Liver Transplantation

Anatomy and Physiology

The liver, the largest organ in the human body, lies beneath the eighth through twelfth ribs on the right side.[5] Anatomically, it consists of 4 lobes: the right and left lobes (divided by the falciform ligament), the quadrate lobe, and the caudate lobe. However, these are not true functional lobes; functionally, the liver is divided into right and left lobes by the Cantlie line, which runs through the gallbladder bed and the notch of the inferior vena cava.[5][6] Each lobe is subdivided into 2 segments, and these are further divided into subsegments based on hepatic arterial and portal venous blood supply, biliary drainage, and hepatic venous outflow. The segments are numbered 1 to 8 in the Couinaud classification, with the caudate lobe designated as segment 1 and the rest numbered clockwise.[7]

The liver’s unique dual blood supply comes from both systemic (hepatic artery) and portal (portal vein) circulations.[8] The liver’s functional unit, the hepatocyte, is organized into zones: zone I (periportal) receives the highest oxygenated blood and focuses on oxidative metabolism; zone II (midzonal) lies between zones I and III; zone III (pericentral) is the farthest from the blood supply and specializes in drug and toxin detoxification.[8] Importantly, bile and blood flow in opposite directions, with bile exiting the liver and blood entering to nourish it.[8] Typically, the liver’s volume comprises about 60% from the right lobe and 40% from the left, with the left lateral segment alone accounting for roughly 20%.[9][10]

Indications

LT is indicated in cases of acute or chronic end-stage liver disease where medical therapy has failed.[11] Patients who experience hepatic decompensation, such as hepatic encephalopathy, variceal hemorrhage, or ascites, should first undergo medical management. If they are potential LT candidates, a thorough transplant evaluation should be initiated.[11] Notably, up to 80% of LTs are performed for decompensated cirrhosis.[12] Patients with cirrhosis are typically classified using the Child-Turcotte-Pugh score, which integrates both biochemical markers (serum albumin, serum bilirubin, and International Normalized Ratio [INR]) and clinical findings (ascites and encephalopathy) to estimate prognosis and guide management.[13]

Model for End-Stage Liver Disease

The model for end-stage liver disease (MELD) score was originally developed to predict survival following the transjugular intrahepatic portosystemic shunt procedure. Still, it was later found to be an effective predictor of survival in patients with cirrhosis and has become widely accepted as a key tool for prioritizing organ allocation for LT.[14][15] The MELD score estimates 3-month mortality by calculating serum creatinine, bilirubin, and INR levels. For pediatric patients, a modified version—the pediatric end-stage liver disease score—replaces creatinine with factors like age, albumin, and failure to thrive.[11] In 2016, the Organ Procurement and Transplantation Network updated MELD to include serum sodium (eg, MELD-Na), as hyponatremia is a common and important marker of cirrhosis severity.

A strong indication for LT evaluation arises when individuals with cirrhosis develop complications such as ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular dysfunction, typically reflected by a MELD score 15 or greater. However, MELD has known limitations, as it does not account for complications like refractory ascites, recurrent gastrointestinal bleeding, chronic encephalopathy, hepatopulmonary syndrome, portopulmonary hypertension, or severe pruritus—all of which significantly increase mortality risk. To address these gaps, MELD exception points are granted for conditions such as hepatocellular carcinoma, Budd-Chiari syndrome, familial amyloidotic polyneuropathy, cystic fibrosis, hereditary hemorrhagic telangiectasia, polycystic liver disease, primary hyperoxaluria, recurrent cholangitis, rare metabolic diseases, and certain malignancies, including cholangiocarcinoma, to ensure fair access to transplantation.[16] Additionally, newer scoring systems—including MELD-Na, integrated MELD, delta MELD, and the recently developed MELD 3.0 (which incorporates sex, serum albumin, and reweighted variables)—aim to improve prognostic accuracy, particularly for women and patients with lower MELD scores.[17]

Specific Indications for LT

Acute liver failure 

Patients with acute liver failure (ALF) rapidly deteriorate and develop severe liver dysfunction, elevated bilirubin, aminotransferases, encephalopathy, and coagulopathy (above 1.5). Acetaminophen is responsible for almost half the cases of ALF in the United States.[18] ALF is considered a strong high (1a) indication for LT as it supersedes all other etiologies of chronic liver disease and takes precedence on the United Network for Organ Sharing waiting list. To achieve priority on the waiting list as an (1a) ALF case, the following criteria must be met:

• Intensive care unit admission
• On ventilatory support
• Requiring hemodialysis
• Elevated INR above 2
• Development of hepatic encephalopathy within 8 weeks of the onset of symptoms

Compared to LT due to chronic disease, the 1-year survival in LT due to ALF is worse, but with higher survival rates following the first year.[11] 

Acute-on-chronic liver failure 

This condition has a very high mortality without transplantation, but outcomes are influenced by multiple factors related to the recipient, intensive care unit (ICU) course, and donor characteristics. Advanced age, particularly in those older than 60, and comorbidities such as diabetes, cardiovascular disease, and a high age-adjusted Charlson Comorbidity Index (≥6) are associated with poor posttransplant survival.[19] Frailty and sarcopenia also impact prognosis, with severe frailty being a contraindication.[20] ICU-related factors, including respiratory failure (PaO₂/FiO₂ ≤200), mechanical ventilation, renal replacement therapy, and vasopressor use, predict worse outcomes, although stabilization before LT improves survival.[21] The timing of LT is critical, with study results suggesting optimal outcomes when performed within 7 to 15 days of ICU admission. Pretransplant infection with multidrug-resistant organisms, active sepsis, and profound leukopenia (<500/mm³) are absolute contraindications. Several risk models, such as the transplantation for acute-on-chronic liver failure (ACLF) grade 3 model and the Sundaram ACLF-LT-mortality model, have been proposed to predict mortality after LT in ACLF; however, clinical judgment remains paramount in selecting candidates for transplantation.[22][23]

Metabolic dysfunction-associated steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is considered among the top indications for LT.[24] MASH is included in the spectrum of nonalcoholic fatty liver disease, ranging from steatosis alone to NASH with accompanying cirrhosis. These liver diseases are linked to metabolic syndrome with increased body mass index and obesity.[25] Because, until now, there was no effective treatment for MASH or fibrosis (recently, drugs have shown fibrosis reversal in MASH), LT has been rising due to NASH.[26][27] Also, it has been noted that patients diagnosed with MASH with and without cirrhosis have an increased risk of developing hepatocellular cancer (HCC). Still, this condition should not be considered an indication for LT without cirrhosis and a high MELD score.[28]

Alcohol-related liver disease 

This condition is currently the most common indication for LT.[29] Patients with alcohol use disorder should be referred for psychosocial and psychiatric support before LT to ensure at least 6 months of abstinence and prevent relapses, especially since these relapses result in delisting the patient from the waiting list.[30][31] In cases of acute alcoholic hepatitis that do not respond to medical therapy, LT may be required while less than 6 months of abstinence is achieved.[32]

Hepatitis B 

This infection previously resulted in increasing numbers of chronic liver disease, but with the use of hepatitis B immunoglobulins and the introduction of antivirals, hepatitis B has resulted in decreased rates of LT.[33] Additionally, treating and controlling the infection is crucial to prevent reinfection after transplantation. Hepatitis B can be complicated by HCC, which serves as an important indication for LT.[11]

Chronic hepatitis C 

Cirrhosis due to chronic hepatitis C infection was the most common indication for LT until 2015.[29] Since 2016, hepatitis C infection has become the third most common indication, surpassed by alcohol-related liver disease and NASH.[29] To prevent reinfection and subsequent graft failure after LT, eradication of chronic hepatitis C infection before transplantation was historically critical.[34] However, the emergence of novel direct-acting antiviral agents over the past decade has transformed management, now enabling the effective treatment of chronic hepatitis C infection even after LT.[34] 

Autoimmune hepatitis 

This infection can lead to liver cirrhosis and failure, even with long-term corticosteroids and immunosuppression therapy. LT is indicated in ALF secondary to autoimmune hepatitis (AIH) or cases of chronic decompensated cirrhosis due to AIH.[35] Poor outcomes and the need for LT can be predicted by the following observations: young age, a MELD score higher than 12, multiple relapses, and a delayed downward slope of aminotransferase after treatment.[36]

Primary biliary cirrhosis 

Patients with decompensated cirrhosis or severe pruritus refractory to other medical interventions require LT. Over the years, the need for LT has decreased with the use of ursodeoxycholic acid to treat primary biliary cirrhosis, which slows disease progression.[37]

