Outcomes of Chronic Infection with Hepatitis B Virus

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The summary below is from the full report titled "Serologic and Clinical Outcomes of 1536 Alaska Natives Chronically Infected with Hepatitis B Virus." It is in the 6 November 2001 issue of Annals of Internal Medicine (volume 135, pages 759-768). The authors are BJ McMahon, P Holck, L Bulkow, and M Snowball.

What is the problem and what is known about it so far?

Hepatitis B is an inflammation of the liver that is caused by a virus. The virus spreads through contact with infected body fluids. Most people who get hepatitis B recover within a few months, but some develop chronic infection. Chronic infection increases one's risk for liver failure and liver cancer. Persons with chronic infection often have viral-related protein substances in their blood (called hepatitis B surface antigens and e antigens) for many years. When e antigen is present, it usually means that the person has very active liver disease and a lot of virus present. Eventually, the body's natural defense system clears e antigen in most persons and surface antigen in a small percentage of persons. Exactly how often the body clears hepatitis B antigens on its own and how many people with chronic infection develop liver failure and liver cancer are not completely understood.

Why did the researchers do this particular study?

To describe the time course of clearance of viral antigens and outcomes in people with chronic hepatitis B.

Who was studied?

1536 Alaska Natives with chronic hepatitis B. The people studied ranged in age from 1 to 87 years; the average age was 20 years.

How was the study done?

Participants were identified by using a registry that had records from multiple statewide surveys done in the 1970s and 1980s. All participants had documented chronic infection, defined as two positive blood tests for hepatitis B surface antigen on two separate occasions at least 12 months apart. All had repeated blood sampling at 6-month intervals as part of a program to try to detect liver cancer at a treatable stage. The duration of follow-up ranged from 1 to 33 years. Computerized medical records and death certificates were reviewed to assess liver failure and liver cancer outcomes. The researchers used special analysis methods to examine the time course of clearance of antigens.

What did the researchers find?

Seven percent of the participants cleared hepatitis B surface antigen during follow-up. About 40% tested positive for hepatitis e antigen at baseline. The probability of clearing e antigen was about 40% within 5 years and 70% within 10 years. About 15% of people who were negative for e antigen became positive again at some time during follow-up. Only 9 people received antiviral therapy (interferon or lamivudine). Eight people died of liver failure, and 36 got liver cancer. People who changed from being negative for e antigen to being positive had higher risk for liver cancer than did those who remained negative for e antigen.

What were the limitations of the study?

The study included only Alaska Natives. Other ethnic groups might have different time courses and outcomes. The study does not address whether antiviral therapy can change the course of chronic hepatitis B.

What are the implications of the study?

Most people (about 70%) with chronic hepatitis B will clear hepatitis e antigen within 10 years without antiviral therapy. A few (about 15%) will revert from being negative for e antigen to being positive. Persons who change from being negative to being positive have a higher risk for liver cancer. These people and people who do not clear e antigen might be good candidates for antiviral therapy.