Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although the availability of donor organs is a major limitation. Liver transplantation is highly regulated and only performed at designated transplant medical centers by highly trained transplant physicians. Favorable outcomes require careful screening for eligible recipients, as well as a well-calibrated live or deceased donor match.
Medical uses Liver transplantation is a potential treatment for acute or chronic conditions that cause irreversible and severe ("end-stage") liver dysfunction. Since the procedure carries relatively high risks, is resource-intensive, and requires major life modifications after surgery, it is reserved for dire circumstances. It has also emerged as an option for people whose colorectal cancer has metastasized to the liver.
Judging the appropriateness or effectiveness of liver transplant on case-by-case basis is critically important (see Contraindications), as outcomes are highly variable.
Allocation Scoring systems are widely used to determine recipient benefit, and hence to allocate organs more fairly for transplantation.
MELD In the US, the Model for End Stage Liver Disease (MELD score) created by Dr. Patrick Kamath, for adults and the Pediatric End Stage Liver Disease (PELD score) for children younger than 12 years old are clinical scoring tools that consider various clinical criteria and are used to assess the need for a liver transplant. Higher scores for each clinical scoring tool indicate a higher severity of liver disease, and thus a greater need for a liver transplant. In those with chronic liver disease, a decompensating event such as hepatic encephalopathy, variceal bleeding, ascites, or spontaneous bacterial peritonitis may also signal a new need for a liver transplant.
Transplant Benefit Score The Transplant Benefit Score is an algorithmic medical scoring system used for making liver transplant waiting list decisions for the National Liver Offering Scheme in the United Kingdom. In 2023, an investigation by the Financial Times stated that the scoring system might result in younger patients not getting transplants under certain circumstances. A publication in The Lancet also showed that the TBS algorithm generated implausible results in some circumstances.
Contraindications Although liver transplantation is the most effective treatment for many forms of end-stage liver disease, the tremendous limitation in allograft (donor) availability and widely variable post-surgical outcomes make case selection critically important. Assessment of a person's transplant eligibility is made by a multi-disciplinary team that includes surgeons, medical doctors, psychologists, and other providers.
The first step in evaluation is to determine whether the patient has irreversible liver-based disease, which can be cured by getting a new liver. Thus, those with diseases that are primarily based outside the liver or have spread beyond the liver are generally considered poor candidates. Some examples include: someone with advanced liver cancer, with known/likely spread beyond the liver. Or those with cancer of any type, if the cancer cannot be treated successfully without rendering them unsuitable for transplant (other than skin cancers). active illicit substance use anatomic abnormalities that prevent liver transplantation severe heart/lung disease, whether it is primary heart/lung disease, or brought on by the liver disease (unless the team thinks they can still proceed) HIV/AIDS, especially if it is not well-managed (some persons with HIV/AIDS that have very low or undetectable viral loads could still be eligible)
Importantly, many contraindications to liver transplantation are considered reversible; a person initially deemed "transplant-ineligible" may later become a favorable candidate if the circumstances change. Some examples include: partial treatment of liver cancer, such that the risk of spread beyond the liver is decreased (for those with primary liver cancer or secondary spread to the liver, the medical team will likely rely heavily on the opinion of the patient's primary provider, the oncologist, and the radiologist) cessation of substance use (period of abstinence is variable) improvement in heart function, e.g. by percutaneous coronary intervention or bypass surgery treated HIV infection (see Special populations)
Other conditions, including hemodynamic instability requiring vasopressor support, large liver cancers or those with invasion to blood vessels, intrahepatic cholangiocarcinoma, frailty, fulminant liver failure with suspected brain injury, alcohol use disorder with recent alcohol consumption, cigarette smoking, inadequate social support, and nonadherence to medical management may disqualify someone from liver transplantation, however these cases are usually evaluated by the multi-disciplinary transplant team on an individual basis.
Risks/complications Graft rejection After a liver transplantation, immune-mediated rejection (also known as rejection) of the allograft may happen at any time. Rejection may present with lab findings: elevated AST, ALT, GGT; abnormal liver function values such as prothrombin time, ammonia level, bilirubin level, albumin concentration; and abnormal blood glucose. Physical findings may include encephalopathy, jaundice, bruising, and a bleeding tendency. Other nonspecific presentations may include malaise, anorexia, muscle aches, low fever, slight increase in white blood count, and graft-site tenderness.
