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Liver Transplantation
Overview
Liver transplantation involves replacing a patient’s own (“native”) diseased liver with a new liver obtained (“harvested”) from an organ donor. The success of liver transplants over the last 30 years has dramatically changed the care of patients with severe and irreversible liver disease, as this lifesaving procedure can offer a return to good health and normal activities. Most adult patients (“recipients”) who undergo a liver transplant have cirrhosis (extensive scarring of the liver) or a primary liver cancer, whereas most pediatric recipients require liver transplantation due to an inherited liver disease or hereditary abnormality of the bile ducts. A liver transplant is a major surgery and waiting times are long, but most recipients will regain their health and can look forward to returning to their normal activities, although they will need to continue long-term medications to prevent rejection of the new liver. The major limitation to the number of patients that can be helped with liver transplant is the shortage of organ donors resulting in many more potential recipients than available organs. It is of note that the donated liver may be obtained from a deceased person or a living person (the second referred to as living or live donor liver transplantation). This can be particularly important in a potential liver transplant recipient who otherwise might have a long wait for liver transplantation due to relatively low MELD score (see below). For adult recipients a large portion of the live donor’s liver, typically the right lobe, is required whereas for pediatric recipients the smaller left lobe from a live donor is usually adequate.
Symptoms
Patients who require a liver transplant can have a variety of symptoms including jaundice (yellowing of the eyes), ascites (fluid in the abdomen), hepatic encephalopathy (confusion or even coma), and bleeding in the upper and lower gastrointestinal tract from varices (large veins that form in the esophagus or food pipe in patients with cirrhosis). Some cirrhotic patients may have years of ill health whereas in other patients symptoms may develop abruptly and suddenly as for instance with bleeding varices. In some types of cirrhosis, for instance Primary Sclerosing Cholangitis (“PSC”), other symptoms may be prominent such as itching. Additional symptoms experienced by patients who require a liver transplant may include severe fatigue, frequent bruising or loss of muscle mass. Patients, or their partners, may also notice diminished sexual drive. In patients with cirrhosis, primary liver cancer (hepatoma or hepatocellular carcinoma) is an important complication, which fortunately can often be detected by ultrasound, CT or MRI scan at an early stage, when it can still be cured by transplant. A patient who requires liver transplant for this reason may have surprisingly few symptoms as they may not have failure of the non-cancerous liver. In children a frequent reason for liver transplant is biliary atresia, which is failure of the bile ducts, the plumbing system in the liver, to develop in the womb. Babies with this condition develop deep jaundice shortly after birth. Although a surgical repair may be successful in some infants ultimately many children with this condition may again become jaundiced and develop other symptoms of liver failure such as ascites. An uncommon but important indication for liver transplant in both children and adults is acute (“fulminant”) liver failure in which a person with a previously normal liver experiences severe damage to their liver and rapidly lapses into coma. Deterioration in renal function is quite common in patients with liver failure. This may occasionally lead to kidney failure requiring dialysis prior to transplant.
Causes
The causes of liver disease requiring liver transplant are by and large the major types of cirrhosis such as chronic hepatitis C infection, long-term alcohol abuse, nonalcoholic fatty liver disease and other less common forms of cirrhosis such as Primary Biliary Cirrhosis. Nonalcoholic fatty liver disease is an increasingly common cause of liver disease and cirrhosis. This is due to abnormal deposition of fat in the liver and is more commonly seen in patients with obesity, diabetes, high blood pressure and/or high cholesterol. A cause of cirrhosis, which has become less common due to vaccination and the availability of effective antiviral drugs, is infection with the hepatitis B virus. In contrast to most other causes of primary liver cancer, chronic infection with hepatitis B can lead to primary hepatocellular carcinoma even if cirrhosis has not yet developed. Another important type of primary liver cancer, cholangiocarcinoma, develops in the bile ducts and can be a complication of Primary Sclerosing Cholangitis, which is a disease with widespread scarring of the bile ducts. It can be very difficult to diagnose cholangiocarcinoma at an early stage in these scarred ducts and may require several different techniques. Although results for liver transplant have not been as good for patients with cholangiocarcinoma as for primary hepatocellular carcinoma at least some patients with cholangiocarcinoma may do well with transplant if given addition treatments with radiotherapy and chemotherapy. In addition to cirrhosis and/or primary liver tumors, acute or fulminant liver failure is a rare but important indication for liver transplant. This type of liver disease occurs in a previously healthy person who suffers major injury to their liver. Causes include an overdose of acetaminophen, acute infection with one of the major hepatitis viruses such as A or B, and a variety of other causes including injury from other drugs, viruses or unknown.
Risk Factors
The major risk factors that lead to needing a liver transplant are by and large the same risk factors for cirrhosis. These include alcohol abuse, infection with hepatitis C and B, poorly controlled diabetes and obesity leading to fatty liver, in addition to a number of other liver diseases whose causes are poorly understood including PSC, Primary Biliary Cirrhosis, Autoimmune Hepatitis and some hereditary diseases such as hemochromatosis (too much iron in the body) and Wilson Disease (too much copper in the body). In many patients who suffer from cirrhosis there may be more than one cause, for instance a combination of alcohol excess and chronic hepatitis C infection. Some inherited diseases such as Wilson Disease are entirely reversed following liver transplantation.
The diagnosis of cirrhosis does not usually mean that a liver transplant needs to be considered. There are effective medical treatments for many of the major causes of cirrhosis, so liver transplant is only required when a patient develops serious complications of their liver disease that cannot be managed by medical treatments alone. However, even if the cirrhotic patient responds to medical treatment for a complication such as ascites using diuretics (“water pills”) the onset of this major complication of cirrhosis is a warning that the patient is likely to develop increasing problems due to their liver disease. Any patient with cirrhosis even without complications of liver disease needs a regular checkup with a gastroenterologist at least twice a year to monitor for complications including primary liver cancer.
