Hepatitis B Treatment

What are Hepatitis B Treatments?

  • Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV). Hepatitis B may cause people to become very ill for several weeks.
  • These patients may have jaundice (yellow skin), poor appetite, and other symptoms. A life-threatening hepatitis B infection is called 'fulminant,' although this occurs in only 1% of symptomatic cases. However, some people, especially children, appear to have almost no symptoms when they acquire hepatitis B. Hepatitis B is spread through exposure to infected blood or secretions.
  • The body's immune system is eventually able to wipe out the virus and cure the infection in 95% of infected adults. Unfortunately, some patients' immune systems are unable to eliminate the virus and they become chronically infected. Children are especially prone to chronic infection, which occurs in 95% of newly-infected infants compared with 5% of newly-infected adults.
  • Patients with chronic hepatitis B carry the virus for years and usually for life, allowing it to continue to cause inflammation and scarring in the liver. Advanced scarring of the liver is called 'cirrhosis.' If the cirrhosis is severe, it can affect the ability of the liver to function, and can lead to liver failure or death.
  • People who are chronic carriers of HBV are also at risk for liver cancer. For these reasons, scientists have developed medications to help reduce the risk of complications in people who are chronically infected with HBV.
  • Although the following sections will focus on medications used for hepatitis B, it is important to note that there are effective vaccines available [haemophilus B/hepatitis B vaccine-injection (Comvax), hepatitis b vaccine-injection (Engerix-B, Recombivax-HB), Heptavax-B, Pediarix)] to prevent the infection in the first place. The vaccine is currently recommended for all children in the United States and for adults who are at increased risk for hepatitis B. Unfortunately, the vaccine does not help people who are already infected.

What causes hepatitis B?

HBV is a tiny organism found in high concentrations in the liver and blood of infected individuals. It is transmitted through contact with infected blood or contact with secretions contaminated with blood cells. For example:

  • intravenous drug users acquire the infection through sharing dirty needles;
  • health care workers can acquire hepatitis B through accidental needle sticks from infected patients;
  • because the virus is present in semen and vaginal fluid, sexual intercourse can also transmit the infection;
  • one of the major routes of infection is from an infected mother to her newborn child. Although these infants may not get very sick, they are very likely to become chronic carriers of the virus and to suffer complications of the infection in later life. Fortunately, prompt vaccination of newborns and other measures can provide significant protection for infants at risk.

What are the risks for hepatitis B?

Adults with a normal immune system who acquire hepatitis B have approximately a 95% chance of eventually eliminating the virus and making a complete recovery. During the weeks that the body is fighting the virus, the person may be very sick and a few (< 1%) may even die. Patients who do not clear the virus are chronically infected. The U.S. Centers for Disease Control and Prevention (CDC) estimates that more than one million Americans are chronically infected with HBV.

As discussed above, chronic infection with hepatitis B can cause cirrhosis, liver failure, or even death. Patients with chronic hepatitis B infection are also at risk for liver cancer (hepatocellular carcinoma). Between 15% and 25% of people with chronic infection will die prematurely from complications of hepatitis B. In the United States, chronic HBV infection was listed as the cause of 1,873 deaths in 2013.

What is the treatment for hepatitis B?

Prevention is vital to avoid hepatitis B virus infection. The current recommendation is that all children be vaccinated. Additionally, the following individuals should receive the hepatitis B vaccine:

  • adults at high risk (health care workers),
  • household contacts of infected persons,
  • individuals on hemodialysis,
  • intravenous drug users, and
  • persons with multiple sexual partners.

If a person is exposed to hepatitis B, then hepatitis B immune globulin (BayHep, H-BIG, Hep-B-Gammagee, Hyper Hep, Nabi-HB) is sometimes recommended. Hepatitis B immune globulin contains antibodies to the virus which can help reduce the risk of disease.

If a person is chronically infected with the hepatitis B virus and has no signs of complications, medications are usually not used. These patients are watched carefully and given periodic blood tests. One test, called the 'viral load' measures the amount of viral DNA in the blood. Doctors may recommend treatment if there are signs the virus is beginning to cause damage or if the viral load is elevated. Another reason to prescribe medication is if the patient has a positive test for the hepatitis B e-antigen (HBeAg) in the blood. HBeAg is associated with an increased risk of complications.

The goal of treatment is to reduce the amount of virus in the body and reduce the risk of complications. Unfortunately, medications do not cure the disease. Doctors track blood tests and may performliver biopsies to determine if the medications are working.

The medications in current use for chronic Hepatitis B include the nucleoside/nucleotide analogues and interferons. New agents are being developed.

How Do Nucleoside/Nucleotide Analogues for Hepatitis B Work?

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.

