Veno-occlusive Disease of the Liver

Veno-occlusive disease of the liver is blockage of the very small (microscopic) veins in the liver.

• Fluid tends to accumulate in the abdomen, the spleen may enlarge, and severe bleeding may occur in the esophagus.
• The skin and whites of the eyes may turn yellow, and the abdomen may enlarge.
• Doctors base the diagnosis on symptoms and results of Doppler ultrasonography.
• If possible, the cause is corrected or eliminated, and symptoms are treated.

Veno-occlusive disease is similar to Budd-Chiari syndrome except that blood flow is blocked within (rather than outside of) the liver. That is, blockages do not affect the large hepatic veins and the inferior vena cava (the large vein that carries blood from the lower parts of the body, including the liver, to the heart).

Veno-occlusive disease may occur at any age. It is more common among people who are malnourished.

Because flow out of the liver is blocked, blood backs up in the liver. This backup (congestion) then reduces the amount of blood entering the liver. Liver cells are damaged because they do not get enough blood (ischemia). The congestion causes the liver to become engorged and enlarged. Such outflow obstruction also is transmitted across the liver, increasing pressure in the portal vein (portal hypertension). Portal hypertension can result in dilated, twisted (varicose) veins in the esophagus (esophageal varices). The elevated pressures in the portal vein and the liver congestion lead to fluid accumulating in the abdomen—a disorder called ascites. The spleen also tends to enlarge.

Such congestion reduces blood flowing into the liver. The resulting liver damage leads eventually to severe scarring (cirrhosis).

Causes

Common causes include the following:

• Ingestion of pyrrolizidine alkaloids, which are found in crotalaria and senecio plants (used in Jamaica to make herbal tea) and in other herbs, such as comfrey
• Use of certain drugs that occasionally have toxic effects on the liver, including cyclophosphamide and azathioprine Some Trade Names
  IMURAN
  (used to suppress the immune system)
• Radiation therapy (used to suppress the immune system before bone marrow or stem cell transplantation)
• A reaction after bone marrow or stem cell transplantation (graft-versus-host disease)

In graft-versus-host disease, white blood cells in the transplanted tissue attack the recipient's tissues. This reaction tends to occur about 3 weeks after transplantation.

Symptoms

Symptoms may begin suddenly. The liver enlarges and becomes tender. The abdomen may swell because of fluid accumulating there. The skin and the whites of the eyes may become yellow—a condition called jaundice.

Varicose veins in the esophagus may rupture and bleed, sometimes profusely, causing people to vomit blood and often go into shock. The blood may pass through the digestive tract, making stools black, tarry, and foul-smelling (called melena). When bleeding is severe, shock ensues. A few may experience liver failure with deterioration of brain function (hepatic encephalopathy), resulting in confusion and coma.

Others develop cirrhosis with time, likely over months, depending upon the cause and repeated exposure to toxic agents.

Diagnosis

Doctors suspect veno-occlusive disease based on symptoms or blood test results that suggest liver dysfunction, particularly if people have ingested substances or have conditions (particularly following bone marrow transplantation) that may cause the disease. Blood tests evaluate the liver and blood clotting.

Doppler ultrasonography often confirms the diagnosis. Occasionally, invasive tests may be necessary. Liver biopsy or blood pressure measurements of the hepatic veins and portal veins rarely are necessary. These are done by inserting a catheter into a vein in the neck (jugular vein) and threading it to the hepatic veins. A biopsy of the liver can be taken at the same time.

Prognosis

The prognosis depends on how extensive the damage is and whether the condition causing it recurs or continues—for example, when people continue to drink senecio tea.

Overall, about one fourth of people with veno-occlusive disease die of liver or other organ failure within 3 months. When the cause is graft-versus-host disease after bone marrow transplantation, veno-occlusive disease often resolves on its own within a few weeks. Increasing the dose of drugs used to suppress the immune system can also cause graft-versus-host disease to resolve. If the cause is an ingested substance, stopping its use helps prevent further liver damage.

Treatment

There is no specific treatment for the blockage. If possible, the cause should be eliminated.

Ursodeoxycholic acid helps prevent veno-occlusive disease from developing after bone marrow or stem cell transplantation.

Problems resulting from the blocked vessels are treated. For example, a low-salt (low-sodium) diet and diuretics help keep fluid from accumulating in the abdomen.

An alternate route for blood flow, bypassing the liver, may be created by directly connecting the portal vein to the inferior vena cava. A catheter is inserted in a neck vein (jugular vein), threaded to the portal vein, and used to make this connection (shunt). Then a wire mesh tube (called a transjugular intrahepatic stent) is inserted to keep the shunt open. The effectiveness of such shunts is unclear.

Liver transplantation may be necessary in extreme cases.

Adapted from: Merck & Co., Inc.

Portal Vein Thrombosis

Portal vein obstruction results from thrombosis (blood clot) or narrowing of the portal vein, which brings blood to the liver from the intestines.

• Most people have no symptoms. Fluid may accumulate in the abdomen, the spleen may enlarge, and severe bleeding may occur in the esophagus.
• Doppler ultrasonography can usually confirm the diagnosis.
• If possible, the cause is treated, and drugs may be used to prevent the clot from enlarging or to dissolve the clot.

Because the portal vein is narrowed or blocked, pressure in the portal vein increases. This increased pressure (called portal hypertension) causes the spleen to enlarge (splenomegaly). It also results in dilated, twisted (varicose) veins in the esophagus (esophageal varices) and often in the stomach (portal hypertensive gastropathy). These can bleed profusely. Fluid accumulation in the abdomen (called ascites) is not common but may develop when the blockage of the portal vein is accompanied by liver congestion or damage or when large amounts of fluids are given intravenously to treat major bleeding from ruptured varices in the esophagus or stomach. Portal vein thrombosis that develops in people with cirrhosis will cause their condition to deteriorate.

Causes

About 25% of adults with cirrhosis have portal vein thrombosis, likely from sluggish blood flow. Portal vein thrombosis also can be caused by any condition that makes blood more likely to clot. Common settings differ by age group:

• Newborns: Infection of the umbilical cord stump (at the navel)
• Older children: Appendicitis
• Adults: Excess red blood cells (polycythemia), certain cancers (liver, pancreas, kidney, or adrenal gland), surgery, and pregnancy

Often, several conditions work together to cause the blockage. The cause is unknown in about one third of people.

Symptoms

Most people do not have any symptoms. In some people, problems gradually develop, resulting from portal hypertension. If varicose veins develop in the esophagus or stomach, they may rupture and bleed, sometimes profusely. People then vomit blood. The blood may also pass through the digestive tract, making stools black, tarry, and foul-smelling (called melena). Another vascular complication of portal hypertension is the development of abnormal small veins and capillaries in the stomach (portal hypertensive gastropathy), which may result in gastrointestinal bleeding.

