹ Further longitudinal studies need to be performed to elucidate the generalizability of these outcomes. 

MELD Exception Points

OPTN prioritizes organ allocation based on medical necessity using the MELD-3.0 score, with higher scores given higher priority access to the donated organs. MELD exception points are granted in certain liver diseases when the severity of the liver disease is not reflected by the calculated MELD score. Typically, the morbidity and mortality is higher in this population subset and the patient is “sicker than the MELD” score. These indications include hepatocellular carcinoma, hilar cholangiocarcinoma, primary hyperoxaluria, metabolic disorders of the urea cycle, hepatopulmonary syndrome, portopulmonary hypertension, cystic fibrosis, and familial amyloid polyneuropathy. If the patient meets specific inclusion criteria, they are OPTN waitlisted with a MELD score equivalent to the median MELD at transplant within the surrounding transplant centers minus 3 points (MMaT-3). The median MELD is calculated from within 150 nautical miles surrounding each donor hospital in the country and is applied to the exception point score for any transplant candidate receiving liver offers from that donor hospital. Patients with primary hyperoxaluria and metabolic diseases, such as urea cycle disorders or organic acidemia, meeting criteria receive MELD exception equivalent to the MMaT.^20,21

Hepatocellular Carcinoma

Hepatocellular carcinoma in a cirrhotic patient is an important indication for liver transplant. A landmark trial by Mazzaferro showed a 4-year post-liver transplant survival benefit of 75% with recurrence-free survival of 83% when the liver cancer was confined to the “Milan criteria”.²²  Hepatocellular carcinoma within “Milan criteria” includes one lesion ≤ 5 cm, or three lesions < 3 cm without metastasis. Hepatocellular carcinoma is diagnosed based on cross sectional CT or MRI with confirmation of tumor dimensions by a radiologist in an OPTN approved transplant center. These patients are eligible for MELD exception points if they meet criteria. HCC can be treated with locoregional therapy while awaiting transplantation. Hepatocellular carcinoma that is beyond the Milan criteria limits can be attempted to be down-staged by loco-regional treatment so as to be brought within Milan criteria, and then can be reconsidered for transplantation without sacrificing post-transplant survival.²³

Cholangiocarcinoma

Cholangiocarcinoma is a bile duct cancer with increased risk of development in patients with underlying primary sclerosing cholangitis (PSC). In general, intrahepatic cholangiocarcinoma is a relative contraindication to liver transplant due to the aggressive nature of the malignancy with poor post-transplant survival. For patients undergoing curative surgical resection, there are high rates of recurrence up to 60-70%. Five-year survival for patients with resectable disease is 20-40%.²⁴ Patients with hilar cholangiocarcinoma are likely not candidates for resection due to the anatomical location of tumor being in the area of the hepatic duct and its bifurcation. The Mayo Clinic has created a highly selective protocol using neoadjuvant chemotherapy prior to liver transplant for early stage unresectable, non-metastatic perihilar cholangiocarcinoma. The five-year survival after liver transplant is 73%, based on their protocol.²⁵ For consideration of liver transplant for perihilar cholangiocarcinoma, UNOS requires the transplant institution to have an approved written treatment protocol, and grants MELD exception points if the patient is suitable. 

HRS – New Nomenclature

Hepatorenal syndrome (HRS) is defined as renal failure in a person with cirrhosis in the absence of intrinsic renal disease. Previous nomenclature of Type 1 HRS is now termed HRS-acute kidney injury (HRS-AKI). Patients with HRS-AKI have a rapid deterioration in renal function with very high morbidity and mortality. AKI is defined as an increase in serum creatinine ≥ 0.3 mg/dL from baseline within 48 hours or a ≥ 50% increase in serum creatinine within the last 7 days.²⁶ After ruling out intrinsic renal disease and post-renal obstruction as a cause, and after failing to improve with 48 hours of intravascular volume repletion, this entity would be considered HRS-AKI. Patients with HRS-AKI should have an expedited referral for liver transplantation. HRS-AKI is usually reversible after liver transplantation. HRS Type 2, now termed HRS-chronic kidney disease (HRS-CKD), is a more gradual impairment in renal function that is less severe than type 1 HRS and is seen typically in patients with refractory ascites, which are resistant to diuretics. The definition of HRS-CKD requires the patient to meet HRS criteria and have eGFR < 60 ml/min per 1.73 m2 for ≥ 3 months, in absence of other structural causes. Select patients with chronic kidney disease and liver disease should be considered for combined liver-kidney transplantation. 

