- 1-800-248-1199
Liver Diseases
|
A. Alagille's Syndrome Biology:Alagille's syndrome is a condition in which the liver contains too few of the tiny bile ducts which are inside the liver. This leads to blockage of bile flow, which causes jaundice. In addition, patients with Alagille's syndrome have several other features. A narrowing of the pulmonary artery, a vessel which leads from the heart to the lungs, is called pulmonic stenosis. While usually the heart disease in Alagille's is mild, some babies have very serious heart problems. Patients with Alagille's syndrome also have a characteristic facial appearance, with deep, wide-set eyes, a round forehead and a pointed chin. An ophthalmologist may detect an eye finding called posterior embryotoxon in most patients with Alagille's. This does not affect vision. Some patients with Alagille's have cysts on their kidneys or a mild kidney problem called renal tubular acidosis, where the body fails to eliminate acid adequately. Sometimes the bones of the back, the vertebrae, are malformed in Alagille's syndrome. This is not apparent when the child is examined, but may be picked up on x-rays which show "butterfly vertebrae". Children with Alagille's syndrome are shorter than children without the syndrome, even if they have good nutrition. About a third of the time, patients with Alagille's have "pancreatic insufficiency". In this condition, the pancreas does not make enough enzymes to help digest the food. Diarrhea can result.Alagille's syndrome is genetic. Since it is "autosomal dominant", a parent with the syndrome has a 50% chance of passing it on to each child. Sometimes an Alagille's patient has newly developed the gene abnormality and did not inherit the disease from a parent. Symptoms of Alagille's syndrome include jaundice in the first weeks of life. The characteristic facial appearance may not be apparent until the child is older, and the facial appearance of Alagille's can vary widely. A heart murmur can often be heard in babies with Alagille's, contributing to the diagnosis of the syndrome. The jaundice in Alagille's syndrome may improve after the first few years of life, when bile flow improves. While these patients remain jaundiced, many are troubled by severe itching. Cholesterol deposits called xanthomata may appear on the skin as a result of poor flow of bile salts, which affect the body's metabolism of cholesterol. Diagnosis:The diagnosis of Alagille's syndrome is suspected in the jaundiced baby with a heart murmur and characteristic appearance. Blood work typically shows an elevated bilirubin with an elevated conjugated fraction. The ALT, AST, alkaline phosphatase and gamma GT are elevated, with a more striking elevation of the alkaline phosphatase and gamma GT. Liver ultrasound in these patients is usually normal. DISIDA scan may show slow bile flow but in general shows no blockage to bile flow in patients with Alagille's. Sometimes, however, the rare and tiny ducts in Alagille's syndrome cause the DISIDA scan to appear as if there is a complete blockage to bile flow when really there is not. The characteristic lack of bile ducts in Alagille's is proven on liver biopsy. In a large enough biopsy specimen, the pathologist counts the areas of the liver called portal areas, which contain bile ducts. When very few portal areas contain bile ducts, the pathologist labels this as "paucity of bile ducts". This is typical in Alagille's syndrome. There is a genetic (blood) test for Alagille's now, but it cannot detect every case.Treatment:There is no specific treatment of Alagille's syndrome. Since the poor bile flow leads to poor absorption of fat, these babies may not grow well. Careful attention must be paid to their nutrition. They often do better on a formula that has fat in the form of MCT oil, which does not require bile salts to be absorbed. Patients with Alagille's syndrome have striking deficiencies in vitamin A, D, E and K, because they lose fat, hence these fat-soluble vitamins, in their stool. Patients with Alagille's require supplementation of these vitamins, sometimes in doses that are 20 times what normal babies require. The pediatric gastroenterologist monitors levels of these vitamins carefully, while supplementing them, to avoid overdosing and to make sure to give enough to avoid vitamin deficiency. Itching in Alagille's is treated with a variety of agents described in the chapter on itching. None of these medicines have been proven to actually affect the course of the disease. Recently, an operation has been described for the treatment of severe itching in Alagille's syndrome. In this operation, the bile flow is diverted away from the intestine, where it normally flows, and instead is directed toward the skin where the bile exits through an opening and is drained into a little bag. This loss of bile salts outside of the body is thought to stimulate better bile flow inside the liver. In some patients, this results in substantial relief of the itching. This has only been described in a few patients and studies are underway. Liver transplant has also been done for Alagille's syndrome. About 20% of patients with Alagille's syndrome ultimately come to liver transplantation because of poor liver function or other complications. Many such patients have done very well after transplant. Obviously, the other problems in Alagille's may require further medical attention, especially if heart or kidney disease is severe.
