How is PALF treated?
All patients with PALF require intensive support, typically in an intensive care unit designed for children. As the liver fails it can affect other organs such as the lungs, heart, brain and kidneys. If other organs are affected, children may require supportive care measures such as a breathing machine, dialysis or intravenous medications to improve their blood pressure. These supportive measures help protect the other organs as the liver tries to heal. In liver injury that is due to a treatable condition, such as autoimmune liver injury or some drug injuries, there may be specific medical treatments that will speed recovery of liver function. Frequently a liver biopsy must be performed to determine these diagnoses. In children who do not have an identifiable cause for their liver failure, all we can offer is supportive care.
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There is no specific treatment for most cases
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Supportive care in an intensive care unit is frequently required
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Injury to other organs is common
Liver Function
Photo taken from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/liver-anatomy-and-functions
The liver has many essential functions
Energy Metabolism
Nutrients from our diet are absorbed through the gut and travel to the liver via the portal vein. This nutrient rich blood passes through the liver before it circulates to the rest of the body. The liver processes sugars, fats and proteins to allow them to supply us with energy or to store them for release during periods of fasting. It regulates how these nutrients are released to the body to support growth. The liver is also responsible for processing the by-products of metabolism, such as ammonia to allow them to be excreted from the body before they accumulate. Patients with liver failure can develop low blood sugar levels that can cause brain and other tissue injury. Liver failure can also lead to a build up of ammonia and other by-products in the circulation that alter brain function. Altered brain function in the setting of liver failure is called hepatic encephalopathy. Some patients with liver failure may require procedures such as blood filtration or dialysis to help remove ammonia and other by-products to help prevent progression of hepatic encephalopathy.
Metabolism of Drugs and Environmental Toxins
Liver cells are equipped with multiple metabolic processes that change the structure of drugs and other chemicals we absorb through our diet to allow these chemicals to be excreted in our urine or bile. These processes are crucial to prevent build-up of harmful products in the blood which could injure other organs. Patients with liver failure may metabolize certain drugs more slowly and physicians caring for these patients need to consider this when selecting drugs and drug doses for patients with liver failure.
Synthesis of Blood Proteins, Including Proteins Essential to Blood Clotting
The liver synthesizes important blood proteins that help maintain the water balance in our tissues and allow our blood to clot when there are injuries to our blood vessels. Patients with failing liver function frequently have spontaneous bruising and bleeding. Infusions of plasma may help correct bleeding when it occurs but must be used cautiously because they can seriously alter the water balance in our body. Procedures such as plasmapheresis may help re-establish a balance of blood proteins when the alterations become life-threatening.
Bile Formation
The liver synthesizes bile which drains through bile ducts into the intestine. Bile is composed of proteins, cholesterol, phospholipids, bile salts and waste by-products including bilirubin. Bile functions like a detergent in the intestine breaking up fat globules into particles that can be absorbed. Extra bile is stored between meals in the gallbladder and is released when we eat. Bile excretion is also the main way that cholesterol is removed from our body. Bilirubin is a pigment and it makes up a small percentage of bile components, but build up of bilirubin in the blood is one of the most important markers for liver malfunction. Bilirubin has a strong yellow color and as it builds up in our blood it causes yellowing of the skin and eyes.
Immunologic Function
The liver is also an important part of our immune system. Blood coming from the gut may contain bacteria from our intestine and this bacteria is filtered out by special immune cells that reside in the liver. These immune cells are also important for regulating immune responses throughout the body and the liver regulates these responses by degrading proteins that fuel immune responses. This regulation helps ensure that immune responses do not lead to harmful inflammation that exceed what is required to handle infections.
Liver Transplantation
Liver transplantation is a surgical procedure that is performed to replace a failing liver with a healthy liver from an organ donor. Approximately 6000 liver transplants are performed per year in the US with 10% of these being performed in children. Acute liver failure is one of the top five disorders that leads to the need for liver transplantation. Deceased organ donors are adults or children that have had a severe neurological injury that has caused brain death. In some circumstances an adult living donor, usually a family member, can donate a portion of their liver to allow transplantation to be performed more quickly than it would be if the patient was waiting for a deceased donor.
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Liver transplantation is a complex procedure and recovery after transplantation takes weeks to months. Patients that receive a liver transplant are critically ill during the first days to weeks as the new liver recovers function and normalizes metabolism and protein synthesis. Patients who receive a liver transplant also need to receive strong medications to suppress the immune system so that their body does not reject the new organ. These medications can also prevent the immune system from fighting infection leading to serious illness that further complicates the recovery. Despite these challenges to recovery, over 90% of patients that receive a liver transplant experience long-term survival. Hospitalization after transplant may extend for weeks to months, but many children return to normal childhood activities within 3 to 6 months of their procedure.
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Supportive Care of Patient with Acute Liver Failure
Children with acute liver failure need detailed medical care that is delivered in a hospital setting and frequently require care in an intensive care unit. Energy metabolism is impaired in acute liver failure which can lead to critically low blood sugar levels. For this reason, children with acute liver failure must have a reliable method to deliver intravenous (IV) fluids that include glucose. The usual method used is a central line catheter. These patients also require frequent blood laboratory monitoring and central line placement can help reduce the number of times a child must be stuck with a needle to obtain a blood sample. It is also very important to monitor brain function in these patients to determine if they are developing hepatic encephalopathy. Progression of hepatic encephalopathy is one of the important signs doctors use to determine if a patient is likely to require a liver transplant to survive.
Some children with acute liver failure develop depressed function of the heart and require IV medications to maintain normal tone in their blood vessels and help their heart pump more effectively. It is also common for children with acute liver failure to develop abnormal kidney function which could require a form of dialysis. When the heart and kidneys are not functioning normally, fluid can build up in the lungs and patients can require support for their breathing. This support includes oxygen, but can progress to require placement of a breathing tube and the support provided by a ventilator (breathing machine). Finally, some children with acute liver failure benefit from exchanging their plasma with plasma from blood donors. This exchange process is called plasmapheresis and helps to eliminate ammonia, other toxins, and inflammatory proteins from the circulation. This process also replaces coagulation factors in a balanced way that may help re-establish normal blood clotting.
Liver Biopsy
A liver biopsy is a small piece of tissue that is removed from the liver, usually through a needle. The piece is processed and then can be examined under a microscope to allow doctors to look directly at the liver cell injury. The pattern of injury that is seen can help determine the cause of the liver damage or at least provide information that can guide a treatment plan. In patients with normal blood clotting, the liver tissue can be removed through a needle that is placed between the ribs on the right side of the body. Children are always given anesthesia and pain medications so that the procedure is less stressful for them.
Bleeding is the most common complication after liver biopsy, but in patients with normal blood clotting serious bleeding is a very rare complication of the procedure. In patients whose blood does not clot normally, the tissue can be obtained through a catheter that enters a vein in the neck and is advanced into the large blood vessels inside the liver. The catheter has a special needle that pulls a piece of liver tissue into the catheter through the wall of one of these blood vessels. With this approach, if the area of liver that is biopsied does bleed, it bleeds directly back into the blood vessel and no blood is lost outside the liver. This approach is called a Transjugular Liver Biopsy and can be performed in children as young as 1-2 years of age depending upon their size. Below is an example of what we can see under the microscope from liver biopsies taken from children with acute liver failure.
PALF Patient Liver
Normal Liver