Three types of graft rejection may occur: hyperacute rejection, acute rejection, and chronic rejection. Hyperacute rejection is caused by preformed anti-donor antibodies. It is characterized by the binding of these antibodies to antigens on vascular endothelial cells. Complement activation is involved, and the effect is usually profound. Hyperacute rejection happens within minutes to hours after the transplant procedure. Acute rejection is mediated by T cells (versus B-cell-mediated hyperacute rejection). It involves direct cytotoxicity and cytokine mediated pathways. Acute rejection is the most common and the primary target of immunosuppressive agents. Acute rejection is usually seen within days or weeks of the transplant. Chronic rejection is the presence of any sign or symptom of rejection after one year. The cause of chronic rejection is still unknown, but an acute rejection is a strong predictor of chronic rejection.
Biliary complications Biliary complications include biliary stenosis, biliary leak, and ischemic cholangiopathy. The risk of ischemic cholangiopathy increases with longer durations of cold ischemia time, which is the time that the organ does not receive blood flow (after death/removal until graft placement). Biliary complications are routinely treated with Endoscopic Retrograde Cholangiopancreatography (ERCP), percutaneous drainage, or sometimes re-operation.
Vascular complications Vascular complications include thrombosis, stenosis, pseudoaneurysm, and rupture of the hepatic artery. Venous complications occur less often compared with arterial complications, and include thrombosis or stenosis of the portal vein, hepatic vein, or vena cava.
Technique Before transplantation, liver-support therapy might be indicated (bridging-to-transplantation). Artificial liver support, like liver dialysis or bioartificial liver support concepts, is currently under preclinical and clinical evaluation. Virtually all liver transplants are done in an orthotopic fashion; that is, the native liver is removed and the new liver is placed in the same anatomic location. The transplant operation can be conceptualized as consisting of the hepatectomy (liver removal) phase, the anhepatic (no liver) phase, and the postimplantation phase. The operation is done through a large incision in the upper abdomen. The hepatectomy involves division of all ligamentous attachments to the liver, as well as the common bile duct, hepatic artery, all three hepatic veins and portal vein. Usually, the retrohepatic portion of the inferior vena cava is removed along with the liver, although an alternative technique preserves the recipient's vena cava ("piggyback" technique).
The donor's blood in the liver will be replaced by an ice-cold organ storage solution, such as UW (Viaspan) or HTK, until the allograft liver is implanted. Implantation involves anastomoses (connections) of the inferior vena cava, portal vein, and hepatic artery. After blood flow is restored to the new liver, the biliary (bile duct) anastomosis is constructed, either to the recipient's own bile duct or to the small intestine. The surgery usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the surgeon.
The vast majority of liver transplants use the entire liver from a non-living donor for the transplant, particularly for adult recipients. A major advance in pediatric liver transplantation was the development of reduced-size liver transplantation, in which a portion of an adult liver is used for an infant or small child. Further developments in this area included split liver transplantation, in which one liver is used for transplants for two recipients, and living donor liver transplantation, in which a portion of a healthy person's liver is removed and used as the allograft. Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3).
Further advance in liver transplant involves only resection of the lobe of the liver involved in tumors, and the tumor-free lobe remains within the recipient. This speeds up the recovery, and the patient's stay in the hospital quickly shortens to within 5–7 days.
Radiofrequency ablation of the liver tumor can be used as a bridge while awaiting liver transplantation.DuBay, D. A., Sandroussi, C., Kachura, J. R., Ho, C. S., Beecroft, J. R., Vollmer, C. M., Ghanekar, A., Guba, M., Cattral, M. S., McGilvray, I. D., Grant, D. R., & Greig, P. D. (2011). Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB: the official journal of the International Hepato Pancreato Biliary Association, 13(1), 24–32. https://doi.org/10.1111/j.1477-2574.2010.00228.x
Cooling Between removal from the donor and transplantation into the recipient, the allograft liver is stored in a temperature-cooled preservation solution. The reduced temperature slows down the process of deterioration from normal metabolic processes, and the storage solution itself is designed to counteract the unwanted effects of cold ischemia. Although the "static" cold storage method has long been a standard technique, various dynamic preservation methods are under investigation. For example, systems which use a machine to pump blood through the explanted liver (after it is harvested from the body) during a transfer have met some success (see Research section for more).
Living donor transplantation
Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma often attributable to one or more of the following: long-term alcohol use disorder, long-term untreated hepatitis C infection, long-term untreated hepatitis B infection. The concept of LDLT is based on (1) the remarkable regenerative capacities of the human liver and (2) the widespread shortage of cadaveric livers for patients awaiting transplant. In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the recipient's diseased liver has been entirely removed.