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WHAT IS HEPATITIS B? Hepatitis B is inflammation of the liver due to a virus called the hepatitis B virus (HBV). Infection with HBV was originally known as serum hepatitis. In 1963, the structure of the virus was identified and named the hepatitis B virus. In fact, HBV was actually the very first hepatitis virus to be identified. Approximately 2 billion people worldwide have been infected by hepatitis B, and almost 400 million people worldwide, including 1.25 million people in the United States chronic carriers of this virus. Approximately 65 million of those chronically infected will die of the disease. HBV is the single most common cause of cirrhosis and liver cancer worldwide. Hepatitis B is endemic (a disease that is extremely widespread in a particular region) in Southeast Asia, China, and Africa. In these areas of the world, more than 50 percent of the population has been exposed to HBV at some point in their lives. Fortunately, the virus has a relatively low prevalence in North America, Western Europe, and Australia, and accounts for only 5-10 percent of all chronic liver diseases in these areas. In most cases, infection with HBV will not prevent a person from leading a normal, productive life. Yet, hepatitis B is not entirely harmless. A long-term infection can lead to cirrhosis, liver failure, and liver cancer. As a result, approximately 1 million people die each year from the complications of hepatitis B, making hepatitis B the ninth leading cause of death worldwide. Hepatitis B can present itself in a variety of ways. The Different Types of Chronic Hepatitis B People with chronic hepatitis B may be divided into three categories- 1] inactive hepatitis B surface antigen (HBsAg) carrier state, 2] chronic hepatitis B, which is divided into HBeAg- positive and HBeAg negative chronic hepatitis B, and 3] resolved chronic hepatitis B. Everyone with chronic hepatitis B is, by definition, both HBsAg and HBcAb positive. (Refer to Table 9.1 of my book for a discussion of these and some related terms.) This means that both the hepatitis B surface antigen and core antibody are detectable in their blood.

Inactive HBsAg Carrier State The first type of chronic hepatitis B is found in a person who carries hepatitis B - HBsAg and HBcAb are positive, but has normal liver enzymes (AST and ALT) a normal physical exam, and is asymptomatic. Such a person is referred to as an inactive carrier of hepatitis B. HBeAg and HBV DNA are negative, and HBeAb is typically positive -indicating that this person is not infectious to others. Inactive carriers of HBV usually have minimal, if any, liver inflammation or damage. They usually live a normal life without any complications due to their liver disease. However, compared with the general population, these people are at a somewhat higher risk for cirrhosis and liver cancer. Therefore, regular observationin the form of visits to the doctor approximately one to two times per year for a physical exam and blood testsis necessary to check for early signs of disease progression. In addition, these people are at risk for reactivation of the virus return of HBeAg positivity. This occurs approximately 20-30 percent of the time. An individuals likelihood of reactivation increases if their immune system become suppressed. Such an occurrence may happen during treatment with immunosuppressive drugs, such as steroids (prednisone, for example), or during a severe illness, such as AIDS or cancer. Inactive carriers
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can also have flares of hepatitis. This may occur with or without return of HBeAg, and is noted by elevations in liver enzymes to approximately 5 10 times the upper limit of normal. Repeated flares with or without reactivation of the virus return of HBeAg positivity, may lead to disease progression, liver scarring and even liver failure. Acute flares of hepatitis B should be distinguished from additional infection with hepatitis A, C or D. This is known as superinfection. It has been estimated that approximately 20 30 percent of such flares are due to superinfection with another hepatitis virus. Superinfection is associated with an increased risk of liver failure.

Chronic Hepatitis B The second type of chronic hepatitis B is termed chronic hepatitis B and is found in a person who, in addition to carrying the HBsAg, also carries HBV DNA. The presence of detectable levels of HBVDNA indicates that a person is highly contagious or infectious to others. People with chronic hepatitis B may be either positive or a negative for HBeAg. In either HBeAg positive or HBeAg negative people, liver enzymes are persistently or intermittently elevated and liver biopsy results typically reveal inflammation and damage. People with chronic hepatitis are likely to have a progressive disease leading to cirrhosis.