Diagnosis

Doctors suspect portal vein thrombosis in people who have some combination of the following:

• Bleeding from esophageal or gastric varices
• An enlarged spleen
• High-risk conditions (for example, children with umbilical cord infection or acute appendicitis)

Blood tests to evaluate the liver often are quite normal.

Doppler ultrasonography usually confirms the diagnosis. It shows that blood flow through the portal vein is reduced or absent. In some, magnetic resonance imaging (MRI) or computed tomography (CT) is necessary.

Angiography is done if a procedure to create an alternate route for blood flow is planned. For angiography, x-rays of the veins are taken after a radiopaque dye (which is visible on x-rays) is injected into the portal vein.

Treatment

If a blood clot suddenly blocks the vein, a drug that dissolves clots (such as tissue plasminogen activator) is sometimes used. The effectiveness of this treatment (called thrombolysis) is unclear.

If the disorder develops gradually, an anticoagulant, such as heparin, is sometimes used long term to help prevent clots from recurring or enlarging. Anticoagulants do not dissolve existing clots.

In newborns and children, the cause (usually an infected umbilical cord or acute appendicitis) is treated.

Problems caused by portal hypertension are also treated. Bleeding from varicose veins in the esophagus can be stopped using several techniques:

• Usually, rubber bands are inserted through a flexible viewing tube (endoscope), placed through the mouth into the esophagus. The bands are used to tie off the varicose veins.
• Antihypertensive drugs, such as beta-blockers and nitrates, reduce pressure in the portal vein and thus prevent bleeding in the esophagus. (Beta blockers also are used in portal hypertensive gastropathy.)
• Octreotide Some Trade Names
  SANDOSTATIN
  , a drug that also lowers blood flow to the liver and thus decreases blood pressure in the abdomen, may be given intravenously to help stop bleeding.

Occasionally, when these treatments are ineffective, a procedure to create an alternate route for blood flow, bypassing the liver, may be done. Here, the intent is to decompress the portal venous system through creation of a shunt (connection) to the inferior vena cava. The difficulty is creating a shunt when the portal vein is blocked. Also, shunts tend to become blocked.

For some people, liver transplantation is necessary.

Adapted from: Merck & Co., Inc.

Ischemic Cholangiopathy, Ischemic Hepatitis

Ischemic Cholangiopathy

Ischemic cholangiopathy is damage to one or more bile ducts caused by inadequate blood flow.

Bile ducts (such as the hepatic ducts and the common bile duct), unlike the liver, are supplied with blood from only one major blood vessel, the hepatic artery. Thus, disruption of blood flow through the hepatic artery can prevent the bile ducts from obtaining enough oxygen. Consequently, the cells lining the ducts are damaged or die—a disorder called ischemic cholangiopathy. Blood flow can be disrupted by the following:

• Surgical trauma during liver transplantation or removal of the gallbladder by laparoscopy
• Injury from radiation therapy
• A disorder that makes blood more likely to clot (blood clotting disorder)
• A procedure to block a bleeding blood vessel that causes clot formation (embolization)

Ischemic cholangiopathy is mostly commonly seen in those who have had a liver transplant.

Symptoms and Diagnosis

The damaged bile duct narrows (causing a stricture) so that the flow of bile slows or is blocked. As a result, bile pigment (bilirubin) is retained, the skin and the whites of the eyes turn yellow (called jaundice) and the urine becomes dark. As bile (containing pigment such as bilirubin) does not enter the small intestine, the stools become pale. Itching (termed pruritus) is common, often beginning in the hands and feet but usually affecting the whole body. Itching is especially worse at night. Bile duct infection (cholangitis) may also occur, producing abdominal pain, chills and fever.

The diagnosis comes from the symptoms and abnormal blood test results, especially in people who have conditions that make ischemic cholangiopathy more likely (eg, liver transplant recipients). Ultrasonography helps doctors visualize the ducts, but the results may be inconclusive. Better definition often requires magnetic resonance imaging of the bile ducts (a procedure called magnetic resonance cholangiopancreatography or MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). ERCP involves inserting a flexible viewing tube (endoscope) through the mouth and into the small intestine and injecting dye into the bile duct system.

Treatment

In addition to detecting the narrowing of the bile ducts, ERCP can be used in treatment. A wire with a deflated balloon at its end is introduced through the endoscope; doctors inflate the balloon to widen (dilate) the narrowing. A mesh tube (stent) then keeps the duct open.

People who have had a liver transplant on occasion may require another transplant.

Ischemic Hepatitis

Ischemic hepatitis is damage throughout the liver caused by an inadequate blood or oxygen supply.

• Heart or respiratory failure may reduce the blood flow or oxygen supply to the liver.
• People feel nauseated and vomit; the liver may be tender and enlarged.

In ischemic hepatitis, liver cells are damaged or die because the liver does not receive enough blood or oxygen.

Ischemic hepatitis differs from other types of hepatitis. Usually, “hepatitis” implies inflammation of the liver, which can have many causes, most commonly a virus (as in hepatitis A or B). In ischemic hepatitis, however, the liver is not inflamed; rather liver cell death (necrosis) occurs. It is termed hepatitis because, as in viral and other types of hepatitis, liver enzymes called aminotransferases leak from damaged liver cells into the blood.

Causes

For ischemic hepatitis to develop, the liver's requirements for blood, oxygen or both are not being met. The most common cause for such unmet needs is when blood flow throughout the body decreases. Causes include the following:

• Heart failure
• Respiratory failure
• Shock
• Massive bleeding
• Severe dehydration

A severe infection that affects all or most of the body, such as sepsis, can increase the liver's need for oxygen and thus contribute to ischemic hepatitis.

Because the liver receives blood from the hepatic artery and portal vein, narrowing or blockage of one of these vessels does not usually cause ischemic hepatitis. This disorder results when blood flow in both vessels is reduced or blocked. The most common cause of blocked blood vessels is a blood clot. (Blockage by a blood clot is termed thrombosis.) Blood clots in the hepatic artery can have many causes, such as the following:

• Injury of blood vessels (as occurs during liver transplantation surgery)
• Aneurysms of the hepatic artery
• Inflammation of the artery (vasculitis)
• Use of cocaine (causing spasm of the artery)
• Tumors, certain medical procedures, or heart infections (endocarditis) that cause emboli—clumps of material, such as a piece of fatty material or blood clot on the wall of an artery—to break off and travel through the bloodstream and become lodged in a blood vessel

Disorders that make blood more likely to clot (blood clotting disorders) can cause blockages in arteries or veins. These disorders may be inherited or acquired.

