Liver Transplantation and Donor Health

Vol. 31, Special Issue 1 (July 2026)

Burcu Gürbüz, MD
Department of Internal Medicine, Gastroenterology and Hepatology
Hacettepe University
Ankara, Türkiye
 

Berat Baran, MD
Department of Internal Medicine
Hacettepe University
Ankara, Türkiye
 

Hatice Yasemin Balaban, MD
Department of Internal Medicine, Gastroenterology and Hepatology
Hacettepe University
Ankara, Türkiye


 

Introduction

Liver transplantation (LT) is the definitive treatment for end-stage liver disease, acute liver failure, certain metabolic disorders, and selected primary and secondary liver malignancies. Since the first successful human LT performed by Dr. Thomas Starzl in 1963, the field has undergone substantial evolution, both in surgical technique and perioperative care.¹ Initially plagued by poor outcomes due to technical challenges and limited immunosuppressive options, the advent of calcineurin inhibitors in the 1980s marked a turning point, enabling dramatic improvements in graft and patient survival rates.² The first successful living-related donor liver transplantation,  performed by Strong et al. İn 1989, represented another major milestone.³

More recent developments include expanded indications such as acute-on-chronic liver failure and transplant oncology, improvements in organ preservation through machine perfusion, and refined allocation systems such as MELD 3.0. Contemporary transplantation practice increasingly emphasizes individualized candidate assessment, frailty, careful donor selection, and comprehensive pre- and post-transplant management. Nevertheless, organ demand continues to exceed supply worldwide, requiring innovation alongside ethical vigilance regarding donor protection and organ trafficking.

Indications

LT is a life-saving procedure for patients with decompensated cirrhosis, acute liver failure (ALF), acute-on-chronic liver failure (ACLF), some metabolic diseases (tyrosinemia, urea cycle defects, or Wilson’s disease), and oncological indications, such as hepatocellular carcinoma (HCC).⁴ Although hepatitis C virus (HCV)-related cirrhosis was historically the leading indication, alcohol-related liver disease (ALD) and metabolic dysfunction associated steatohepatitis (MASH) have become increasingly prominent.⁵ Other indiciations include hepatitis B virus (HBV), autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), alpha-1 antitrypsin deficiency, and inherited metabolic disorders. According to the OPTN/SRTR (Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients) 2023 Annual Data Report, ALD accounts for approximately 40 % of adult LT candidates in the United States, while MASH is the second most common indication. This transition reflects the declining burden of viral hepatitis following effective antiviral treatment. The availability of direct-acting antivirals has also enabled HCV-negative recipients to receive grafts from HCV-infected donors, thereby expanding the donor pool.⁶

i. Cirrhosis

Cirrhosis remains the leading indication for LT worldwide. Progressive architectural distortion and portal hypertension lead to complications such as ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, and variceal bleeding. Once decompensation occurs, median survival sharply decines, with estimates ranging from one to two years in the absence of transplantation.⁷ LT is the only curative intervention capable of correcting both hepatic insufficiency and portal hypertension. Timely referral improves survival and quality of life, whereas delayed assessment increases the likelihood of infection, renal dysfunction, frailty, sarcopenia, and waitlist mortality. Early identification and multidisciplinary management are therefore essential.

Transplant referral and organ allocation are guided primarily by prognostic scores.⁸ The original Model for End-Stage Liver Disease (MELD) score incorporates serum creatinine, bilirubin, and international normalized ratio (INR) to estimate three-month mortality. Seryn sodium was subsequently added to create MELD-Na because hyponatremia independently predicts mortality. MELD 3.0 further incorporates serum albumin and female sex to improve prediction and address disadvantages experienced by women because of lower muscle mass and serum creatinine.⁹ Contemporary evidence supports MELD 3.0 as the most accurate available tool for determining urgency and guiding organ allocation in LT.

ii. Acute Liver Failure

Acute liver failure (ALF) is characterized by the sudden onset of hepatic dysfunction, coagulopathy, and hepatic encephalopathy in a person without preexisting liver disease.¹⁰ Common causes in developed countries include acetaminophen toxicity, acute viral hepatitis, autoimmune hepatitis, and idiosyncratic drug-induced liver injury. 

