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Editorial Board: Emmet B. Keeffe, MD (Chair);
Anna Lok, MD; Brian McMahon,
MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD;
Bruce Tung, MD
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HBV
Watch™
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Timely Information for Practicing Physicians
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TOPIC REVIEW
Healthcare workers (HCWs) who are
chronically infected with hepatitis B virus (HBV). In 1991 the CDC published a document entitled “Recommendations for Preventing
Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Patients
during Exposure-Prone Invasive Procedures (MMWR Vol. 40/No. RR-8).”
Many clusters of outbreaks of HBV linked to transmission from HCWs to patients
were cited in this publication, and several additional reports have occurred
since 1991. Most episodes of
transmission involved HCWs performing invasive procedures, commonly surgeons or
dentists, and most of the HCWs were HBeAg-positive. Fortunately, OSHA requirements for vaccination
of HCWs have dramatically reduced the incidence of HBV infection in HCWs and
thus reduced reports of transmission from HCWs to patients. The CDC document states that currently
available data provide no basis for the
recommendation that an HBV-infected HCW be restricted from performing invasive
procedures not identified as exposure prone, provided the infected HCW
practices recommended universal precautions.
The CDC recommends that HCWs with exudative dermatitis not have direct
patient contact and not handle patient-care equipment or devices used for
invasive procedures. The CDC also
recommends that HBV carriers who are HBeAg-positive not perform invasive
procedures without prior counseling and advice from an expert review panel and
that they be advised under what circumstances, if any, they should not perform
these procedures. These circumstances
would include notifying prospective patients of the carrier’s HBV status prior
to performing procedures. These
recommendations were made prior to the availability of tests for
determination of quantitative serum HBV DNA levels. It is now known that while almost all
HBV-infected persons with detectable HBeAg have high levels of HBV DNA, some
persons with anti-HBe also have high serum HBV DNA levels. In addition, new potent antiviral drugs that
have become available since the CDC recommendation was originally published
offer the opportunity for HCWs infected with HBV to receive therapy, if they
fit the criteria recommended in treatment guidelines. Treatment of infected HCWs may potentially
reduce the level of serum HBV DNA and render the HCV at less risk of infecting
patients undergoing invasive procedures.
Infected HCWs should consult with a provider with expertise in the
management of chronic HBV to determine if treatment might be appropriate. In the future, more widespread use of HBV DNA
testing to monitor infected HCWs may be recommended. Future updates of the CDC recommendations are
eagerly awaited.
NEW THERAPEUTIC AGENT
Dose-escalating
trial of clevudine. Clevudine is a novel pyrimidine analogue that has potent activity
against HBV. The mechanism of its
antiviral effects is mediated by intracellular formation of its monophosphate,
diphosphate, and triphosphate forms.
Clevudine enters cells by both facilitated nucleoside transport and
passive diffusion and is a substrate for 3 intracellular kinases responsible
for its phosphorylation. In the
woodchuck hepatitis model, clevudine produced up to 1000-fold decreases in
plasma woodchuck hepatitis virus DNA that were durable following 12 weeks of
dosing. Preclinical studies also
demonstrated that clevudine had no effect on mitochondrial structure, DNA
content, and DNA function. Patrick Marcellin and colleagues now report the results of a
multicenter, dose-escalation study of clevudine in 32 patients with chronic HBV
infection. Eligible patients had HBV DNA
levels of ≥ 3 x 106 copies/mL, had not undergone prior
nucleoside treatment, and were not coinfected with HIV or HCV. Clevudine was administered at doses of 10,
50, 100, and 200 mg once daily for 28 days.
Median HBV DNA log10 changes from baseline were -2.5, -2.7, -3.0,
and -2.6 after 28 days and -1.2, -1.4, -2.7, and -1.7 after 6
months, for the 10, 50, 100, and 200 mg doses, respectively. Modeling indicated that the increase in
activity with clevudine doses higher than 50 mg was minimal. Pharmacokinetic studies showed dose
proportionality. Clevudine was well
tolerated and no dose-limiting toxicities were observed, but a transient increase
in alanine aminotransferase up to 7.8 times the upper limits of normal was
observed in 6 patients in the 100 mg cohort.
This study demonstrated the tolerability and potent activity of
clevudine in patients with chronic HBV infection. Further studies of clevudine are warranted. (Marcellin P et al. Hepatology
2004;40:140-148.)
RISK FACTORS FOR HBV REACTIVATION
Cancer
patients undergoing cytotoxic chemotherapy.
HBV
reactivation is a recognized complication of cancer patients with chronic HBV
infection who receive cytotoxic chemotherapy.
In order to assess risk factors associated with HBV reactivation, W. Yeo
and others at the Prince of Wales Hospital in Hong Kong identified 138 consecutive cancer
patients who were chronic HBV carriers and followed them throughout their courses
of cytotoxic chemotherapy treatments.
Tumor types included breast cancers (39), gastrointestinal cancers (29),
head and neck cancers (17), lung cancers (13), lymphomas (12), and other
cancers (18). During the study period,
HBV reactivation developed in 36 patients (26%). Multivariate analysis identified the
following factors to be associated with a higher risk of developing HBV
reactivation: (1) detectable HBV DNA levels by PCR; (2) use of steroids as part
of the chemotherapy regimen; and (3) a diagnosis of lymphoma or breast
cancer. A predictive model was developed
using a logistic regression model. The
findings of this study provide a means to identify patients who are most likely
to benefit from anti-HBV prophylactic therapy, but further studies are needed
to determine if only selected carriers based on risk profile or all carriers
should receive prophylaxis. (Yeo W et
al. Br J Cancer 2004;90:1306-1311.)
HBV Watch is produced through an
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and 
Hepatology Watch is a registered trademark of Market Development Group
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