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Chronic Hepatitis

by Anna E. Rutherford, MD, MPH

Chronic hepatitis is inflammation of the liver that lasts at least 6 months.

  • Common causes include hepatitis B and C viruses and certain drugs.

  • Many people have no symptoms, but some have vague symptoms, such as a general feeling of illness, poor appetite, and fatigue.

  • Chronic hepatitis can result in cirrhosis, with an enlarged spleen, accumulation of fluid within the abdomen, and deterioration of brain function.

  • A biopsy is done to confirm the diagnosis.

  • Drugs, such as antiviral drugs or corticosteroids, may be used, and for advanced disease, liver transplantation may be needed.

Chronic hepatitis, although much less common than acute hepatitis, can persist for years, even decades. In many people, it is quite mild and does not cause significant liver damage. However, in some people, continued inflammation slowly damages the liver, eventually resulting in cirrhosis (severe scarring of the liver—see Cirrhosis of the Liver), liver failure (see Liver Failure), and sometimes liver cancer ( Primary Liver Cancers).

Hepatitis C virus was not identified until 1989. People may have been infected before this time without knowing it. Because unrecognized infection is possible, researchers tested various age groups for hepatitis C. They found that among adults in the United States, about three fourths of all chronic hepatitis C cases occur in people born between 1945 and 1965.

Causes

Chronic hepatitis is usually caused by one of the hepatitis viruses (see Table: ).

Hepatitis C virus causes about 60 to 70% of cases, and at least 75% of acute hepatitis C cases become chronic.

About 5 to 10% of hepatitis B cases, sometimes with hepatitis D coinfection, become chronic. (Hepatitis D does not occur by itself. It occurs only as a coinfection with hepatitis B.)

Rarely, hepatitis E virus causes chronic hepatitis in people with a weakened immune system, such as those who are taking drugs to suppress the immune system after an organ transplant, who are taking drugs to treat cancer, or who have HIV infection.

Hepatitis A virus does not cause chronic hepatitis.

Certain drugs can cause chronic hepatitis, particularly when they are taken for a long time. They include isoniazid, methyldopa, and nitrofurantoin.

Other causes include alcoholic hepatitis and fatty liver disease not related to alcohol use (nonalcoholic steatohepatitis). Less often, chronic hepatitis results from alpha 1 -antitrypsin deficiency (a hereditary disorder), celiac disease, a thyroid disorder, or, in children and young adults, Wilson disease—a rare hereditary disorder involving abnormal retention of copper in the liver (see Wilson Disease).

In many people with chronic hepatitis, no obvious cause can be identified. In some of these people, the chronic inflammation resembles inflammation caused by the body attacking its own tissues (an autoimmune reaction—see Autoimmune Disorders). This type of inflammation, called autoimmune hepatitis, is more common among women than men.

No one knows exactly why a particular virus or drug causes chronic hepatitis in some people but not in others or why the degree of severity varies.

Did You Know...

  • Chronic hepatitis may not be suspected until after cirrhosis develops.

Symptoms

In about two thirds of people, chronic hepatitis develops gradually, often without causing any symptoms of a liver disorder until cirrhosis occurs. In the remaining one third, it develops after a bout of acute viral hepatitis that persists or returns (often several weeks later).

Symptoms often include a vague feeling of illness (malaise), poor appetite, and fatigue. Sometimes affected people also have a low-grade fever and some upper abdominal discomfort. Jaundice is rare.

Often, the first specific symptoms are those of chronic liver disease or cirrhosis. They can include an enlarged spleen, small spiderlike blood vessels visible in the skin (called spider angiomas), redness of the palms, and accumulation of fluid within the abdomen (ascites—see Ascites). Liver malfunction may lead to deterioration of brain function, called hepatic (portosystemic) encephalopathy (see Hepatic Encephalopathy) and a tendency to bleed (coagulopathy). Brain function deteriorates because toxic substances build up in the blood and reach the brain. The liver normally removes them from the blood, breaks them down, then excretes them as harmless by-products into the bile or blood (see Functions of the Liver). The damaged liver is less able to remove them.

A few people have jaundice, itchiness, and stools that are greasy and foul-smelling (called steatorrhea) and light-colored. These symptoms develop because the flow of bile out of the liver is blocked.

Autoimmune hepatitis may cause other symptoms that can involve virtually any body system, especially in young women. Such symptoms include acne, cessation of menstrual periods, joint pain, scarring of the lungs, inflammation of the thyroid gland and kidneys, and anemia.

In many people, chronic hepatitis does not progress for years. In others, it gradually worsens. The outlook depends partly on which virus is the cause:

  • Chronic hepatitis C, if untreated, causes cirrhosis in about 20 to 30% of people. However, cirrhosis may take decades to develop. The risk of liver cancer is increased only if cirrhosis is present.

  • Chronic hepatitis B tends to worsen, sometimes rapidly but sometimes over decades, leading to cirrhosis. Chronic hepatitis B also increases the risk of liver cancer.

  • Chronic coinfection with hepatitis B and D, if untreated, causes cirrhosis in up to 70%.

  • Autoimmune hepatitis can be effectively treated in most people, but some develop cirrhosis.