Symptoms and Diagnosis

Symptoms include nausea and vomiting. The liver may be tender and enlarged.

Doctors suspect ischemic hepatitis when results of liver biochemical and blood clotting tests are abnormal, especially in people who have a condition that can cause the disorder. Blockage of the hepatic artery can be detected using ultrasonography, magnetic resonance angiography, or x-rays taken after a radiopaque dye (which is visible on x-rays) is injected into an artery (arteriography).

Treatment

Doctors focus on treating the condition that is reducing blood flow to the liver. If blood flow can be restored, ischemic hepatitis commonly resolves. Liver failure can occur if people already have severe scarring of the liver (cirrhosis).

Adapted from: Merck & Co., Inc.

Congestive Hepatomegaly , Ischemic Cholangiopathy

Congestive Hepatomegaly

Congestive hepatomegaly is a backup of blood in the liver, resulting from heart failure.

Severe heart failure causes blood to back up from the heart into the inferior vena cava (the large vein that carries blood from the lower parts of the body to the heart). Such congestion increases pressure in this vein and other veins that carry blood to it, including the hepatic veins (which drain blood from the liver). If this pressure is high enough, the liver becomes engorged (congested) with blood and malfunctions.

In most people, the congested liver causes only mild abdominal discomfort. The liver (in the upper right part of the abdomen) is tender and enlarged. In severe cases, the skin and whites of the eyes may turn yellow—a disorder called jaundice. Fluid may accumulate in the abdomen—a disorder called ascites. The spleen also tends to enlarge. If congestion is severe and chronic, liver damage or even severe scarring (cirrhosis) develops.

Doctors suspect the disorder in people with heart failure who have typical symptoms and abnormal results on blood tests done to evaluate the liver.

Management focuses on treating the heart failure. Such treatment may restore normal liver function.

Ischemic Cholangiopathy

Ischemic cholangiopathy is damage to one or more bile ducts caused by inadequate blood flow.

Bile ducts (such as the hepatic ducts and the common bile duct), unlike the liver, are supplied with blood from only one major blood vessel, the hepatic artery. Thus, disruption of blood flow through the hepatic artery can prevent the bile ducts from obtaining enough oxygen. Consequently, the cells lining the ducts are damaged or die—a disorder called ischemic cholangiopathy. Blood flow can be disrupted by the following:

• Surgical trauma during liver transplantation or removal of the gallbladder by laparoscopy
• Injury from radiation therapy
• A disorder that makes blood more likely to clot (blood clotting disorder)
• A procedure to block a bleeding blood vessel that causes clot formation (embolization)

Ischemic cholangiopathy is mostly commonly seen in those who have had a liver transplant.

Symptoms and Diagnosis

The damaged bile duct narrows (causing a stricture) so that the flow of bile slows or is blocked. As a result, bile pigment (bilirubin) is retained, the skin and the whites of the eyes turn yellow (called jaundice) and the urine becomes dark. As bile (containing pigment such as bilirubin) does not enter the small intestine, the stools become pale. Itching (termed pruritus) is common, often beginning in the hands and feet but usually affecting the whole body. Itching is especially worse at night. Bile duct infection (cholangitis) may also occur, producing abdominal pain, chills and fever.

The diagnosis comes from the symptoms and abnormal blood test results, especially in people who have conditions that make ischemic cholangiopathy more likely (eg, liver transplant recipients). Ultrasonography helps doctors visualize the ducts, but the results may be inconclusive. Better definition often requires magnetic resonance imaging of the bile ducts (a procedure called magnetic resonance cholangiopancreatography or MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). ERCP involves inserting a flexible viewing tube (endoscope) through the mouth and into the small intestine and injecting dye into the bile duct system.

Treatment

In addition to detecting the narrowing of the bile ducts, ERCP can be used in treatment. A wire with a deflated balloon at its end is introduced through the endoscope; doctors inflate the balloon to widen (dilate) the narrowing. A mesh tube (stent) then keeps the duct open.

People who have had a liver transplant on occasion may require another transplant.

Adapted from: Merck & Co., Inc.

Porphyria

Porphyria is a term that refers to a group of disorders—the porphyrias—that affect the nervous system or skin, or both. Each type of porphyria is due to the deficiency of one of the enzymes needed to make a substance in the body called heme. Enzymes are proteins that help chemical reactions happen in the body. Making heme involves a series of eight different enzymes, each acting in turn.

Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has important functions in the body. The largest amounts of heme are in the blood and bone marrow in the form of hemoglobin within red blood cells. Hemoglobin gives blood its red color and carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that have many functions, including breaking down hormones, drugs, and other chemicals and generating high-energy compounds that keep liver cells alive and functioning normally.

The body makes heme mainly in the bone marrow and the liver. The process of making heme is called the heme biosynthetic pathway. Each step of the process is controlled by one of eight enzymes. If any one of the enzymes is deficient, the process is disrupted. As a result, porphyrin or its precursors—chemicals formed at earlier steps of the process—may build up in body tissues and cause illness.

What are the types of porphyria?

The table below lists each type of porphyria and the deficient enzyme responsible for the disorder. Porphyrias are often classified as acute or cutaneous. Acute types of porphyria affect the nervous system, whereas cutaneous types mainly affect the skin. Two forms of porphyria—hereditary coproporphyria and variegate porphyria—may be either acute or cutaneous, or both.

What are the types of porphyria?

The table besides lists each type of porphyria and the deficient enzyme responsible for the disorder. Porphyrias are often classified as acute or cutaneous. Acute types of porphyria affect the nervous system, whereas cutaneous types mainly affect the skin. Two forms of porphyria—hereditary coproporphyria and variegate porphyria—may be either acute or cutaneous, or both.

The most common type of porphyria overall is porphyria cutanea tarda. In the United States, acute intermittent porphyria is the most common acute porphyria.

What causes porphyria?

Most porphyrias are inherited disorders, meaning they are caused by abnormalities in genes passed from parents to children. Scientists have identified the genes for all eight enzymes in the heme pathway. Some forms of porphyria result from inheriting an abnormal gene from one parent. Other forms are due to inheriting two abnormal genes—one from each parent. The risk that members of an affected family will have the disease or transmit it to their children depends on the type of porphyria.

One type of porphyria—porphyria cutanea tarda—is most often an acquired disorder. It occurs when factors other than genes cause an enzyme deficiency in the liver.

Porphyria can be triggered by

• drugs such as barbiturates, tranquilizers, birth control pills, and sedatives
• chemicals
• fasting
• smoking
• drinking alcohol, especially heavy drinking
• infections
• excess iron in the body
• emotional and physical stress
• menstrual hormones
• exposure to the sun

What are the symptoms of porphyria?

