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LiverTransplantation¶

Chapter 356 | Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 356

Key Clinical Points¶

Liver transplantation has evolved from an experimental procedure to a standard life-saving treatment with 1-year survival rates exceeding 90%.
The MELD score (range 6–40) is the primary tool for determining organ allocation; MELD-Na and MELD-3.0 offer improved accuracy.
Tacrolimus is the preferred primary immunosuppressant over cyclosporine due to better safety and more predictable absorption.
Absolute contraindications include uncontrolled extrahepatobiliary infection, active untreated sepsis, life-limiting congenital anomalies, cholangiocarcinoma (except those meeting specific protocols), and advanced cardiopulmonary disease.
Relative contraindications include advanced age, extensive portal vein thrombosis, severe obesity, severe malnutrition/wasting, medical noncompliance, and severe pulmonary hypertension or hypoxemia.
Living-donor transplantation accounts for approximately 1/3 of all pediatric liver transplant procedures but only ~6% of total US transplants in 2023.
Primary graft nonfunction (PGNF), hepatic artery thrombosis (HAT), and biliary complications are the primary post-operative concerns.
Posttransplantation lymphoproliferative disorders (B-cell lymphoma) are associated with immunosuppressive drugs and Epstein-Barr virus (EBV).
Donor organs from individuals up to age 60 are acceptable if they meet specific health criteria (e.g., no infection, no trauma).
Cold ischemic time is ideally limited to 12 hours, though up to 20 hours is possible with UW solution.

DEFINITION & OVERVIEW¶

• Definition: Liver transplantation—the replacement of the native, diseased liver by a normal organ (allograft). • Procedure Type: Orthotopic transplantation is the preferred and most advanced technique. • Success Rates: Improved from ~30% in the 1970s to >90% today due to improved surgical techniques, procurement/preservation, immunosuppression, and better patient selection.

EPIDEMIOLOGY¶

• US Statistics (2022): 9528 total liver allografts; 8925 were deceased donor (94%) and 603 were living donor (6%). • Waitlist Status: As of September 2023, 10,285 patients were on the waiting list. • Living-Donor Trends: ◦ Accounts for approximately one-third of all liver transplantation procedures in children. ◦ Increasing frequency in adults for larger right lobe grafts. ◦ Cannot be expected to solve the donor organ shortage.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Primary Indications: End-stage cirrhosis of all causes, Sclerosing cholangitis, Caroli's disease, and Steatotic liver disease (SLD). • Steatotic Liver Disease (SLD): Includes alcohol-associated liver disease (ALD) and metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). • Viral Hepatitis: ◦ Chronic Hepatitis C: Improved outcomes with Direct-Acting Antivirals (DAA). ◦ Chronic Hepatitis B: Survival improved by HBIg and oral antivirals (entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide). • Other Conditions: Budd-Chiari syndrome (hepatic vein thrombosis), Acute liver failure (ALF) before cerebral edema, and specific nonmetastatic primary hepatobiliary tumors.

CLINICAL FEATURES¶

Indications for Transplantation¶

• Pediatric Indications: Biliary atresia, Neonatal hepatitis, Congenital hepatic fibrosis, Alagille's syndrome, Byler's disease, Inherited disorders of metabolism, Wilson's disease, Tyrosinemia, Glycogen storage diseases, Lysosomal storage diseases, Protoporphyria, Crigler-Najjar disease type I, Familial hypercholesterolemia, Primary hyperoxaluria type I, Hemophilia. • Adult Indications: Primary biliary cholangitis, Primary sclerosing cholangitis, Caroli's disease, Secondary biliary cirrhosis, Autoimmune hepatitis, Hemochromatosis, α-1 antitrypsin deficiency, MASH, Alcohol-associated cirrhosis, and Acute liver failure (ALF). • Malignancy Criteria: ◦ Hepatocellular carcinoma (HCC) restricted to: single tumors <5 cm in diameter or three or fewer lesions all <3 cm. ◦ Cholangiocarcinoma: Only highly selected patients after intensive chemotherapy and radiation.