Contraindications for Liver Transplantation

An important concept of liver transplantation is to recognize contraindications to liver transplantation. Universal absolute contraindications include severe cardiopulmonary disease, active extrahepatic malignancy, metastatic hepatocellular carcinoma, uncontrolled sepsis, brain death, AIDS, active alcohol or illicit substance abuse, persistent noncompliance or lack of social support, and anastomotic barriers to liver transplantation.²⁷ Many transplant centers require a minimum alcohol abstinence of 6 months with substance dependence program attendance. Literature suggests the risk of recidivism is lower in patients who complete at least 6 months of sobriety compared to those with shorter periods.²⁸ The recommendation remains controversial, as other studies suggest the length of pre-transplantation abstinence is a relatively poor predictor of post-transplantation abstinence.²⁹ An exception to the “six-month rule” may be considered when patients are being transplanted for alcohol-induced hepatitis in a center with a protocol for this situation. Conversely, hepatic function may improve with alcohol abstinence in patients with alcohol-induced cirrhosis to the extent a transplant is less urgent.³⁰

Relative Contraindications

Physiologic, not chronologic, age should be considered in a patient undergoing liver transplant evaluation. There has been an increasing median age of patients being evaluated and waitlisted for transplantation. Registrants for UNOS liver transplant waitlist aged ≥ 65 years increased from 8% in 2002 to 17% in 2014.³¹ Post transplant survival for patients over age 65, compared to younger cohorts, was overall lower in earlier studies.^32,33 More recent studies do not indicate higher rates of mortality or lower graft survival in young compared to elderly liver recipients in early transplant outcomes, however increased malignancy rates are seen in older patients.³⁴

It is also feasible that being transplanted at an older age is associated with increased morbidity and mortality due to natural shorter life expectancy in older patients. A detailed evaluation to assess for functional and nutritional status, as well as medical comorbidities including cardiopulmonary status and malignancy, is highly recommended. In the absence of significant comorbidities, age > 70 years is not a contraindication for liver transplant.

Patients will need curative treatment for isolated primary extrahepatic malignancy with oncologic clearance prior to liver transplant. Typically, there is a waiting period to ensure absence of tumor recurrence after definitive treatment prior to transplant listing. There is heightened concern for risk of tumor recurrence for patients with prior malignancy who are on long-standing immunosuppression after transplant. The Israel Penn database is a collection of patients who developed malignancy after organ transplants. Based on the Israel Penn data, malignancies which have a low risk of recurrence are incidental renal tumors, lymphoma, testicular, cervical, and thyroid cancers. Malignancies with intermediate risk of recurrence are uterine, Wilms’ tumor, colon cancer, prostate, and breast cancer. Tumors associated with a high risk of recurrence include bladder cancer, sarcoma, melanoma, symptomatic renal cancer, and myelomas.³⁵ A judicious individualized, multidisciplinary approach by the transplant team is used to decide on optimal candidates and timing of listing. 

Although AIDS is a contraindication for transplant, HIV patients are eligible for transplantation in the presence of adequate immune function with CD4 >100/µL with undetectable viral load at the time of liver transplant. Co-management with an infectious disease specialist is recommended.⁵

Class III obesity (body mass index (BMI) ≥ 40) is a relative transplant contraindication. It is associated with coronary artery disease, hyperlipidemia, diabetes mellitus, renal dysfunction, and obstructive sleep apnea.⁵ Obesity increases the risk of perioperative complications and length of post-operative hospital stay and reduces long term survival. Primary graft non function, immediate, 1-year, and 2-year mortality were significantly higher in the morbidly obese group. Five-year mortality was significantly higher both in the severely and morbidly obese subjects, mostly due to cardiovascular events.³⁶ Weight loss is recommended prior to transplant in patients with class III obesity. While patients with severe obesity and/or metabolic-associated fatty liver disease can be considered for bariatric surgery, this is contraindicated in decompensated liver disease due to risk of worsening hepatic dysfunction with surgery. Studies investigating the performance of gastric sleeve placement simultaneously with liver transplant, to assist with weight management, demonstrate safety and may be helpful in long term total body weight loss.³⁷

Patients with severe ascites can be seen as “overweight”, but this should not be confused for obesity as oftentimes that patient has co-existing anasarca and sarcopenia.  The presence of ascites is associated with an increased risk of postoperative morbidity and mortality post-transplant. A study performed by Leonard et al. showed that correction of BMI for ascites volume placed 11-20% of the studied patients who received a liver transplant into a lower BMI classification. It was calculated that each liter of ascites removed during the transplant was associated with a 7% increased relative risk of mortality.³⁸ Special care should be utilized to prevent further malnutrition, as patients with ascites will still require high protein diets as cirrhosis is a catabolic state. 

