Fatty Liver

Explore this section to learn more about fatty liver, what effect it has upon the liver's condition and ability to function, and how it can lead to more serious liver disease.

What is fatty liver?

Fatty liver is just what its name suggests: the build-up of excess fat in the liver cells. It is normal for your liver to contain some fat. But if fat accounts for more than 10% of your liver’s weight, then you have fatty liverand you may develop more serious complications.

Fatty liver may cause no damage, but sometimes the excess fat leads to inflammation of the liver. This condition, called steatohepatitis, does cause liver damage. Sometimes, inflammation from a fatty liver is linked to alcohol abuse; this is known as alcoholic steatohepatitis. Otherwise the condition is called nonalcoholic steatohepatitis, or NASH.

An inflamed liver may become scarred and hardened over time. This condition, called cirrhosis , is serious and often leads to liver failure.

NASH is one of the top three leading causes of cirrhosis.

What are the symptoms of fatty liver?

A fatty liver produces no symptoms on its own, so people often learn about their fatty liver when they have medical tests for other reasons. NASH can damage your liver for years or even decades without causing any symptoms. If the disease gets worse, you may experience fatigue, weight loss, abdominal discomfort, weakness and confusion.

What causes fatty liver?

Eating excess calories causes fat to build up in the liver. When the liver does not process and break down fats as it normally should, too much fat will accumulate. People tend to develop fatty liver if they have certain other conditions, such as obesity, diabetes, or high triglycerides. Alcohol abuse, rapid weight loss and malnutrition may also lead to fatty liver. However, some people develop fatty liver even if they have none of these conditions – so everyone should know about it.

How is fatty liver diagnosed?

Your doctor may see something unusual in your blood test or notice that your liver is slightly enlarged during a routine checkup. These could be signs of a fatty liver. To make sure you don’t have another liver disease, your doctor may ask for more blood tests, an ultrasound, a CT scan or an MRI. If other diseases are ruled out, you may be diagnosed with NASH. The only way to know for sure is to get a liver biopsy. Your doctor will remove a sample of liver tissue with a needle and check it under a microscope.

What new treatments for fatty liver are being studied?
Fatty liver is currently the focus of intense research to provide us with better tools for treatment in the future. Scientists are studying whether various medications can help reduce the inflammation on your liver, including new diabetes medications that may help you even if you don’t have diabetes.

How is fatty liver treated?

There are no medical or surgical treatments for fatty liver, but there are some steps you can take that may help prevent or reverse some of the damage. In general, if you have fatty liver, and in particular if you have NASH, you should:

• Lose weight – safely! That usually means losing no more than one or two pounds a week.
• Lower your triglycerides through diet, medication or both
• Avoid alcohol
• Control your diabetes, if you have it
• Eat a balanced, healthy diet
• Increase your physical activity
• Get regular checkups from a doctor who specializes in liver care

If I’ve been diagnosed with fatty liver, what questions should I ask my doctor?

• “What is the likely cause of my fatty liver?”
• “Do I have NASH? If not, how likely am I to develop NASH?”
• “Do I have cirrhosis? If not, how likely am I to develop cirrhosis?”
• “Do I need to lose weight? How can I do so safely?”
• “Should I be taking any medication to control my triglyceride levels?”
• “What medications or other substances should I avoid to protect my liver?”

Who is at risk for fatty liver?

Most (but not all) fatty liver patients are middle-aged and overweight. The risk factors most commonly linked to fatty liver disease are:

• Overweight (body mass index of 25-30)
• Obesity (body mass index above 30)
• Diabetes
• Elevated triglyceride levels

What is the best way to prevent fatty liver?

The best way to reduce your risk of developing fatty liver is to maintain a healthy weight and normal triglyceride levels. You should also avoid excess alcohol and other substances that could harm your liver.

Adapted from: American Liver Foundation

Budd-Chiari Syndrome

Budd-Chiari syndrome is caused by blood clots that completely or partially block the large veins that carry blood from the liver (hepatic veins) into the inferior vena cava.

• Some people have no symptoms, but others experience fatigue, abdominal pain, nausea, and jaundice.
• Fluid may accumulate in the abdomen, the spleen may enlarge, and sometimes severe bleeding occurs in the esophagus.
• Doppler ultrasonography can detect narrowed or blocked veins.
• Drugs may be used to dissolve or decrease the size of the clot, or a connection may be made between veins to allow blood to bypass the liver.

Budd-Chiari syndrome usually occurs when a clot narrows or blocks the hepatic veins.

Because blood flow out of the liver is impeded, blood accumulates in the liver, causing it to enlarge. The spleen may also enlarge. The backup of blood (congestion) in the hepatic veins causes blood pressure in the portal vein to increase. This increased pressure, called portal hypertension, can result in dilated, twisted (varicose) veins in the esophagus (esophageal varices). Portal hypertension, plus the engorged and damaged liver, leads to fluid accumulating in the abdomen, a condition termed ascites. The kidneys contribute to the problem by causing salt and water to be retained.