Primary sclerosing cholangitis

Since there is no effective medical therapy for PSC, LT is considered an effective treatment modality among patients with the decompensated disease or those who develop perihilar cholangiocarcinoma (within certain criteria) or recurrent bouts of bacterial cholangitis.[38] PSC is associated with inflammatory bowel disease; therefore, frequent colonoscopy is necessary to screen for colorectal cancer before and after LT.[39][40]

HCC

Patients with HCC must meet the Milan criteria to be eligible for LT. This criterion includes:

• One tumor less than 5 cm in diameter, or 3 tumors each having a diameter less than 3 cm, that must be confirmed by computed tomography (CT) or magnetic resonance imaging
• Without any metastasis documented by chest CT and bone scan
• Absence of major vessel involvement
• An unresectable tumor [41]

Patients with HCC usually have a normal liver function, and their MELD score is usually normal or low. Therefore, they undergo an MELD exception to obtain a score that allows them to be prioritized on the waiting list for LT.[42]

Cholangiocarcinoma

LT is considered in the management of patients with early-stage cholangiocarcinoma with nonresectable perihilar lesions (<3 cm in diameter) or underlying parenchymal liver disease such as primary sclerosing cholangitis with cirrhosis. In addition to the tumor criteria, LT should be performed in combination with neoadjuvant chemotherapy regimens to ensure higher survival rates than those achieved previously without neoadjuvant therapy.[11] Patients are granted a MELD exception if they meet the eligibility criteria on the United Network for Organ Sharing waiting list.[43]

Metabolic liver diseases

• Wilson disease
  • LT is indicated in patients with ALF due to Wilson disease or in cases of decompensated cirrhosis that have failed all medical therapies.[44] LT in Wilson disease has great outcomes, even in cases with metabolic complications like renal failure, which resolves after LT.[45] Parents of patients who are heterozygous can serve as living donors for transplantation with successful results.[46] Other cirrhosis-related complications, such as hepatopulmonary syndrome and portopulmonary hypertension, are also indications for LT.
• Alpha-1 antitrypsin deficiency 
  • This disease is usually diagnosed in adults without any previous history of liver disease. LT is considered the main and only treatment modality for decompensated liver disease secondary to alpha-1 antitrypsin deficiency.[47] There is no risk of recurrence due to the expression of the donor's alpha-1 antitrypsin gene after LT. Patients should undergo screening for lung disease by chest imaging and pulmonary function testing.[48]
• Hereditary hemochromatosis
  • LT is indicated in decompensated cirrhosis or in patients with HCC who have hereditary hemochromatosis (HH). Cirrhosis, due to HH, accounts for the highest risk of developing HCC among all other causes of cirrhosis.[49] The use of iron reduction therapy through phlebotomy before LT has resulted in improved outcomes posttransplantation.[50]
• Familial amyloid polyneuropathy
  • LT has proven effective in familial amyloid polyneuropathy due to a mutation in the transthyretin gene. LT is most effective in patients younger than 50 because LT neither improves nor reverses neurological symptoms, but rather prevents disease progression.[46] Also, patients with hereditary renal amyloidosis inherited as an autosomal dominant gene usually benefit from liver and renal transplantation. LT doesn't seem to affect the ocular or cardiac effects of amyloidosis.[51]
• Primary hyperoxaluria type I 
  • This is an autosomal recessive defect that results in a deficiency of alanine: glyoxylate aminotransferase in the liver, impairing the metabolism of glyoxylate and leading to the overproduction of oxalate.[52] This disease usually leads to end-stage renal disease at 20 to 40 years. LT is effective in curing the disease.[53] Both liver and renal transplants are reported to be successful in patients with end-stage renal disease and liver failure, and improve cardiomyopathy in these patients.[54]
• Other metabolic liver diseases that have indications for LT include:
  • Cystic fibrosis 
  • Glycogen storage diseases

Graft failure 

This is a significant indication for liver retransplantation. Hyperacute rejection, which causes hepatic artery thrombosis and graft failure, typically occurs immediately after surgery. Although retransplantation can be done, the outcomes are worse than those of the primary transplant.[11]

Contraindications

While the indications for LT are becoming broader, the contraindications are becoming fewer due to advancements in LT techniques. Still, LT has some absolute and relative contraindications.

