A liver transplant is an operation that replaces a patient's diseased liver with a whole or partial healthy liver from another person. This article explains the current indications for liver transplantation, types of donor livers, the operation itself, and the immunosuppression that is required after transplantation.
Liver transplantation surgically replaces a failing or diseased liver with one that is normal and healthy. At this time, transplantation is the only cure for liver insufficiency or liver failure because no device or machine reliably performs all of the functions of the liver. People who require liver transplants typically have one of the following conditions.
Acute Liver Failure
Acute liver failure, also known as fulminant hepatic failure, occurs when a previously healthy liver suffers massive injury resulting in clinical signs and symptoms of liver insufficiency. Any number of things can lead to acute liver failure but the most common causes are acetaminophen (Tylenol®) overdose, viral infections (known or yet unknown virus), ingestion of a toxin such as poisonous mushrooms, or an idiosyncratic drug reaction.
The hallmark of this condition is the development of confusion (encephalopathy) within eight weeks after the onset of yellowing of the skin (jaundice). Confusion occurs because toxins typically metabolized by the liver accumulate. Unlike patients with chronic liver disease, who can survive weeks to months to years while awaiting liver transplantation, patients with acute liver failure may die within days if not transplanted. These patients are listed at highest priority (Status I), placing them at the top of local, regional and national waiting lists for a donor liver.
Chronic Liver Failure
The liver has a remarkable ability to repair itself in response to injury. Nevertheless, repeated injury and repair, typically over many years and even decades, scars the liver permanently. The end stage of scarring is termed cirrhosis and corresponds to the point where the liver can no longer repair itself. Once a person has cirrhosis, he or she may begin to show signs of inadequate liver function. This is termed "decompensated liver disease." Although medications can decrease the symptoms caused by the liver failure, liver transplantation represents the only permanent cure.
• Gastrointestinal bleeding: As the liver becomes increasingly scarred, the resistance to portal blood flow increases leading to increased pressure in the portal venous system. This portal hypertension necessitates alternative routes for blood to return to the heart. Small veins throughout the abdomen, but outside of the liver, then become enlarged and thin-walled due to the abnormally high amount of blood flowing through them under increased pressure. These fragile veins, called varices, often line portions of the gastrointestinal tract, especially the esophagus and the stomach, and are prone to rupture and bleeding. When bleeding occurs into the intestinal tract, it can be life-threatening.
• Fluid retention: One function of the liver is to synthesize many of the proteins circulating in the bloodstream, including albumin. Albumin and other proteins in the blood stream retain fluid in the vascular space by exerting what is known as an oncotic (or osmotic) pressure. In liver failure, low albumin levels force fluid out of the bloodstream, which cannot be re-absorbed. Fluid therefore accumulates in tissues and body cavities, most commonly, in the abdominal cavity, which is termed "ascites." Fluid can also accumulate in the legs (peripheral or pedal edema), or in the chest cavity (hydrothorax). Fluid retention is treated first by strict limitation of dietary salt intake, second with medications (diuretics) that force increased salt and water loss through the kidneys and, lastly, by intermittent drainage through insertion of a needle into the abdominal or chest cavity.
• Encephalopathy: Failure of the liver to clear ammonia and other toxins from the blood allows these substances to accumulate. These toxins result in cognitive dysfunction that ranges from disturbed sleep-wake cycle patterns to mild confusion to coma.
• Jaundice: One of the main functions of the liver is to eliminate the degradation products of hemoglobin, the molecule that carries oxygen in our blood. Bilirubin is one of those degradation products processed and excreted by the liver. In liver failure, bilirubin is not cleared from the body and bilirubin levels increase in the blood. The skin and all tissues of the body will then assume a yellow color.
• Hepatitis B: Hepatitis B infection accounts for 5% of all liver transplants performed in the United States but accounts for a larger proportion of liver transplants in other parts of the world, especially Asia and Australia / New Zealand.
Hepatitis C: This is the most common indication for liver transplantation in the United States, affecting nearly 50% of all liver transplant recipients.
Alcoholic Liver Disease
Liver failure due to alcohol abuse is the second most common indication for liver transplantation in the United States. Most centers require at least a six-month period of abstinence, often within a recognized substance abuse program such as Alcoholics Anonymous, as a condition of listing for transplantation.
