Introduction: Liver transplantation is a life-saving surgery for patients with acute and chronic liver diseases. The major disorders that may result in consideration for liver transplantation include acute liver failure, chronic liver disease with advanced cirrhosis, hepatocellular carcinoma, and liver-based metabolic defects (Figure 1). In 2012, more than 6000 liver transplants were performed in the United States, and chronic hepatitis C virus (HCV) infection was the most common indication for the transplantation. Advances in the field of transplantation have improved post-transplant survival rates in the United States to 87.7% at one year after liver transplantation, 79.9% at 3 years, and 74.3% at 5 years.
Acute Liver Failure: Acute liver failure is the development of hepatic encephalopathy and coagulopathy (international ionized ratio [INR] greater than or equal to 1.5) within 26 weeks from the onset of symptoms related to acute hepatitis (e.g. jaundice) in patients without pre-existing liver disease. Causes of acute liver failure include acetaminophen overdose, acute viral hepatitis, drug-induced liver injury, autoimmune hepatitis, and fatty liver of pregnancy. These patients should be urgently transferred to a liver transplant center for acute care. Liver transplantation should be considered in patients with poor prognosis or low probability of spontaneous recovery. Given the rapidity of clinical deterioration, these candidates receive a special listing category (Status 1) to prioritize for deceased donor organs. Acute infection with hepatitis C virus rarely causes acute liver failure and thus is a very rare indication for liver transplantation.
Cirrhotic Liver Disease: Chronic liver diseases that cause cirrhosis are by far the most common indication for liver transplantation in the United States. Specific chronic liver diseases that can lead to cirrhosis include chronic viral hepatitis (e.g. hepatitis B and hepatitis C), autoimmune hepatitis, alcoholic liver disease, cholestatic liver diseases (e.g. primary biliary cirrhosis, primary sclerosing cholangitis, and cystic fibrosis), metabolic disorders (e.g. alpha-1-antitrypsin deficiency, Wilson disease, non-alcoholic steatohepatitis, and hereditary hemochromatosis), and vascular disorders (e.g. Budd-Chiari syndrome).
Hepatocellular Carcinoma (HCC): Patients with cirrhosis are at risk for developing hepatocellular carcinoma. The highest risk of HCC is in those with hereditary hemochromatosis, chronic hepatitis B, and chronic hepatitis C, with incidence rates estimated at around 2 to 8% per year. In the United States, hepatitis C with cirrhosis is the most common cause of HCC. Hepatic resection is considered a treatment option for patients with HCC and compensated cirrhosis without significant portal hypertension, but more than 50% who undergo hepatic resection will develop recurrence of HCC within 5 years. The same risk of recurrent HCC results from locoregional therapy, such as radiofrequency ablation, percutaneous ethanol injection, and chemoembolization. Early experience with transplantation of unresectable HCCs demonstrated a high rate of early recurrence and limited survival. Later analysis, however, has demonstrated improved results for transplantation limited to patients who meet Milan criteria (solitary HCC lesion less than 5 cm or up to 3 nodules smaller than 3 cm). Patients with HCC who meet Milan criteria and have no radiographic evidence of extrahepatic disease, but who are not candidates for surgical resection, are considered liver transplantation candidates, and granted priority for liver transplantation. In an attempt to match the risk of death in patients with decompensated cirrhosis, the MELD score is automatically adjusted to a MELD exception score of 22 for initial listing; the score is then increased every 3 months while on the transplant waiting list to reflect a corresponding 10% increase in mortality for each 3-month interval that transpires. The 1-year and 5-year post-transplant survival rates for patients with tumors meeting Milan criteria are 89% and 61%, respectively, which are considered acceptable rates. Certain transplantation centers in the United States have expanded transplant criteria (HCC that does not meet Milan criteria or downstaging of HCC through neoadjuvant locoregional therapy to within the Milan criteria) that may provide a patient consideration for transplantation under investigational or specialized protocols.
Other Conditions: Liver transplantation is also considered for those with metabolic diseases originating in the liver with severe extrahepatic manifestations, such as amyloidosis, hyperoxaluria, urea cycle defects, and branched-chain amino acid disorders. Other rare conditions for which liver transplantation is considered include fibrolamellar HCC, hemangioendothelioma, hereditary hemorrhagic telangiectasia, hepatoblastoma, neonatal hemochromatosis, tyrosinemia, glycogen storage disease, homozygous familial hypercholesterolemia, metastatic neuroendocrine tumors, erythropoietic protoporphyria, polycystic liver disease, and cholangiocarcinoma (under investigation in certain transplant centers.)