Underweight patients also pose a concern, as patients at both extremes of BMI have significantly higher wait list mortality and worse liver transplant outcomes as compared with those with normal BMI (18.5 to <25). Underweight patients (BMI < 18.5) have higher risk of hemorrhagic complications and cerebrovascular events. Overweight patients (BMI > 40) have a higher risk of infectious complications and cancer events. Given this disparity, innovative means are required to target high risk groups.³⁹ A comprehensive nutrition assessment and dietary management should be utilized in patients who are at extremes of BMI to help minimize complications. 

Understanding the General
Liver Transplant Evaluation Process 

Patients should be referred to a liver transplant center if there is decompensated liver disease or MELD-3.0  ≥ 15. The PCP should be familiar with their local transplant centers. Oftentimes, there will be local outreach clinics if the nearest center is distant. The patient should understand that a referral does not mean they will be automatically listed for a liver transplant. Generally, the multidisciplinary transplant team consists of the transplant hepatologist and surgeon, nurse coordinator, financial coordinator, social worker, psychiatrist, dietician, physical therapist, anesthesiologist, and pharmacist, all of whom will interact with the patient. During the initial evaluation, the transplant process will be discussed with the patient, and individual evaluations performed. The patient’s motivation and insight to comply with medication therapy and long term follow up, social support, functional and nutritional status, and substance abstinence duration are assessed. The hepatologist ensures medical management has been maximized and appropriate treatments are up to date. The transplant surgeon evaluates surgical contraindications for liver transplant, as well as suitability for living donor evaluation if applicable.  Standard blood tests, including blood type, screening for liver disease, and determining the infection status of HBV, HCV, EBV, CMV, VZV, RPR, and HIV are performed. Status of tuberculosis exposure is typically performed with interferon-gamma release assay (i.e., Quantiferon gold) or tuberculin skin testing. Cardiopulmonary testing may include echocardiogram, cardiac stress test, heart catheterization as needed, and pulmonary function testing. These are used to screen for significant valvular disease, heart failure, coronary artery disease, significant respiratory diseases, hepatopulmonary syndrome, and portopulmonary hypertension. Testing is based on individualized risk. Cross sectional abdominal imaging with CT or MRI are performed to rule out intra- and extra-hepatic malignancy, especially hepatocellular carcinoma, and anatomic contraindications. Standard preventative care measurements such as age- and indication-appropriate malignancy screening with mammogram, colonoscopy, low dose contrast CT chest, and pap smear are reviewed. Screening for osteoporosis with DEXA scan and vitamin D levels are incorporated into the process. Dental exam should be completed to assess for necessary extractions prior to transplant. After an extensive evaluation is completed and the patient/family comprehends the aspects of the transplant process, the multidisciplinary team discusses whether the patient should be waitlisted for organ transplant. 

Understanding Liver Donation

Deceased Donor vs. Living Donor 

Transplanted livers may be received from a living or a deceased donor. Almost 20% of patients on the US waiting list die or become too sick for the transplant. Deceased liver donation remains the primary source of organs for liver transplantation. However, the scarcity of deceased donor organs has led to the utilization of living donors to expand the donor pool to provide timely transplants for recipients. Deceased liver donors are typically individuals who have experienced irreversible brain damage or cardiac arrest and are declared legally brain dead. These donors are often individuals who have registered as organ donors or have consented to donation through their families. The process involves meticulous matching of the donor liver with a suitable recipient based on factors such as blood type, body size, and urgency of need. Organs from deceased donors are carefully preserved and transported to the recipient’s transplant center. 

Living donor liver transplantation (LDLT) occurs when an individual readily volunteers to donate a portion of their liver to someone in need. This is possible because of the liver’s incredible ability to regenerate. Candidates being considered for living donor transplantation will need to meet evaluation criteria set forth by the transplant center. The decision to accept a liver donor is determined by a multidisciplinary team in a transplant center.

Along with the assignment of an Independent Living Donor Advocate (ILDA) by the recovery hospital, the evaluation and selection of an adult liver donor involves a comprehensive assessment of their medical and psychosocial health status to determine eligibility. The ILDA, either an individual or a team, must be qualified and understand the full transplant protocol of the recovery hospital, function independently of the recipient’s team, advocate for the donor, and ensure that the donor has received all information required to make an informed decision. The living donor must undergo psychosocial testing with a team of psychiatrists and psychologists prior to organ recovery to ensure that there are no detrimental psychosocial issues (including high risk behaviors, mental health issues, substance use disorders, etc.) that precludes organ donation or would affect long term recovery. This team also must determine that the donor is free of coercion, can make informed decisions, and understands the long and short term psychological and medical risks.⁴⁰ Advantages of living donor liver transplantation (LDLT) include reduced wait time for the recipient, use of a graft with minimal ischemic time, and sufficient time to plan for an elective surgery. The evaluation process is otherwise similar to deceased donor.⁴¹