People with cutaneous forms of porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. Symptoms of acute forms of porphyria include pain in the abdomen, chest, limbs, or back; numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. Acute attacks of porphyria can develop over hours or days and last for days or weeks.

Symptoms can vary widely in severity. Some people with gene mutations that can cause porphyria have no signs or symptoms of the disorder. These people are said to have latent porphyria.

How is porphyria diagnosed?

Doctors diagnose porphyria using blood, urine, and stool tests. Interpreting test results can be complex, and initial tests may be followed by further testing to confirm the diagnosis. Diagnosis may be delayed because the symptoms of porphyria are similar to symptoms of other disorders.

How is porphyria treated?

Each type of porphyria is treated differently. Treatment may involve avoiding triggers, receiving heme through a vein, taking medicines to relieve symptoms, or having blood drawn to reduce iron in the body. People who have severe attacks may need to be hospitalized.

Points to Remember

• Porphyria is a group of disorders—the porphyrias—that affect the nervous system or skin, or both.
• Each type of porphyria results from a deficiency of one of the enzymes needed to make heme.
• Most porphyrias are inherited disorders, but porphyria cutanea tarda is usually an acquired disorder.
• Cutaneous types of porphyria affect the skin, causing symptoms such as blistering, itching, and swelling.
• Acute types of porphyria affect the nervous system, causing symptoms such as abdominal pain, vomiting, numbness, and mental disorders.
• Each type of porphyria is treated differently.

Liver Cysts and Tumors

Liver cysts occur in approximately 5% of the population. However, only about 5% of these patients ever develop symptoms. In general, cysts are thin-walled structures that contain fluid. Most cysts are single, although some patients may have several. The symptoms associated with liver cysts include upper abdominal fullness, discomfort, or pain. A small number of patients bleed into the cyst, which causes sudden and severe right upper quadrant and shoulder pain. The bleeding stops on its own, and the pain then improves over the next several days. Liver cysts do not impair the liver’s ability to function. The cyst(s) are usually found by ultrasound (US) or computed tomography (CT scan). Simple liver cysts are always benign. The only patients who require treatment for a liver cyst(s) are those who develop symptoms. Simply removing the fluid from the cyst with a needle is not effective because the cyst fills up again within several days. The best treatment is to remove a large portion of the cyst wall. This surgical procedure can usually be done through the laparoscope, which requires only 2-3 small incisions and an overnight stay in the hospital. Most patients recover fully within 2 weeks. The risk of the cyst recurring is very low. A very small number of patients (0.6% of the general population) have polycystic liver (PLD) disease, which is characterized by the liver appearing like a cluster of very large grapes. Over the course of several years, patients with PLD may develop massive enlargement of the liver, which results in abdominal swelling and discomfort. In extreme cases, the patient may have a very poor quality of life because of the pain and fluid. Unlike the inevitable kidney failure associated with polycystic kidney disease, which can coexist with PLD, PLD does not cause liver failure. The only long-term solution for patients with severe PLD is liver transplantation.

Cystic Tumors

Unlike simple liver cysts, cystic tumors are actually growths that may become malignant over the course of many years. The benign cystic tumor seen most frequently is called a cystadenoma; its malignant counterpart is a cystadenocarcinoma. The symptoms caused by cystic tumors are the same as those seen with simple cysts; fullness, discomfort, and pain. The liver blood tests usually remain normal, unless a cancer has developed. US and CT scans are the best imaging studies to show the cystic tumors, which contain both liquid and solid areas. Because of the possibility of malignancy, cystic tumors must be completely removed surgically with an open (not laparoscopic) operation. The recurrence rate after surgery is very low and the long-term prognosis is excellent.

Benign Tumors

The benign tumors of the liver seen most frequently include cavernous hemangiomas, liver cell adenomas, and focal nodular hyperplasia (FNH). Of these, hemangiomas are by far the most common and occur in about 2% of the population. Hemangiomas are soft, spongy tumors composed of small blood vessels. Most cause no symptoms and they are found incidentally when either an US or CT scan is performed for some other reason. Liver function is not affected and surgical removal is required only in those patients who develop symptoms. Some patients may have pain; rarely, bleeding may occur into the hemangioma. Adenomas occur primarily in women, especially those who take or have taken birth control pills for an extended period of time. The symptoms associated with adenomas include abdominal discomfort and pain. A small percentage of patients may experience spontaneous rupture and potentially life-threatening hemorrhage from the adenoma. The adenomas may also become malignant after several years. As a result of the risk of bleeding and malignant transformation, all adenomas 5 centimeters (2 inches) or larger require surgical removal. In most instances, an open operation is necessary. Focal nodular hyperplasia (FNH) is also a tumor that is found almost exclusively in young women. However, FNH is not associated with birth control pills and rarely causes symptoms. There is no associated risk of either spontaneous rupture or malignancy, as is seen in adenomas. The only patients who require surgical removal are those who have symptoms, or the diagnosis is uncertain; ie, the imaging studies and/or needle biopsy suggest that the tumor may be an adenoma.

Malignant Tumors

Primary Liver Cancer
A cancer that begins in the liver is called a primary liver cancer or hepatocellular carcinoma (HCC). HCC is relatively uncommon in the US. However, HCC is quite common in the Far East and Africa, in part because of the high prevalence of hepatitis B infection in those parts of the world. Cirrhosis from any cause, such as hepatitis or alcoholism, increases the risk of developing a HCC. The spectrum of symptoms seen with HCC vary widely. Some patients feel well and others become quite ill. Liver blood tests are often abnormal, especially if cirrhosis is present. US, CT, and MRI scanning show the tumors. A needle biopsy performed under the guidance of either US or CT may be necessary to confirm the diagnosis. A needle biopsy of the non-tumor bearing portion of the liver is also necessary to see if cirrhosis is present. Surgery offers the only potential cure for patients with HCC. In some patients, the tumor may be removed surgically, if cirrhosis is not present in the remainder of the liver. If cirrhosis is present, the tumor may be ablated (destroyed) with alcohol injection, freezing the tumor (cryotherapy), or heat (Radio Frequency Ablation; RFA). Alcohol ablation is effective in tumors that are less than 5 centimeters in diameter . The procedure is performed by a radiologist under the guidance of either US or CT. Cryotherapy and RFA are surgical procedures that may be performed with either an open operation or laparoscopically. Liver transplantation is also an option in patients with cirrhosis and small (less than 5 centimeters) cancers. If surgery is not an option, other treatments available include either intravenous chemotherapy or chemotherapy directly into the artery feeding the liver. However, neither of these therapies are curative.

