http://www.medscape.com/viewprogram/5414
Chronic Hepatitis B With Worsening Liver Function Tests on Antiviral
Therapy: A Clinical Conundrum CME/CE
Authors: Sonja K. Olsen, MD; Robert S. Brown Jr, MD, MPH
Disclosures
Background and Introduction
Hepatitis B affects approximately 350 million people worldwide and an
estimated 1.25 million individuals in the United States.[1] There are an
estimated 100,000 people who become infected with hepatitis B in the United
States each year, despite universal vaccination practices for children and
widespread vaccination programs for adults thought to be at high risk for
infection.[2] Although most persons infected with the virus do not develop
significant hepatic disease, 15% to 40% will develop serious
complications.[3] These complications include cirrhosis, hepatocellular
carcinoma, and hepatic decompensation. Hepatitis B can be acquired sexually,
perinatally, or parenterally. The most common mode of transmission depends
on geography. In areas of low prevalence, such as the United States and
Canada, the most common mode of transmission is sexual contact and
intravenous-drug use. It is estimated that more than 50% of hepatitis B
virus (HBV) in the United States is acquired sexually.[4] In areas of high
prevalence, such as Southeast Asia and China, HBV is most commonly acquired
perinatally.[5-7] The infection rate of newborns born to mothers who are
hepatitis B e antigen (HBeAg)-positive approaches 90%.[6] Unfortunately, the
earlier the age of acquisition, the greater the chance of developing chronic
hepatitis B and its potential complications. Vaccination is now required in
the United States for all infants as well as all high-risk patients. Those
at high risk include healthcare workers, sexually active adults, patients on
hemodialysis, and those with chronic liver disease.[8]
The goals of therapy in HBV infection are not uniform. Because virologic
cure is usually not possible, and the ability to achieve durable viral
suppression varies, treatment decisions usually hinge on the patient's
serologic profile, the degree of liver injury, and the state of viral
replication. Suppression of viral replication and prevention of the
development of fibrosis and hepatocellular carcinoma are the primary goals
for any patient. Cure, with seroconversion from hepatitis B surface antigen
(HBsAg) positivity to hepatitis B surface antibody (HBsAb) positivity, is
the rarely achieved but ultimate goal of therapy. For those patients with
wild-type virus (HBeAg-positive), an important endpoint is seroconversion to
HBeAb positivity, which generally leads to a durable response with low
levels of HBV-DNA and normal alanine aminotransferase (ALT) levels. Patients
who do not express HBeAg can be thought of as 2 distinct populations --
those who are actively replicating but do not express the e antigen protein,
and those who are replicating at very low levels. Patients in the latter
group were previously referred to as "healthy carriers," but this term is
erroneous as there is low-level viral replication in these patients despite
relatively normal ALT levels.[9] Patients who are actively replicating and
not producing HBeAg are generally known as precore mutants. This refers to a
specific mutation in the HBV genome, a substitution of guanine to adenine (G
to A) in the precore region of the DNA that introduces a stop codon that
prevents the production of HBeAg.[10] This type of e antigen-negative HBV
infection is rarely acquired as a de novo infection but instead evolves
during wild-type virus replication.[11] HBeAg-negative patients tend to fall
into 1 of 2 clinical categories: 30% to 40% of patients have persistently
elevated ALT, whereas 45% to 65% have a fluctuating ALT level with frequent
flare-ups of disease activity.[12]
There are currently 5 medications approved by the US Food and Drug
Administration (FDA) for the treatment of hepatitis B: interferon alfa-2b,
pegylated interferon alfa-2a, lamivudine, adefovir, and entecavir. The
arsenal of therapeutic options, diverse patient population, and lack of
clear guidelines makes the treatment of hepatitis B a daunting task.
Section 1 of 18
FULL TEXT AT: http://www.medscape.com/viewarticle/532036
| 
发表于 2006-9-20 17:19