Contraindications¶

• Absolute Contraindications: ◦ Uncontrolled extrahepatobiliary infection ◦ Active, untreated sepsis ◦ Life-limiting congenital anomalies ◦ Cholangiocarcinoma (except those that fit into protocols) ◦ Advanced cardiopulmonary disease • Relative Contraindications: ◦ Advanced age ◦ Extensive portal vein thrombosis ◦ Severe obesity ◦ Severe malnutrition/wasting ◦ Medical noncompliance ◦ Severe hypoxemia secondary to right-to-left intrapulmonary shunts (PaO_2 < 50 mmHg) ◦ Severe pulmonary hypertension (mean pulmonary artery pressure > 35 mmHg)

DIAGNOSTIC APPROACH¶

MELD Score Calculation: Used to determine allocation of remaining donor organs.
Formula (≥18 years): 1.33 (if female) + [4.56 imes log(bilirubin)] + [0.82 imes (137 - sodium)] - [0.24 imes (137 - sodium) imes log(bilirubin)] + [9.09 imes log(INR)] + [11.14 imes log(creatinine)] + [1.85 imes (3.5 - albumin)] - [1.83 imes (3.5 - albumin) imes log(creatinine)] + 6.
Formula (12–17 years): [4.56 imes log(bilirubin)] + [0.82 imes (137 - sodium)] - [0.24 imes (137 - sodium) imes log(bilirubin)] + [9.09 imes log(INR)] + [11.14 imes log(creatinine)] + [1.85 imes (3.5 - albumin)] - [1.83 imes (3.5 - albumin) imes log(creatinine)].
Donor Selection:
Deceased donors: Acceptable up to age 60 if hemodynamically stable, no infection, and no hepatic dysfunction.
Living donors: Used for pediatric cases or when wait times are prohibitive; can reduce waiting time and cold ischemia time.
Malignancy Screening:
Confirm HCC meets size/count criteria (single <5cm or ≤3 lesions all <3cm) before inclusion.

MANAGEMENT & TREATMENT¶

Surgical Procedure¶

Anastomosis Sequence (Figure 356-1):
Suprahepatic and infrahepatic vena cava
Portal vein
Hepatic artery
Common bile duct-to-duct anastomosis.

Postoperative Management¶

Immunosuppression:
Primary: Tacrolimus (preferred over cyclosporine).
Hepatitis B Prophylaxis: HBIg and oral antivirals (entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide).
Complication Monitoring (Table 356-4 & 356-5):
Cardiovascular: Monitor for arrhythmias, congestive heart failure, and cardiomyopathy.
Renal: Monitor for prerenal azotemia, hypoperfusion injury (ATN), and drug nephrotoxicity; monitor for \downarrow renal blood flow due to \uparrow intraabdominal pressure.
Infection: Monitor for early bacterial infections; late fungal/parasitic or viral infections (including recurrent hepatitis).
Hepric Complications:
Prehepatic: Monitor for pigment load, hemolysis, and blood collections (hematomas).
Intrahepatic: Monitor for hepatotoxic drugs/anesthesia effects, hypoperfusion (shock), and benign postoperative cholestasis.
Posthepatic: Monitor for biliary obstruction and \downarrow renal clearance of conjugated bilirubin.
Specific Risks:
Primary graft nonfunction (PGNF)
Vascular compromise (Portal vein obstruction, Hepatic artery thrombosis)
Bile duct disorders (Stenosis, obstruction, leak)
Rejection and Recurrent primary hepatic disease.

PROGNOSIS & COMPLICATIONS¶

• Survival: 1-year survival >90%. • Malignancy Recurrence: High risk for cholangiocarcinoma; HCC recurrence depends on size/number of lesions. • Viral Re-infection: Risk of recurrence in Hep B and C managed with prophylaxis and DAAs.

SPECIAL CONSIDERATIONS¶

HIV-Positive Patients¶

• Eligible if: CD4+ count >100/μL and pharmacologic suppression of HIV viremia. ◦ Outcomes for Hep B in HIV patients are comparable to HIV-negative patients with prophylaxis.