Metabolic Liver Disease
Non-alcoholic steatohepatitis (NASH): Deposition of fat within liver cells may result in inflammation that injures and scars the liver. Risk factors for the development of fatty liver and NASH include obesity and metabolic conditions such as diabetes and hyperlipidemia (increased cholesterol). The percentage of patients being transplanted for this condition has increased 35 fold from 2000 to 2005.
Autoimmune Liver Disease
• Autoimmune hepatitis (destruction of the liver by the patient's own immune system)
• Cholestatic Liver Diseases
• Primary Biliary Cirrhosis (PBC) (destruction of small bile ducts within the liver)
• Primary Sclerosing Cholangitis (PSC) (destruction of bile ducts inside and outside the liver). Seventy percent of patients with PSC also suffer from ulcerative colitis, an autoimmune disorder of the colon.
• Neonatal sclerosing cholangitis (infection and scarring of the bile ducts in the liver of an infant)
• Biliary atresia (absence of bile ducts outside the liver)
• Caroli's disease (abnormality of the bile ducts within the liver)
• TPN-induced cholestasis. Patients who receive intravenous nutrition, termed total parenteral nutrition (TPN) sometimes develop bile stasis (slowing or stopping of normal bile flow) that can, over time, lead to liver injury and failure.
Genetic Liver Disease
• Hemachromatosis: excess iron deposition in the liver
• Wilson's disease: abnormal copper metabolism
• Alpha-1 anti-trypsin deficiency: lack of a gene product that limits the activity of trypsin, an enzyme that digests protein. Over time this leads to progressive destruction of the liver and lung.
• Glycogen storage disease (type I, III, IV): an inherited metabolic disorder
• Tyrosinemia: a disorder of tyrosine metabolism
Vascular Liver Disease
Budd-Chiari syndrome is thrombosis (clotting) of the hepatic veins which leads to poor blood flow though the liver.
Hepatocellular carcinoma (HCC) is a primary cancer of the liver, meaning that it originates from abnormal liver cells. HCC occurs only rarely in a normal, non-cirrhotic liver. Its incidence is, however, strikingly increased in the background of cirrhosis and, in particular, by certain types of liver disease that lead to cirrhosis (hepatitis B and C, hemachromatosis, and tyrosinemia). Although the cancer first starts within the liver, as it grows it can spread to other organs, a process called metastasis. HCC most frequently spreads to the lungs or to bones. The risk of spread outside of the liver increases with the size of the cancer.
Liver transplantation definitively cures a patient of HCC, provided that the tumor has not spread beyond the liver. Because there are far more people in need of liver transplants than there are available organs, specific guidelines, called the Milan Criteria, have been established to define which patients with HCC are eligible for transplantation. These criteria define limits of tumor number and size that ensure a very low likelihood of cancer spread outside of the liver.
There are many people with cirrhosis and decompensated liver disease but not all are appropriate candidates for liver transplantation. A patient must be able to survive the operation and the potential post-operative complications, reliably take the medications that prevent rejection and opportunistic infections, comply with frequent clinic visits and laboratory tests, and not engage in activity that would injure the liver, such as drinking alcohol. The conditions listed below are generally considered to be absolute contra-indications to liver transplantation.
• Severe, irreversible medical illness that limits short-term life expectancy
• Severe pulmonary hypertension (mean pulmonary artery pressure greater than 50mmHg)
• Cancer that has spread outside of the liver
• Systemic or uncontrollable infection
• Active substance abuse (drugs and/or alcohol)
• Unacceptable risk for substance abuse (drugs and/or alcohol)
• History of non-compliance, or inability to adhere to a strict medical regimen
• Severe, uncontrolled psychiatric disease
A liver transplant involves the removal of and preparation of the donor liver, removal of the diseased liver, and implantation of the new organ. The liver has several key connections that must be re-established for the new organ to receive blood flow and to drain bile from the liver. The structures that must be reconnected are the inferior vena cava, the portal vein, the hepatic artery, and the bile duct. The exact method of connecting these structures varies depending on specific donor and anatomy or recipient anatomic issues and, in some cases, the recipient disease.
For someone undergoing liver transplantation, the sequence of events in the operating room is as follows:
2. Evaluation of the abdomen for abnormalities that would preclude liver transplantation (for example: undiagnosed infection or malignancy)
3. Mobilization of the native liver (dissection of the liver attachments to the abdominal cavity)
4. Isolation of important structures (the inferior vena cava above, behind, and below the liver; the portal vein; the common bile duct; the hepatic artery)
5. Transection of the above mentioned structures and removal of the native, diseased liver.
6. Sewing in the new liver: First, venous blood flow is re-established by connecting the donor's and the recipient's inferior vena cava and portal veins. Next, arterial flow is re-established by sewing the donor's and recipient's hepatic arteries. Finally, biliary drainage is achieved by sewing the donor's and recipient's common bile ducts.
