hcspFACTsheet

a series of fact sheets written by experts in the eld of liver disease

Hepatitis C Support Project www.hbvadvocate.org

have had such limited success, the goals of treatment have been remarkably unambitious. Instead of aiming for a total cure, signaled by the immune systems production of surface antibodies, current treatment goals are simply to: Lower the volume of viruses (viral load), which is measured by HBV DNA in the bloodstream.

Whats New in Hepatitis B

Treatment

2008

Stop liver damage and achieve normal alanine aminotransferase or ALT levels. ALT is released by liver cells when they die, and above normal levels indicate liver damage.

Spur the immune system to create the antibody to the hepatitis B e antigen (HBeAg). When HBeAg is THERE ARE tWO tYPES OF DRUGS AVAILABLE tO tREAt present, it usually signals a high viral load and high A CHRONIC HEPAtItIS B VIRUS (HBV) INFECtION: risk of liver damage.
Christine Kukka, HBV Project Manager

Interferons boost the immune system so it will aggressively wage war against the HBV infection. Antivirals or nucleoside analogues are designed to deliberately interfere with HBVs DNA so it cant reproduce itself. These two treatments are usually used one at a time, but some doctors are experimenting to see if using them in combination to first knock down the amount of virus, and then boost the immune system to vanquish the remaining HBV, could be successful.

Doctors generally do not treat patients unless there is liver damage, including ALT levels that are more than twice normal, a liver biopsy that indicates inflammation and scarring, and a high viral load. Interferons Doctors usually prescribe interferon when ALT levels are elevated. Elevated ALTs indicate the immune system has noticed the infection and is attacking and killing the infected liver cells. To prescribe interferon when ALT levels are not elevated is tantamount to giving bullets to an army that is not at war. Conventional and pegylated interferon, administered by injection, works best when ALT is elevated and viral load is low - when the army is on the attack and there are few viruses to vanquish. Pegylated interferon, which is a time-release interferon requiring only one injection per week, is much more effective at spurring the immune system to target HBV than conventional interferon.

The U.S. Food and Drug Administration (FDA) has approved two types of interferon for hepatitis B treatment. The interferon available to adults and children is called conventional or interferon alpha-2b. Pegylated interferon, approved only for adults to date, is the newest interferon approved for hepatitis B. Fourantivirals lamivudine (brand name Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), and telbivudine (Tyzeka), have been approved for hepatitis B in adults. Only lamivudine Pegylated interferon (Pegasys) has also shown promise in people who experience liver damage and high has been approved for treatment of children. viral load even when they do not test positive for the New hepatitis B drugs under development aim to im- e (HBeAg) antigen. This is called HBeAg-negative prove on the antiviral and immune boosting qualities hepatitis B. About 43 percent of people with HBeAgof these drugs. Because the current arsenal of drugs negative hepatitis B experienced lowered viral load with
HCSP VERSION 4.1 September 2008 1

pegylated interferon and about 59 percent achieved HBeAg. The immune system has a hard time identifying normal ALT levels. and zeroing in on this type of hepatitis B virus. When an HBV infection exists and lab tests cant find the e Also, pegylated interferon can be effective when both antigen, despite high viral loads and elevated ALT, it is HBV DNA and ALT levels are elevated. called HBeAG-negative hepatitis.

Antivirals

The four FDA-approved antiviral medications available to HBV-infected patients are lamivudine, approved for adults in 1998 and for children in 2000, adefovir, approved for adults in 2002, and currently in clinical trials for children, entecavir approved for adults in 2005, and telbivudine, approved for adults in October 2006. Antivirals are valuable because they can lower the rate of HBV replicating in the liver. Generally, when viral load drops, liver damage declines because there are fewer viruses invading liver cells and ALT levels also normalize. Lamivudine (brand name Epivir-HBV): Administered as a daily pill or oral solution, lamivudine generally produces normal ALT levels and undetectable HBV DNA in about 65 percent of adults who take it.

If a patient is to be treated for the first time, which antiviral is best? To date, no medical organization has endorsed one antiviral over the other. It is important to discuss all the pros and cons of each antiviral with a doctor. Entecavir (brand name Baraclude): Entecavir is a potent inhibitor of HBV replication. In lab tests, this antiviral has shown the ability to reduce viral CCC DNA levels, which are believed to promote development of liver cancer. In studies that compared entecavir with lamivudine, entecavir was more effective in reducing HBV DNA levels, even when ALT levels were only slightly elevated. Early studies also suggest that entecavirtreated patients had a longer, sustained response to the drug, even after treatment ended, including those with HBeAg-negative hepatitis B. There have been a couple reports of viral resistance to entecavir developing, but nearly all occurred in patients who had already developed lamivudine-resistant viruses.