Biology:Alpha-1-Antitrypsin Deficiency is a disease which occurs when the body makes an abnormal protein which accumulates in liver cells. The accumulation of this protein can cause jaundice in infants, and can cause cirrhosis (scarring of the liver), portal hypertension and liver failure later in life. The jaundice in infants with alpha-a-antitrypsin usually resolves in the first year of life. Less than half of those children will develop chronic liver disease later. Sometimes older children or adults with a new diagnosis of cirrhosis and portal hypertension are found to have alpha-1-antitrypsin deficiency. The disease can also cause emphysema. Patients with alpha-1-antitrypsin deficiency may develop emphysema in their 40's, particularly if they are exposed to cigarette smoke.Not everyone with alpha-1-antitrypsin deficiency, however, develops liver disease. A large study in Sweden revealed that actually only 15% of people who have alpha-1-antitrypsin deficiency actually develop obvious liver disease. The same abnormality in the other 85% of people causes no obvious disease. Researchers are actively investigating why some patients with alpha-1-antitrypsin deficiency may develop progressive liver disease while others are essentially normal. It seems that a second abnormality in liver cells in addition to the abnormally folded protein may stimulate the progression of liver disease. Alpha-1-antitrypsin deficiency is a genetic disease. This means that it is transmitted through an abnormal gene. It is an "autosomal recessive" gene, which means that if the mom and the dad both carry the alpha-1-antitrypsin deficiency Z gene, 1 out of 4 of their children will inherit both abnormal copies of the gene, making a child who has alpha-1-antitrypsin deficiency (called ZZ since the child inherits an abnormal gene from each parent). Prenatal diagnosis of alpha-1-antitrypsin deficiency is possible, although parents wishing testing should remember that most children who have the alpha-1-antitrypsin deficiency (ZZ) do not have clinical liver disease. Diagnosis:Alpha-1-antitrypsin deficiency can be diagnosed through a simple blood test. First of all, an alpha-1-antitrypsin level in the blood can be done. Patients with alpha-1-antitrypsin deficiency have a very low alpha-1-antitrypsin level. The more specific test is an alpha-1-antitrypsin phenotype. This test actually looks for the abnormal protein (or the Z protein). A normal person has the phenotype MM. A carrier, who is in general a healthy person, will have MZ. A person affected with alpha-1-antitrypsin deficiency will be ZZ. There are other less common abnormal proteins such as the S protein. An S in combination with a Z can cause liver disease like alpha-1-antitrypsin ZZ does. Most authorities agree that alpha-1-antitrypsin MZ carriers do not manifest serious liver disease. Other testing for alpha-1-antitrypsin deficiency can include routine biochemical tests of liver function (see appropriate chapter) or may include a liver biopsy. The liver biopsy in alpha-1-antitrypsin deficiency can show inflammation and scarring. The liver cells, when stained with a special substance, show accumulation of red globules of alpha-1-antitrypsin protein within the cells.Treatment:Scientists are working actively to discover a treatment for alpha-1-antitrypsin liver disease. No effective treatment exists at this time. During the period when the baby is jaundiced and the liver is not working normally, nutritional support and supplementation of fat-soluble vitamins is very important. Once the jaundice resolves the child should be followed at regular intervals for the development of evidence of progressive liver disease. Half of these previously jaundiced babies will have no later evidence of liver disease. Children with alpha-1-antitrypsin deficiency often have an enlarged liver. If scarring of the liver progresses, enlargement of the spleen may also be seen. Blood studies can be done to assess liver function; liver enzymes may remain elevated. In the event of severe liver disease due to alpha-1-antitrypsin deficiency, liver transplantation can be done with excellent success.Biology:Autoimmune hepatitis is a form of liver disease which occurs when the immune system of the body attacks the liver. This attack of immune cells on the liver causes elevation of liver enzymes as liver cells are injured and burst, releasing enzymes into the bloodstream. Decreased liver function may make the child appear to be jaundiced due to high bilirubin levels. Fatigue can be seen. Many patients with autoimmune hepatitis have no symptoms at all; their elevated liver enzymes are discovered accidentally when routine blood work is done. Other patients with autoimmune hepatitis, however, may present suddenly with acute liver disease with jaundice, abdominal pain and sometimes even liver failure.Diagnosis:There are several pieces of information that lead to the diagnosis of autoimmune hepatitis. First of all, the liver enzymes (SGOT and SGPT/AST and ALT) are typically elevated due to the injury to liver cells. An immune protein in the blood, IgG, is often elevated as well. Further testing for autoantibodies is done. An autoantibody is an abnormal protein that forms against normal proteins of the body. One test called an ANA looks for an antibody against nuclei of cells. A second test is called anti-smooth muscle antibody. As the name implies, this is a protein that reacts to the muscles in the lining of the intestine and other tissues. In type I autoimmune hepatitis, the ANA and anti-smooth muscle antibody are elevated, helping doctors to make the diagnosis. There is a less common form of autoimmune hepatitis in children. The blood test that is abnormal in this disease is called anti-liver-kidney microsomal antibody (LKM). In this autoimmune disease of young people, other autoimmune diseases outside of the liver can be seen (thyroid problems, celiac disease, white patches of skin, etc).A liver biopsy is helpful in making the diagnosis of autoimmune hepatitis. The pathologist sees a typical picture of immune cells chewing away at the liver in the areas around the bile ducts and blood vessels. Cirrhosis or scarring of the liver is often present. In some young patients with autoimmune hepatitis, the initial biopsy may not have typical findings and may instead look like "acute hepatitis". Treatment:Autoimmune hepatitis is treated by suppressing the immune system so the body cannot react to and injure the liver. High dose prednisone (corticosteroid) therapy is the most common way to begin. Liver enzymes typically drop rapidly. Efforts are made to lower the prednisone dose while keeping the liver enzymes close to normal. A drug named Imuran or azathioprine may help suppress the immune system so that less prednisone is needed. Many patients require this immuno-suppressive therapy lifelong in order to keep the inflammation and injury to the liver under control. Sometimes patients can be weaned from immunosuppression; these patients should be followed closely