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Hepatitis B, Chronic

By Anna E. Rutherford, MD, MPH, Assistant Professor of Medicine;Clinical Director of Hepatology, Harvard Medical School;Brigham and Women’s Hospital

Chronic hepatitis B is inflammation of the liver that is caused by the hepatitis B virus and that has lasted more than 6 months.

  • Most people with chronic hepatitis B have no symptoms, but some feel generally ill and tired and lose their appetite.

  • Having chronic hepatitis B increases the risk of liver cancer.

  • Doctors diagnose hepatitis B based on blood tests and usually do a liver biopsy to determine how damaged the liver is.

  • Not all patients with chronic hepatitis B need treatment, but if chronic hepatitis B is damaging the liver (causing inflammation or scarring), an antiviral drug is started.

  • Treatment with antiviral drugs can help suppress the virus and prevent further inflammation and scarring in the liver.

An estimated 850,000 to 2.2 million people in the United States and about 240 million people worldwide have chronic hepatitis B.

In the Far East and parts of Africa, hepatitis B virus accounts for many cases of chronic hepatitis, cirrhosis (severe scarring of the liver), and liver cancer.

Whether acute hepatitis B becomes chronic depends on the person's age. About 5 to 10% of infected adults develop chronic hepatitis B or become carriers. However, up to 90% of infected newborns and up to 25 to 50% of infected young children develop chronic hepatitis B. The younger the child, the greater the chance of developing chronic hepatitis B.

Acute hepatitis B becomes chronic in about 40% of people being treated with hemodialysis and in up to 20% of people with a weakened immune system.

Carriers are people with chronic infection who typically have no symptoms and may not be aware that they are infected. However, they can infect others.

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. About 20% of people with chronic hepatitis B develop cirrhosis or liver cancer and may die prematurely.

Many people who have chronic hepatitis B also have chronic hepatitis D. If untreated, the combination causes cirrhosis in up to 70% of affected people.

Symptoms

Symptoms of chronic hepatitis B vary depending on how badly the liver is damaged.

Many people with chronic hepatitis B, particularly children, have no symptoms. People who have symptoms usually feel generally ill and tired and lose their appetite. Some people have a low-grade fever and vague discomfort in the upper abdomen.

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

  • Accumulation of fluid within the abdomen (ascites)

  • A tendency to bleed (coagulopathy)

  • Jaundice (yellowing of the skin and whites of the eyes)

  • Deterioration of brain function due to malfunction of the liver (hepatic encephalopathy)

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. The badly damaged liver is less able to remove them.

People have a tendency to bleed because the damaged liver can no longer synthesize enough of the proteins that help blood clot.

People with chronic hepatitis B may have jaundice, itchiness, and light-colored stools. Jaundice and itchiness develop because the damaged liver cannot remove bilirubin from the blood as it normally does. Bilirubin then builds up in the blood and is deposited in the skin. (Bilirubin is a yellow pigment produced as a waste product during the normal breakdown of red blood cells.) Stool is light-colored because the flow of bile out of the liver is blocked, so that less bilirubin is eliminated in stool. Bilirubin is what gives stool its typical brown color.

Diagnosis

  • Blood tests

  • Liver biopsy

Doctors may suspect chronic hepatitis B when

  • People have typical symptoms.

  • Blood tests (done for other reasons) detect abnormally high liver enzymes.

  • People have previously been diagnosed with acute hepatitis.

Testing for chronic hepatitis B usually begins with blood tests to determine how well the liver is functioning and whether it is damaged (liver function tests). Liver function tests involve measuring the levels of liver enzymes and other substances produced by the liver. These tests may help establish or exclude the diagnosis of hepatitis, 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.

Tests to identify the specific virus do the following:

  • Detect antibodies produced by the person's immune system in response to the specific hepatitis virus

  • Detect antigens of the specific hepatitis virus (antigens are any substances that can trigger an immune response in the body)

  • Determine how much of the virus's genetic material is present

These tests can confirm the diagnosis of chronic hepatitis B.

If chronic hepatitis B is confirmed, doctors also check for antibodies to hepatitis D, which is often also present, and for HIV infection and hepatitis C because these infections are often spread in the same ways (through contact with bodily fluids, such as blood or semen).

If no virus is identified, other blood tests are needed to check for other causes, such as autoimmune hepatitis.

A liver biopsy may be done to determine how badly the liver is damaged and to check for other possible causes of liver disease.

Screening for liver cancer

If people have chronic hepatitis B, screening for liver cancer is done every 6 months. The following are done:

  • Ultrasonography

  • Sometimes measurement of levels of alpha-fetoprotein

Levels of alpha-fetoprotein—a protein normally produced by immature liver cells in fetuses—usually increase when liver cancer is present.

Treatment

  • Antiviral drugs

  • Sometimes liver transplantation

Antiviral drugs are used when people have one or both of the following:

  • Abnormally high levels of liver enzymes

  • Symptoms of worsening disease

  • Biopsy results indicating that liver damage is continuing

Most people treated for chronic hepatitis B must be treated indefinitely. Thus, treatment may be very expensive.

Stopping treatment prematurely can lead to relapse, which may be severe. However, treatment may be stopped if blood tests no longer detect any active hepatitis B virus infection.

One of the following antiviral drugs is usually used first:

  • Entecavir

  • Tenofovir

These drugs are taken by mouth, are very effective, and have few side effects.

Other drugs that are sometimes used include adefovir, lamivudine, interferon alfa, pegylated interferon alfa, and telbivudine.

Interferon alfa, given by injection under the skin, is effective but is not often used to treat chronic hepatitis B because it can have side effects, including flu-like symptoms, fatigue, a general feeling of illness (malaise), and depression. Interferon alfa is not usually given to pregnant women because its safety during pregnancy has not been determined.

Pegylated interferon alfa, also given by injection, can be used instead of interferon alfa. Pegylated interferon alfa is a form of interferon alfa that has been modified to keep the drug from breaking down as quickly so that it can be given less frequently. Side effects of pegylated interferon alfa are similar to those of interferon alfa but may be less severe.

Liver transplantation should be considered if liver function is severely impaired. The transplanted liver is more likely to survive and hepatitis B is less likely to recur if

  • People with chronic hepatitis B have been taking antiviral drugs for a long time.

  • They are treated with hepatitis immune globulin before and often after transplantation.

Hepatitis B immune globulin is obtained from the blood of people who have high levels of antibodies to hepatitis B. It is given by injection into a muscle or into a vein. It helps the body fight infection.

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