Metastatic Tumors

Most cancers that are found in the liver started in another organ, such as the colon, pancreas, stomach, or breast. The presence of metastatic cancer in the liver is usually a sign of an advanced stage of disease and a very limited life expectancy. However, patients with a primary cancer from either the colon, rectum, or a neuroendocrine cancer who do not have cancer outside the liver, may benefit from surgical treatment of liver metastases. Metastases from colorectal cancers are by far the most common encountered in the US. Of the approximately 160,000 patients who develop colorectal cancer annually, about one third will develop liver metastases. Ten percent of these patients may benefit from surgical therapy. Removing a portion of the liver which contains the cancer (liver resection) is the most effective surgical treatment for colorectal metastases. It may be necessary to remove only a small portion of the liver, or the entire right or left half, depending on the size and number of metastases. The patients who have the best results are those who have one or two metastases which are 5 centimeters or less in size and are confined to one lobe of the liver. The 5 and 10 year survivals in these patients are 30% and 20%, respectively. A liver resection is a major operative procedure that carries a 2-3% risk of dying as a result of the operation. Other surgical options to treat metastatic liver cancer include cryotherapy (freezing the tumor) or radio frequency ablation (RFA), which destroys the cancer with heat. Both of these techniques can be performed either open or via the laparoscope. Currently, these two therapies are not felt to be as effective as surgical removal. Patients who are offered cryotherapy or RFA are, for a variety of reason(s), not candidates for surgical resection. The long term survival associated with these two therapies and their role in the treatment of metastatic liver cancer continues to unfold as more follow-up information becomes available.

(MUHUK69CCPE2)
Adapted from: Cleveland Clinic

Cirrhosis of the Liver

Cirrhosis refers to scarring of the liver. Scar tissue forms because of injury or long-term disease. It replaces healthy tissue.

Scar tissue cannot do what healthy liver tissue does—make protein, help fight infections, clean the blood, help digest food, and store energy for when you need it. Scar tissue also blocks the normal flow of blood through the liver. Too much scar tissue means that your liver cannot work properly. To live, you need a liver that works.

Cirrhosis can be life-threatening, but it can also be controlled if treated early.

What are the symptoms of cirrhosis?

You may have no symptoms at all in the early stages. As cirrhosis progresses you may

• feel tired or weak
• lose your appetite
• feel sick to your stomach
• lose weight

Cirrhosis can also lead to other problems.

• You may bruise or bleed easily, or have nosebleeds.
• Bloating or swelling may occur as fluid builds up in the abdomen or legs. Fluid build up in the abdomen is called ascites (ah-SI-teez) and in the legs is called edema.
• Medications may have a stronger effect on you because your liver does not break them down as quickly.
• Waste materials from food may build up in the blood or brain and may cause confusion or difficulty thinking. For example, protein that you eat breaks down into chemicals like ammonia. When red blood cells get old, they break down and leave a substance called bilirubin (bil-ih-ROO-bun). A healthy liver removes these byproducts, but a diseased liver leaves them in the body.
• Blood pressure may increase in the vein entering the liver, a condition called portal hypertension.
• Enlarged veins, called varices (VARE-ah-seez), may develop in the esophagus and stomach. Varices can bleed suddenly, causing vomiting of blood or passing of blood in a bowel movement.
• The kidneys may not work properly or may fail.

As cirrhosis progresses, your skin and the whites of your eyes may turn yellow, a condition called jaundice (JON-diss). You may also develop severe itching or gallstones.

In the early stages, cirrhosis causes your liver to swell. Then, as more scar tissue replaces normal tissue, the liver shrinks.

About 5 percent of patients with cirrhosis also get cancer of the liver.

What causes cirrhosis?

Cirrhosis has many causes, including

• alcohol abuse (alcoholic liver disease)
• chronic viral hepatitis (hepatitis B, C, or D)
• autoimmune hepatitis, which is destruction of liver cells by the body’s immune system
• nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NASH), which is fat deposits and inflammation in the liver
• some drugs, toxins, and infections
• blocked bile ducts, the tubes that carry bile from the liver
• some inherited diseases such as
  • hemochromatosis (HEE-moh-KROH-muh-TOH-sus), a disease that occurs when the body absorbs too much iron and stores the excess iron in the liver, pancreas, and other organs
  • Wilson disease, which is caused by the buildup of too much copper in the liver
  • protoporphyria (PROH-toh-pour-FEAR-ee-uh), a disorder that affects the skin, bone marrow, and liver

Sometimes the cause of cirrhosis remains unknown even after a thorough medical examination.

How is cirrhosis diagnosed?

Your symptoms, a physical examination, and certain tests can help your doctor diagnose cirrhosis. Some tests are

• Blood tests to see whether your liver is working properly. Routine blood tests may be normal in cirrhosis. However, with advanced cirrhosis, blood tests may reveal abnormal levels of bilirubin and other substances.
• X rays, magnetic resonance imaging, or ultrasound images, which are pictures developed from sound waves, may show an enlarged or shrunken liver.
• Liver biopsy, an examination of a piece of your liver under a microscope, to look for scar tissue. This is the most accurate way to diagnose cirrhosis.

How is cirrhosis treated?

Once you have cirrhosis, nothing can make the scar tissue go away completely. However, treating the cause will keep cirrhosis from getting worse. For example, if cirrhosis is due to alcoholic liver disease, the treatment is to completely stop drinking alcohol. If cirrhosis is caused by hepatitis C, then that disease may be treated with medication.

Your doctor will suggest treatment based on the cause of your cirrhosis and your symptoms. Early diagnosis and carefully following an appropriate treatment plan can help many people with cirrhosis. In very advanced cirrhosis, however, certain treatments may not be possible. In that situation, your doctors will work with you to prevent or manage the complications that cirrhosis can cause.

How can I prevent cirrhosis if I already have liver disease?

• See your doctor for treatment of your liver disease. Many of the causes of cirrhosis are treatable, and early treatment may prevent cirrhosis.
• Follow a healthy lifestyle, eat a healthy diet, and stay active.
• Try to keep your weight in the normal range. Being overweight can make several liver diseases worse.
• Do not drink alcohol. Alcohol can harm liver cells, and chronic alcohol use is one of the major causes of cirrhosis.
• Stay away from illegal (street) drugs, which can increase your chances of getting hepatitis B or hepatitis C.
• See your doctor if you have chronic viral hepatitis. Effective treatments for both hepatitis B and hepatitis C are available. If you are on treatment, follow your treatment directions exactly.
• If you have autoimmune hepatitis, take medications and have regular check-ups as recommended by your doctor or a liver specialist (hepatologist).