to make sure their hepatitis does not relapse. Some physicians do repeat liver biopsy later during treatment to make sure that the hepatitis is under good control, limiting further injury or scarring.General:Biliary atresia is a disease which presents in infancy with jaundice. Babies with biliary atresia are born with underdeveloped or blocked bile ducts. This means that bile from the liver is unable to reach the intestine, where it normally works to help digest food. These babies usually look yellow at a few weeks of age. They may have white-colored stools and dark urine. Without treatment, biliary atresia progresses to liver failure and death within the first two years of life. Fortunately, surgical advances in the last few decades offer hope to these children.Biology:The cause of biliary atresia is not known. Causes that have been considered before have included infection, environment, genetics, or a combination of these. Exciting research is now giving doctors clues to the answers of some of these questions.Diagnosis: Blood Work:Babies with biliary atresia have a high bilirubin (see lab section); the conjugated bilirubin, the kind of bilirubin that is released from the liver, is elevated. The liver enzymes ALT and AST are usually elevated several times above normal. The GGT and alkaline phosphatase, which often reflect bile duct problems, are markedly elevated in this condition.X-Rays:An ultrasound of the liver is often performed in babies with suspected biliary atresia. Unfortunately, the poorly formed ducts do not show up so that biliary atresia cannot be diagnosed on ultrasound. 90% percent of biliary atresia babies have no gallbladder; this finding on ultrasound may be helpful. More importantly, the ultrasound can help to exclude other problems that might block bile flow. These might include a tumor near where the bile ducts enter the intestine, or a congenital abnormality called a choledochal cyst, where a large dilated duct structure interferes with bile flow. A nuclear medicine study called a hepatobiliary scan is often done (see x-ray section). Failure to excrete the radioactive dye into the intestine at 24 hours suggests the possibility of blockage to bile ducts, although other liver problems may cause this picture as well.Liver Biopsy:Liver biopsy can also help support the diagnosis of biliary atresia. Babies with biliary atresia have a lot of inflammation (immune cells) in their liver accompanied by lots of scar tissue; because the large bile ducts are blocked, the biopsy shows increased numbers of the tiny bile ducts present in the liver.Surgery:A characteristic biopsy might lead the gastroenterologist to recommend a more certain test. The "gold standard" or most accurate way to diagnose biliary atresia is the intraoperative cholangiogram. The baby is taken to the operating room and the abdomen is opened up by a surgeon. A small tube is placed into the bile duct and dye is injected. If the dye cannot make it down to the intestine or up into the liver, then biliary atresia is present. If the dye goes through the bile duct down into the intestine and up into the liver, the baby does not have biliary atresia. A liver biopsy is taken during this operation.Treatment:Prior to the 1950's there was no effective treatment for biliary atresia and almost all of these babies died in the first two years of life. In the late 1950's, Dr. Morio Kasai in Japan pioneered an operation in which the underdeveloped bile duct is opened up very close to the liver. A loop of the baby's intestine is sewn to that area of the liver so that bile can drain from the liver into the intestine. This procedure is called a portoenterostomy or Kasai operation. The procedure, which should be done as early as possible (before 2-3 months of age preferably), is only successful in establishing bile flow in about half of all patients. Long-term relief from liver problems is only seen in about a third of babies who undergo the Kasai procedure.When the Kasai operation fails, there is no bile flow into the intestine and the bilirubin fails to return to normal. These babies usually require liver transplantation in the next year. Liver transplantation has contributed remarkably to the treatment of babies with biliary atresia. While these jaundiced babies with failed Kasai operations await liver transplantation, their nutritional status must be preserved. Those babies are usually fed a formula which is predigested and contains MCT oil so that bile is not required to absorb the fat. Vitamins A, D, E and K may need to be supplemented, since vitamins which dissolve in fat may be lost in the stool of babies with poor bile flow. Aggressive nutritional support, monitoring of fat-soluble vitamin levels, and monitoring for complications of biliary atresia are important while these babies await a new liver. When the Kasai operation is successful, the bilirubin gradually drops over the next weeks to normal and the stools once again get a dark or green color. Babies who have undergone a successful Kasai operation usually grow and develop normally. Sometimes after months and often after many years, the babies do go on to develop advanced scarring in the liver (cirrhosis), even though their operation was successful. These children suffer complications of portal hypertension (see chapter on cirrhosis) which may include ascites (fluid in the abdomen), bleeding from the intestine, etc. More than 80% of children who have had a successful Kasai will require liver transplant some time in their lives. The Kasai operation, however, often gives the child years to grow and develop before liver transplantation is required. Complications of Biliary Atresia:Follow-up with a pediatric gastroenterologist is key for infants with biliary atresia, so that growth can be assessed and the child can be monitored for the development of progressive liver disease. A potential complication of biliary atresia is called ascending cholangitis. Germs from the intestine climb up through the loop of intestine placed during the Kasai operation and into the liver and bile ducts. Fever is the most important symptom of cholangitis, though right upper abdominal pain, jaundice, as well as other GI symptoms may occur. Episodes of cholangitis are treated with intravenous antibiotics; in some centers, corticosteroids are used as well. Many biliary atresia patients are kept on an antibiotic all of the time to prevent infection. Portal hypertension develops in many children with biliary atresia whether the Kasai operation was successful or not. Enlargement of the spleen, fluid collecting in the abdomen or intestinal bleeding may result. While cirrhosis from biliary atresia may be stable for years, liver failure can develop over time.E. Cirrhosis and Portal Hypertension Cirrhosis is a term used to describe extensive scarring of the liver. A variety of conditions lead to the deposition of scar tissue or "fibrosis" in the liver. When this fibrosis is advanced, it reorganizes the liver into units that do not have normal