| What is the natural progression or course of chronic hepatitis B?
An hepatitis B viral infection can progress from an immune tolerant phase (in which the immune system ignores the virus), through an immune clearance phase (in which the immune system attempts to eliminate the virus), to a quiescent phase (in which the virus is inactive). The course of chronic hepatitis B, however, is variable and relates to several factors, including the patient's age at which the infection begins. Thus, the course of hepatitis B virus in people who are infected at a young age is quite different from those who are infected in adulthood. Ultimately, however, the course depends, in large part, on the interaction or balance between the immune system and the virus.
What is the immune tolerant phase?
For individuals infected at a young age (for example, children born in Southeast Asia or Sub-Saharan Africa), the immune system initially does not recognize or react to the hepatitis B virus. This phase of the infection is known as the immune tolerant phase because the immune system seems to tolerate the virus. Many factors probably account for this tolerance. For one thing, the immune system is exposed to the hepatitis B virus while the immune system is still immature and, therefore, perhaps unable to recognize the hepatitis B virus as foreign material. For another, the virus may express itself in the liver cells during the early years differently (for example, less obviously) than in the later years of infection.
During the immune tolerant phase, little or no damage is done to the liver despite high levels of the virus in the body. Moreover, the standard liver blood tests are normal and the affected person does not have symptoms. This phase typically lasts for many years, even up to two or three decades. The results of hepatitis B virus blood tests during this phase are HBsAg positive, HBeAg positive, and hepatitis B virus DNA positive. It is important to know that the immune tolerant phase is generally not seen in individuals who become infected during adulthood, as usually occurs in North America and Western Europe.
What is the immune clearance phase?
The immune clearance phase begins during the third to fourth decade of an hepatitis B viral infection that was acquired in childhood. The immune system in these patients no longer ignores the viral infection. An hepatitis B viral infection acquired in adulthood, in contrast, usually begins with the immune clearance phase. In this phase, the immune system attacks and injures the hepatitis B virus-infected liver cells. This phase is called the immune clearance phase because the immune system is attempting to clear, or eliminate, the virus. Yet, because of the paradoxical liver injury that occurs during this phase, the standard liver blood tests are abnormal (elevated), especially the ALT and AST. In addition, the liver biopsy may show significant liver injury (inflammation) and formation of scar tissue (fibrosis). The severity of liver cell destruction and the duration of this phase determine whether the individual develops significant liver disease or even cirrhosis (severe scarring of the liver). The more severe the destruction and the longer the phase, the more likely is the development of cirrhosis.
What is the quiescent phase?
Following the immune clearance phase, the viral infection enters the quiescent (quiet, dormant, or inactive) phase. The levels of hepatitis B virus become very low, the standard liver blood tests are near normal or normal, and few or no injured (inflamed) liver cells are seen on the liver biopsy. Advanced fibrosis or cirrhosis that may have developed earlier, however, remains. In the quiescent phase, the individual will almost always remain HBsAg positive, signifying an ongoing presence of hepatitis B viral infection. At this time, however, the markers of viral reproduction (HBeAg and hepatitis B virus DNA) become negative and anti-HBe (denoting a more inactive state of the virus and less risk of spread) becomes positive.
What about flares and progression of chronic hepatitis B during the quiescent phase?
Occasionally, during the quiescent phase, the virus can become active again. This reactivation or flare, as it is commonly called, is often associated with symptoms, abnormal liver blood tests, and injury to the liver. The flares are caused by a disturbance in that delicate balance between the immune system and the virus. They can be very severe and result in further scarring of the liver. Asian men over the age of 40 are particularly at risk for having flares of their hepatitis B virus disease. In fact, the disease in many of these individuals will progress to cirrhosis and eventually to advanced or end-stage cirrhosis, with its associated complications, including liver cancer.
The progression to cirrhosis, however, is insidious in most individuals with hepatitis B virus. This means that the condition progresses with few or no symptoms to indicate the seriousness of the disease. Once cirrhosis occurs, the risk of developing the main complications of portal hypertension (fluid retention, hepatic encephalopathy, or bleeding from esophageal varices) is about 20 to 25% over 5 years. (These complications are discussed above.) What's more, the risk of developing primary liver cancer (hepatocellular carcinoma) is about 200 to 300 times higher than in healthy individuals without hepatitis B viral infection.
What are healthy carriers of hepatitis B virus?
Hepatitis B virus-infected individuals who have a brief and mild immune clearance phase before moving into the quiescent (inactive) phase tend to do very well. This means that they have normal liver tests and do not have symptoms. They are known as healthy carriers of hepatitis B virus. Healthy carriers, however, can transmit the hepatitis B viral infection to others. The risk of hepatitis B virus carriers developing cirrhosis and liver cell cancer is very small, although the risk is slightly higher as compared to people without chronic hepatitis B viral infection. Rarely, healthy carriers spontaneously become HBsAg negative (signifying an absence of ongoing hepatitis B viral infection), although this only occurs in individuals who acquired hepatitis B virus in adulthood.
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