ALF is distinguished by its rapid progression and unpredictable course, with many patients developing multi-organ failure within days to weeks.¹¹ Spontaneous recovery varies according to etiology, age, and the severity of extrahepatic organ dysfunction; acetaminophen-related ALF generally has a more favorable progrnosis. For patients with progressive encephalopathy and severe coagulopathy, however, LT remains the only definitive treatment.¹² Listing decisions must be made rapidly to prevent irreversible neurological injury or sepsis. Prognostic tools such as the King's College criteria are commonly used to guide listing decisions, but clinical judgment remains paramount due to the dynamic nature of ALF.¹³ Although ALF accounts for less than 5% of liver transplants in the United States and Europe, one-year post-transplant survival generally exeeds 80%. Early referral to a liver transplant center is therefore crucial.

iii. Acute-on-Chronic Liver Failure

Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of chronic liver disease, accompanied by organ failures and increased short-term mortality. ACLF is most commonly precipitated by events such as bacterial infection, gastrointestinal bleeding, or active alcohol consumption.¹⁴ Severity is graded according to the number and type of organ failures; grade 3 ACLF representing the most severe form, frequently involving renal, circulatory, respiratory, or cerebral dysfunction, and may carry a 28-day mortality exceeding 75% at 28 days without LT.¹⁵

Although patients with ACLF were previously considered poor transplant candidates because of perioperative risk amd cpmcerms about futility, current evidence indicates that selected patients can achieve substantial survival benefit. Potentially reversible extrahepatic organ failures, a controllable precipitating event, and timely transplatation are key considerations. Selected patients, including some with ACLF grade 3, may achieve one-year post-transplant survival comparable to recipients without ACLF.¹⁶

ACLF should be differentiated from acute decompensation (AD) of cirrhosis. The term AD is used if one or more significant consequences of liver disease occurs in a short time. Unlike ACLF, AD is not accompanied by an inflammatory state. The European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF) Group had modified the Sequential Organ Failure Assessment score (SOFA) that is used for intensive care patients into the prognostic scores for cirrhotic patients with acute organ failure:

• CLIF-SOFA – for organ failure in cirrhosis in general, and includes bilirubin for liver failure, creatinine for renal failure, West-Haven hepatic encephalopathy grade for neurological failure, INR for hematology, mean arterial pressure (MAP) for circulation, partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) for respiratory system.
• CLIF-C ACLF – for ACLF, and include age and WBC in addition to CLIF-SOFA score.
• CLIF-C AD – for acute decompensation, and includes age, creatinine, INR, WBC, and Na.

These scores may aid in identifying suitable candidates for transplantation, though expert multidisciplinary assessment remains crucial.¹⁷

iv. Metabolic Diseases

Inherited metabolic diseases constitute a significant and expanding indication for LT, particularly in pediatric practice. Disorders such as Wilson’s disease, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, primary hyperoxaluria, and a variety of urea cycle and organic acidemias can result in progressive hepatic dysfunction, acute liver failure, or life-threatening systemic complications despite maximal medical management. In many disorders, LT replaces the deficient hepatic enzyme, prevents further toxic-metabolite accumulation, and may provide a definitive metabolic cure.¹⁸ Timing is critical because delayed transplantation can lead to irreversible neurological or renal injury.

Inherited metabolic diseases requiring LT can be broadly categorized according to their pathophysiological mechanisms and the extent of hepatic versus extrahepatic involvement. Group A includes disorders such as Wilson’s disease, hereditary tyrosinemia type I, and alpha-1 antitrypsin deficiency, where progressive hepatocellular injury leads to cirrhosis and liver failure. In these conditions, LT restores normal hepatic function and prevents further hepatic decompensation. Group B includes urea cycle disorders, porphyrias and primary hyperoxaluria. Here, these patients rarely have ESLD; LT is performed for extrahepatic organ involvement. LT not only replaces deficient enzymes to correct the metabolic defect but also halts the accumulation of toxic metabolites, thereby preventing irreversible neurological damage or other systemic complications. Group C includes maple syrup urine disease and mitochondrial hepatopathies. In such cases, transplantation can stabilize or slow disease progression but may not completely reverse extrahepatic manifestations.¹⁹

Overall, disease-specific assessment and timely referral are essential for optimal outcomes.

v. MELD Exceptions

Classic examples of standardized MELD exceptions include patients with HCC meeting specific criteria (such as the Milan criteria), cholangiocarcinoma (CCA), familial amyloid polyneuropathy (FAP), cystic fibrosis, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH).²⁰ Exception requests are reviewed by regional or national committees to promote consistency and prevent misuse.