circulation. This condition is called cirrhosis. Cirrhosis describes scarring of the liver but does not tell how the liver works. A patient with cirrhosis may have normal functioning of the liver for a long time. A patient with cirrhosis may also develop advanced liver disease. Portal hypertension is a term used to describe a condition in which there is high pressure or backup of blood in the portal vein, the vein that leads from the intestine into the liver. The most common cause of portal hypertension is cirrhosis. If the liver is very scarred, blood flow cannot enter the liver normally. Blood backs up and the pressure in the portal vein is high. Portal hypertension can lead to a number of complications. The blood can back up into the splenic vein causing an enlarged spleen. This can be felt on physical exam. The enlarged spleen may trap white cells and platelets so that the patient's white blood cell count and platelet count are low. The blood from the portal vein can also back up into veins in the esophagus called varices. These varices are large vertical linear veins in the esophagus that resemble hemorrhoids. These can break open and cause the patient to throw up blood. Varices can also appear in the small intestine and even in the large intestine around the rectum. A third potential complication of portal hypertension is ascites. Ascites is the collection of fluid in the abdomen outside the organs. This may cause the abdomen to appear very distended and full of fluid. This can make the patient uncomfortable. A fourth problem that can occur in portal hypertension is encephalopathy (see the section on encephalopathy). Patients with portal hypertension do not have normal blood flow through the liver, which normally permits the liver to purify the blood. Substances which should have been cleaned up by the liver instead back up into the portal vein and circulate through the patient's body. This may cause behavioral or mental changes. Often complications of portal hypertension can be managed medically. Please refer to the Endoscopy Section for endoscopic management of GI bleeding. Ascites can often be managed with medications or with paracentesis, a procedure in which some of the extra fluid is removed with a needle temporarily inserted into the abdomen. Medications can be used for encephalopathy. When problems from portal hypertension are severe, however, more invasive treatment may be needed. If the patient has severe and unmanageable ascites, or severe and difficult to treat GI bleeding from the portal hypertension, procedures can be done to decrease the portal pressures. The TIPS procedure (see procedure section), can be done to bypass the portal vein so that pressures do not build up in it. Surgical shunts can also be done to relieve portal hypertension. These procedures are usually reserved for severe symptoms. Several prevention measures are recommended for patients with cirrhosis. Because patients with cirrhosis are especially susceptible to certain infections, they should be immunized with pneumococcal, hepatitis A (usually by request), and hepatitis B (usually routine) vaccines. Ibuprofen should be avoided since it can cause bleeding and injure the kidneys of patients with cirrhosis. Tylenol can be used cautiously since it can also hurt the liver. Sometimes, especially in children, portal hypertension occurs without liver disease. This is called extrahepatic portal hypertension, and results from a clot or narrowing in the portal vein leading to the liver. These children have normal liver function but have a buildup of pressure in the portal vein which can result in an enlarged spleen, GI bleeding, etc. These patients are different from patients with cirrhosis in that the liver itself is normal and functions well. If intestinal bleeding or ascites are persisting problems in these children, TIPS or surgical shunts can be done to reduce the pressure. F. Cystic Fibrosis - Related Liver Disease Cystic fibrosis (CF) is a genetic disease in which thick secretions cause chronic lung disease. Because bile is also too thick to flow properly, scarring of the liver occurs. In most CF patients, the mild scarring does not cause clinical problems. In a few percent, however, significant liver disease develops. As the liver develops cirrhosis, blood backs up into the spleen and esophagus (see section on cirrhosis/portal hypertension). Bleeding, ascites, and other problems can develop. In advanced disease, jaundice and poor blood clotting are seen. The only treatment for CF-related liver disease is supportive. That means nutrition and medicines are used to keep the patient as healthy as possible. URSO (Actigall) may be used to promote bile flow. Liver transplant has been done successfully in CF liver disease. Fulminant hepatic failure (FHF) is defined as severe liver failure occurring within 6 weeks of onset of jaundice. The term is used to describe sudden liver failure in someone who was previously healthy. FHF may be due to a virus, an overactive immune system ("autoimmune"), a drug reaction or other causes. Often, its cause cannot be determined at all. The hallmark of FHF is encephalopathy. When the liver is failing, toxins accumulate and the brain does not function well. Patients with FHF may be confused and combative early on, but may progress to coma. Death due to brain swelling can occur. Infection is another very common complication in FHF. Since the liver cannot make clotting factors, bleeding can be life threatening. Because the liver cannot conjugate or excrete bilirubin, the patient is deeply jaundiced. Children with FHF require intensive care unit (ICU) support. While recovery can occur, as coma deepens the chance of recovery becomes very low. Liver transplant can be a lifesaving solution for patients with FHF. Biology:Hepatitis B is a virus which infects the liver. It lives in liver cells and also in cells of the immune system. When the hepatitis B virus infects the liver, immune cells are attracted to the liver to help fight the infection. These immune cells cause a lot of the damage that is caused by hepatitis B.Hepatitis B used to be called "serum hepatitis" because it is transmitted through blood and body fluids. Before blood was screened so carefully, it was frequently transmitted by blood transfusions. Hepatitis B can be transmitted if a person is cut or poked with a needle or sharp object that has blood from a patient with hepatitis B on it. That makes piercings, tattoos and IV drug abuse ways that patients acquire hepatitis B. Hepatitis B can also be transmitted through sexual intercourse. Hepatitis B is not transmitted through urine or stool. Hepatitis B behaves differently in different people. Most adults who acquire hepatitis B get over it completely (they develop surface antibody). Only 10% of adults who are infected with hepatitis B are chronically infected. In contrast, most babies who are infected with hepatitis B carry the virus their whole lives and become "chronically infected". Some patients who are chronically infected