Chronic Hepatitis B HBeAg positive. People with HBeAg positive chronic hepatitis B have only an 8- to 15-percent probability each year of becoming negative for HBeAg and HBV DNA. This is known as a spontaneous remission. When this happens, a brief, temporary gross elevation in transaminases (AST and ALT) is observed, followed by a rapid return to normal levels. Antibodies to HBeAg -HBeAb are formed. This is known as seroconversion. These people are no longer contagious to others and further liver damage is minimal, if it occurs at all. In fact, liver damage often resolves within the next few years. This heralds the transition from chronic hepatitis B into the inactive HBsAg carrier state, as discussed above. Women, older people, and those individuals with genotype B are more likely to seroconvert. Unfortunately, reactivation to the infectious state can occur in some of these people. Thus, these people must be observed carefully. It is not clear which factors play a role in causing some people to relapse into an infectious state. Certainly, excessive alcohol intake may have a harmful effect on people with chronic hepatitis B. And it has been demonstrated that excessive iron intake may promote persistent HBV replication in some people. (Excessive iron in itself is damaging to the liver potentially leading to cirrhosis and liver cancer. This is discussed in more detail in Chapters 18 and 23.) Therefore, people with chronic hepatitis B are advised to refrain from alcohol intake and should avoid excess iron supplementation. Furthermore, people whose immune systems subsequently become compromised are at risk for a relapse. Immune-system function can become impaired by a number of factors, including infection with the human immunodeficiency virus (HIV), treatment with chemotherapeutic agents for cancer, or use of corticosteroids, such as prednisone, for various reasons.

Chronic Hepatitis B HBeAg negative.

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People with chronic hepatitis B who are negative for HBeAg

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have a mutant strain of chronic hepatitis B. A mutation is a permanent alteration of the hepatitis B viruss genetic makeup. There are many different types of hepatitis B mutations. In this case, the genetic mutation is characterized by the failure of the virus to make the hepatitis B e antigen (HBeAg). This is known as a precore mutation. This mutation does not affect the viruss ability to replicate. Therefore, on blood tests, these people are negative for HBeAg, but positive for HBV DNA. Men are more likely than women to have this mutation, and HBeAg negative chronic hepatitis B does not occur with genotype A. Precore mutant hepatitis B has been responsible for several cases of unsuspected transmission of disease to others, as these people are highly infectious, yet lack HBeAg. This strain of hepatitis B may be genetically superior to HBeAg positive chronic hepatitis B. Thus, liver disease is usually more active and liver scarring more advanced. These individuals are more likely to develop cirrhosis compared with HBeAg positive people. Furthermore, this strain is usually more resistant to treatment.

Resolved Chronic Hepatitis B In some instances, a person can become HBsAg negative. This last category of chronic hepatitis B is known as resolved chronic hepatitis B. However, this is very uncommon and only occurs at a rate of approximately 0.5 2 percent each year. Loss of HBsAg is more likely to occur in women compared with men, and is rare in people with the mutant strain. Most people, but not all, will develop HBsAb. Liver enzymes (ALT and AST) normalize. Clearance of HBsAg decreases the risk of progression to liver failure and liver cancer. Most people who have resolved have a benign course of disease. However, approximately half of these people continue to have very low levels of HBV DNA. A low level or noninfectious level of HBVDNA is considered to be less than 10,000 copies/mL. These low HBVDNA levels are only detectable if a very sensitive laboratory assay known as the polymerase chain reaction (PCR) is used. The PCR assay has a lower limit of detection of less than 200 copies/ml. (These test results are often reported in picograms/milliliter (pg/mL) 1pg/mL = 280,000 copies/mL). The significance of finding a low level of HBVDNA not known, as people with low levels are considered to be noninfectious to others. In situations where people with resolved hepatitis B are exposed to severe immune suppression, such as cancer chemotherapy or organ transplantation, chronic hepatitis B can be reactivated. This means that HBsAg will again become positive. All contents of this article are Copyright Melissa Palmer, MD Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).
The offices of Melissa Palmer, M.D. are located at: 1097 Old Country Road Suite 104 Plainview, N.Y 11803 or 500 Portion Road Lake Ronkonkama, N.Y. 11779 To arrange an appointment with Dr. Palmer, call
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Hepatitis B

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