What can I do to keep cirrhosis from getting worse?

• Stop drinking alcohol completely.
• Do not take any medications, including those you can buy without a prescription such as vitamins and herbal supplements, without discussing them with your doctor. Cirrhosis makes your liver sensitive to certain medications.
• Get vaccinated against hepatitis A and hepatitis B. These forms of liver disease are preventable. Also, ask your doctor about getting a flu shot and being vaccinated against pneumonia.
• Avoid eating raw oysters or other raw shellfish. Raw shellfish can harbor bacteria (Vibrio vulnificus) that cause severe infections in people with cirrhosis.

Adapted from: National Institute of Diabetes and Digestive and Kidney Diseases

Cholestasis

Cholestasis is reduction or stoppage of bile flow.

• Disorders of the liver, bile duct, or pancreas can cause cholestasis.
• The skin and whites of the eyes look yellow, the skin itches, urine is dark, and stools may become light-colored and smell foul.
• Laboratory and often imaging tests are needed to identify the cause.
• Treatment depends on the cause, but drugs can help relieve itching.

With cholestasis the flow of bile (the digestive fluid produced by the liver) is impaired at some point between the liver cells and the duodenum (the first segment of the small intestine). When bile flow is stopped, the pigment bilirubin (a waste product formed when old or damaged red blood cells are broken down) escapes into the bloodstream and accumulates.

Causes

The causes of cholestasis are divided into two groups: those originating within the liver and those originating outside the liver.

Within the Liver: Causes include acute hepatitis, alcoholic liver disease, primary biliary cirrhosis with inflammation and scarring of the bile ducts, cirrhosis due to viral hepatitis B or C (also with inflammation and scarring of the bile ducts), drugs, hormonal effects on bile flow during pregnancy (a condition called cholestasis of pregnancy (see ), and cancer that has spread to the liver.

Outside the Liver: Causes include a stone in a bile duct, narrowing (stricture) of a bile duct, cancer of a bile duct, cancer of the pancreas, and inflammation of the pancreas (pancreatitis).

Symptoms

Jaundice, dark urine, light-colored stools, and generalized itchiness are characteristic symptoms of cholestasis. Jaundice results from excess bilirubin deposited in the skin, and dark urine results from excess bilirubin excreted by the kidneys. Retention of bile products in the skin may cause itching, with subsequent scratching and skin damage. Stools may become light-colored because the passage of bilirubin into the intestine is blocked. Stools may contain too much fat (a condition called steatorrhea) because bile cannot enter the intestine to help digest fat in foods. Fatty stools may be foul-smelling. The lack of bile in the intestine also means that calcium and vitamin D are poorly absorbed. If cholestasis persists, a deficiency of these nutrients can cause loss of bone tissue. Vitamin K, which is needed for blood clotting, is also poorly absorbed from the intestine, causing a tendency to bleed easily.

Prolonged jaundice due to cholestasis produces a muddy skin color and fatty yellow deposits in the skin. Whether the person has other symptoms, such as abdominal pain, loss of appetite, vomiting, or fever, depends on the cause of cholestasis.

Diagnosis

A doctor tries to determine whether the cause is within or outside the liver on the basis of symptoms and the results of a physical examination.

Recent use of drugs that can cause cholestasis suggests a cause within the liver. Small, spiderlike blood vessels visible in the skin, an enlarged spleen, and fluid in the abdominal cavity (ascites), which are signs of chronic liver disease, also suggest a cause within the liver.

Findings that suggest a cause outside the liver include certain kinds of abdominal pain (such as intermittent pain in the upper right side of the abdomen and sometimes also in the right shoulder ) and an enlarged gallbladder (felt during the physical examination or detected by imaging studies).

Some findings do not indicate whether the cause is within or outside the liver. They include heavy alcohol intake, loss of appetite, nausea, and vomiting.

Typically, the blood levels of two enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase, are very high in people with cholestasis. A blood test that measures the level of bilirubin indicates the severity of the cholestasis but not its cause. An imaging study, usually ultrasonography, is almost always done if blood test results are abnormal. Computed tomography (CT) or sometimes magnetic resonance imaging (MRI) may be done in addition to or instead of ultrasonography. If the cause appears to be within the liver, a liver biopsy may be done and usually establishes the diagnosis. If the cause appears to be blockage of the bile ducts, more precise images of these ducts are usually needed. Typically, either endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) is done. MRCP uses magnetic resonance imaging. In ERCP, a contrast agent is injected and x-rays are taken.

Treatment

A blockage of the bile ducts can usually be treated with surgery or endoscopy (using a flexible viewing tube with surgical instruments attached). A blockage within the liver may be treated in various ways depending on the cause. If a drug is the suspected cause, the doctor stops its use. If acute hepatitis is the cause, cholestasis and jaundice usually disappear when hepatitis has run its course. A person with cholestasis is advised to avoid or stop using any substance that is toxic to the liver, such as alcohol and certain drugs.

Cholestyramine, taken by mouth, can be used to treat itchiness. This drug binds with certain bile products in the intestine, so they cannot be reabsorbed to irritate the skin. Unless the liver is severely damaged, taking vitamin K can improve blood clotting. Supplements of calcium and vitamin D are often taken if the cholestasis persists, but they are not very effective in preventing loss of bone tissue.

Adapted from: Merck & Co., Inc.

Biliary Atresia (BA)

Biliary atresia is a disease of the bile ducts that affects only infants. Bile is a digestive liquid that is made in the liver. It travels through the bile ducts to the small intestine, where it helps digest fats.

In biliary atresia, the bile ducts become inflamed and blocked soon after birth. This causes bile to remain in the liver, where it starts to destroy liver cells rapidly and cause cirrhosis, or scarring of the liver.

What causes biliary atresia?

The cause of this disease is not known. In some infants, the condition is most likely congenital, meaning present from birth. About one in 10 babies with biliary atresia have other congenital defects. Some research indicates that an early viral infection may be linked to biliary atresia.

Scientists do know that biliary atresia is not hereditary; parents do not pass it on to their child. It is also not contagious, and it is not preventable. It is also not caused by anything an expectant mother did or did not do.

What are the symptoms of biliary atresia?

Symptoms of biliary atresia usually appear between two and six weeks after birth. The baby will appear jaundiced, with yellowing of the skin and whites of the eyes. The liver may harden and the abdomen may become swollen. Stools appear pale grey and the urine may appear dark. Some babies may develop intense itching.

How is biliary atresia diagnosed?

Since other conditions lead to symptoms similar to those of biliary atresia, doctors must perform many tests before a conclusive diagnosis can be made. These tests may include blood and liver tests, an ultrasound examination, X-rays and a liver biopsy, in which a small amount of liver tissue is removed with a needle for examination in a laboratory.