with hepatitis B are called "carriers". Carriers have the virus in their liver and bloodstream, but the virus is not causing significant ongoing damage. Those patients have normal liver enzymes. While carriers are usually not biopsied, liver biopsy will show relatively normal liver. Other patients, however, develop "chronic active hepatitis" from their hepatitis B. That means that the liver is undergoing damage from the hepatitis B and the immune cells that it causes to accumulate in the liver. Patients with chronic active hepatitis will have abnormal liver biopsies. They will have elevated liver enzymes which imply ongoing damage to the liver. Over years, usually over decades, hepatitis B can progress to serious liver disease with cirrhosis and liver failure. Again, this is usually after many years and is very uncommon during childhood. Hepatitis B patients, particularly those with cirrhosis, are at increased risk for liver cancer, which the hepatitis B virus helps to grow. Those patients should be monitored, usually with blood tests and ultrasound, for development of liver cancer. Diagnosis:Your doctor will probably order blood work to confirm your child's hepatitis B. Several blood tests can be ordered.
Treatment:Doctors have had great difficulty coming up with a good treatment for hepatitis B. There has been, to date, no effective treatment for hepatitis B carriers. Carriers, people who are surface antigen positive and have normal liver enzymes, are not usually treated. There are two possible treatments that have been studied for chronic active hepatitis B in children. (These children, unlike carriers, have elevated liver enzymes and abnormal biopsies). The first treatment that was studied and subsequently FDA-approved was Interferon. Interferon is a protein that the body normally makes to modulate the immune system and to fight viruses. This has been made in pure form in the test-tube and can be given in high doses. Treatment consists of injections of Interferon under the skin three times a week for a six-month period. This treatment has a number of side effects which can include (see medication section) fevers, chills and flu-like symptoms for the first few doses, low white blood cell counts, depression and GI symptoms. Less commonly eye, lung, heart, skin and seizure problems have been reported. This treatment is effective only about 25% of the time. When the treatment works, patients lose hepatitis Be antigen and become Be antibody positive. The liver enzymes in responders return to normal and the hepatitis B DNA in the blood becomes negative. In spite of this, however, most responders remain surface antigen positive and continue to carry the virus, even though the liver disease improves. Only about 10% of patients treated with Interferon completely get over the hepatitis B virus, becoming hepatitis B surface antigen negative and surface antibody positive.More recently, a second drug for hepatitis B in children has been licensed by the FDA. This drug is called Lamivudine, (its old name was 3TC). This drug is given daily in a pill or liquid form and treatment is continued for a year or more. This drug has very few serious side effects, although it can rarely cause acidosis (an excess of acid in the bloodstream) or pancreatitis. The drug can induce the virus to "mutate" or change so that the drug no longer works on it; this occurs as much as 40% of the time, although this mutated virus does not usually appear to be very harmful. Again, about 25% of treated children respond to the drug by becoming hepatitis Be antigen negative/Be antibody positive, normalizing their liver enzymes, and becoming hepatitis B DNA-negative in the blood. Almost all of these patients continue to be surface antigen carriers. There is active research going on looking for new treatments for hepatitis B, and several new drugs and combinations are being investigated. Patients with chronic active hepatitis B should be followed carefully. Their blood counts and liver enzymes should probably be checked at least yearly with an occasional alfa-fetoprotein test and ultrasound. Yearly physical exams should be done to look at liver size and to make sure the spleen is not increasing in size (which would imply progressive scarring of the liver). At follow-up visits, possible new therapies can be discussed. Patients with hepatitis B should be immunized against hepatitis A so that the liver is protected from getting a second infection. They should be cautioned that alcohol is a toxin to the liver and can cause further liver injury. Prevention is an important concern to the patient with hepatitis B and to his or her family. Hepatitis B is a preventable disease because hepatitis B immunization is available. All household contacts of patients with hepatitis B should be immunized to prevent transmission within the household. If someone who is not immunized is exposed to hepatitis B because he is poked with a contaminated needle or razor, hepatitis B immune globulin can be given to prevent transmission of the infection. Any blood spills should be cleaned with a solution of 5% bleach and the person cleaning the spill should wear gloves. Because the virus is sexually transmitted, condom/barrier contraception should be used to prevent sexual transmission of the infection. Obviously, when having children is planned the sexual partner can be immunized. Babies of mothers with hepatitis B can be treated with immunizations and hepatitis B immune globulin at birth; infection can be prevented 90% of the time. The family should be careful not to share nail clippers, razors, toothbrushes or any other item that might be contaminated with blood. Parents often struggle with issues of who to inform regarding the child's hepatitis B. Some parents disclose fully to classmates, the teacher, the school nurse, etc. Other parents chose to tell only a limited number of people about the hepatitis B. The American Academy of Pediatrics Infectious Disease Red Book states that children with hepatitis B who have no special risk factors (such as aggressive behavior with biting, bleeding problems or severe skin rashes) should be admitted to childcare/school without restrictions. Biology:Hepatitis C is a virus which infects the liver. Like hepatitis B, some of the injury to the liver that accompanies hepatitis C infection occurs because of the immune system that is attracted to the liver to help fight the infection.Hepatitis C can be transmitted a number of ways. Before blood was screened carefully beginning 1991, blood transfusion was a common means of transmitting hepatitis C. People who received blood transfusions prior to 1991 are at risk for hepatitis C and should be tested. Hepatitis C can also be transmitted via needles and sharp objects contaminated with blood which breaks the skin (tattoos, piercings, etc). Hepatitis C is not commonly sexually transmitted. Babies born to mothers with hepatitis C acquire the infection from their mother only about 5% of the time. Interestingly, as many as 40% of