Liver transplantation is surgery to remove a diseased liver and replace it with a donated whole or partial healthy liver. Liver transplantation is a treatment option for acute liver failure, end-stage liver disease, and primary hepatic malignancy. Box E1 summarizes indications for liver transplantation.

• Cirrhosis remains the twelfth-leading cause of death for adults in the U.S., with a death rate of 9.2 cases per 100,000 people
• Accounts for 1.1% of total deaths in the U.S.
• Hepatocellular carcinoma is a primary cancer originating in the liver. Hepatocellular carcinoma is responsible for more than 12,000 deaths per yr in the U.S. and is the highest rising malignancy in the U.S. It is more common in men than women and in those of African descent than Whites

• Cirrhosis alone does not warrant transplantation. Transplantation is considered when a patient presents with manifestations of compromised hepatic function such as portal hypertension or a manifestation of compromised hepatic function. Complications of portal hypertension include esophageal varices, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, hepatopulmonary syndrome.
• Physical findings and clinical presentation that warrant liver transplantation in patients with end-stage liver disease are recurrent variceal hemorrhage, intractable ascites, spontaneous bacterial peritonitis, refractory encephalopathy, severe jaundice, portal venous thrombosis, worsening hepatic synthetic dysfunction, sudden deterioration, and fulminant hepatic failure.

The etiology of a liver transplant is from end-stage liver disease that has resulted in cirrhosis scarring. The most common are chronic hepatitis C virus (30%), alcoholic cirrhosis (18%), fatty liver disease including nonalcoholic steatohepatitis (NASH), primary liver cancer, acute or chronic hepatitis B virus, bile duct disease, genetic disease, and autoimmune liver disease.

• Patients with end-stage liver disease requiring a transplant are assessed by using the MELD-Na score (Model for End-Stage Liver Disease-Na). The MELD-Na score measures the severity of chronic liver disease and can predict mortality within 3 mo of surgery in patients who received a transjugular intrahepatic portosystemic shunt procedure. The score prioritizes who needs a transplant as soon as possible.
• MELD-Na score testing includes: Serum bilirubin, serum creatinine, international normalization ratio for prothrombin time, and serum sodium
• MELD-Na = [[3.78 × ln [serum bilirubin (mg/dl)] + 11.2 × ln [INR] + 9.57 × ln [serum creatinine (mg/dl)] + 6.43]] + 1.59 (135-Na),
  1. Maximum and minimum Na of 135 and 120 mmol/L, respectively
• 40 or more: 71.3% mortality
• 30 to 39: 52.6% mortality
• 20 to 29: 19.6% mortality
• 10 to 19: 6.0% mortality (MELD ≥15 warrants liver transplantation workup for waitlist)
• <9: 1.9% mortality

MELD score testing: Serum bilirubin, serum creatinine, serum sodium, and the international normalization ratio for prothrombin time.

• Abdominal ultrasound (US), computed tomography, or MRI to screen for hepatocellular carcinoma.
• Patients with underlying cirrhosis should be screened for hepatocellular carcinoma with abdominal US every 6 to 12 mo.

• Living donor: The scarcity of cadaveric organs has prompted some centers to use living donors, which guarantees transplantation but entails a risk to the donor. Donor compatibility is based on candidates who are family members or close friends of the recipient. The donor must be aged 18 to 60 yr, have compatible blood type with the recipient, be the same physical size or larger, and in excellent health with no history of uncontrolled high blood pressure, liver disease, diabetes, or heart disease. Donor risk includes wound infections, hernia, abdominal bleeding, bile leakage, narrowing of the bile duct, intestinal problems including blockages and tears, organ impairment or failure that leads to the need for transplantation, and death.
• Deceased donor: Orthotopic liver transplantation is effective for nonresectable early hepatocellular carcinoma, acute liver failure, and end-stage liver disease.

• University of California San Francisco (UCSF) criteria: Criteria for liver transplant are as follows: Single tumor <6.5 cm, maximum of three total tumors with none >4.5 cm, and cumulative tumor size <8 cm, or exceeded UCSF criteria.
• Acute liver failure:
  1. In the case of acute liver failure, the patient is evaluated for liver transplantation based on the “Kings College Criteria,” which is based on:
     1. pH <7.3 OR, in a 24-h period, all three of:
     2. International normalized ratio (INR) >6 (PT >100s) + Cr >300 mmol/L + grade III or IV encephalopathy
  2. Patients who fulfill these criteria and do not have underlying chronic liver disease should be referred to liver transplant centers for urgent evaluation.
• Pretransplant care: Pretransplantation treatment is focused on testing the patients’ ability to handle stress of the surgery, immunosuppression, and posttransplantation care. This is achieved by extensive cardiopulmonary evaluation, screening for occult infection or cancer, and psychosocial evaluation. Additional testing includes ABO-Rh blood typing; liver biochemical and function tests (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, INR); CBC with differential; creatinine clearance; serum alpha-fetoprotein; calcium and vitamin D levels; serologies for cytomegalovirus, Epstein-Barr virus, varicella, HIV, hepatitis A, hepatitis B, hepatitis C, rapid plasma regain; urinalysis; and urine drug screen.
• Posttransplant care: The primary goal is to prevent posttransplant rejection of the donated liver. This is accomplished with immunosuppression of the immune system with corticosteroids, calcineurin inhibitors such as tacrolimus (FK-506, Prograf), mycophenolate mofetil (CellCept, Myfortic), mechanistic target of rapamycin (mTOR) inhibitors (Sirolimus; everolimus), antibodies that remove T cells from the circulation (Thymoglobulin, OKT-3).

Gastroenterologist and liver transplant team

Average survival rate is 92% after 1 yr and 75% to 85% after 5 yr.

• Cirrhosis alone does not warrant transplantation. Liver transplantation is considered when a patient has suffered either an end-stage liver disease or a manifestation of compromised hepatic function.
• Liver transplantation is always a last option, as the overall determining factor is the number of donor livers available at any time.

Nongenetic factors such as lifestyle modification and hepatitis B vaccination to avoid developing end-stage liver disease.

Patients who have a genetic predisposition to developing end-stage liver disease from having hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, glycogen storage disease, and tyrosinemia would be advised to have genetic screening of immediate family members.

Acute Liver Failure (Related Key Topic)

Cirrhosis (Related Key Topic)