Liver Disease

In the past, people with HIV faced serious health problems from infections that took advantage of a weakened immune system. Powerful anti-HIV drugs can now help control such infections.

Yet, a new risk exists. Although people on anti-HIV therapy now live longer, they are more likely to develop liver disease. These include hepatitis B and C.

Hepatitis C affects more than a third of people with HIV. It can lead to cirrhosis, liver failure or death. Hepatitis B is the leading cause of chronic liver disease and liver cancer, and is the ninth leading cause of death worldwide, according to the World Health Organization.

And, men infected with both hepatitis B and HIV are 17 times more likely to die from liver disease than men with just hepatitis B alone, according to a study by researchers at Johns Hopkins. 

Liver-related problems that can affect a person with HIV include:

• Cirrhosis
• Fatty liver steatosis
• Lactic acidosis
• Liver cancer
• Liver failure

Symptoms

Most liver problems donÕt produce symptoms, especially at first. Liver problems are usually found through a blood test ordered by a doctor. This test measures liver enzymes in the blood. Rising enzyme levels may be a sign of possible liver problems.

Over time symptoms appear, including:

• Dark, tea-colored urine
• Easy bleeding or bruising
• Fatigue
• Pain or tenderness in the upper right side of the abdomen
• Stools that are clay-colored
• Yellowish eyes and skin

Causes

Liver problems can develop in a person with HIV for several reasons, including:

• The effect of anti-retroviral drugs. The liver processes food and drugs. Some HIV drugs put a heavy burden on the liver. Protease inhibitors such as Crixivan¨ (indinavir) or Viracept¨ (nelfinavir) and non-nucleosides such as Sustiva¨ (efavirenz) or Viramune¨ (nevirapine) can cause liver damage.
• Weakening of the immune system. This makes it hard for the body to fight viral infections such as hepatitis. People who already have viral hepatitis are five times more likely to have liver side effects from anti-HIV drugs.
• Factors that cause liver problems in anyone, with HIV or not. These include heavy drinking, street drug use and allergic reactions to over-the-counter and prescription drugs. (Drug-related liver problems make up more than half of the liver failure cases in the United States, according to a recent New England Journal of Medicine study.) For instance, because HIV and hepatitis B are transmitted in the same ways, up to 10 percent of HIV-infected individuals also have a hepatitis B infection.

Risk Factors

The following factors can increase the risk of developing liver problems for those living with HIV:

• Having hepatitis. Men infected with a combination of hepatitis B and HIV have a greater risk of death from liver disease than men infected with hepatitis B alone. Those with hepatitis C already have liver damage and HIV medications will make it worse.
• Being on highly active antiretroviral therapy. Some anti-HIV drugs are riskier than others. Norvir (ritonavir) and Videx and Videx EC (didanosine) can cause liver damage. Nucleoside reverse transcriptase inhibitors (NRTIs) cause liver enlargement and build-up fat in the liver, called steatosis, and may damage the liver. Protease inhibitors (PIs) have been linked to liver toxicities.
• Being treated for an HIV-related infection with certain drugs. Three antibiotics -- trimethoprim-sulfamethoxazole, isoniazid and rifampin Ð pose a greater risk of causing liver damage.

Prevention

Avoiding alcoholic drinks and recreational drugs reduces the strain on the liver. Some individuals may also benefit from vaccines against hepatitis A and B. There is no vaccine for hepatitis C. Physicians need to closely monitor those on HIV therapy to reduce the risks of liver damage.

Diagnosis

Regular tests to check how well the liver is working are important because of the known effects of anti-HIV drugs, some antibiotics and anti-viral drugs. Also, HIV disease and AIDS can lead to infections that can settle into and cause liver problems.

Monthly testing is recommended for the first two or three months on anti-HIV therapy. After that, tests should be done every other month.

Blood tests are used to check how the liver is working and if it is inflamed. The tests check enzymes that spill into the bloodstream whenever the liver is irritated by a medication or an infection. Other tests check the liverÕs ability to filter blood and toxins from the body.

If liver enzyme levels go up, HIV therapy may need to be adjusted. While most drug-induced liver problems are mild, they can be very serious and may even cause death in some patients.

People with early HIV infection and adequate CD4 counts who are not taking antiretroviral therapy found to have liver disease, usually have a common type, such as viral hepatitis or alcoholic liver disease.

In contrast, people with advanced HIV infection and low CD4 counts found to have liver disease, usually have opportunistic liver and biliary tree infections.

Treatment

If liver tests indicate serious problems, sometimes a rest is all the liver needs to recover. In other words, a two- to three-month break from medications can rebuild the liver. It is a delicate balance. Doctors decide the risks and benefits for each individual.

Some drugs may have to be stopped. But, because HIV treatment usually involves a combination of drugs, a similar drug may be used instead. It is important to understand that stopping treatment, even for a few months, usually means a slow reduction in infection-fighting immune cells. This may lead to the return of detectable levels of HIV in the body. Again, physicians work with each individual to decide the best treatment.

Some doctors also recommend alternative treatments for the liver such as acupuncture and supplements to encourage the liver to remain healthy or to rebuild.

If jaundice (yellowing of the eyes or skin) develops, this is a sign of serious liver damage and HIV treatment may have to be stopped. In the past, this led to fears about drug resistance. But, researchers have found that stopping the drug cocktail does not commonly lead to drug resistance.

In addition, some drugs that work for HIV may also treat hepatitis B. So, both infections can be treated at once.

ItÕs different for HIV patients with hepatitis C. They may have problems when treated with HIV medications because their liver is already damaged. For them, their liver problems may get a lot worse once they start HIV medications, and the hepatitis seems to get worse faster.

HIV therapy is interrupted probably less than 5 percent of the time for liver problems. And, only a very small percentage of patients have to stop therapy altogether. It all depends on the patient and the individual situation. If a person has active hepatitis or is an alcoholic, that increases the chance that therapy will be stopped. For the most part, people can be treated as long they are regularly observed by their doctors and have regular liver function tests.