Surgical techniques for living donor liver transplantation involve the partial resection of the donor’s liver, either the right or left lobe, which can regenerate to near-normal size and function in both the donor and recipient within a few months. With regards to outcomes, graft failure occurs in 5.9% (6 months), 7.9% (1 year), 14.7% (3 year), 20.7% (5 year), and 40.6% (10 year) of deceased donor recipients. There is a slightly lower graft failure rate for living donor recipients: 4.9% (6 months), 7.4% (1 year), 12.2% (3 year), 23.7% (5 year), and 36.7% (10 year). It is notable that overall recipient mortality has continued to improve over the last decade.⁴²

Given the current allocation policies in the United States, patients with MELD scores <15 on the waiting list rarely receive a liver in a timely fashion. Patients with low MELD scores must rely on either living donors or expanded-criteria deceased donors if they are to receive a transplant. In the landmark Adult-to-Adult Living Donor Liver Transplantation Cohort (A2ALL) study, the survival benefit of an LDLT was demonstrated at MELD-Na scores less than 15.⁴³

An ideal patient for LDLT would be one with a low MELD score but decreased quality of life due to underlying end stage liver disease. Life altering manifestations from end stage liver disease, such as refractory hepatic encephalopathy, ascites/hepatic hydrothorax, sexual dysfunction, sarcopenia, and pruritus can occur, and are not reflected in the MELD 3.0 score. A study performed in the United States by Jackson et al. showed significant survival benefit of LDLT in patients with end-stage liver disease, even at MELD-Na scores as low as 11. For patients with low MELD scores and significant quality of life issues from liver disease, LDLT is a good alternative to waiting for a deceased donor as it will significantly increase survival compared with remaining on the waitlist.⁴⁴

Although the number of living donor transplants performed annually has increased slowly over the years, it still accounts for only about 5% of liver transplants in the United States.⁴⁵ Of the 8,906 liver transplants performed in the US in 2020, 7,979 (89%) patients received organs from a deceased donor and 425 (11%) from a living donor.⁴⁶

Medical Management of Patients
Awaiting Liver Transplantation 

The matching of a donor and recipient is prioritized based on recipient MELD score per UNOS and compatible ABO blood type. As such, the waitlist time for liver transplant is variable. For patients with low MELD scores, waitlist time can be years, between listing and getting called for their transplant. It is therefore essential to continue management of the cirrhotic patient during this time period to help reverse or delay the need for transplant. The management of the cirrhotic patient can be complex. It is recommended to communicate with the transplant team for major medical decisions, however “day to day” management of portal hypertension, HCC surveillance, counseling on substance dependence and tobacco cessation, weight loss counseling for obese patients, screening for malnutrition and monitoring of functional status, vaccination for Hepatitis A and B, and preventative measures such as ensuring PAP smear, mammogram, colonoscopy and DEXA scan are up to date can be performed by the PCP. Early referral for liver transplant is recommended for patients with alcohol-related liver disease to facilitate prompt treatment for substance addiction. 

PCPs should recognize that non-transplant peri-operative risk is substantially increased in patients with decompensated cirrhosis, especially CTP class C. PCPs should consult with the transplant hepatologist/transplant team prior to any, particularly abdominal, surgery to weigh the risks and benefits, as surgery can increase morbidity and mortality. In addition, patients should be counseled on eating a high protein diet to counteract sarcopenia and development of hepatic encephalopathy. Typically, the recommended protein intake is 1.2 to 1.5 g/kg per day, based on ideal body weight, with protein included with each meal and snack. A protein-based bedtime snack can reduce the incidence of sarcopenia.⁴⁷

Summary

In conclusion, it cannot be overstated that liver transplantation is a life-saving procedure for patients with acute or chronic end-stage liver disease. The evaluation process involves a comprehensive assessment of a patient’s medical history, comorbidities, and psychosocial factors that play a key role in identification of suitable candidates for this life saving procedure. The decision to undergo liver transplantation is complex and requires a collaborative approach involving multiple healthcare professionals. As a PCP, the understanding of key aspects of the evaluation process is crucial for recognizing patients who may benefit from liver transplantation and ensuring their timely referral to transplant centers. Candidates for liver transplant referral include, but are not limited to, patients with acute liver failure, decompensated liver disease, primary unresectable hepatic malignancy, inherited metabolic liver disease, and MELD score ≥ 15. The role of the primary care provider does not end with timely referral to transplant centers, but also involves being knowledgeable about pre-transplant management, including optimizing patient health, managing complications, and providing appropriate long term follow up. PCPs can make a significant difference in improving patient quality of life and long-term survival rates by actively participating in the care of patients with chronic liver disease. By collaborating closely with transplant teams and staying updated on the indications, evaluation criteria, and potential contraindications, PCPs can enhance patient outcomes and contribute to the overall success of liver transplantation. 

References

Download Tables, Images & References