MELD 3.0 improves allocation equity, particularly for women and candidates with hypoalbuminemia. Nevertheless, adjudicating exceptions remains difficult for diseases with variable natural histories or limited outcome data. Exception policies should therefore be periodically reviewed using registry evidence to ensure that allocation reflects both medical urgency and expected transplant benefit.

vi. Transplant Oncology

Liver transplantation for oncologic indications is firmly established selected patients with HCC who satisfy criteria such as the Milan or University of California, San Francisco criteria.  For eligible patients with early-stage HCC and underlying cirrhosis, LT not only removes both the tumor and the underlying liver disease, resulting in five-year survival rates above 70% in many series. Locoregional ablation and transarterial chemoembolization may be used as bridging therapies while patients await transplantation.²¹

Recent studies have broadened the oncologic indications for LT beyond conventional HCC. Selected patients with intrahepatic cholangiocarcinoma have acieved promising outcomes under strict protocols incorporating neoadjuvant therapy.²² LT has also been invesitgated for unresectable colorectal liver metastases and selected neuroendocrine tumors.²³

Because non-HCC malignancies generally carry greater recurrence risk, expansion of transplant oncology must be balanced against organ scarcity, utility, justice, and expected survival. Candidate selection should involve multidisciplinary tumor boards and prospective registries. Future progress will likely depend on improved molecular profiling, risk stratification, and careful integration of systemic and immune-based therapies.

Donor Issues

i. Organ Trading and Trafficking

Organ trafficking is a critical global health and human rights issue, estimated to account for up to 10% of all solid organ transplants performed worldwide.²³ It is driven by the persistent imbalance between organ supply and demand, socioeconomic inequality, and unregulated transplant markets. Migrants, refugees, and people from low-income settings are particularly vulnerable to coercion, deception, and commercial exploitation. These practices are frequently associated with inadequate medical assessment, poor postoperative care, and increased infectious and surgical complications.²⁴

The Declaration of Istanbul, endorsed by major transplant societies and the World Health Organization (WHO), prohibits commercial organ trade and emphasizes transparency, traceability, voluntariness, and donor protection.²⁵ Nevertheless, trafficking networks remain difficult to detect and prosecute because of their transnational structure, limited reporting systems, and occasional involvement of healthcare professionals. Transplant teams must therefore verify the legitimacy of donation and ensure that consent is informed and free from coercion.

Effective prevention requires international cooperation, harmonized legal standards, reliable donor registries, professional accountability, and public education. Combating organ trafficking is both a legal obligation and an ethical requirement for preserving trust and integrity in the liver transplantation field.

ii. Donor Selection Criteria

a. Living Donor Criteria
Living donor liver transplantation (LDLT) offers several advantages, including the reduction of waitlist mortality and the opportunity to schedule transplantation electively. Donor safety, voluntariness, and autonomy are the central principles of the evaluation process. Potential donors must receive comprehensive information about operative risks, possible effects on quality of life, and available alternatives.

Comprehensive evaluation protocols encompass medical, surgical, and psychosocial assessments. Donor-recipient matching considers blood type, size compatibility, and absence of contraindicating anatomical variants. Typically, donors are aged 18–55, though carefully selected older individuals may also be suitable candidates. Candidates should be in good overall health, without significant cardiovascular, pulmonary, metabolic, infectious, or chronic liver disease. Serological testing, CT or MRI assessment of vascular and biliary anatomy, and evaluation for hepatic steatosis and fibrosis by noninvasive methods or biopsy are required. Psychosocial assessment should confirm informed motivation and exclude coercion.