How is biliary atresia treated?

Unfortunately, there is no cure for biliary atresia. The only treatment is a surgical procedure in which the blocked bile ducts outside the liver are replaced with a length of the baby’s own intestine, which acts as a new duct. This surgery is called the Kasai procedure after Dr. Morio Kasai, the Japanese surgeon who developed it.

The aim of the Kasai procedure is to allow drainage of bile from the liver into the intestine through the new duct. The operation is completely or partially successful about 80 percent of the time if performed early (before 3 months of age). In babies who respond well, jaundice and other symptoms usually disappear after several weeks.

In cases where the Kasai procedure does not work, the problem often lies in the fact that blocked bile ducts are “intrahepatic,” or inside the liver, as well as extrahepatic, or outside the liver. No procedure, except for liver transplant, has been developed to replace blocked intrahepatic ducts.

The Kasai procedure is most successful in babies younger than 3-months-old, so early diagnosis is important.

If the Kasai procedure is not successful, the only other option is a liver transplant. However, a suitable donor organ must be found quickly, before damage to the liver from the backed-up bile becomes deadly.

What happens after surgery?

The aim of treatment after surgery is to encourage normal growth and development. If bile flow is good, the child is given a regular diet. If tests show that bile flow is reduced, a low-fat diet and vitamin supplements will be required, since the absorption of fats and vitamins is impaired.

What is the outlook for babies with biliary atresia?

Without successful treatment, few children with biliary atresia live beyond age two. In some cases, where the Kasai procedure is completely successful, the child may recover and live a normal life. However, in most cases, even when surgery is successful, patients will suffer gradual damage to the liver. These children will need specialized medical care throughout their lives, and many will ultimately need a liver transplant.

Is a liver transplant the solution?

In children with biliary atresia, a liver transplant is generally not attempted unless the Kasai procedure has been tried. In cases where that operation is unsuccessful, the child may become a candidate for a liver transplant. Success depends on the timely availability of a matching donor liver. Fortunately, survival rates for liver transplant recipients have increased dramatically with improved surgical techniques and the development of drugs that help overcome the problem of organ rejection.

What can the family do?

Watching a newborn suffer from biliary atresia is a heart-breaking experience. Parents are frustrated because so little is known about the disease and treatment options are so limited. Many parents find comfort in support groups because it allows them to talk to other parents in similar situations. Finding out that others feel the way they do, and learning how other parents are coping with a child’s disease, is often a great comfort.

Adapted from: American Liver Foundation

Ascites

Ascites is the accumulation of protein-containing (ascitic) fluid in the abdominal cavity.

• Many disorders can cause ascites, but cirrhosis is the most common.
• If large amounts of fluid accumulate, the abdomen becomes very large, sometimes making people lose their appetite and feel short of breath.
• Analysis of the fluid can help determine the cause.
• Usually, bed rest, a low-salt diet, and diuretics help eliminate excess fluid.

Ascites tends to occur in long-standing (chronic) rather than in short-lived (acute) disorders. It occurs most commonly in cirrhosis (severe scarring of the liver), especially in cirrhosis caused by alcoholism or viral hepatitis. It may occur in other liver disorders, such as severe alcoholic hepatitis without cirrhosis, chronic hepatitis, and obstruction of the hepatic vein (Budd-Chiari syndrome). Ascites can also occur in disorders unrelated to the liver, such as cancer, heart failure, kidney failure, inflammation of the pancreas (pancreatitis), and tuberculosis affecting the lining of the abdominal cavity.

In people with a liver disorder, ascitic fluid leaks from the surface of the liver and intestine. A combination of factors is responsible. They include portal hypertension, decreased ability of the blood vessels to retain fluid, fluid retention by the kidneys, and alterations in various hormones and chemicals that regulate bodily fluids.

Symptoms and Diagnosis

Small amounts of fluid in the abdominal cavity usually produce no symptoms, but massive amounts may cause abdominal swelling (distention) and discomfort. Pressure on the stomach from the swollen abdomen may lead to loss of appetite, and pressure on the lungs may lead to shortness of breath. When a doctor taps (percusses) the abdomen, the fluid makes a dull sound. When the abdominal cavity contains large amounts of fluid, the abdomen is taut, and the navel is flat or even pushed out. In some people with ascites, the ankles swell with excess fluid (edema). However, a doctor may not be able to detect ascitic fluid unless the volume is about a quart or more.

If the presence of ascites or its cause is not clear, the doctor may use ultrasonography. In addition, a small sample of ascitic fluid can be withdrawn by inserting a needle through the abdominal wall—a procedure called diagnostic paracentesis. Laboratory analysis of the fluid can help determine the cause.

Treatment

The basic treatment for ascites is bed rest and a salt-restricted diet, usually combined with drugs called diuretics, which make the kidneys excrete more water into the urine. If ascites makes breathing or eating difficult, the fluid may be removed through a needle inserted into the abdomen—a procedure called therapeutic paracentesis. The fluid tends to reaccumulate unless the person also restricts salt consumption and takes a diuretic. Because a large amount of albumin (the major protein in plasma) is usually lost from the blood into the abdominal fluid, albumin may be administered intravenously.

An infection called spontaneous bacterial peritonitis occasionally develops in ascitic fluid for no apparent reason, especially in people with alcoholic cirrhosis. Untreated, this infection can be fatal. Survival depends on early vigorous treatment with antibiotics.

Adapted from: Merck & Co., Inc.

Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (Alpha-1) is a hereditary genetic disorder which may lead to the development of lung and/or liver disease. It is the most common genetic cause of liver disease in children. Adults can also be affected by Alpha-1 and may develop lung conditions such as emphysema as well as liver problems. Fortunately, many persons diagnosed with Alpha-1 never develop any of the associated diseases.

What are the symptoms of Alpha-1 Antitrypsin Deficiency?

In newborns, the typical symptoms of Alpha-1 are jaundice, swelling of the abdomen, and poor feeding. Alpha-1 may also appear in late childhood or adulthood and be detected because of fatigue, poor appetite, swelling of the abdomen and legs or abnormal liver tests.

What causes Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin is a protein made in the liver which plays an important role in preventing the breakdown of enzymes in various organs. Individuals with Alpha-1 have a genetic disorder that prevents their body from creating enough of this protein. This trait must be inherited from both parents (who are, by definition, carriers) in order to cause the disorder.

How is Alpha-1 Antitrypsin Deficiency diagnosed?

