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Fibrosis of the Liver

By Jesse M. Civan, MD, Gastroenterologist, Thomas Jefferson University Hospital

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Fibrosis is the formation of an abnormally large amount of scar tissue in the liver. It occurs when the liver attempts to repair and replace damaged cells.

  • Many conditions can damage the liver.

  • Fibrosis itself causes no symptoms, but severe scarring can result in cirrhosis, which can cause symptoms.

  • Doctors can often diagnose fibrosis and estimate its severity based on results of blood and imaging tests, but sometimes liver biopsy is required.

  • Treatment involves correcting the underlying condition when possible.

Fibrosis develops when the liver is repeatedly or continuously damaged. A single episode of injury, even if severe (as when acute hepatitis damages many liver cells), does not usually cause fibrosis. If injury is repeated or continuous (as occurs in chronic hepatitis), liver cells attempt to repair the damage, but the attempts result in scar tissue. Fibrosis can develop more rapidly when it is caused by a blockage in the bile ducts.

Scar tissue replaces the liver cells and, unlike liver cells, performs no function. Scar tissue can interfere with blood flow to and in the liver, limiting the blood supply for the liver cells. Without enough blood, these cells die, and more scar tissue is formed. Also, blood pressure in the vein that carries blood from the intestine to the liver (portal vein) increases—a condition called portal hypertension.

Fibrosis can sometimes be reversed if the cause is identified promptly and corrected. However, after months or years of repeated or continual damage, fibrosis becomes permanent. The scar tissue can form bands throughout the liver, destroying the liver’s internal structure and impairing the liver’s ability to regenerate itself and to function. Such severe scarring is called cirrhosis.

Causes

Various disorders and drugs can repeatedly or continuously damage the liver and thus cause fibrosis (see Table: Some Conditions and Drugs That Can Cause Fibrosis of the Liver).

The most common causes in the United States are

Nonalcoholic fatty liver usually occurs in people who have excess body weight, high levels of fats (lipids) and cholesterol in the blood, and/or a high blood sugar level (as occurs in diabetes). Worldwide, viral hepatitis B (see Table: The Hepatitis Viruses) is a common cause. Sometimes the cause of fibrosis is not known.

Some Conditions and Drugs That Can Cause Fibrosis of the Liver

Type

Examples

Comments

Certain hereditary metabolic disorders

Alpha-1 antitrypsin deficiency

These disorders affect how foods are absorbed, broken down, and/or processed (metabolized) in the body. If foods are not broken down normally, substances can accumulate in various organs (such as the liver) and cause damage.

Infections

Viral infections such as chronic hepatitis B or C

Some infections can affect almost any organ of the body, including the liver. Some, such as hepatitis, affect mainly the liver.

Autoimmune disorders

The body attacks its own tissues (an autoimmune reaction).

In primary biliary cirrhosis and primary sclerosing cholangitis, bile ducts become inflamed, scarred, and blocked.

Disorders that affect blood flow to, in, and out of the liver

Budd-Chiari syndrome (blockage of blood flow out of the liver by a blood clot)

Heart failure

Portal vein thrombosis (blockage of the main vein to the liver by a blood clot)

Veno-occlusive disease of the liver (blockage of the small veins in the liver)

When blood cannot leave the liver, the liver enlarges.

When liver cells do not receive enough blood, they die and are replaced with scar tissue.

Veno-occlusive disease is sometimes caused by pyrrolizidine alkaloids. These substances are present in certain herbal products such as bush (rooibos) teas, which are sometimes used for their supposed health benefits.

Drugs

Alcohol

Amiodarone

Chlorpromazine

Corticosteroids

Isoniazid

Methotrexate

Methyldopa

Oxyphenisatin

Tolbutamide

Most drugs must be processed in the liver. Some can harm the liver.

Other disorders

Congenital hepatic fibrosis

Nonalcoholic fatty liver (steatohepatitis)

Congenital hepatic fibrosis damages primarily the liver, gallbladder, and kidneys. It causes fibrosis in the liver and other symptoms. This disorder is present at birth.

In nonalcoholic fatty liver, fat accumulates in the liver and fibrosis develops. This disorder tends to occur in people who have metabolic syndrome.

Symptoms

Fibrosis itself does not cause symptoms. Symptoms may result from the disorder causing fibrosis. Also, if fibrosis progresses, cirrhosis may develop. Cirrhosis can cause complications (such as portal hypertension) that cause symptoms.

Diagnosis

  • A doctor's evaluation

  • Sometimes blood tests, imaging tests, or both

  • Sometimes liver biopsy

Doctors suspect fibrosis when people have a disorder or take a drug that could cause fibrosis or when routine blood tests to evaluate the liver (liver function tests) indicate that the liver is damaged or is malfunctioning. Tests are then done to confirm the diagnosis, and if fibrosis is present, tests are done to determine its severity. These tests can include imaging tests, blood tests, liver biopsy, and sometimes specialized imaging tests to determine how stiff the liver is.

Imaging tests such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) do not detect early or moderately advanced fibrosis. However, these tests may show abnormalities that can accompany cirrhosis and portal hypertension (such as an enlarged spleen or varices).

Certain combinations of blood tests can distinguish between two levels of fibrosis:

  • Absent or mild

  • Moderate to severe

These tests cannot reliably differentiate between degrees of moderate or severe fibrosis.

Liver biopsy is the most reliable way to detect and stage (determine the amount of) fibrosis and to identify the disorder causing fibrosis. Biopsy is often done when the diagnosis is unclear. It is also done to determine whether fibrosis has progressed to cirrhosis (for example, in people with hepatitis C). Because liver biopsy is invasive and can cause problems, doctors may first do blood tests to determine the level of fibrosis and then do a liver biopsy only if blood tests indicate that fibrosis is moderate or severe. Doctors are starting to use certain specialized imaging tests as noninvasive alternatives to biopsy.

Specialized imaging tests can determine how stiff the liver is. The stiffer liver tissue is, the more severe fibrosis is likely to be. These tests (ultrasound elastography, magnetic resonance elastography, and acoustic radiation force impulse imaging) use sound waves, applied to the abdomen, to determine how stiff the liver tissue is. Unlike liver biopsy, these tests are not invasive and thus have some advantage. Ultrasound elastography and magnetic resonance elastography are being used in people with viral hepatitis C to diagnose fibrosis. Additionally, these tests are used in patients with fatty liver disease. Although conventional ultrasonography can be unreliable in extremely overweight people (who are at risk of fatty liver disease), specialized attachments are available to allow reliable ultrasound elastography measurements in obese people.

Treatment

Doctors focus on treating the cause, which often stops or slows further scarring of the liver and sometimes results in improvement. Such treatment may include

Drugs used to reduce fibrosis (such as corticosteroids or penicillamine) are usually too toxic to be taken for long-time use. Other drugs that may reduce fibrosis are under study. Silymarin, a powerful antioxidant present in the medicinal herb called milk thistle, is sometimes used to treat fibrosis. It appears to be safe but does not appear to be effective. Drinking coffee, may help protect the liver against fibrosis.

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  • CORDARONE
  • LANIAZID
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  • CUPRIMINE
  • OTREXUP