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Hepatitis B Treatment (cont.)

Nucleoside/Nucleotide Analogues

Examples of nucleoside/nucleotide analogues used to treat hepatitis B include:

How do nucleoside/nucleotide analogues work?

Hepatitis B virus reproduces by making copies of its viral DNA nucleosides and nucleotides. The nucleoside/nucleotide analogues fool the hepatitis B virus into thinking they are normal building blocks for DNA. Essentially, the virus is unable to reproduce. Nucleoside/nucleotide analogues do not prevent all viral reproduction, but they can substantially lower the amount of virus in the body.

Over time, the hepatitis B virus can become resistant to nucleoside/nucleotide analogues. Once this happens, the viral load rises again, and the doctor may recommend switching to a different medication. Lamivudine has been used for more than 10 years and has a good side effect profile, but HBV often becomes resistant over months or years. It is estimated that 15% to 30% of hepatitis B viruses will become resistant to lamivudine after one year of treatment and that more than 70% will be resistant after five years of treatment. Newer analogues like adefovir, entecavir, and telbivudine are less likely to cause resistance, but have not been used against hepatitis B as long as lamivudine.

Who should not use these nucleoside/nucleotide analogues?

Individuals who have experienced an allergic reaction to a particular nucleoside/nucleotide analogue should not take that medication. The nucleoside/nucleotide analogues are used in other viral infections including HIV (human immunodeficiency virus). However, they are not used by themselves because HIV can rapidly become resistant, and HIV requires higher doses. For this and other reasons, persons who are co-infected with both HBV and HIV should consult an expert before starting treatment with nucleoside/nucleotide analogues. Most of these agents are not approved in women who are pregnant or breastfeeding. Some are approved for use in children.

Dosing of nucleoside/nucleotide analogues

The nucleoside/nucleotide analogues are pills or capsules that are taken orally. If kidney function is diminished, the doctor will decrease the dose of some of these medicines.

Drug or food interactions of nucleoside/nucleotide analogues

Drugs that decrease kidney function may increase blood concentrations of these agents. When given with nucleotide/nucleoside analogues, ribavirin (Rebetol, Copegus) - a medication used to treat HIV - may increase the risk of side effects, including a metabolic disturbance known as lactic acidosis.

Zalcitabine (Hivid) may inhibit the action of lamivudine. Trimethoprim-sulfamethoxazole (Bactrim/Septra) may increase concentrations of lamivudine, although these two drugs are used together successfully. Other interactions are less common, but it is important that the physician be made aware of all medications being taken by the patient.

Side effects and complications of nucleoside/nucleotide analogues

Although usually well-tolerated, nucleoside/nucleotide analogues may have a variety of side effects in some people. The following list provides a few examples. (Please consult your doctor or pharmacist for more complete information.)

  • If the virus becomes resistant or the patient stops taking the medications, hepatitis will recur or worsen. This can cause symptoms including fatigue, fever, and nausea. In severe cases, this may cause an enlarged liver, liver failure, or even death.
  • These agents may cause lactic acidosis, which is a build-up of lactic acid in the blood. If severe, lactic acidosis can interfere with normal body processes and even cause death.
  • These agents may cause inflammation of the pancreas in children.
  • These agents may cause body fat to increase, including in unusual areas such as the upper back (buffalo hump).
  • Other side effects may occur including reduced kidney function or blood cell problems. A doctor will draw blood to monitor kidney and liver function, measure blood acidity, measure muscle enzymes, and check for low blood cell counts, such as decreases in the number of white cells, red cells, or platelets.

Effectiveness of nucleoside/nucleotide analogues

In patients who have hepatitis e antigen (HBeAg) in their blood, treatment with nucleoside analogues eliminates the HBeAg and allows antibody formation in 12% to 20% of patients and eliminates viral DNA from the blood in 40% to 65% of patients.

In patients who do not have HBeAg in their blood, treatment with nucleoside analogues eliminates viral DNA from the blood 60% to 90% of the time.

Even when there is no detectable virus in the blood, the patient still has virus in the liver. However, the risk of liver complications is significantly reduced. Once virus is eliminated from the bloodstream, it can rebound after the treatment is stopped.

Interferon alfa-2b (Intron A) and pegylated interferon alfa-2a (Pegasys). Both medications are given by a subcutaneous injection for six months to one year.

Medically Reviewed by a Doctor on 7/30/2014
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