Surgical planning for LDLT is technically complex, involving selection of the optimal liver graft (right lobe, left lobe, or left lateral segment) based on recipient needs and donor safety. Three-dimensional imaging and virtual surgical planning are increasingly used to estimate graft and future liver remnant volumes, which are critical for minimizing the risk of small-for-size syndrome in the recipient and ensuring adequate residual function for the donor. Detailed mapping of vascular and biliary anatomy allows for safe resection and reconstruction. The graft-to-recipient weight ratio should ideally be ≥0.8%, and the donor’s future liver remnant should exceed 30% of their original liver volume.²⁶

LDLT is associated with low donor mortality of approximately 0.1–0.2%, and available evidence does not indicate reduced long-term life expectancy compared with the general population. Nevertheless, donors remain at risk of biliary complications, infection, bleeding, venous thromboembolism, and, rarely, acute liver failure. Long-term complications may include incisional hernia, fatigue, chronic pain, depression, or adjustment difficulties, although most donors report high satisfaction with their decision.

b. Cadaveric Donor Criteria
Cadaveric (deceased) donor selection aims to maximize graft viability while minimizing the transmission of infection or malignancy. Evaluation includes review of the donor’s medical and social history, laboratory testing, and imaging, ensuring there are no active systemic infections, high-risk malignancies, or other contraindications such as uncontrolled sepsis, untreated HIV, or recent high-risk behaviors. Exclusion criteria may also encompass hemodynamic instability, prolonged hypotension, and severe steatosis or fibrosis.⁶

Deceased donation are classified as either donation after brain death (DBD) or donation after circulatory death (DCD). DBD remains the main source of cadaveric livers globally, but the increasing acceptance of DCD has significantly expanded the donor pool. While DCD grafts are associated with a higher risk of ischemic cholangiopathy and primary nonfunction, improved procurement methods and the implementation of normothermic machine perfusion have markedly enhanced graft preservation, reduced complications, and allowed for successful transplantation from donors previously deemed marginal.

Successful donor-recipient matching is achieved by careful consideration of ABO blood group compatibility and size (especially in pediatric and small adult recipients), and human leukocyte antigen (HLA) typing, when possible. Additional factors such as donor age, liver function tests, cold ischemia time, and presence of anatomical variants further guide allocation and perioperative planning. The integration of comprehensive donor risk indices, such as the Donor Risk Index (DRI), aids transplant teams in stratifying grafts and predicting post-transplant outcomes, thus supporting clinical decision-making.

In summary, deceased donor selection requires multidisciplinary assessment that balances recipient safety, organ utility, equitable allocation, and the risks associated with broader donor acceptance.

iii. Living Donor Follow-up

Post-donation monitoring protocols require structured lifelong follow-up addressing both physical and psychological outcomes. Early monitoring includes liver function tests and assessment for bile leaks, bleeding, infection, thromboembolism, vascular complications, and, rarely, liver failure. Longer-term surveillance should evaluate biliary or vascular abnormalities, incisional hernia, persistent fatigue, chronic pain, metabolic changes, and occult liver dysfunction.

Psychosocial follow-up is equally important, particularly when the recipient experiences graft failure or death. Donors should be assessed for anxiety, depression, adjustment difficulties, or regret, using structured interviews or validated tools where available. Access to dedicated psychosocial support should form part of routine donor care.

With appropriate selection and follow-up, living liver donors generally have survival comparable to the general population, and most report high satisfaction and willingness to donate again. Centralized registries and national reporting systems are essential for identifying late complications and refining donor selection, surgical practice, and long-term monitoring. Multidisciplinary follow-up therefore remains fundamental to maintaining the safety and ethical integrity of LDLT programs.

Pretransplant Evaluation of Recipient

i. Routine Tests

Multidisciplinary pretransplant evaluation aims to confirm transplant eligibility, identify modifiable risks, and reduce perioperative complications. The standard evaluation protocol begins with a comprehensive laboratory work-up, including liver biochemistry and synthetic function, renal function and electrolytes, complete blood count, and metabolic parameters. Abdominal imaging, typically with ultrasound and multiphasic CT or MRI, evaluates the liver parenchyma, vasculature, and biliary system, and screens for hepatocellular carcinoma, portal vein thrombosis, and other structural abnormalities.

Cardiopulmonary evaluation generally includes electrocardiography and transthoracic echocardiography, with stress testing, myocardial perfusion imaging, or coronary assessment in selected patients. Chest imaging, pulse oximetry, and pulmonary function testing are used to identify underlying pulmonary disease. Arterial blood gas analysis, contrast echocardiography, or right-heart catheterization may be required when hepatopulmonary syndrome or portopulmonary hypertension is suspected.