The diagnosis of Alpha-1 is made by blood tests showing the low levels of alpha-1 antitrypsin and abnormal liver tests. Other tests such as ultrasound imaging or tests using specialized X-ray techniques may be necessary. A liver biopsy may be performed to check for damage to the liver.

How is Alpha-1 Antitrypsin Deficiency treated?

Currently, there is no cure for Alpha-1. Treatment is designed to maintain normal nutrition, to provide the liver and the body with essential nutrients, and to identify complications early in order to treat them better. Multiple vitamins and vitamins E, D, and K are often given. Certain abnormalities can be treated or controlled. Jaundice, severe itching, and fluid retention can all be dealt with through medication.

If I or my child has been diagnosed with Alpha-1 Antitrypsin Deficiency, what should I ask my doctor?

Speak with your doctor about the particular symptoms you are experiencing and the best methods for treating them. Also discuss the best ways to check for future progression of the disease.

Who is at risk for Alpha-1 Antitrypsin Deficiency?

Worldwide, approximately 1 in 2,500 individuals has Alpha-1 Antitrypsin Deficiency. This disorder is found in all ethnic groups; however, it occurs most frequently in whites of European ancestry.

Adapted from: American Liver Foundation

Alagille Syndrome

Alagille syndrome is a rare, inherited disorder in which bile flow from the liver is decreased and the there are fewer than normal bile ducts.

Alagille syndrome is a disorder that often affects the liver and other organs, including the heart, eyes, spine and kidneys.

Often, patients with alagille syndrome have distinctive facial appearances. A small number of patients (about 15%) go on to develop severe liver disease and require liver transplantation.

This disorder is usually present at birth. Alagille syndrome is one of the most common inherited disorders that causes reduced bile flow within the liver. It occurs about once in every 100,000 births.

What are the causes of alagille syndrome?

Recent studies have discovered that defects of a specific gene cause alagille syndrome. The disease usually is inherited from one parent.

A single copy of the diseased gene (received from either the mother or father) "dominates" the other normal gene and results in this disease.

There is a 50% chance a parent with alagille syndrome will transmit this disorder to their child. Family members with Alagille syndrome may be affected very differently by the disorder.

Bile is produced in the liver and then travels through the many small bile ducts in the liver into one large bile duct, and eventually into the intestines. In patients with alagille syndrome, the lack of small bile ducts inside the liver slows down the flow of bile from the liver to the intestines.

Bile is composed of bilirubin, bile salts, cholesterol and metals such as copper. Bile acids are necessary to absorb fat and certain vitamins. When the bile flow is decreased, each of its components builds up in the body, and the body is not able to properly absorb fat and vitamins. This causes a wide range of symptoms.

What are the signs and symptoms of alagille syndrome?

Symptoms of alagille syndrome range from mild to severe. Symptoms within the first three months of life often include:

• Jaundice, usually present at birth (yellowing of the skin)
• Severe itching (caused by the buildup of bile salt in the body)
• Pale, loose or clay-colored stools (this happens because there is little or no bile reaching the intestine to color the bowel movements)
• Poor weight gain (due to a lack of bile needed to digest and absorb fat)
• Poor growth
• Deficiency of vitamins A, D, E and K which depends on bile acids for absorption; this may result in vision changes, rickets, difficulty with balance and poor clotting of the blood
• Heart murmurs, due to narrowing of the blood vessels in the lung (peripheral pulmonary artery stenosis)

Other symptoms that may develop later include:

• Jaundice that will not go away
• Continued growth and development problems in early childhood
• Enlarged liver (feels larger and harder than normal)
• Hard, whitish nodules (called xanthonmas) that develop in the skin due to cholesterol and fatty deposits; the nodules usually occur in spots of repeated trauma in young children, such as knees and elbows
• Urine appears very dark yellow or brown (due to high levels of bilirubin in the bloodstream which pass to the kidneys)
• Persistent itching

How is alagille syndrome diagnosed?

A diagnosis of alagille syndrome is made based on either tests or a physical examination. While there are specific findings that indicate alagille syndrome, all patients do not demonstrate all of them.

Reduced bile flow is one finding that indicates alagille symdrome. Symptoms of reduced bile flow include jaundice, itching and cholesterol deposits in the skin.

A liver biopsy may be done to show examine the bile ducts and degree of scarring in the liver. Liver function tests are blood tests used to assess the general state of the liver or biliary system.

A nuclear scan may be done to show how much bile is flowing from the liver. Genetic testing may be available through research laboratoraties but as of 2006, it is not routinely available.

Other findings that may indicate alagille syndrome include:

• Heart murmur (due to narrowing of the blood vessel connecting the heart to the lungs)
• Bone defects (shape of the bones in the spinal column may look like a butterfly's wings)
• Kidney problems or kidney failure
• Distinct physical features, such as a broad forehead, straight nose, deep set eyes, a small, pointed chin, and fingers that are shorter than normal
• Problems with the eye -- an extra thickening of a line, known as the Schwalbe's line on the surface of the eye

What is the treatment?

There is no cure for alagille syndrome. Management of the disorder is aimed at preventing complications, increasing the flow of bile from the liver, maintaining normal growth and development and reducing blood cholesterol levels.

Medications. Medicine may be used to increase bile flow and to relieve severe itching caused by buildup of bile in the blood and skin. These same medicines may be used to treat high cholesterol levels that cause the hard, whitish nodules that develop in the skin in alagille syndrome patients.

Vitamin supplements. Reduced bile flow can lead to difficulty digesting fat and vitamins from a child's diet. Fat-soluble vitamin supplements (A, D, E, and K) may be used.
Baby formula rich in triglyceride. Baby formula rich in a type of fat that can be digested despite reduced bile flow may be used to help with fat absorption in infants.

High-calorie diet. Alagille syndrome patients often have difficulty absorbing the calories they eat. To prevent malnutrition and growth failure, a high-calorie diet with a lot of protein may be recommended. A feeding tube that delivers large quantities of nutrients overnight may be used.

Liver transplantation. A small percentage of patients will develop cirrhosis (severe damage to the liver). Liver transplantation is the only option for these patients.

A liver transplant also may be the last resort for patients with severe itching, portal hypertension (high blood pressure) and severe growth failure that is not responding to medication. Liver transplantation has been used successfully in these cases.

What is the long-term prognosis for alagille syndrome patients?

Prognosis depends on the severity of the bile flow obstruction and scarring of the liver, and the severity of other problems that may develop -- such as heart or lung problems or problems related to poor nutrition.

A typical course of liver disease with alagille syndrome patients is worsening cholestasis (decreasing bile flow) for several years, and then some improvement after that time.
Children with alagille syndrome generally have a better outcome than children with other liver disorders at the same age. Many adults with alagille syndrome lead normal lives