adults with hepatitis C do not know how they acquired the infection. More than 80% of patients who acquire hepatitis C are chronically infected. That means that most patients with hepatitis C have the infection lifelong. Some of these patients have very little active liver disease and behave almost like "carriers" of the virus. Another approximately third of chronically affected patients do have ongoing chronic liver injury which is mild and takes many years to do significant damage. In another approximately third of chronically infected patients, progressive liver disease occurs, usually after many years. These patients can progress to cirrhosis, liver failure, and liver cancer. Some encouraging reports of patients who are accidentally discovered as having hepatitis C during routine blood donor screening show very little progression to serious liver disease even after 20 year follow-up. Other follow-up papers describing patients followed in liver clinics are more concerning, showing progression to cirrhosis in a significant proportion of patients over a few years. Progression of liver disease may be slower in children, depending on when and how they acquired the infection. Diagnosis:A number of blood tests can be used to evaluate the patient with hepatitis C. The initial screening test which is done to evaluate the patient with hepatitis C is called a hepatitis C antibody. This test is positive in most patients who have had hepatitis C previously. Sometimes, however, this test result is wrongly or falsely positive. Sometimes a confirmatory test called a RIBA is done. A RIBA looks for antibody to several specific viral proteins. This test is less likely to give a false result if multiple parts of the test are positive. A hepatitis C PCR may be done to look for actual virus in the bloodstream. A qualitative PCR is either positive or negative. A positive PCR shows that there is virus present in the bloodstream. A quantitative PCR gives an estimate of how much virus there is in the bloodstream (this is called viral load). Viral load is typically expressed in International Units/ml or in copies/ml (1,000,000 IU/ml = approximately 2,000,000 copies/ml). More than 2,000,000 copies/ml is considered a high viral load. Occasionally, physicians will order a test called an HCV genotype. This shows which strain of virus is present in the liver. Some genotypes of hepatitis C, such as genotype 3, may have better prognosis and a much better response to interferon than genotype 1B. Most Americans are infected with genotype 1B. Alpha-fetoprotein testing is done in patients who have had hepatitis C for many years to evaluate for liver cancer, which can complicate hepatitis C. Liver enzymes are done as an approximate measure of disease activity. Elevated liver enzymes imply more damage to liver cells and thus more inflammation. Lower enzymes are more reassuring. It should be commented, however, that adult patients with hepatitis C with normal liver enzymes may sometimes have significant inflammation on liver biopsy.Ultrasound scanning is sometimes done in patients with hepatitis C to look at the texture of the liver and to exclude liver cancer. Ultrasound screening for liver cancer once or twice a year is recommended for adult patients with hepatitis C. Liver biopsy is sometimes done to assess the activity of hepatitis C. The biopsy is examined for the degree of inflammation around liver cells as well as the degree of scar tissue formation. Fat deposits are sometimes seen in liver biopsies of patients with hepatitis C. Treatment:Much work is yet to be done to discover an effective treatment for hepatitis C. In adults, interferon therapy alone has been found to clear the virus in less than 20% of treated patients. A combination of ribavirin (an oral drug) and interferon shots three times a week can result in clearance of the virus and normalization of liver enzymes almost 50% of the time. These drugs must be used carefully by an expert since interferon can cause fever, chills, flu-like symptoms, dropping of the white count, depression and other side effects. Ribavirin must be used carefully as well since it can cause red blood cells to burst causing a significant anemia. Even more importantly, it can be very damaging to the developing fetus and must not be used in women who are or might become pregnant. At present, the only FDA-approved treatment for hepatitis C in children ribavirin combined with 3 times a week interferon injections. Recently, work has been done with a long-acting form of interferon called pegylated interferon. Instead of the 3-times-a-week traditional interferon injections, pegylated interferon is given once a week. Combination therapy with either regular or pegylated interferon and ribavirin is usually carried out for an initial 12 weeks. If the patient becomes negative for virus, the therapy is continued for a year. If the patient remains positive for virus, he or she is unlikely to respond to drug, which may be discontinued. Presently, a study is beginning evaluating the combination of pegylated interferon once a week along with ribavirin. Hopefully, more effective therapies are around the corner.Like patients with hepatitis B, patients with chronic hepatitis C should be followed carefully. Blood counts and liver enzymes should be checked at least yearly with an occasional alpha-fetoprotein test and ultrasound. Yearly checkups can evaluate liver size as well as spleen size; the spleen may increase in size if liver scarring progresses. Patients with hepatitis C should be immunized against hepatitis A so that the liver does not acquire a second infection. The patient should be strongly cautioned against drinking alcohol since it is proven that alcohol accelerates the development of scar tissue in patients with hepatitis C. Patients with hepatitis C should be careful not to share razors, nail clippers or other objects which may be contaminated with blood. Any spill of blood should be cleaned with a 5% bleach solution. As we discussed in the section on hepatitis B, families often debate as to whom to inform of their child's hepatitis C status. Once again, the American Academy of Pediatrics Infectious Disease Red Book states that children with hepatitis C with no special risk factors such as aggressive behavior with biting or bleeding problems or skin rashes should be admitted to child care settings without restriction. J. NASH (Non-Alcoholic Steatohepatitis or Fatty Liver) Biology: Fat can sometimes accumulate in the liver. Most commonly, this is due to obesity. Fatty liver can also occur in diabetics, in patients with high cholesterol or triglycerides, and in patients on certain drugs. Sometimes fat accumulates in the liver without causing injury; this is called hepatic steatosis or (non-alcoholic) fatty liver (NAFL). In some patients, however, the fat damages the liver, causing inflammation and scarring. This is called NASH. Researchers are still trying to figure out why this liver damage occurs. It can lead to cirrhosis, even in children.
