Hepatology
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Chronic Hepatitis

by Anne Larson, MD
Definition
Chronic hepatitis (CAH) is ongoing injury to the cells of the liver with inflammation that lasts for longer than six months. The causes of chronic hepatitis are several: viruses, metabolic or immunologic abnormalities, and medications/drugs/toxins. Chronic hepatitis may follow acute hepatitis B or C (formerly called non-A, non-B), or may develop quietly without an acute illness.
 
Symptoms
Symptoms result from the liver cell injury, the inflammation, or from the resulting scarring (which is called cirrhosis). Fatigue, mild discomfort in the upper abdomen, loss of appetite and aching joints are the common symptoms of chronic hepatitis. Fatigue is by far the most common symptom and it might be quite disabling. Often it gets worse as the day wears on. Some patients, however, may have no symptoms. Others may have signs of liver failure - including jaundice, abdominal swelling (due to fluid retention called ascites), or liver coma (also called encephalopathy), depending on the severity of the liver disease and whether or not cirrhosis has developed. Most complications are vague and may be mistaken for other diseases or simply a consequence of aging. Disorders of other organs like the thyroid, intestine, eyes, joints, blood, spleen, kidneys, and skin may occur in about 20% of patients depending on the cause of the chronic hepatitis.
 
Diagnosis
Liver biopsy is extremely helpful in that it confirms the diagnosis, aids in establishing the cause (etiology) of the liver disease, and can demonstrate the presence of cirrhosis. It is also useful to determine prognosis. It is less helpful in judging the response to treatment.
 
Causes
  • Viral
    Hepatitis B (HBV, formerly called "infectious hepatitis") and C (HCV, "non-A non-B hepatitis") are the most common causes of chronic hepatitis. Together they account for more than 75% of the cases in the world. HBV is transmitted mainly through infected blood (such as transfusion or IV drug use) or sexual contact. About 10-15% of adults infected with HBV will develop chronic disease (up to 90% of children infected develop chronic disease). HCV is also transmitted through infected blood, but sexual transmission is much less common. About 85% of persons infected with HCV will develop chronic disease. Chronic HCV behaves differently from HBV. The disease is generally mild, with fatigue being the main symptom. Ten or more years later, however, the complications of cirrhosis appear in some patients, sometimes unexpectedly. By contrast, with HBV the percentage of patients infected who develop cirrhosis is much greater. While primary liver cancer can also develop from HCV, it appears to be more common with HBV.

    Hepatitis A and E (formerly called "epidemic" or "enteric" non-A, non-B) are rarely, if ever, responsible for chronic hepatitis.

    Hepatitis D (HDV) infection requires the presence of the hepatitis B virus to multiply. HDV can cause acute hepatitis in someone who is a carrier of the HBV and can cause acute hepatitis at the same time that the hepatitis B virus does. In any event, the combination of hepatitis B and D is worse than hepatitis B alone, and is more likely to cause serious chronic hepatitis and cirrhosis. IV drug users have a high incidence of hepatitis D.

  • Other Viral
    Viruses of the herpes family, which cause cold sores, genital herpes, chicken pox, shingles, and infectious mononucleosis, can cause acute hepatitis, especially when the immune system is not functioning properly. It is unlikely that they will produce chronic hepatitis. Other viruses, as yet undiscovered, may be responsible for some of the cases of chronic hepatitis.
     
  • Autoimmune Hepatitis
    This varies from mild to serious disease. The percentage of patients who develop cirrhosis is high and it may appear early in the course of disease. Only a few cases of primary liver cancer have been reported with this disease. Twenty-five percent of cases of chronic hepatitis result from damage to the liver by the immune system. The trigger for autoimmune chronic hepatitis is unknown, but the damage to the liver is caused by the individual's lymphocytes (white blood cells) and by antibodies produced in the individual's own tissue. Autoimmune hepatitis is usually a progressive disease ending in cirrhosis and liver failure.
     
  • Drug-Induced Hepatitis
    A few medications still in use, and several that have been withdrawn from the market can also cause chronic hepatitis. These include: isoniazid (used for tuberculosis), methyldopa (used for hypertension), nitrofurantoin (used for urinary tract infections), phenytoin (used for seizure disorders), and selected other prescription medications. These medication must be taken for long periods of time and the number of cases of chronic hepatitis produced by these medications is small. Chronic hepatitis caused by drugs is usually recognized early. Stopping the medication before cirrhosis has developed usually reverses the disease. Many of the herbs and "naturopathic" medications can also cause chronic hepatitis.
     
  • Inherited Disorders
    Some inherited disorders of metabolism also can appear as chronic hepatitis. The most frequent of these conditions is Wilson's Disease, a disorder of copper metabolism. Alpha-1-Antitrypsin Deficiency and Tyrosinemia may appear as chronic hepatitis, although other features help in distinguishing these rare conditions from those caused by viruses. A disorder of iron metabolism, Hereditary Hemochromatosis, can also lead to chronic hepatitis and cirrhosis.

 
Treatment
Interferon has been approved for the treatment of Hepatitis B and C. The treatment has been shown to reduce the inflammation and liver damage caused by the virus in up to 40% of patients with HBV and 25% of cases of HCV by eliminating the virus, thus reducing the development of scar tissue. This avoids the development of cirrhosis. In HCV, interferon alone is associated with a large relapse rate. Combination therapy with intron/ribavirin or high dose therapy with Infergen shows improved responses in relapsing patients. Combination therapy is superior to standard dose interferon alone. Research is ongoing on to address the relapse rates and differing treatment regimens.

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