Absolute Contraindications

• MELD score of less than 15 (without MELD exception)
• Advanced cardiac or pulmonary disease
• Active alcohol or illicit substance use
• HCC or perihilar cholangiocarcinoma with metastatic spread
• Untreated septic shock or sepsis
• An anatomic abnormality that precludes LT
• Intrahepatic cholangiocarcinoma
• Extrahepatic malignancy, unless the patient is tumor-free for more than 2 years, with a low probability for recurrence
• Hemangiosarcoma
• Fulminant hepatic failure leading to sustained intracranial pressure above 50 mm Hg or cerebral perfusion pressure less than 40 mm Hg
• Lack of psychosocial support and severe psychological disease
• Severe pulmonary hypertension [11][55]

Although acquired immunodeficiency syndrome used to be considered an absolute contraindication for LT, recent centers are selecting patients with human immunodeficiency virus alone as candidates for LT.[56]

Relative Contraindications

• General debility
• Persistent noncompliance
• Advanced age
• Extensive previous abdominal surgery
• Extensive portal or mesenteric thrombosis

Personnel

To deliver the highest quality of patient care in LT, a coordinated interprofessional team approach is essential. In the pretransplant phase, evaluation by a hepatologist, transplant surgeon, and transplant nurse coordinator is critical to assess the patient’s medical status, review necessary vaccinations, medications, and required lifestyle modifications, explain the surgical options, and provide a detailed overview of the posttransplant phase—including immunosuppression, potential complications, and expected outcomes. Psychiatric assessment by a transplant psychiatrist is important to address any issues of alcohol or substance abuse and to ensure the patient has appropriate insight and preparedness for the procedure and its consequences. Social workers play a key role in evaluating the patient’s social support system, especially to ensure adequate posttransplant home care and adjustment. Additionally, a specialized administrative team works to secure insurance coverage for the transplant surgery and long-term immunosuppressive medications. Nutritionists are essential both before and after transplant to optimize nutritional status and guide dietary changes, particularly in patients managing chronic comorbidities such as diabetes, hypertension, and hyperlipidemia.[11]

Preparation

The preoperative evaluation must address numerous important aspects and health concerns in LT candidates. This evaluation should include a detailed and comprehensive history and physical examination, as well as laboratory tests and imaging studies, to conduct a full systematic review of the patient and manage them accordingly. An extensive review is available at the American Association for the Study of Liver Disease's Practice Guidelines website. Below is a summary of those guidelines:

• Obesity
  • Patients should be evaluated for increased body mass index (BMI) as it increases the perioperative risks and reduces survival in patients with LT.[57] Patients with a BMI of 30 kg/m² or higher should be referred to a dietitian. A BMI above 40 kg/m² is considered a relative contraindication for an LT.
• Coronary artery disease
  • Perioperative cardiac risk assessment is crucial. All patients should undergo an electrocardiogram, as well as cardiac stress testing (especially if the patient is 50 or older), which can be either physical or chemical stress testing. If patients were found to have stenosis, coronary revascularization should be done before LT.[58]
• Age
  • Although the prognosis of transplant in patients older than 70 is not as good as in younger patients, older age is not a contraindication to LT in patients without or with controlled comorbidities.[59] Recently, it has been demonstrated that carefully selected older adult candidates can benefit from LT, thereby restoring their expected lifespan.[60]
• Pulmonary hypertension
  • When the mean pulmonary artery pressure (MPAP) is equal to or above 25 mm Hg and is associated with portal hypertension (HTN), the condition is referred to as portopulmonary HTN. Moderate to severe portopulmonary HTN is associated with a higher mortality rate after LT; the mortality rate can reach 100% if MPAP is above 50 mm Hg.[61][62] Pulmonary HTN is diagnosed by echocardiography, and if severe, right heart catheterization is a gold standard test to confirm the diagnosis. Vasodilators treat this condition, and LT is indicated in patients who respond to vasodilator therapy, reducing MPAP to less than 35 mm Hg and pulmonary vascular resistance less than 400 dynes/s/cm.[11]
• Hepatopulmonary syndrome
  • In this syndrome, patients with chronic liver disease experience shortness of breath and hypoxemia, especially those with portal HTN. This is due to microvascular dilation of the pulmonary vessels, resulting in an intrapulmonary shunt.[63] Patients should be screened with pulse oximetry prior to LT.[64] Affected patients may require a longer recovery period and long-term supplemental oxygen posttransplant, depending on the severity of hepatopulmonary syndrome.[65] Hepatorenal syndrome is not a contraindication for LT. 
• Renal dysfunction
  • Patients with renal disease must be diagnosed before LT, as renal dysfunction significantly increases mortality.[66] Simultaneous liver and kidney transplants are indicated if a patient has a glomerular filtration rate less than 30 mL/min, indicating chronic kidney disease or acute kidney failure that requires dialysis for more than 6 weeks. This is also indicated in case severe glomerulosclerosis is present.[67] Hepatorenal syndrome is not a contraindication for LT and is sometimes the treatment of choice. Some forms of kidney disease, such as immunoglobulin A nephropathy, may improve after LT.[68]
  • The United Network for Organ Sharing renal safety net ensures priority access to kidney transplantation for LT recipients who develop end-stage renal disease within 12 months post-LT, promoting equitable organ allocation. This policy is particularly relevant for patients with hepatorenal syndrome, who frequently experience severe pretransplant renal dysfunction, with some progressing to persistent kidney failure despite hepatic recovery. By facilitating timely kidney transplantation for those ineligible for simultaneous liver-kidney transplantation, the safety net aims to mitigate long-term dialysis dependence and improve posttransplant outcomes.[68]
• Cigarette smoking
  • Smoking increases mortality among LT recipients due to cardiac disease and also increases the risk of hepatic artery thrombosis.[69][70] Smoking should be prohibited, and many hospitals consider smoking cessation a requirement to be listed for LT.[11]
• Extrahepatic malignancy
  • Patients should undergo all age-appropriate screening before undergoing LT. If they have any increased risk factors for a specific cancer, they should undergo further testing for the specific cancer type.[11] Any patient with a previously diagnosed malignancy should be treated and cured before undergoing LT.
• Infectious disease
  • All infectious diseases should be treated effectively before LT. Screening serologies in the blood should include viral infections such as hepatitis A and B (to ensure immunity through vaccination and absence of active infection), cytomegalovirus, Epstein-Barr virus, bacterial infections (including tuberculosis and syphilis), and fungal infections (such as Strongyloides and Coccidioidomycosis). All live attenuated viral vaccines should be administered before LT as they are contraindicated once immunosuppression is initiated after transplantation.[71]
• Nutrition
  • A nutritionist should evaluate patients before undergoing LT, as it is essential to address all nutritional deficiencies related to chronic liver disease and fat malabsorption. Adequate dietary control, particularly regarding other comorbidities such as diabetes mellitus, HTN, and hyperlipidemia, should be emphasized.[72] Sarcopenia is a serious problem in cirrhosis and can be assessed by measuring the skeletal muscle index at the L3 level using CT scan images.[73] The thickness of the psoas muscle also has a prognostic role. Assessment of frailty using simple tools, such as the Liver Frailty Index, is recommended before transplantation, followed by prehabilitation measures. Evaluation of osteoporosis using bone densitometry is also essential and should be performed for all patients.[74]
• Bone disease
  • Densitometry, vitamin D, and calcium levels should be obtained before LT in all candidates. Osteoporosis is relatively common in all patients with chronic liver disease due to malabsorption of vitamin D and in cases of autoimmune hepatitis due to corticosteroid use.[75]
• Human immunodeficiency virus
  • Patients affected by the condition can be considered candidates for LT only if their CD4 counts are above 100 µL and their viral load is undetectable before the procedure. Human immunodeficiency virus is not considered a contraindication to LT due to the advent of effective antiretroviral therapy.[11]
• Psychological evaluation
  • LT candidates must be evaluated for any psychiatric disorders that might affect their prognosis, compliance with medication, and medical directives. Their social support systems and caregiver availability should also be assessed, especially in patients with encephalopathy.[11] For example, patients who have depressive symptoms, mainly in the immediate postoperative period, usually have a poor outcome after LT.[76] Substance use should also be carefully evaluated.[77]
• Portal vein thrombosis 
  • This is not an absolute contraindication to transplantation. However, a dynamic 3-phase CT scan should be performed pretransplant in all candidates to assess the extent and severity of thrombosis. Extensive portal vein thrombosis (PVT) involving the entire splenoportal axis may pose significant surgical challenges and could serve as a contraindication to LT. Careful preoperative evaluation is essential to determine the feasibility and potential need for surgical or interventional strategies to manage PVT in transplant candidates.[78]

Technique or Treatment

Any LT procedure consists of 2 main components: the donor and the recipient. Recipient operations involve complete removal of the patient’s native liver following dissection of the hepatic ligamentous attachments and hilar structures, with the inferior vena cava (IVC) encircled to secure blood control. Donors may be either deceased or living, as detailed below:

• Living donor liver transplantation
  • Initially reserved for pediatric cases, living donor liver transplant is now also performed in adults due to the rising demand and shortage of deceased donor organs.[79] Unlike whole grafts from deceased donors, living donor grafts are partial and involve smaller hepatic arteries, hepatic veins, and portal veins, requiring careful dissection and precise implantation. Adequate space is created by incising along the hepatic vein’s sides to enable proper arterial, portal, and biliary reconstruction.[80] The anastomoses are performed sequentially: hepatic vein (ensuring sufficient length), portal vein, hepatic artery (challenging due to short tributaries), and finally, duct-to-duct bile duct anastomosis.[81] Living donor grafts may include the left lateral sector (approximately 20% of liver volume), the left lobe (approximately 40%), or the right lobe (approximately 60%). In some cases, dual grafts (2 left lobes from 2 donors) are implanted into 1 recipient.[55] Donors undergoing hepatectomy typically receive a right subcostal incision extending into the midline, sparing dissection of the rectus muscles on both sides.[82] For right lobe donations, the left lobe should be secured to the anterior abdominal wall before wound closure.[83]
• Deceased donor liver transplantation
  • Whole LT is the most common approach. Brain-dead donor transplantation uses grafts from donors with confirmed brain death, while donation after cardiac death involves graft procurement after irreversible cardiac arrest. The donor’s liver is usually prepared separately. Once the recipient’s surgical field is ready, the donor liver is brought in and anastomosed, beginning with the suprahepatic IVC, followed by the infrahepatic IVC, and then the portal vein. Once these connections are complete, clamps are removed, allowing the portal vein to initiate blood inflow and perfuse the liver. The hepatic arteries are connected near the gastroduodenal artery anastomoses, and finally, the bile duct is reconstructed.[15] 
  • Domino LT is primarily used in familial amyloid polyneuropathy (FAP), where the native liver (which functions normally but carries the genetic defect) is transplanted into another recipient, typically older than 55, to reduce the risk of disease transmission. This requires precise bench reconstruction of suprahepatic veins, as the IVC is preserved in the FAP donor.
  • Partial LT is used when a full graft is unavailable or to address certain metabolic deficiencies, ensuring a graft-to-recipient weight ratio of at least 0.8% to achieve adequate posttransplant function.
  • Auxiliary LT involves implanting a partial graft alongside the native liver to provide temporary support in ALF or to correct metabolic conditions, often in younger patients with viral or autoimmune ALF. This can be performed orthotopically or heterotopically, depending on the clinical context.
  • Split LT enables a single donor liver to be divided between 2 recipients. When shared between an adult and a child, the right lobe (including segment IV) is allocated to the adult, while the left lateral segment (segments II and III) is given to the pediatric recipient. In cases where 2 adults receive a split graft, the liver is divided into 2 hemilivers to ensure sufficient mass for each. The first attempt at split grafting was reported in 2003, where a deceased donor liver was divided, resulting in the right lobe (without the middle hepatic vein) functioning as an allograft, similar to the modified right lobe technique in living donor LT, while the left part retained the IVC and common hepatic artery.[84]

Complications

Complications that occur after LT are classified as either early or late.

Early Complications

These include:

• Primary nonfunction of the liver allograft
• Hepatic artery thrombosis
• Acute cell rejection
• Biliary complications
• Infection

In the first postoperative week, liver enzymes typically trend downward as the graft recovers and begins to regenerate. However, close monitoring is essential, as several serious complications can arise during this critical period. The most serious early complication is primary nonfunction of the liver allograft, which presents immediately after transplantation. Clinically, this is characterized by the absence of bile production or the production of clear bile, accompanied by worsening liver enzymes and rising bilirubin levels. Without urgent retransplantation, the patient’s survival is at extreme risk.

During the first 48 to 72 hours posttransplant, it is common to observe elevated liver enzymes due to graft injury from cold and warm ischemia during organ removal and implantation. However, it is vital to exclude hepatic artery thrombosis in this setting, as this complication often occurs early but can also develop later.[85] Hepatic artery thrombosis may present asymptomatically or with fever and rising liver enzymes, and if untreated, can progress to hepatic ischemia, necrosis, and ischemic cholangiopathy. Severe cases, especially those occurring within the first week, often necessitate urgent retransplantation. Diagnosis is made using Doppler ultrasound.

