•hcspFACTsheet• Hepatitis C Support Project • www.hbvadvocate.

org
a series of fact sheets written have had such limited success, the goals of treatment
by experts in the field of liver have been remarkably unambitious. Instead of aiming
disease for a total cure, signaled by the immune system’s pro-
duction of surface antibodies, current treatment goals
are simply to:
What’s New in • Lower the volume of viruses (viral load), which is
measured by HBV DNA in the bloodstream.
Hepatitis B • Stop liver damage and achieve normal alanine ami-

Treatment
notransferase or ALT levels. ALT is released by liver
2008 cells when they die, and above normal levels indicate
liver damage.
• Spur the immune system to create the antibody to
Christine Kukka, HBV Project Manager
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.

• Interferons boost the immune system so it will ag- Doctors generally do not treat patients unless there is
gressively wage war against the HBV infection. liver damage, including ALT levels that are more than
• Antivirals or nucleoside analogues are designed to twice normal, a liver biopsy that indicates inflammation
deliberately interfere with HBV’s DNA so it can’t re- and scarring, and a high viral load.
produce itself.
Interferons
These two treatments are usually used one at a time, Doctors usually prescribe interferon when ALT levels
but some doctors are experimenting to see if using are elevated. Elevated ALTs indicate the immune system
them in combination to first knock down the amount of has noticed the infection and is attacking and killing
virus, and then boost the immune system to vanquish the infected liver cells. To prescribe interferon when ALT
the remaining HBV, could be successful. levels are not elevated is tantamount to giving bullets to
an army that is not at war. Conventional and pegylated
The U.S. Food and Drug Administration (FDA) has ap- interferon, administered by injection, works best when
proved two types of interferon for hepatitis B treatment. ALT is elevated and viral load is low - when the army
The interferon available to adults and children is called is on the attack and there are few viruses to vanquish.
conventional or interferon alpha-2b. Pegylated inter- Pegylated interferon, which is a time-release interferon
feron, approved only for adults to date, is the newest requiring only one injection per week, is much more
interferon approved for hepatitis B. Fourantivirals – la- effective at spurring the immune system to target HBV
mivudine (brand name Epivir-HBV), adefovir (Hepsera), than conventional interferon.
entecavir (Baraclude), and telbivudine (Tyzeka), have
been approved for hepatitis B in adults. Only lamivudine Pegylated interferon (Pegasys) has also shown prom-
has been approved for treatment of children. ise in people who experience liver damage and high
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 HBeAg-
of these drugs. Because the current arsenal of drugs negative hepatitis B experienced lowered viral load with

HCSP • VERSION 4.1 • September 2008 

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 can’t 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 If a patient is to be treated for the first time, which

The four FDA-approved antiviral medications available antiviral is best? To date, no medical organization has
to HBV-infected patients are lamivudine, approved endorsed one antiviral over the other. It is important to
for adults in 1998 and for children in 2000, adefovir, discuss all the pros and cons of each antiviral with a
approved for adults in 2002, and currently in clinical doctor.
trials for children, entecavir approved for adults in
2005, and telbivudine, approved for adults in October Entecavir (brand name Baraclude): Entecavir is
2006. Antivirals are valuable because they can lower a potent inhibitor of HBV replication. In lab tests, this
the rate of HBV replicating in the liver. Generally, when antiviral has shown the ability to reduce viral CCC DNA
viral load drops, liver damage declines because there levels, which are believed to promote development of
are fewer viruses invading liver cells and ALT levels liver cancer. In studies that compared entecavir with
also normalize. lamivudine, entecavir was more effective in reducing
HBV DNA levels, even when ALT levels were only slightly
Lamivudine (brand name Epivir-HBV): Administered elevated. Early studies also suggest that entecavir-
as a daily pill or oral solution, lamivudine generally treated patients had a longer, sustained response to
produces normal ALT levels and undetectable HBV DNA the drug, even after treatment ended, including those
in about 65 percent of adults who take it. with HBeAg-negative hepatitis B. There have been a
couple reports of viral resistance to entecavir develop-
While lamivudine is safe and rarely causes side effects, ing, but nearly all occurred in patients who had already
it is not a permanent or complete cure. It keeps the virus developed lamivudine-resistant viruses.
in check for only as long as it is taken. When treatment
stops, HBV DNA and ALT levels usually rebound. Telbivudine (brand name Tyzeka): Stops HBV repli-
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 lamivudine’s 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
patients develop lamivudine-resistant HBV. it produced more significant declines in HBV DNA than
adefovir.
Adefovir (brand name Hepsera): Adefovir appears
to have all of lamivudine’s 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 resis-
patients 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 success-
viruses 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 tri-
als 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/hepati-
tis/hepatitis_B.asp
• Hepatitis B Foundation’Drug Watch at: www.hepb.org/02-
0098.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 effec-
tive 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 resis-
tance 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 nor-
mal ALT levels six months after treatment ended, which
is longer than with other antivirals. Clevudine, produced •hcspFACTsheet•
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
Executive Director
Editor-in-Chief, HCSP Publications designed to help you understand and
Alan Franciscus manage HCV and is not intended as
Combination Treatment medical advice. All persons with HCV
Design
Following the successes posted by doctors who use two Paula Fener
should consult a medical practitioner for
diagnosis and treatment of HCV.
or more drug combinations or “cocktails” to treat HIV
Production
and hepatitis C, many expect future HBV treatment will C.D. Mazoff, PhD This information is provided by the
utilize a combination or sequential dosing of antivirals Contact information:
Hepatitis C Support Project • a nonprofit
organization for HCV education, support
and interferons. However, to date they have not identi- Hepatitis C Support Project
and advocacy• © 2008 Hepatitis C
PO Box 427037
fied what drugs, and what treatment sequence, will be San Francisco, CA 94142-7037 Support Project • Reprint permission is
granted and encouraged with credit to
most effective in treating hepatitis B. Clinical trials are alanfranciscus@hcvadvocate.org the Hepatitis C Support Project.
continuing to develop a successful combination treat-
ment to stop liver damage from hepatitis B.

HCSP • VERSION 4.1 • September 2008