While lamivudine is safe and rarely causes side effects, it is not a permanent or complete cure. It keeps the virus in check for only as long as it is taken. When treatment Telbivudine (brand name Tyzeka): Stops HBV replistops, HBV DNA and ALT levels usually rebound. cation and normalizes ALT levels better than lamivudine Lamivudine has one serious drawback. Some hepatitis and adefovir. Several trials compared the lamivudine B viruses develop resistance to lamivudines antiviral and telbivudine and, after one year, telbivudine-treated punch. Over time, the non-resistant viruses decline, patients had healthier ALT levels and lower viral load but the lamivudine-resistant HBV rebound until viral than those treated with lamivudine. One year-long study load and ALT levels start to climb once again. After four that compared telbivudine to adefovir in 135 patients years of lamivudine treatment, more than 60 percent of with HBeAg-positive hepatitis B and elevated ALT found it produced more significant declines in HBV DNA than patients develop lamivudine-resistant HBV. adefovir. Adefovir (brand name Hepsera): Adefovir appears to have all of lamivudines antiviral clout, but none of Telbivudine, to date, appears to cause no adverse side its viral resistance. Today, doctors frequently switch effects and there have been no reports of viral resispatients who have developed viral resistance to lami- tance to this drug. vudine to adefovir. Tenofovir (Viread): The newest antiviral, was approved Adefovir also appears effective against hepatitis B by the FDA in August 2008. It has been used successviruses that are able to replicate without secreting fully against HIV for years. Viread (tenofovir disoproxil
HCSP VERSION 4.1 September 2008 

fumarate) is a nucleotide analog reverse transcriptase and HBV polymerase inhibitor that blocks an enzyme that the hepatitis B virus needs to replicate in liver cells. The recommended dose for chronic hepatitis B is one 300-mg tablet a day. Two ongoing Phase III clinical trials comparing Viread with Hepsera found that chronic hepatitis B patients on Viread achieved a higher rate of complete treatment response compared with patients taking Hepsera, according to the company, which says the two drugs should not be used together.

For more information about HBV Drugs please visit: HBV Advocate: http://www.hbvadvocate.org/hepatitis/hepatitis_B.asp
Hepatitis B FoundationDrug Watch at: www.hepb.org/020098.hepb. For more information on clinical trials in the United States, visit the National Institutes of Health Clinical Trials website at www.clinicaltrials.gov and enter hepatitis B to search for related clinical trials.

New Antivirals:

There are several experimental antiviral medications that are currently in Phase III clinical trials. Emtricitabine (FTC, Emtriva), already approved by FDA for treatment of HIV, has been found to be effective in lowering HBV DNA. Gilead Sciences reported treatment with emtricitabine reduced liver fibrosis in 62 percent of patients who received the drug, compared to 25 percent of patients who received placebo, and substantially lowered HBV DNA in 56 percent. However, researchers have found some instances of viral resistance to emtricitabine. Clevudine (L-FMAU) has demonstrated potent antiviral activity and the ability to produce a sustained response, For more information about hepatitis C, hepatitis B and even months after treatment ended. In one study, 71 HCV coinfections, please visit www.hcvadvocate.org. percent of patients who took clevudine maintained normal ALT levels six months after treatment ended, which is longer than with other antivirals. Clevudine, produced A publication of the Hepatitis C Support Project by Gilead, appeared to be well tolerated, and no HBV have developed resistance to clevudine to date. The information in this fact sheet is

hcspFACTsheet

Combination Treatment

Following the successes posted by doctors who use two or more drug combinations or cocktails to treat HIV and hepatitis C, many expect future HBV treatment will utilize a combination or sequential dosing of antivirals and interferons. However, to date they have not identified what drugs, and what treatment sequence, will be most effective in treating hepatitis B. Clinical trials are continuing to develop a successful combination treatment to stop liver damage from hepatitis B.

Executive Director Editor-in-Chief, HCSP Publications designed to help you understand and Alan Franciscus manage HCV and is not intended as medical advice. All persons with HCV Design should consult a medical practitioner for Paula Fener diagnosis and treatment of HCV. Production This information is provided by the C.D. Mazoff, PhD Hepatitis C Support Project a nonprot Contact information: organization for HCV education, support Hepatitis C Support Project and advocacy 2008 Hepatitis C PO Box 427037 Support Project Reprint permission is San Francisco, CA 94142-7037 granted and encouraged with credit to the Hepatitis C Support Project. alanfranciscus@hcvadvocate.org

HCSP VERSION 4.1 September 2008