Acute cellular rejection occurs in up to 50% of LT recipients, typically within the first 2 months after transplantation. Most cases respond well to corticosteroid therapy. For corticosteroid-resistant rejection, antithymocyte globulin is used. A definitive diagnosis of acute cellular rejection is made through liver biopsy, and despite the high incidence, long-term outcomes with appropriate treatment are generally favorable. Biliary complications are also common, with the biliary anastomosis representing the most frequent site of biliary strictures. Management includes endoscopic dilation, stenting, or, in rare cases, surgical revision. Nonanastomotic (ischemic) strictures may develop as a result of hepatic artery thrombosis, ABO blood type incompatibility, prolonged graft ischemia time (either warm or cold), or when using grafts donated after cardiac death.

Finally, infection is a significant early risk due to the required immunosuppression after LT. Opportunistic infections are common and include cytomegalovirus, the most frequent viral infection; Candida species, the most common fungal pathogens; and other serious infections such as Pneumocystis jirovecii, Aspergillus, Nocardia, and Cryptococcus. Additionally, immunosuppressive agents such as tacrolimus and cyclosporine can cause neurologic and renal impairment, as well as the development of hyperglycemia.

Late Complications

The long-term toxic effects of immunosuppressive medications predominantly drive late complications following LT. Late complications are also a result of recurrent disease posttransplant and de novo malignancies. 

The most common late complications include:

• Chronic kidney disease 
• HTN
• Diabetes mellitus 
• Dyslipidemia

Calcineurin inhibitors, when combined with preexisting chronic kidney disease and HTN, significantly contribute to the development of posttransplant renal failure. Management strategies involve strict blood pressure control and either dose reduction or discontinuation of calcineurin inhibitors.[86] Cardiovascular disease risk is markedly elevated in LT recipients due to immunosuppression-related increases in diabetes mellitus, HTN, obesity, and dyslipidemia. When combined with preexisting high-risk lifestyle factors, this leads to a substantial rise in atherosclerotic disease burden.

Bone health complications are also notable, particularly the increased risk of osteoporosis. Long-term corticosteroid use, along with malnutrition and vitamin D deficiency associated with chronic liver disease, exacerbate bone loss. However, this complication has become less frequent due to successful interventions with bisphosphonate therapy and efforts to reduce corticosteroid dosing.[87]

Neurologic impairments are another recognized late complication, most commonly manifesting as tremors, but also including insomnia and paresthesias, primarily as a result of calcineurin inhibitor toxicity. Recurrent liver diseases can occur after transplantation. These include the recurrence of hepatitis C virus and hepatitis B virus infections, both of which can now be effectively managed posttransplant. Additionally, other chronic liver diseases may recur, including nonalcoholic steatohepatitis, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, and hepatocellular carcinoma.

Malignancies that arise de novo are a major long-term cause of mortality in LT recipients.[88] Several factors increase the risk of posttransplant malignancy, including chronic immunosuppression, viral infections, alcohol use, cigarette smoking, and older recipient age. The most frequently observed malignancies in this population include skin cancers, posttransplant lymphoproliferative disease, and anogenital cancers such as cervical, vulvar, and anal cancers.

Clinical Significance

LT is 1 of the most transformative and lifesaving procedures in modern medicine, offering definitive treatment for both acute and chronic end-stage liver disease when medical therapies fail. Transplantation has profoundly reshaped the prognosis of patients with chronic decompensated cirrhosis, due to causes such as alcohol-related liver disease, hepatitis C infection, nonalcoholic steatohepatitis, and autoimmune hepatitis (AIH), as well as acute liver failure from drug-induced injury, viral hepatitis, AIH, or indeterminate causes. Without transplantation, these conditions carry extremely poor prognoses, with mortality rates exceeding 80% in many advanced cases. LT dramatically changes this outlook, providing the possibility of long-term survival, with current 1-year survival rates above 85% and 10-year survival approaching 60% to 70% at experienced transplant centers.

Beyond extending life, LT restores key physiologic and functional capacities, leading to dramatic improvements in quality of life. Following LT, patients often experience resolution of hepatic encephalopathy, ascites, variceal bleeding, and jaundice, along with restoration of appetite, muscle mass, and physical capacity. Many return to work, school, and social engagement, and in children, transplantation supports normal growth, neurodevelopment, and long-term health.