Interferons for Hepatitis B

How interferons work

Interferons are naturally occurring proteins in the body that help the body's natural defense system fight viruses. Interferon alfa-2b and pegylated interferon alfa-2a are proteins specifically designed to attach to the surface of the hepatitis B virus. Once attached, the proteins start a cascade of events leading to increased viral cell death. Pegylated interferon works in the same way as interferon alfa-2b, but it has an added structure that enables it to stay in the body longer and does not need to be administered as often. For this reason, and because studies have shown increased effectiveness, pegylated interferon is usually the agent of choice when an interferon product is used.

Who should not use interferons?

  • Individuals who have experienced an allergic reaction to interferons should not take this medication.
  • A "black box" warning has been issued by the FDA warning patients and clinicians to watch for serious psychiatric, autoimmune, ischemic, or infectious disease disorders that may be side effects of interferons. Caution is especially urged if patients already have a history of depression or another serious psychiatric condition.
  • Pegylated interferon is not used in newborn infants (it contains benzyl alcohol), in patients with autoimmune hepatitis, or in those with severe liver failure (it may cause a temporary increase in liver inflammation, which a failing liver could not handle).
  • The safety and efficacy of pegylated interferon has not been established in patients under the age of 18.

Dosing of interferons

Interferons are administered by a subcutaneous injection into the thigh or abdomen at various dosage schedules. Interferon alfa-2b is approved for children as young as one year old as well as adults. Pegylated interferon alfa-2a is approved only in adults 18 years of age or older. While taking these medications, it is important to have routine blood work done to monitor for possible side effects.

Drug or food interactions of interferons

  • Interferon increases theophylline (Theo-Dur, Respbid, Slo-Bid, Theo-24, Theolair, Uniphyl, Slo-Phyllin) levels by 100%.
  • Interferon may increase levels of methadone in persons taking this drug.

Side effects of interferons

Common side effects of the interferons include flu-like symptoms such as muscle aches, fatigue, fevers, and chills.

Other common side effects include:

More serious side effects include:

Effectiveness of interferons

In patients who have hepatitis e antigen (HBeAg) in their blood, treatment with pegylated interferon eliminates the HBeAg and allows antibody formation in approximately 27% of patients. Treatment eliminates viral DNA from the blood in approximately 25% of patients with HBeAg. In patients who do not have HBeAg in their blood, treatment with pegylated interferon eliminates viral DNA from the blood 65% of the time. Again, viral DNA can rebound after the treatment is stopped.

Treatment Decisions for Hepatitis B

Treatment is usually considered when the risk of complications is high. This would include individuals who have a persistently high viral load, those who have HBeAg in their blood, and those who have signs or symptoms of liver dysfunction. There is no 'rule' for when to start treatment, and the decision is usually made jointly between the physician and the patient. If a decision is made not to treat, patients are monitored regularly to ensure that their disease is not progressing quickly and to evaluate their candidacy for new agents that might be available on the market.

The decision of whether to use nucleotide/nucleoside analogues or pegylated interferon is also individualized. Patients at high risk for neuropsychiatric side effects of pegylated interferon may choose to start with a nucleotide/nucleoside analogue. Nucleotide/nucleoside analogues, especially lamivudine, are more likely to induce resistance in the virus, rendering the drug ineffective after a few months or years.

Investigational Medications for Hepatitis B

New nucleoside/nucleotide analogues are being developed to try to improve outcomes or limit side effects or resistance in hepatitis B. One example is emtricitabine (Emtriva), which is already approved for use in HIV. Other examples include clevudine (L-FMAU), pradefovir, alamifovir, valtorcitabine, and medications that are currently identified only with drug numbers such as ANA380 (LB80380), ANA-975, and others.

Although currently available vaccines against hepatitis B are not effective in patients who already have chronic hepatitis B, new vaccines are being developed that may one day help stimulate the body's immune system in combination with medical treatment.

Combination therapies using two nucleoside/nucleotide analogues or analogues plus pegylated interferon have not shown superiority to single-agent therapy.

Hepatitis B

Hepatitis B Symptoms

What are the symptoms of hepatitis B?

Common symptoms of hepatitis B include:

  • Appetite loss<
  • Feeling tired (fatigue)
  • Nausea and vomiting
  • Itching all over the body
  • Pain over the location of the liver (on the right side of the abdomen, under the lower rib cage)
  • Jaundice (a condition in which the skin and the whites of the eyes turn yellow in color)
  • Dark urine (the color of cola or tea)
  • Pale-colored stools (grayish or clay colored)
Medically reviewed by Robert Cox, MD; American Board of Internal Medicine with subspecialty in Infectious Disease


"Overview of the management of hepatitis B and case examples"