About one third of people with chronic hepatitis develop it after a bout of acute viral hepatitis. The remaining two thirds of people develop the disease gradually without any obvious symptoms, although most cases of chronic hepatitis are still caused by one of the hepatitis viruses.

Hepatitis C virus is the most common cause of chronic hepatitis; at least 75% of acute hepatitis C cases become chronic. Hepatitis B virus, sometimes together with hepatitis D virus, causes a smaller percentage of chronic infections. Hepatitis A and E viruses do not cause chronic hepatitis.

Drugs such as methyldopa,isoniazid,nitrofurantoin,and possibly acetaminophen can cause chronic hepatitis, particularly when they are taken for prolonged periods. Wilson's disease, a rare hereditary disease involving abnormal retention of copper in the liver (see Wilson's Disease: When Copper Accumulates), may cause chronic hepatitis in children and young adults.

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. In many people with chronic hepatitis, no obvious cause can be found. In some of these people, there appears to be an overactive immune system response that is responsible for the chronic inflammation. This response may occur because the body is attacking its own tissues (an autoimmune reaction (see Autoimmune Disorders), although this has not been proven. This disease, called autoimmune hepatitis, is more common among women than men.

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