Infectious disease screening is mandatory for all candidates and includes serologies for HBV and HCV, HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and screening for tuberculosis, syphilis, and, where relevant, endemic infections (e.g., Strongyloides, Chagas disease). Identification of active infection is a contraindication to transplantation until adequately treated. Vaccination status should also be reviewed, and indicated vaccines—including hepatitis A and B, pneumococcal, influenza, and varicella vaccines—should ideally be administered before immunosuppression.

Nutritional status, frailty, substance use, psychological health, treatment adherence, and social support must also be assessed because they influence perioperative and long-term outcomes. Evaluation therefore requires collaboration among hepatology, transplant surgery, cardiology, infectious diseases, nutrition, and psychosocial care teams.

ii. Treatment Targets for Underlying Liver Disease

Viral Hepatitis (HBV and HCV)
For patients with chronic HBV infection, achieving and maintaining viral suppression is essential before LT using potent nucleos(t)ide analogues, such as entecavir or tenofovir, which minimize the risk of HBV reactivation and graft reinfection after LT. Prophylactic strategies —including hepatitis B immunoglobulin in selected cases— may be individualized according to virological risk profile and institutional practice.

Direct-acting antivirals (DAAs) achieve virological response in nearly all patients with HCV, and may be administered pre- or post-transplant. HCV-positive grafts can also be used in HCV-negative recipients when prompt post-transplant antiviral therapy is available, thereby expanding the donor pool.

Alcohol-Associated Liver Disease (ALD)
Alcohol-related liver disease is a leading indication for LT in Europe and North America. Pretransplant management emphasizes a comprehensive psychosocial evaluation and multidisciplinary care, including addiction specialists, psychiatry, and social work. Although traditional protocols required a 6-month period of abstinence before transplantation, recent evidence and guidelines support early transplantation in carefully selected patients with severe ALD who fail medical therapy. Selection criteria focus on psychosocial stability, family support, absence of comorbid psychiatric illness, and demonstrated motivation for sustained abstinence. Continued addiction care and relapse monitoring are essential after transplantation.

Autoimmune Liver Diseases (AILD)
In AIH, PBC, and PSC, the diagnosis should be confirmed and disease-specific treatment optimized before LT. Patients with acute severe AIH should receive early corticosteroid therapy, but nonresponders and those with progressive hepatic failure require prompt transplant referral. Adherence, social support, associated diseases, and the risk of post-transplant recurrence should be assessed in all patients with autoimmune liver disease.

iii. Sarcopenia, Cardiomyopathy Evaluation

Assessment of sarcopenia and cardiomyopathy has become an integral component of pretransplant evaluation in candidates for LT, as both conditions have significant negative impact on perioperative risk and long-term outcomes.

Sarcopenia (defined as the loss of skeletal muscle mass and function) is highly prevalent in patients with advanced liver disease and is associated with increased waitlist mortality, higher rates of postoperative complications, and impaired quality of life.²⁷ Guidelines recommend systematic screening for sarcopenia using objective tools such as cross-sectional imaging (e.g., CT or MRI to quantify psoas muscle area), handgrip strength, and functional performance tests.  Identification of sarcopenia should prompt prehabilitation interventions, including tailored nutritional support, resistance exercise programs, and management of underlying factors such as chronic inflammation or hormonal disturbances. Early recognition and intervention can improve physical function and potentially enhance transplant candidacy and post-transplant recovery.²⁸

Cardiomyopathy and, more broadly, cardiac dysfunction is another critical aspect of pretransplant assessment. Patients with cirrhosis are at increased risk for cirrhotic cardiomyopathy, characterized by blunted cardiac contractility, diastolic dysfunction, and electrophysiological abnormalities, which may be unmasked by the hemodynamic shifts of transplantation. The guidelines advise a comprehensive cardiac work-up, including echocardiography for structural and functional assessment, electrocardiography for arrhythmias or conduction defects, and, when indicated, stress testing or advanced imaging to evaluate for coronary artery disease or high-risk features. Early detection of cardiomyopathy or significant cardiac disease may necessitate further evaluation, medical optimization, or, in some cases, consideration of combined heart-liver transplantation.²⁹

Early Complications

i. Surgical Complications: Vascular and Biliary Complications

Vascular complications occur in approximately 7% of LT recipients and can lead to early graft loss and mortality, particularly if diagnosis is delayed. Early detection (primarily using doppler ultrasound, and when needed, angio-CT or angiography) is critical for optimal management.³⁰