The clot may extend to also block the inferior vena cava (the large vein that carries blood from the lower parts of the body, including the liver, to the heart). Varicose veins in the abdomen near the skin's surface may develop and become visible.

Eventually, severe scarring of the liver (cirrhosis) occurs.

Causes

Usually, the cause is a disorder that makes blood more likely to clot, such as the following:

• Excess red cells (polycythemia)
• Sickle cell disease
• Inflammatory bowel disease
• Connective tissue disorders
• Injury

Sometimes Budd-Chiari syndrome begins suddenly and rather severely, typically during pregnancy. During pregnancy, the blood normally coagulates more readily. In some women, a blood clotting disorder may first become apparent during pregnancy. Other causes include disorders that develop near the hepatic veins, such as parasitic infections and liver or kidney tumors that press on or invade the veins. In Asia and South Africa, the cause is commonly a membrane (web) that blocks the inferior vena cava. Often, the cause is unknown.

Symptoms

Symptoms vary somewhat depending on whether they appear suddenly or develop more slowly.

Usually, symptoms develop gradually over weeks or months. Fatigue is common. The enlarged liver becomes tender, and people have abdominal pain.

Fluid may accumulate in the legs, causing swelling (edema), or in the abdomen, causing ascites. Varicose veins in the esophagus can rupture and bleed, sometimes profusely. People may vomit blood. Such bleeding is a medical emergency.

If cirrhosis develops, it can lead to liver failure with deterioration of brain function (hepatic encephalopathy), resulting in confusion and even coma

Sometimes symptoms begin suddenly, such as hepatic vein thrombosis during pregnancy. In this case, people feel tired, and the liver is enlarged and tender. Abdominal pain occurs in the upper abdomen. Additional symptoms include vomiting and a yellow discoloration of the skin and whites of the eyes—a condition called jaundice. Liver failure infrequently develops.

Diagnosis

Doctors suspect the Budd-Chiari syndrome in people with either of the following:

• An enlarged liver, ascites, liver failure, or cirrhosis when there is no obvious cause, even after testing
• Abnormal results of blood tests done to evaluate liver function plus conditions that increase the risk of blood clots

If results of liver function tests are abnormal, an imaging test, typically Doppler ultrasonography, is done. If results are unclear, magnetic resonance imaging of blood vessels (magnetic resonance angiography) or computed tomography (CT) is done.

If surgery is planned, venography is necessary. For this procedure, x-rays of the veins are taken after a radiopaque dye (which is visible on x-rays) is injected into a vein in the groin.

A liver biopsy may be done to confirm the diagnosis and identify if cirrhosis has developed.

Prognosis

When the vein remains completely blocked, most people, if untreated, die of liver failure within 3 years. When the blockage is incomplete, life expectancy is longer but varies.

Treatment

Treatment depends on how rapidly the disorder has developed and how severe it is.

When symptoms begin suddenly and the cause is a clot, fibrinolytic (thrombolytic) drugs, which dissolve clots, help. On a more long-term basis, anticoagulant drugs prevent clots from enlarging or recurring.

If a vein is narrowed or blocked by a web, angioplasty may be done to widen it. For this procedure (called percutaneous transluminal angioplasty), a catheter with a deflated balloon at its tip is inserted through the skin into a blood vessel (such as the femoral vein in the groin) and threaded to the blocked vein. The balloon is inflated, widening the vein. A wire mesh tube (stent) is then inserted and left in place to keep the vein open.

Another solution is to create an alternate route for blood flow, bypassing the liver. This procedure, called transjugular intrahepatic portal-systemic shunting (TIPS), reduces pressure in the portal vein. For the procedure, a local anesthetic is used to numb the neck, and a catheter with a cutting needle is inserted into a vein in the neck (jugular vein). The catheter is threaded through the inferior vena cava to the hepatic vein. The needle is used to create a connection (called a shunt) between two veins, usually a branch of the hepatic vein and the portal vein, so that blood can bypass the liver. Then, an expandable metal tube (stent) is threaded to and placed in the shunt to keep it open. The shunt enables blood to bypass the liver, flowing from the portal vein (which normally brings blood to the liver) directly to the hepatic veins (which drain blood away from the liver). The blood returns to the heart through the inferior vena cava. However, such shunts increase the risk of hepatic encephalopathy (deterioration of brain function due to liver dysfunction). Also, shunts occasionally become blocked, especially in people who have a tendency to form blood clots.

Liver transplantation can be life-saving, particularly for people with severe liver failure.

Problems resulting from the disorder are also treated:

• Bleeding from varicose veins in the esophagus: Several techniques can be used to stop the bleeding. 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 (termed ligation).
• Fluid accumulation in the abdomen: A low-salt (sodium) diet and diuretics can help prevent too much fluid from accumulating in the abdomen.

Most people need to take anticoagulants indefinitely to prevent new blockages from developing.

Adapted from: Merck & Co., Inc.

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.