liver transplantation liver transplantation 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 availability of donor organs is a major limitation. the most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. the surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. the duration of the surgery ranges from 4 to 18 hours depending on outcome. favorable outcomes require careful screening for eligible recipient, as well as a well-calibrated live or cadaveric donor match. liver transplantationa healthy human liver removed at autopsyspecialtyhepatology, transplant surgerycomplicationsprimary nonfunction of graft, hepatic artery thrombosis, portal vein thrombosis, biliary stenosis, biliary leak, ischemic cholangiopathy medical uses liver transplantation is a potential treatment for acute or chronic conditions which 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. judging the appropriateness/effectiveness of liver transplant on case-by-case basis is critically important (see contraindications), as outcomes are highly variable. 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 will be cured by getting a new liver. thus, those with diseases which 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 active alcohol/substance use severe heart/lung disease existing high cholesterol levels in the patient severe wilson's disease dyslipidemia importantly, many contraindications to liver transplantation are considered reversible; a person initially deemed "transplant-ineligible" may later become a favorable candidate if their situation changes. some examples include: partial treatment of liver cancer, such that risk of spread beyond 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 (time period of abstinence is variable) improvement in heart function, e.g. by percutaneous coronary intervention or bypass surgery treated hiv infection (see special populations) for those with high cholesterol or triglyceride levels or other dyslipidemias, using lifestyle changes (diet, portions, exercise) and drugs and counseling to lower one's levels, and to control any hyperglycemia or (pre-)diabetes or obesity 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 bleeding tendency. other nonspecific presentation may include malaise, anorexia, muscle ache, 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 and symptom of rejection after one year. the cause of chronic rejection is still unknown, but an acute rejection is a strong predictor of chronic rejections. 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). 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 are 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, hepatic vein 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 large 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 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. cooling between removal from 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 "static" cold storage method has long been 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 volume rendering image created with computed tomography, which can be used to evaluate the volume of the liver of a potential donor 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. historically, ldlt began with terminal pediatric patients, whose parents were motivated to risk donating a portion of their compatible healthy livers to replace their children's failing ones. the first report of successful ldlt was by silvano raia at the university of sao paulo faculty of medicine in july 1989. it was followed by christoph broelsch at the university of chicago medical center in november 1989, when two-year-old alyssa smith received a portion of her mother's liver. surgeons eventually realized that adult-to-adult ldlt was also possible, and now the practice is common in a few reputable medical institutes. it is considered more technically demanding than even standard, cadaveric donor liver transplantation, and also poses the ethical problems underlying the indication of a major surgical operation (hemihepatectomy or related procedure) on a healthy human being. in various case series, the risk of complications in the donor is around 10%, and very occasionally a second operation is needed. common problems are biliary fistula, gastric stasis and infections; they are more common after removal of the right lobe of the liver. death after ldlt has been reported at 0% (japan), 0.3% (usa) and <1% (europe), with risks likely to decrease further as surgeons gain more experience in this procedure. since the law was changed to permit altruistic non-directed living organ donations in the uk in 2006, the first altruistic living liver donation took place in britain in december 2012. in a typical adult recipient ldlt, 55 to 70% of the liver (the right lobe) is removed from a healthy living donor. the donor's liver will regenerate approaching 100% function within 4–6 weeks, and will almost reach full volumetric size with recapitulation of the normal structure soon thereafter. it may be possible to remove up to 70% of the liver from a healthy living donor without harm in most cases. the transplanted portion will reach full function and the appropriate size in the recipient as well, although it will take longer than for the donor. living donors are faced with risks and/or complications after the surgery. blood clots and biliary problems have the possibility of arising in the donor post-op, but these issues are remedied fairly easily. although death is a risk that a living donor must be willing to accept prior to the surgery, the mortality rate of living donors in the united states is low. the ldlt donor's immune system does diminish as a result of the liver regenerating, so certain foods which would normally cause an upset stomach could cause serious illness. donor requirements ct scan performed for evaluation of a potential donor. the image shows an unusual variation of hepatic artery. the left hepatic artery supplies not only left lobe but also segment 8. the anatomy makes right lobe donation impossible. even used as left lobe or lateral segment donation, it would be very technically challenging in anastomosing the small arteries. any member of the family, parent, sibling, child, spouse or a volunteer can donate their liver. the criteria for a liver donation include: being in good health having a blood type that matches or is compatible with the recipient's, although some centres now perform blood group incompatible transplants with special immunosuppression protocols. having a charitable desire of donation without financial motivation being between 20 and 60 years old (18 to 60 years old in some places) have an important personal relationship with the recipient being of similar or larger size than the recipient before one becomes a living donor, the donor must undergo testing to ensure that the individual is physically fit, in excellent health, and not having uncontrolled high blood pressure, liver disease, diabetes or heart disease. sometimes ct scans or