Hepatic artery thrombosis (HAT) is the most frequent arterial complication and remains the leading cause of graft failure. Risk factors include endothelial injury, extended cold ischemia, transfusions, hypercoagulability, technical problems and pediatric transplantation. Early HAT can present with fever, mental changes, and rapid liver enzyme elevation, often leading to graft ischemia, biliary necrosis, abscesses, or multiorgan failure. Without intervention, graft failure and high mortality are likely. Early detection protocols such as serial doppler ultrasounds are recommended, and endovascular interventions (thrombolysis/thrombectomy) are increasingly successful.³¹ Other arterial issues include hepatic artery stenosis, hepatic artery pseudoaneurysm (rare but life-threatening), and arterial conduit occlusion. Stenosis is treated with angioplasty or stenting, while pseudoaneurysm may require surgical intervention or retransplantation if rupture occurs.

Portal vein complications such as portal vein thrombosis or stenosis are often due to technical problems and low portal flow. These may present with acute liver failure or portal hypertension. Treatment may involve anticoagulation, angioplasty, or surgical revision. Hepatic vein or inferior vena cava outflow obstruction can also occur, especially in the early postoperative period, requiring angioplasty, stenting, or occasionally surgical revision.³²

Biliary complications are frequent after liver transplantation, with reported incidences ranging from 2% to 19%. They are major causes of post-transplant morbidity and can be life-threatening.³¹ Bile leaks commonly develop in the first month after transplantation, with risk factors including technical errors, ischemic injury, and T-tube placement. Most leaks can be managed conservatively or with endoscopic or radiological drainage, but surgical revision is occasionally necessary. Biliary strictures are the most common biliary issue post-transplant, particularly extrahepatic anastomotic strictures, which typically present within the first year. Endoscopic management with ERCP and stenting is the preferred first-line therapy, with surgery reserved for refractory cases. Intrahepatic biliary strictures (ischemic cholangiopathy) are especially associated with ischemic injury, prolonged preservation, or arterial problems (e.g., HAT), and are more frequent after DCD transplantation. These strictures are difficult to treat and often result in the need for retransplantation.

Machine-perfusion techniques may reduce ischemic injury, but close postoperative surveillance and rapid intervention remain essential because vascular and biliary complications may initially present with subtle clinical findings.

ii. Hyperacute and Acute Rejection

Hyperacute rejection is a rare but catastrophic complication that manifests within hours of transplantation triggered by preformed recipient antibodies directed against donor antigens, most often in the context of ABO blood group incompatibility or pre-existing anti-donor HLA antibodies. Rapid complement activation and endothelial injury cause diffuse vascular thrombosis and immediate graft failure. Clinically, hyperacute rejection presents with signs indistinguishable from severe ischemic injury, with coagulopathy, hemodynamic instability, and rapid graft failure. Due to its fulminant course, urgent re-transplantation is typically the only therapeutic option. Improved compatibility testing and antibody screening have markedly reduced its incidence.

Acute rejection occurs in approximately 15–25% of recipients, most commonly during the first two to six weeks, although it may develop later. It is predominantly T-cell mediated and is associated with inadequate immunosuppression, younger age, and autoimmune or viral liver disease. Calcineurin inhibitors have substantially reduced its frequency and severity.³³ Patients may present with nonspecific symptoms such as fever, malaise, right upper quadrant pain, jaundice, and altered liver biochemistry, especially elevation of transaminases and cholestatic enzymes. Diagnosis relies on a combination of clinical suspicion, laboratory findings, and most definitively histological confirmation via liver biopsy, which typically reveals portal inflammation, bile duct damage, and endothelitis. The percutaneous or transjugular approach may be employed depending on coagulopathy and patient stability. First-line therapy consists of high-dose corticosteroids along with intensification of baseline immunosuppressive regimens. The majority of cases respond to standard therapy, but steroid-resistant rejection may require additional immunosuppressants such as mycophenolate mofetil or anti-thymocyte globulin.

iii. Infections

Infections remain a major cause of post-transplant morbidity and mortality. Risk is determined by the intensity of immunosuppression, surgical complexity, high MELD score, prolonged intensive care, retransplantation, invasive procedures, and prior antimicrobial exposure. Bacterial infections are the most prevalent, accounting for up to 70% of post-OLT infections especially in the first month postoperatively when nosocomial pathogens, surgical site infections, and device-related infections predominate. The growing challenge of multidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), and Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, has complicated management and increased mortality, particularly among patients with prior antibiotic exposure or invasive procedures.