  • Chronic hepatitis caused by a drug may completely resolve once the drug is stopped.

Diagnosis

Doctors may suspect chronic hepatitis when people have typical symptoms, when blood tests (done for other reasons) detect abnormally high liver enzymes, or when people have had acute hepatitis before. Also, everyone born between 1945 and 1965, regardless of whether symptoms are present, should be tested once for hepatitis C. Such testing is recommended because hepatitis C is common among this age group and is often unrecognized.

Blood tests to determine how well the liver is functioning and whether it is damaged (liver function tests) are done. They may help establish or exclude the diagnosis, identify the cause, and determine the severity of liver damage. Blood tests are also done to help doctors identify which hepatitis virus is causing the infection. If no virus is identified, other blood tests are needed to check for other causes, such as autoimmune hepatitis. However, a liver biopsy (see Biopsy of the Liver) is essential to confirm the diagnosis. The liver biopsy also enables a doctor to determine how severe the inflammation is and whether any scarring or cirrhosis has developed. The biopsy may help identify the cause of hepatitis.

If people have chronic hepatitis B, ultrasonography is done every 6 months to screen for liver cancer. Levels of alpha-fetoprotein—a protein normally produced by immature liver cells in fetuses—may increase when liver cancer is present and thus may also be checked to screen for liver cancer. People with chronic hepatitis C are screened similarly, but only if they have cirrhosis.

Treatment

If a drug is the cause, the drug is stopped. If another disorder is the cause, it is treated.

Hepatitis B and C

If chronic hepatitis B or C is worsening or if liver enzyme levels are high, people are usually given antiviral drugs.

For hepatitis B, entecavir or tenofovir is usually used. These drugs are taken by mouth. These drugs are very effective, and the chance that viruses will develop resistance to them is slight. Other drugs that can be used include telbivudine and lamivudine (taken by mouth) and interferon alfa and pegylated interferon alfa (given by injection under the skin).

In some people, hepatitis B tends to recur once drug treatment is stopped and may be even more severe. Thus, these people may need to take an antiviral drug indefinitely.

For hepatitis C, treatment varies based on which type of hepatitis C virus causes it. There are several types of hepatitis C virus (called genotypes). Each type has slightly different genetic material. For some types, the most effective treatment is the following combination of drugs:

  • Pegylated interferon alfa (given by injection), ribavirin (taken by mouth), plus sofosbuvir (taken by mouth) or a protease inhibitor (taken by mouth), such as telaprevir, boceprevir, or simeprevir

For other types of hepatitis C virus, treatment consists of

  • Only sofosbuvir and ribavirin (given by mouth)

Treatment can last from 12 to 48 weeks. Treating hepatitis C can eliminate the virus from the body and thus stop inflammation and prevent scarring, which can lead to cirrhosis.

Many antiviral drugs taken by mouth (such as entecavir, tenofovir, telbivudine, and lamivudine) have few side effects. Lamivudine may have fewer side effects than the others. Ribavirin, telaprevir, boceprevir, and simeprevir can cause birth defects. Both men and women who have to take these drugs should use birth control during treatment and for 6 months after treatment ends.

Pegylated interferon alfa can cause a flu-like illness at first. Later, it can cause fatigue, a general feeling of illness (malaise), and depression. The drug may also suppress activity in the bone marrow, including the production of blood cells. It is usually not given to pregnant women because whether it is safe during pregnancy is unclear.

Pegylated interferon alfa should not be taken by people who have certain conditions:

  • Advanced cirrhosis due to hepatitis B

  • A transplanted organ

  • Kidney failure

  • A weakened immune system

  • A reduced number of blood cells (cytopenia), such as red blood cells (anemia)

  • Substance abuse

If family members and close contacts of people with chronic hepatitis B have not been vaccinated, they should be (see Hepatitis B Vaccine).

If people come in contact with the blood of someone who has hepatitis B, they are given hepatitis B immune globulin by injection, and if they have not been vaccinated against hepatitis B, they are also vaccinated. Such measures are not effective for chronic hepatitis C.

Hepatitis E

Ribavirin appears to be an effective treatment for chronic hepatitis E.

Autoimmune hepatitis

Usually, corticosteroids (such as prednisone) are used, sometimes with azathioprine, a drug used to suppress the immune system. These drugs suppress the inflammation, relieve symptoms, and improve long-term survival. Nevertheless, scarring in the liver may gradually worsen. Stopping these drugs usually leads to recurrence of the inflammation, so most people have to take the drugs indefinitely.

Treatment of complications

Regardless of the cause or type of chronic hepatitis, complications require treatment.

For example, treating ascites involves restricting salt consumption and taking a drug that helps the kidneys excrete more sodium and water into the urine (a diuretic—see Ascites : Treatment).

If brain function deteriorates, drugs can be given to help the body eliminate the toxic substances that can cause the deterioration (see Hepatic Encephalopathy : Treatment).

Liver transplantation

Transplantation (see Liver Transplantation) may be considered for people with severe liver failure. However, in people with hepatitis C, the virus virtually always recurs in the transplanted liver, and transplantation is less likely to be successful than transplantation done for other reasons.

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