Screening/Diagnosis
Once cirrhosis is suspected, the patient requires a number of tests to determine its cause and severity. The cause of liver disease may be obvious from the history. For instance a history of heavy drinking in a patient suggests that liver disease is due to alcohol excess. In most patients, the accurate diagnosis of the cause of liver disease requires additional workup including blood tests, X-Rays and on occasion liver biopsy. Blood work that is usually ordered includes tests for hepatitis B or C, antibody tests for autoimmune hepatitis and Primary Biliary Cirrhosis, and other tests to exclude excessive iron (hemochromatosis) or excessive copper (Wilson Disease). For some common disorders, like Fatty Liver Disease, there is no single diagnostic test. As a result, the diagnosis is made in patients whose blood tests are negative for other causes of liver disease and whose medical history and physical examination are consistent. Additional blood tests include bilirubin, albumin and INR which indicate the liver’s ability to produce proteins and remove toxic substances from the blood. X-rays are another important part of the workup and include ultrasound, CT Scan and MRI. Although they do not usually diagnose the cause of liver disease they may help in assessing the severity of liver disease in patients who possibly have cirrhosis. These X-rays may show that the liver looks “nodular” or lumpy due to scarring. In addition, X-rays provide details about the blood vessels that provide the blood supply to the liver and drain it. A blood clot in one of these vessels can make the liver disease worse. It is also important for the transplant surgeon to have this information to plan the transplant operation. In addition, X-rays of the liver are useful to look for primary liver cancer (hepatocellular carcinoma) which is common in cirrhosis and affects decisions about liver transplantation. A liver biopsy is not always necessary to diagnose cirrhosis and generally, a combination of blood tests and X-rays are sufficient. In some cases a biopsy may be required to confirm that the patient has cirrhosis or to try to find the cause of the liver disease.
In addition to X-rays and blood tests, other special tests may be performed. These include endoscopy to examine the esophagus (the swallowing tube) and stomach looking for varices, which are veins that form in patients with cirrhosis and can cause major bleeding. Fortunately it may be possible to prevent this by using a type of blood pressure pill (“beta-blocker”) or placing rubber bands (“banding”) during endoscopy to reduce the risk of bleeding.
Treatment
Once a patient’s specialist, typically a gastroenterologist, decides that a patient may need a liver transplant, a referral is made to a transplant center where a number of doctor visits and additional testing occurs. The reason for these is to make sure that the patient does not have any treatment options for their liver disease apart from a liver transplant and that he or she doesn’t have any conditions such as severe heart disease or ongoing drug or alcohol use which would make a transplant less likely to be successful. The patient is assigned a nurse coordinator to oversee their care. The patient typically sees the transplant hepatologist and transplant surgeon in addition to other specialists such as cardiologists if needed. An important part of the workup is a meeting with the social worker to make sure the patient and family have the resources, both emotional and financial, to support the patient before and after the transplant. If the patient has a history of drug or alcohol use they also may be seen by a psychiatrist to come up with a plan to make sure they will not have a relapse after transplant.
Once the patient has completed the workup their case is discussed by all the specialists and staff involved. If everybody agrees the patient is placed on the liver transplant list (“listed”) to wait for new liver. Patients are generally listed according to their Model for End Stage Liver Disease “MELD” score which is a mathematical formula to measure the severity of a patient’s liver disease. MELD scores vary between 5 and 40, with a higher score indicating a worse outcome and therefore a higher priority on the waiting list for available donors. Donor livers are generally assigned based on how high the MELD score is as well as by blood group. In most cases, the time on the waiting list has little bearing on the priority for transplantation. In general, patients are evaluated for placement on the liver transplantation list when their MELD score exceeds 15. There are some exceptions to this, including patients with liver cancer, who are given MELD exemptions to receive a transplant before their cancer progresses especially as liver cancer patients may not have liver failure to give them a MELD score high enough to receive a transplant. Patients who have kidney failure associated with liver failure are sometimes considered for combined liver and kidney transplantation on a case by case basis. While the patient is waiting they are seen for regular checkups including blood tests and X-rays at the transplant center. The patient needs to keep in close contact with their transplant coordinator while waiting for liver transplant.
Once a potential donor organ is identified the patient is notified that there is an “offer”. If the offer looks like it may be suitable the patient is advised to come to the hospital to be prepared for surgery. The operation is generally at least several hours long and involves a team of surgeons. After the surgery the patient is moved to the Intensive Care Unit for the first few days post-transplant. After this, if the recovery is on schedule, the patient will be moved to a regular hospital floor for several days before being discharged from the hospital. The patient will receive medications to prevent rejection. In addition, because these anti-rejection medications make a patient more liable to various types of infection, antibiotics are prescribed. Following transplant the patient is seen to monitor liver function and adjust the doses of the major rejection medications based on blood levels. If the liver tests become abnormal a liver biopsy may be performed to find out if there is rejection present. If so the patient may require additional rejection medications.
Other important issues in the patient who has undergone liver transplant include side effects of the rejection medications such as high blood pressure and diabetes. In addition any patient who has a liver transplant is at increased risk of developing various types of tumors, most frequently skin, so a regular checkup with a dermatologist is crucial.
Despite these concerns, a successful liver transplant allows a patient to return to a nearly normal lifestyle with an increased sense of wellbeing and much better prognosis. With time, the amount of rejection medications can be reduced, further improving the patient’s quality of life.
Liver transplant is truly a modern medical miracle.
Author(s) and Publication Date(s)
Paul Martin, MD, FACG, University of Miami, Miami, FL – Published May 2008. Updated July 2013.