Diagnosis:NASH is sometimes first identified when blood-work shows elevated liver enzymes such as AST and ALT. There is no specific blood test for NASH. Fatty liver may be detected on ultrasound or CT, although these x-rays do not reveal how much damage is taking place. When liver enzymes are abnormal and NASH is suspected, liver biopsy may be done. This can confirm the presence of fat and determine how much inflammation and fibrosis (scar tissue) is present.Treatment:Researchers are trying to figure out what the best treatment for NASH is. Right now, slow and steady weight loss is the best approach. Limiting calorie intake, avoiding high-fat foods, and decreasing fast food are all helpful approaches. Thirty minutes to an hour of aerobic "break a sweat" exercise each day is recommended. The American Academy of Pediatrics suggests that TV/video/computer activities, which have a strong association with childhood obesity, be kept to less than 1-2 hours/day. Studies are underway to see if vitamin E or metformin (a diabetes drug) may help.Neonatal hepatitis is a term to describe the appearance of jaundice and/or elevated liver enzymes in infants. Typically, babies with the neonatal hepatitis syndrome will have visible jaundice and an elevated serum bilirubin. The conjugated fraction of bilirubin is elevated (this is the part of the bilirubin that reflects liver dysfunction). Liver enzymes such as ALT, AST, GGT or alkaline phosphatase may also be elevated. Infants with neonatal hepatitis may have jaundice as their only symptom. Others may grow poorly or may have an enlarged liver or spleen. Neonatal hepatitis is a term that covers many liver diseases of infants. Some babies who present with neonatal hepatitis will end up having a blockage of bile flow such as that seen in biliary atresia. Others will have a viral infection. A variety of metabolic diseases can also cause a picture of neonatal hepatitis. There remains a group of infants with jaundice and abnormal liver chemistries who never receive a specific diagnosis. Many of these babies with neonatal hepatitis have on liver biopsy a finding called idiopathic giant cell hepatitis. Idiopathic means "we do not know why this is happening". Giant cells are abnormal groups of liver cells fused together. Often, this injury pattern is seen in young livers without reflecting a specific disease. Most babies with idiopathic neonatal hepatitis without a known cause do well, although a few do develop chronic liver disease. Biology:Primary sclerosing cholangitis (PSC) is a disease in which the bile ducts of the liver are abnormal. The ducts develop narrow, scarred areas which obstruct bile flow. These narrowed areas may alternate with swollen areas where bile backs up due to a blockage. The sclerosing cholangitis may occur in the large ducts that drain the liver, in the ducts branching throughout the liver, and sometimes even at a microscopic level. The mechanism of sclerosing cholangitis is thought to be immune in origin, although no one knows exactly why the bile ducts are damaged in this condition.Most patients with sclerosing cholangitis are adults. Teenagers are occasionally diagnosed with sclerosing cholangitis. Some may present to medical attention because they are already known to have ulcerative colitis (90% of patients with sclerosing cholangitis also have an inflammatory bowel disease called ulcerative colitis). Occasionally, they may present to a physician because liver enzymes on routine blood work are abnormal. The child with sclerosing cholangitis may also present with unexplained jaundice due to blockage of bile ducts. Infection in these obstructed bile ducts is called "cholangitis". Fever, right upper abdominal pain and jaundice may occur with cholangitis. Lastly, the child with unrecognized sclerosing cholangitis can present with cirrhosis or scarring of the liver without any obvious jaundice. There is a small group of patients with sclerosing cholangitis who present in the first year or two of life. Many of these children have associated diseases in the immune system. These young patients are rare. Diagnosis:Blood work in the patient with sclerosing cholangitis may show merely mild abnormalities in liver enzymes, but most typically shows an elevation in the gamma GT and alkaline phosphatase; an elevated conjugated and total bilirubin is seen when bile flow is poor. Ultrasound in sclerosing cholangitis may be helpful in revealing dilated ducts, or thickened ducts. Newly developed technology called magnetic resonance cholangiopancreatography (MRCP) may also give good x-ray information regarding the bile ducts and any narrowing or blockage which may be present. The most definitive test is called an ERCP (endoscopic retrograde cholangiopancreatography). In this procedure a scope is placed through the mouth down into the stomach and then the small intestine and a small catheter is placed up into the bile duct. Dye is squirted in and images show the highly typical narrowing and swollen areas of sclerosing cholangitis. Narrow, blocked ducts can sometimes be opened up and drained during ERCP.Treatment:There is no proven treatment for sclerosing cholangitis. Clearly, it is important to diagnose and treat cholangitis, or infection of the bile, in this condition. Ursodeoxycholic acid, which promotes bile flow, has been shown to improve the liver enzymes in patients with sclerosing cholangitis, but does not affect progression of the disease. When one area of the bile duct is extremely