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Guide to Hepatitis B for People Living With HIV

June 2009

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Section 3: Natural History

HBV infection primarily affects the liver, the largest organ inside the human body, found on the right side, underneath the rib cage. Your liver works as a filter and processing plant: anything you eat, drink, or inhale passes through the liver. Your liver also breaks down drugs, herbal remedies, and vitamins.

Each day, your liver:

  • filters waste from the blood;
  • stores vitamins, minerals, and iron;
  • changes food into energy;
  • makes bile (a liquid that your body uses to digest fat);
  • helps balance sugar and hormone levels;
  • makes cholesterol; and
  • creates many of the proteins needed for blood clotting.

HBV and Liver Damage

The hepatitis B virus infects liver cells, where it reproduces. Newly made hepatitis B virus particles, called virions, are released into the blood stream and in turn infect more liver cells. The hepatitis B virus does not directly cause liver damage. Instead, your immune system tries to prevent HBV from infecting other cells by surrounding already-infected liver cells and walling them off, causing liver scarring.

As the scarring worsens over time, the liver hardens and becomes less elastic, making it increasingly difficult for blood and other fluids to flow freely through it. Serious liver damage makes it difficult for the liver to regulate sugar-, hormone-, fat-, and platelet levels. As the liver slowly loses its ability to filter waste products, they can build up to toxic levels in your bloodstream.

Liver damage from HBV happens slowly, usually over decades in people without HIV. HIV-positive people, especially those who have lower CD4 cell counts, can develop liver damage faster. Even though a damaged liver can keep working, the ongoing inflammation and scarring can slowly interfere with liver function and lead to additional health complications.

Acute HBV

The first six months of HBV infection are referred to as the acute phase; during this phase, about 30-50% of infected people will experience symptoms. Symptoms usually appear between one and three months after people are infected -- symptoms that can include nausea; vomiting; appetite loss; fever; fatigue; abdominal and joint pain; liver swelling; and jaundice (yellow skin and eyes). In very rare cases (<1%), these symptoms can arise very rapidly and severely (this is known as fulminant hepatitis) and can be fatal. People experiencing severe symptoms should seek medical attention immediately.

HBV treatment is usually not recommended in the acute phase, as it is not effective and might interfere with the natural immune process and cause chronic disease. However, treatment may be used in some acute cases when liver transplantation is considered in patients with fulminant hepatitis B.

Spontaneous Clearance

During acute HBV infection, some people will eliminate the virus from the blood (HBsAg seroconversion from positive to negative, meaning HBsAg can no longer be detected in the blood) and develop antibodies (anti-HBs) that protect against future HBV infection. This is called spontaneous clearance. During spontaneous clearance, the immune system recognizes HBV and responds by marking and destroying HBV in the blood, and by killing off infected liver cells.

The rate of HBV spontaneous clearance differs, depending on the robustness of your immune system when you were infected.

HBV Infection at Birth
Because the immune system takes many years to mature enough to recognize HBV infection passed on by the mother, infants and children cannot clear the virus as successfully; 90% will develop chronic (lifelong) HBV infection.

HBV Infection in Adults
Most adults with acute HBV will spontaneously clear the virus. Less than 1% of adults with a healthy immune system will develop chronic disease.

HIV-Positive Adults
People with weakened immune systems have a harder time clearing the virus. HIVpositive adults who become infected with HBV are significantly more likely to develop chronic disease than people without HIV.

Chronic HBV

If there is no spontaneous clearance, the HBV infection becomes chronic (lifelong). Having chronic HBV does not always mean that you will have serious liver damage or that you'll need treatment. Some people live with chronic HBV for many years and will never have serious liver damage. If HBV is untreated, the lifetime risk of death from serious HBV-related liver disease is about 25-40% among people without HIV.

Spontaneous clearance still happens at the rate of 1-2% per year during chronic HBV; one large study from Asia reported that 45% of people spontaneously cleared HBV over a 25-year period in younger adults. The reason for this is not clear, but is likely due to the maturing of the immune-system. This group of people generally has an excellent long-term outcome and will stay disease-free. Spontaneous clearance is less likely to happen in people over 35 years old.

HIV-coinfected people have a higher risk of developing serious liver disease without treatment; however, since effective treatment became available in the mid-1990s, the prognosis for coinfected people has significantly improved. When their regimens include drugs that are also active against HBV, HIV/HBV-coinfected people respond just as well to their HIV drugs as do people with HIV alone. Studies have also found that treating HIV and HBV can lower the risk of HBV disease progression, and in some cases, even reverse liver damage from HBV.

Liver Damage Progression

While some people never develop serious liver damage from HBV, others may develop mild-to-moderate liver scarring, called fibrosis. They may experience symptoms such as fatigue, depression, and confusion; however, some people who have liver fibrosis will experience no symptoms. There does not seem to be a clear relationship between symptoms and the degree of liver damage.

Having HBV and being overweight can cause fat to build up in the liver, a condition called steatosis. Some HIV drugs (especially zidovudine, didanosine, and stavudine) can also cause steatosis. People with steatosis are at higher risk for liver damage.

Serious liver scarring is called cirrhosis. Compensated cirrhosis means the liver is still able to function even though it is scarred. People with compensated cirrhosis are at risk for developing liver failure and other serious complications.

Liver failure, also called decompensated cirrhosis, or end-stage liver disease (ESLD), means that the liver can no longer do its job, and that a liver transplant may be necessary.

Liver cancer (also called hepatocellular carcinoma, or HCC) is a very serious complication of HBV infection. It is very difficult to treat successfully, especially if it is not caught early.


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This article was provided by Treatment Action Group.
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