Alcohol Use¶

• Candidates must meet strict criteria for abstinence and reform. ◦ Note: 25% of these patients may still relapse into alcohol use.

KEY PEARLS & CLINICAL TRAPS¶

• MELD Score: Essential for organ allocation; includes a 1.33 multiplier for females. • Tacrolimus vs Cyclosporine: Tacrolimus is the standard due to better safety and predictability. • HCC Criteria: Only single tumors <5 cm or ≤3 lesions all <3 cm are eligible. • Hepatitis B Management: Use HBIg + Antivirals (entecavir, tenofovir) for prophylaxis. • Surgical Sequence: Vena cava → Portal vein → Hepatic artery → Bile duct.

Reference Tables¶

TABLE 356-1 Indications for Liver Transplantation CHILDREN Biliary atresia Neonatal hepatitis Congenital hepatic…¶

Harrison's 22e, p.2718

CHILDREN	ADULTS
Biliary atresia	Primary biliary cholangitis
Neonatal hepatitis	Primary sclerosing cholangitis
Congenital hepatic fibrosis	Caroli’s diseasea
Alagille’s syndromeb	Secondary biliary cirrhosis
Byler’s diseasec	Autoimmune hepatitis
Inherited disorders of metabolism	Hemochromatosis-associated cirrhosis
Wilson’s disease	α Antitrypsin deficiency 1
Tyrosinemia Glycogen storage diseases Lysosomal storage diseases Protoporphyria Crigler-Najjar disease type I Familial hypercholesterolemia Primary hyperoxaluria type I Hemophilia	Metabolic dysfunction–associated steatohepatitis (MASH)d
	Alcohol-associated cirrhosis
	Severe alcohol-associated hepatitis
	Cryptogenic cirrhosis
	Chronic viral hepatitis with cirrhosis
	Hepatic venous outflow obstruction (Budd-Chiari syndrome)
	Acute liver failure (ALF)
	Hepatocellular carcinoma
	Select cases for the following indications:
	Hepatic adenomas
	Familial amyloidosis
	Hepatic epithelioid hemangioendothelioma (HEHE)
	Erythropoietic protoporphyria (EPP)
	Metastatic neuroendocrine tumors
	Polycystic liver disease

TABLE 356-2 Contraindications to Liver Transplantation ABSOLUTE Uncontrolled extrahepatobiliary infection Active…¶

Harrison's 22e, p.2719

ABSOLUTE	RELATIVE
Uncontrolled extrahepatobiliary infection	Advanced agea
Life-limiting congenital anomalies	Extensive portal vein thrombosis
Advanced cardiopulmonary disease	Extrahepatobiliary malignancy
	Severe obesity
	Severe malnutrition/wasting
	Medical noncompliance
Life-threatening systemic diseases	Severe hypoxemia secondary to right-to-left intrapulmonary shunts (PO <50 mmHg) 2
	Severe pulmonary hypertension (mean pulmonary artery pressure >35 mmHg)

Harrison's 22e, p.2720

Status 1	Acute liver failure (including primary graft nonfunction and hepatic artery thrombosis)a

TABLE 356-4 Nonhepatic Complications of Liver Transplantation CATEGORY Cardiovascular instability Pulmonary compromise¶

Harrison's 22e, p.2722

CATEGORY	COMPLICATION
Cardiovascular instability	Arrhythmias
	Congestive heart failure
	Cardiomyopathy
Renal dysfunction	Prerenal azotemia
	Hypoperfusion injury (acute tubular necrosis)
	Drug nephrotoxicity
	↓ Renal blood flow secondary to ↑ intraabdominal pressure
Infection	Bacterial: early, common postoperative infections
	Fungal/parasitic: late, opportunistic infections
	Viral: late, opportunistic infections, recurrent hepatitis
Diseases of donor	Infectious
	Malignant

TABLE 356-5 Hepatic Complications of Liver Transplantation Hepatic Dysfunction Common after Major Surgery Prehepatic¶