narrowed and causes blockage and/or cholangitis, the ERCP scope can be used to insert a balloon to dilate or open up the narrowed area or stricture; the endoscopist can place a stent, a straw-like tube, across the narrowing to allow bile to flow across the obstruction. ERCP can thus be used to treat the strictured bile ducts when they are causing trouble, and to drain an infected area as well. When liver disease is progressive, liver transplantation can be used to treat sclerosing cholangitis as well.As mentioned above, most patients with primary sclerosing cholangitis also have ulcerative colitis and these patients should be monitored for the development of bloody stools or diarrhea. The colitis is often silent in these patients. Sclerosing cholangitis tends to progress over a number of years as the bile ducts become more and more abnormal. This may result in jaundice with progressive decrease in liver function. Recurrent episodes of cholangitis may occur. Even without jaundice, however, significant scarring in the liver may occur, progressing to cirrhosis and end-stage liver disease. The most dreaded complication of sclerosing cholangitis is cholangiocarcinoma, a cancer of the bile duct. This very aggressive tumor can occur in 10% of PSC patients after they have had the disease for ten years. There are few effective treatments to offer patients with cholangiocarcinoma. Biology:Wilson's disease is a metabolic disease in which copper accumulates in the liver. Wilson's disease is inherited as an autosomal recessive, so that two parents who are carriers have a one in four chance of their child having Wilson's. Wilson's disease may present in the teenage or adult years; it rarely presents in small children. A patient with Wilson's disease may be discovered incidentally when liver enzymes are done for another reason and evaluation takes place. Patients with Wilson's disease can also present with severe acute liver failure. After decades, adults with Wilson's disease can present with neuropsychiatric problems as well. Early diagnosis and treatment of Wilson's is essential.Diagnosis:The first screening test often done in Wilson's disease is a serum ceruloplasmin. This copper binding protein is decreased in Wilson's disease. A more accurate test is a 24-hour urine copper collection. The urine copper is elevated in patients with Wilson's disease. It should be noted that there may be mild increases in copper in other chronic liver diseases besides Wilson's. The gold standard for diagnosis of Wilson's disease is a liver biopsy. A piece of the liver tissue is sent to a laboratory that measures the actual copper content of the fragment of liver. A very elevated liver copper content strongly suggests Wilson's disease (again, cirrhosis and other liver diseases can cause mild accumulations of copper). Interestingly, in many patients with Wilson's disease, an eye exam reveals a characteristic finding called Kayser-Fleischer rings.Treatment: Wilson's disease is a treatable disease if it is caught early, before it progresses to severe liver disease, cirrhosis or neurologic problems. Wilson's can be treated a number of ways. Penicillamine is a drug that "chelates" copper, binding it and causing it to be eliminated from the body. This drug has been a mainstay of treatment of Wilson's disease. Penicillamine can cause side effects including poor skin healing, anemia, low white blood cell counts or kidney abnormalities. The doctor will monitor blood and urine studies while penicillamine is being taken. A vitamin called pyridoxine is given since patients on penicillamine can become deficient in this vitamin. It is critical to continue taking penicillamine lifelong, even when the patient feels well, because stopping it can cause liver failure. A second drug that is used in Wilson's disease is zinc. In some centers, this drug is used as first-line therapy. High doses of zinc block the uptake of copper and decrease absorption of copper, helping the body get rid of copper. There are very few side-effects of this therapy. A third drug that is sometimes used is called trientine. This drug also chelates (binds to) copper as does penicillamine. Patients with Wilson's disease are also asked to stay on a low copper diet. Foods high in copper include liver and shellfish. Examination of the home drinking water for increased copper is also sometimes recommended. Occasionally, when liver disease is progressive or when the disease presents with liver failure, liver transplantation may be necessary in Wilson's disease. Excellent results have been seen in this setting.
[Keywords: Gastroenterology, liver diseases, Alagille's Syndrome, Alpha-1-Antitrypsin Deficiency, Autoimmune Hepatitis, Biliary Atresia, Cirrhosis and Portal Hypertension, Cystic Fibrosis, Fulminant Hepatic Failure, Hepatitis B, Hepatitis C, NASH, Fatty Liver, Neonatal Hepatitis, Sclerosing Cholangitis, Wilson's Disease.] Disclaimer: The information provided is not intended to replace the advice of a medical professional. If you have medical concerns, seek the guidance of a medical professional. Consult your physician about any medications, supplements or treatments you are considering, and when seeking treatment, disclose all medications you are taking or treatments you are receiving. Riley Hospital for Children, University Pediatric Associates and IU School of Medicine disclaim any liability for the decisions you make based on this information. |
|
|
Copyright © 2000-2008 Web Design: NetMediaOne |