7. Ensuring adequate control of bleeding
8. Closure of the incision
As with any surgical procedure, complications related to the operation may occur, in addition to the many possible complications that may happen to any patient who is hospitalized. Some of the problems specific to liver transplantation that may be encountered include:
Primary non-function or poor function of the newly transplanted liver occurs in approximately 1-5% of new transplants. If the function of the liver does not improve sufficiently or quickly enough, the patient may urgently require a second transplant to survive.
• Hepatic artery thrombosis, or clotting of the hepatic artery (the blood vessel that brings oxygenated blood from the heart to the liver) occurs in 2-5% of all deceased donor transplants. The risk is doubled in patients who receive a living donor transplant. The liver cells themselves typically do not suffer from losing blood flow from the hepatic artery because they are primarily nourished by blood by the portal blood flow. In contrast, the bile ducts depend strongly on the hepatic artery for nutrition and loss of that blood flow may lead to bile duct scarring and infection. If this occurs, then another transplant may be necessary.
• Portal vein thrombosis or clotting of the large vein that brings blood from the abdominal organs (the intestines, the pancreas, and the spleen - the organs that belong to the portal circulation) to the liver occurs infrequently. This complication may or may not require a second liver transplant.
• Biliary complications: In general, there are two types of biliary problems: leak or stricture. Biliary complications affect approximately 15% of all deceased donor transplants and up to 40% of all living donor transplants.
1. Biliary leak means that bile is leaking out of the bile duct and into the abdominal cavity. Most frequently, this occurs where the donor and recipient bile ducts were sewn together. This is often treated by placing a stent, or plastic tube, across the connection through the stomach and small intestine and then allowing the connection to heal. In the case of living donor or split liver transplants, bile can also leak from the cut edge of the liver. Typically, a drain is placed and left during the transplant operation along the cut edge to remove any bile that may leak. As long as the bile does not collect in the abdomen, the patient does not become ill. Leaks will often heal with time, but may require additional treatment procedures.
2. Biliary stricture means narrowing of the bile duct, resulting in relative or complete blockage of the bile flow and possible infection. Most frequently, the narrowing occurs at a single site, again where the donor and recipient ducts are sewn together. This narrowing can often be treated by dilating the narrowed area with a balloon and/or inserting a stent across the stricture. If these methods are unsuccessful, surgery is often done to create a new connection between the liver's bile duct and a segment of intestine. Rarely, biliary strictures occur at multiple or innumerable sites throughout the biliary tree. This occurs most frequently because the biliary tree was poorly preserved during the period when the liver was not in either the donor or recipient circulation. Livers procured from cardiac death donors are at higher risk than those from brain dead donors. Alternatively, diffuse biliary strictures may occur if the biliary tree has inadequate blood supply because of an abnormality with the hepatic artery.
• Bleeding is a risk of any surgical procedure but a particular risk after liver transplantation because of the extensive nature of the surgery and because clotting requires factors made by the liver. Most transplant patients bleed a minor amount and may get additional transfusions after the operation. If bleeding is substantial or brisk, return to the operating room for control of bleeding is often necessary. In general, approximately 10% of transplant recipients will require a second operation for bleeding.
• Infection - Infections can occur during the healing of the wound created by any operation. Liver transplant recipients are also at risk for infections deep within the abdomen, particularly if there is a collection of blood or bile (from a bile leak). The immunosuppressive medications along with the history of liver failure increase the liver transplant recipient's risk for developing an infection after transplantation.
MBBS (Gold medalist), MS (Gold medalist), DNB (All India Gold medalist), MNAMS (IND), MRCS (UK), FICS (USA), DNB (SGE & HPB), FMAS (AMASI), Fellow HPB & Liver Transplant (Sir Gangaram, Apollo, Del), CC Lap Solid Organ Surgery (Ethicon), CC Endohernia (Ethicon), CC Lap Colorectal (Galaxy, Pune) / Lap UGI surgery and VATS (Calicut), OB. Fellow HPB & GIS (SGPGIMS, Lucknow / GB Pant, Del).
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