Importantly, advances in living donor LT (LDLT) have further expanded access and improved outcomes. When LDLT was first introduced, its results were inferior to those of deceased donor LT.[89] However, LDLT has since been proven to significantly reduce mortality by shortening waiting list times, particularly in both pediatric and adult populations. East Asian countries, where deceased donor availability remains limited, have played a pivotal role in refining LDLT by developing advanced surgical techniques, improving graft selection, and optimizing portal and hepatic blood flow. These innovations have revolutionized LT worldwide, leading to comparable survival rates between deceased donor LT and LDLT and markedly improving the quality of life of patients with chronic liver disease or acute liver failure, even among those with high MELD scores above 30.[90]

LT has also driven broader innovations in surgery and ethics, including the development of split LT, where 1 donor liver is divided between 2 recipients, and domino transplantation, where livers with metabolic disease are used in select older recipients. Additionally, expanding the donor pool through the use of donation after circulatory death and marginal grafts has improved equitable access to transplantation. However, these advances raise complex ethical questions about consent, allocation, and distributive justice.

Beyond surgery, LT has propelled advances in transplant immunology. The development of calcineurin inhibitors, mechanistic (or mammalian) target of rapamycin inhibitors, and monoclonal antibodies has improved both acute and chronic rejection rates; at the same time, efforts to achieve immune tolerance and implement minimization protocols continue to evolve. The lessons learned from LT immunology extend beyond the liver, benefiting the fields of kidney, heart, and lung transplant as well.

From a public health perspective, LT reduces healthcare system burdens by decreasing hospitalizations for complications of decompensated cirrhosis, lowering the frequency of ICU stays, and minimizing the costs associated with end-stage care. Additionally, recipients who regain health are often able to return to work and participate in their communities, contributing economically and socially. However, the long-term costs of immunosuppressive therapy, cancer surveillance, cardiovascular risk management, and recurrent disease monitoring remain significant and require ongoing attention.

Despite its remarkable success, LT faces major challenges. Organ shortages persist worldwide, leading to high waitlist mortality. Disparities in access to transplantation disproportionately affect minority and socioeconomically disadvantaged populations, and long-term complications—such as chronic kidney disease, cardiovascular disease, metabolic syndrome, and de novo malignancies—remain common. Additionally, recurrent liver diseases such as hepatitis C, hepatitis B, nonalcoholic steatohepatitis, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, and hepatocellular carcinoma can reemerge after transplantation, necessitating vigilant posttransplant monitoring and management.

In conclusion, LT is a life-saving, quality-of-life-transforming intervention that not only improves individual outcomes but also drives innovations in surgery, immunology, and public health. The evolution of techniques such as LDLT, along with advancements in immunosuppression and innovations in graft preservation, will continue to shape the future of LT and extend its life-changing benefits to an even broader patient population.

Enhancing Healthcare Team Outcomes

Effective liver transplantation care requires the seamless integration of skills, strategies, and interprofessional communication among clinicians, nurses, pharmacists, dietitians, social workers, and other healthcare professionals. Clinicians and transplant surgeons lead the complex diagnostic evaluation, surgical planning, and perioperative management, while hepatologists and advanced practitioners, such as nurse practitioners or physician assistants, coordinate the management of chronic liver disease, immunosuppression titration, and long-term follow-up. Nurses play a crucial role in patient education, bedside monitoring, and the early recognition of postoperative complications, thereby ensuring patient safety through vigilant assessment and timely communication. Pharmacists contribute expertise in immunosuppressive drug selection, drug interaction management, and patient education on adherence, which is crucial to preventing rejection and minimizing adverse effects. Dietitians ensure patients maintain appropriate nutritional status before and after transplant, while social workers coordinate psychosocial support, insurance navigation, and home care planning to promote sustained recovery.

To enhance patient-centered care, the liver transplant team must employ clear, structured communication strategies such as multidisciplinary rounds, shared electronic medical records, standardized handoff protocols, and checklists. Regular team meetings facilitate the alignment of care plans, discussion of patient progress, and identification of barriers to adherence or recovery, thereby promoting collaborative problem-solving and effective patient care. Prioritizing patient and family involvement in decision-making ensures that care aligns with individual values, preferences, and goals. Effective coordination reduces medical errors, improves transplant outcomes, minimizes hospital readmissions, and strengthens team performance, ultimately delivering safer, more efficient, and more compassionate care for this vulnerable patient population.