Liver 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 Live Failure
Acute liver failure, also know 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 metabolised by the liver accumulate. Unlike patients within 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 terms “decompensated liver disease.” Although medications can decrease the symptoms caused by the liver failure, liver transplantation represents the only permanent cure.
 

When Is a Liver Transplant Needed?

The initial approach to any liver disease and/or damage is medical treatment. The liver has an amazing ability to regenerate but extensive damage to it caused by some conditions is irreversible. If the treatment or therapy has been proven unsuccessful and the liver can no longer function, a liver transplant remains the only option. Liver transplantation is a surgical procedure whereby a diseased or failing liver is removed and replaced by a whole new liver from a deceased donor (cadaveric) or part of a healthy liver from a living donor (or live donor). Most liver diseases can damage the liver and prevent it from functioning at all, a condition known as liver failure.

About 80% to 90% of people survive liver transplantation. Survival rates have improved over the years due to advances in immunosuppressant drugs which prevent the immune system from attacking the transplanted liver.
 

Types of Liver Transplant

Although liver transplant is considered as the last option for patients with end-stage liver disease, nonetheless it offers patients hope for a second chance at life. There are three types of liver transplantation – cadaveric, living (or live) donor and split-liver (or reduced size).

Cadaveric Liver Transplantation
It is also known as deceased donor liver transplantation. The majority of livers that are transplanted come from brain-dead organ donors where consent is available. A liver transplant from a brain-dead donor (cadaver) needs to occur within 12 to 24 hours after the liver has been removed from the donor for the organ to remain viable. During this time, the surgeon will do a final assessment of the donor liver to ensure that it is healthy and a good match.

Due to personal or religious reasons, or lack of awareness, many people do not come forward to be an organ donor in this way. This causes a shortage of livers for transplantation and many people who needs a liver transplant die while waiting for a compatible liver.

Split-Liver Transplantation
In the past, due to the shortage of paediatric cadaveric donors, there was a higher death rate among children with end-stage liver disease. Changes in the HOTA (Human Organ Transplant Act) led to greater donation and a better understanding of split-liver transplant, which dramatically reduced the number of deaths among children with end-stage liver diseases. In split-liver transplantation, the donor’s liver (an adult) is split into two, and transplanted into a child and another adult both of which are suffering from end-stage liver disease.

Living Donor Liver Transplantation (LDLT)
With the prevalence of liver diseases including Asia, there is an increasing demand for liver transplantation for patients with end-stage liver disease. There is also a worldwide shortage of cadaveric livers and a long waiting list in every country.

Hence, living donor liver transplantation has become an important and effective life-saving option particularly for those with acute liver failure and liver cancer (such as hepatocellular carcinoma, HCC).
 

Who Are Not Candidates for a Liver Transplant?

These are many people with cirrhosis and decompensated liver diseases 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 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

 

Signs and Symptoms of Decompensated Liver Disease

Gastrointestinal bleeding
As the liver becomes increasingly scarred, the resistance to portal blood flow increases leading to increase 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 synthesise many of the proteins circulating in the bloodstream, including albumin. Albumin and other proteins in the blood stream retain fluid in the vascular sparce 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 terms “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 needed into the abdominal or chest cavity.

Encephalopathy
Failure of th eliver 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.
 

Causes of Chronic Liver Injury

Viral Hepatitis

  • Hepatitis B:
  • Hepatitis B is due to a viral infection that causes inflammation, fibrosis and cirrhosis. The hepatitis B virus spreads through contact with infected blood, such as by needle-stick accident, injection drug use, or receiving a blood transfusion before the mid-1980s. Hepatitis B also spreads through sexual contact with an infected person and from an infected mother to child during childbirth.

  • Hepatitis C:
  • Hepatitis C due to a viral infection that causes inflammation, or swelling and damage to the liver. The hepatitis C virus spreads through contact with infected blood, such as from a needle-stick accident, injection drug use, or receiving a blood transfusion before 1992. Less commonly, hepatitis C can be spread by sexual contact with an infected person or at the time of childbirth from an infected mother to her newborn. Hepatitis C often becomes chronic, with long-term persistence of the viral infection. Chronic hepatitis C causes damage to the liver that, over years or decades, can lead to cirrhosis.

Alcoholic Liver Disease
Toxins, including alcohol, are broken down by the liver. However, if the amount of alcohol is too high the liver will be overworked and liver cells can eventually become damaged. Heavy, regular, long-term drinkers are much more likely to develop cirrhosis, compared to other healthy people.

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).

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)
  • 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 through the liver.

Hepatocellular Carcinoma
Hapatocellular carcinoma (HCC) is a primary cancer of the liver, meaning that it originates from abnormal liver cells. Hepatocellular carcinoma 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. Hepatocellular carcinoma most frequently spreads to the lungs or to bones. The risk of spread outside the liver increases with the size of the cancer.

Liver transplantation definitively cures a patient of hepatocellular carcinoma, provided that the tumour 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 hepatocellular carcinoma are eligible for liver transplantation. These criteria define limits of tumour number and size that ensure a very low likelihood of cancer spread outside of the liver.
 

The Liver Transplant Operation

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:

    1. Incision
    2. Evaluation of the abdomen for abnormalities that would preclude liver transplantation (for example: un-diagnosed infection or malignancy)
    3. Mobilisation 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 common bile ducts.
    7. Ensuring adequate control of bleeding
    8. Closure of the incision

 

MELD Score

Much research has gone into trying to understand how to accurately determine how sick a person is from his or her liver disease. A scoring system, called MELD (Model for End-stage Liver Disease), has been identified as highly predictive of the risk of death posed by chronic liver disease.

The MELD score is determined by the results of three objective and readily available laboratory tests:

    1. Total bilirubin, a measure of jaundice
    2. Prothrombin time, a measure of clotting ability
    3. Creatinine, a measure of kidney function. Inputting these three numbers into the following formula yields the actual numerical score.

MELD = 3.8 X log e(total bilirubin [mg/dL]) + 11.2 X log e(creatinine [mg/dL])