Medications:

Medications for Chronic Hepatitis B

Seven drugs are currently approved in the United States for treatment of chronic hepatitis B:

• Peginterferon alfa-2a (Pegasys)
• Interferon-alfa-2b (Intron A)
• Lamivudine (Epivir-HBV)
• Entecavir (Baraclude)
• Telbivudine (Tyzeka)
• Adefovir (Hepsera)
• Tenofovir (Viread)

These drugs block the replication of hepatitits B in the body. They may also help prevent the development of progressive liver disease (cirrhosis and liver failure) and the development of liver cancer.

A doctor will decide which drug to prescribe based on a patient's age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed. Interferons are generally used for a time-limited course of treatment (16 - 48 weeks), while lamivudine, entecavir, telbivudine, adefovir, and tenofovir may be used on a long-term basis.

It is not always clear which patients with chronic hepatitis B should receive drug therapy and when drug therapy should be started. Therapy is generally indicated for patients who have experienced a rapid deterioration in liver function, or patients with cirrhosis complications such as ascites and hemorrhage. [For more information on complications of cirrhosis, see In-Depth Report #75: Cirrhosis.]

Patients who are receiving immunosuppressive therapy for other medical conditions or who have had reactivation of chronic hepatitis B are also appropriate candidates.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir-HBV).

Common side effects include flu-like symptoms, such as fever, chills, muscle aches, joint pains, and headaches. This drug can also cause depression, anxiety, irritability, and insomnia and should be used with caution in patients with a history of mental illness. This drug can also increase the risk for infections, and worsening of hepatitis as marked by sudden severe increases in ALT levels. Patients who show signs of ALT flares should have frequent blood tests to monitor their liver function.

Unlike other drugs used to treat chronic hepatitis B, drug resistance is less of a problem with peginterferon alfa-2a.

Interferon Alfa-2b. For many years, interferon alfa-2b (Intron A) was the standard drug for hepatitis B. It is now generally second line to peginterferon The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear. Like peginterferon alfa-2a, this drug can increase the risk of depression.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir-HBV) is also used in another formulation to treat human immunodeficiency virus (HIV). About 20% of patients who take lamivudine develop drug resistance. Lamivudine, along with interferon alfa-2b, are the only drugs approved for treatment of chronic hepatitis B in children. The Food and Drug Administration (FDA) approved entecavir (Baraclude) in 2005, and telbivudine (Tyzeka) in 2006, for treatment of adults with chronic hepatitis B. Some studies have suggested that these newer drugs work better than lamivudine.

If patients develop resistance to one of these nucleoside analog drugs, a nucleotide-analog drug such as adefovir or tenofovir may be added as combination therapy.

Common side effects of these drugs include headache, fatigue, dizziness, and nausea. (For more serious side effects, see "Drug Complications and Warnings" below.)

Adefovir and Tenofovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir may be effective against lamivudine-resistant strains of hepatitits B. The drug must be taken on a long-term basis. Tenofovir (Viread) is also a nucleotide analog drug. In 2008, the FDA approved tenofovir for treatment of chronic hepatitis B. Tenofovir was previous approved in 2001 for treatment of HIV infection. Common side effects of these drugs include weakness, headache, stomach pain, and itching.

Drug Complications and Warnings for Nucleoside/Nucleotide Analog Drugs. Patients who discontinue anti-HBV drug therapy are at risk for severe and sudden worsening of hepatitis. These patients should be closely monitored for several months after stopping treatment. If necessary, drug treatment may need to be reinstated.

Lactic acidosis (buildup of acid in the blood) is a serious complication of nucleoside/nucleotide analog drugs. Signs and symptoms of lactic acidosis include feeling extremely tired, unusual muscle pain, difficulty breathing, stomach pain with nausea and vomiting, feeling cold (especially in the arms and legs), feeling dizzy or light-headed, or a fast or irregular heartbeat. Immediately contact your doctor if you experience these symptoms.

Liver hepatotoxicity (liver damage) is another serious complication. Signs and symptoms include yellowing of skin or white part of eyes (jaundice), dark urine, light-colored stool, or lower stomach pain. Immediately contact your doctor if you experience these symptoms.

These drugs may also cause kidney damage (nephrotoxicity), particularly for people who already have kidney function problems.

Investigational Drugs for Chronic Hepatitis B.

• Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B. Some studies have suggested that it offers no advantage over lamivudine.
• Clevudine a nucleoside analog drug that is being studied in combination with tenofovir for chronic hepatitis B.

Medications for Chronic Hepatitis C

Pegylated interferon combined with the nucleoside analog drug ribavirin (Copegus) is the gold standard treatment for chronic hepatitis C in both adults and children. During a standard 24-week course of treatment, this drug combination achieves response rates of up to 50% for patients infected with hepatitis C genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavirin. Pegylated interferon is given as an injection once a week. Ribavirin is taken as a pill.

Two types of pegylated interferon are available for chronic hepatitis C treatment:

• Peginterferon alfal-2a (Pegasys)
• Peginterferon alfa-2b (Peg-Intron)

Candidates for Treatment. While all patients with chronic hepatitis C are potential candidates for treatment, doctors usually decide whether treatment is appropriate based on many different factors.

Treatment is generally recommended for patients with chronic hepatitis C who are at least 18 years old and have:

• Detectable virus levels as measured by an HCV RNA test
• An increased risk of developing cirrhosis
• Indication of liver scarring (fibrosis) as detected by liver biopsy
• Abnormal levels of alanine aminotransferase (ALT), an indication of liver cell damage

Treatment is generally not recommended for people who have:

• Advanced cirrhosis or liver cancer
• Major uncontrolled depression, particularly if they have attempted suicide in the past
• Autoimmune hepatitis or other autoimmune disorders such as hyperthyroidism
• Received bone marrow, lung, heart, or kidney organ transplantation
• Severe high blood pressure, coronary artery disease, heart failure, kidney disease, or other serious non-liver disorders that may affect life expectancy
• Severe anemia (low red blood cell count) or thrombocytopenia (low blood platelet count)
• Women who are pregnant or who do not use birth control
• Patients who actively abuse drugs or alcohol may not be appropriate candidates.

Side Effects of Treatment. Side effects of combination treatment include those caused by both pegylated interferon and ribavirin.

Side effects and complications of pegylated interferon include:

• Fatigue
• Flu-like symptoms (such as fever, chills, and muscle aches)
• Nausea and vomiting
• Headaches
• Weight loss
• Irritability
• Depression
• Hair thinning
• Bone marrow suppression
• Soreness at the injection site
• Serious infections

Side effects and complications of ribavirin include:

• Anemia, which can worsen heart disease
• Fatigue
• Severe itching
• Rash
• Cough
• Shortness of breath
• Birth defects

Investigational Drugs for Chronic Hepatitis C. The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs being tested in combination with interferon-ribavirin therapy that are showing particular promise in clinical trials include:

• Telaprevir is a protease inhibitor drug currently in phase III trials
• Boceprivir is another protease inhibitor drug, currently in phase II trials