Invasive fungal infections, notably candidiasis and aspergillosis, are more common among high-risk patients especially those requiring retransplantation, prolonged ICU care, or reoperation. Prophylactic antifungal regimens and early intervention with echinocandins or azoles have improved outcomes, yet mortality rates remain significant in invasive cases. Viral pathogens, including cytomegalovirus (CMV), Ebstein-Barr virus (EBV), herpes simplex virus (HSV), and varisella zoster virus (VZV), pose ongoing threats, particularly within the first six months, and often manifest as systemic or graft-complicating disease. In particular, CMV is associated with direct allograft injury, chronic rejection, and increased susceptibility to other opportunistic infections. Antiviral prophylaxis or pre-emptive viral-load monitoring is standard practice. Latent infections such as tuberculosis, strongyloidiasis, and toxoplasmosis must be screened for and treated pre-transplant in endemic populations to prevent life-threatening reactivation after the transplantation.³⁴

Long Term Follow-up of Transplanted Patients

i. Immunization

Liver transplant recipients have an increased risk of vaccine-preventable infections complications because of chronic immunosuppression and pre-existing cirrhosis-associated immune dysfunction. The principle of vaccination strategy is to maximize protection against vaccine-preventable diseases, recognizing that both innate and adaptive immune responses are attenuated not only as a result of immunosuppressive therapy but also due to pre-existing cirrhosis-associated immune dysfunction (CAID). Importantly, live attenuated vaccines are generally contraindicated after LT because of the risk albeit theoretical of vaccine-derived infection. Recombinant and inactivated vaccines remain the mainstay. Administration of all indicated vaccines should ideally be completed prior to transplantation. Despite concerns, real-world evidence indicates that vaccines including those for hepatitis A and B, pneumococcus, influenza, and COVID-19 are safe in LT recipients, with serious adverse events and episodes of allograft rejection being exceedingly rare.

Indeed, the responses to vaccines such as hepatitis B, hepatitis A, pneumococcus, influenza, and COVID-19 are frequently suboptimal, and vaccine efficacy diminishes further with advancing liver disease and in the immediate post-LT setting. Although blunted, the immune responses are still clinically meaningful, and observational studies demonstrate significant reductions in disease incidence, complications, and mortality in vaccinated LT cohorts. Strategies to improve vaccine immunogenicity in LT recipients include using newer adjuvanted formulations (such as Heplisav-B for HBV), booster dosing, and optimizing vaccine timing (ideally at least 3 months post-LT if not done pre-LT). Importantly, COVID-19 vaccination has proven highly effective in reducing symptomatic infection, severe disease, and mortality, and current guidelines endorse a complete primary series with an mRNA vaccine and regular boosters for all LT patients.

Given persistent gaps in vaccine uptake often due to provider hesitancy, lack of awareness, or unfounded safety concerns, transplant teams must prioritize pre-LT immunization and ensure that post-LT patients remain up to date on recommended schedules.³⁵

ii. Recurrence

Recurrence of the underlying disease (e.g., HBV, HCV, AILD) is a known risk and requires long-term monitoring. Antiviral prophylaxis and periodic surveillance are recommended. In autoimmune and metabolic liver diseases, close coordination with hepatology is necessary to promptly detect and manage relapse.

iii. Metabolic Complications

Metabolic syndrome, including post-transplant diabetes, hypertension, dyslipidemia, and obesity, is increasingly prevalent and impacts both patient and graft survival. Long-term management includes dietary counseling, pharmacologic therapy, and lifestyle interventions.

iv. Malignancy Screening

The risk of de novo malignancy, particularly skin cancers and post-transplant lymphoproliferative disorder (PTLD), is elevated due to chronic immunosuppression. Regular screening (dermatologic, colonoscopic, and imaging as indicated) is essential for early detection and improved outcomes.

Conclusion

LT is a life-saving method and standard of care in patients with liver diseases. However, knowledge-based and delicate evaluation of both recipient and donor has paramount importance for a successful LT. The follow up of living donors and all liver transplantation recipients must be according to updated protocols. Each transplantation center might have their own approaches determined by their experience and facilities, but national and international hepatology societies must be guiding and supervising them.

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