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发表于 2002-1-13 01:23
Canadian Journal of Infectious Diseases
November/December 2001, Volume 12, Number 6
Hepatitis
Mel Krajden MD FRCPC
British Columbia Centre for Disease Control, Vancouver, British Columbia
Worldwide, approximately 170 million people are chronically infected
with hepatitis C virus (HCV) and another 350 million individuals are
chronically infected with hepatitis B virus (HBV) (1,2). Canada is estimated
to have 240,000 to 300,000 HCV and 200,000 to 280,000 HBV chronic carriers
(3,4). Without intervention, over multiple decades, approximately 15% to 30%
of chronic HBV- and HCV-infected individuals will develop cirrhosis,
end-stage liver disease or liver cancer, or will require liver
transplantation (1,2,5). From a public health perspective, the major
challenge is how best to avoid acute (incident) infections in at-risk
populations, and for those already chronically infected, how to prevent
consequent morbidity and mortality.
For HCV, primary prevention is difficult, because a vaccine is not
available nor is one likely to be available in the near future. Although the
blood product transmission of HCV has been virtually eliminated by the
effective serological screening of blood donors, parenteral substance abuse
continues to be the major source of ongoing transmission (6-8).
Despite the lack of a HCV vaccine, new and effective but costly HCV
treatments (interferon, pegylated interferons with and without ribavirin)
can cure (ie, eliminate HCV RNA from the body) in 30% to 90% of treated
individuals (1). Recently Jaeckel et al (9) reported that the early
treatment of acute HCV with interferon monotherapy prevented chronic
infection in 98% of treated cases. The efficacy of currently available
treatments for HCV will drive future demands for treatment and the ensuing
costs. Recent estimates suggest that the cost of HCV to our health care
system is similar to the cost of asthma, or approximately US$5.4
billion/year in the United States (10).
For HBV, a safe and effective vaccine is available for primary
prevention, but many decades of population-based vaccination will be
required before the entire population is adequately protected because of the
large numbers of chronic carriers in the global population (11). HBV vaccine
escape mutants have been described; these refer to mutations in the
hepatitis B surface antigen that may result in failed protection from the
current HBV vaccine (12,13). In some cases, this may affect the ability of
current enzyme immunoassays to detect active infection, ie, hepatitis B
surface antigen in serum or plasma (12,13). Clearly, surveillance systems
need to be in place to ensure that HBV vaccines remain effective and that
vaccine escape mutants do not replace current HBV strains.
Treatment for HBV is also evolving rapidly (eg, lamivudine, adefovir
dipivoxil, entecavir, fluorothiacytidine and interferons) (14). Both
lamivudine and interferon can suppress HBV viral replication and improve the
outcome of chronic HBV infection. Typically, 15% to 50% of treated HBV
patients have a durable response after interferon or long term lamivudine
treatment, but unlike HCV, complete viral elimination from the body may not
be possible, because viral DNA is incorporated into the host genome (5). The
patient seroconverting from being hepatitis B e antigen-positive to being
anti-hepatitis B e antigen-positive typically indicates treatment response.
The complete loss of hepatitis B surface antigen is rare, generally
occurring less than 10% of the time (2,5). Some patients, however, may have
viral mutations (eg, precore mutations) that prevent the expression of
hepatitis B e antigen. For these patients, HBV DNA tests are required to
monitor treatment response (5). At this point in time, there is a pressing
need for more standardized serological and/or nucleic acid tests, or other
markers that predict the patients who are most likely to have a durable
treatment response and/or that define the optimal treatment duration
(15-17). Another challenge to clinicians is that lamivudine monotherapy is
associated with the rapid emergence of antiviral resistance in 15% to 60% of
treated individuals. Therefore, the utility of combination therapy needs to
be investigated (14-16).
For hepatitis A virus (HAV) infection, while it does not result in
chronic disease, its public health impact relates to its ease of
transmission (fecal-oral), the rare occurence of fulminant hepatitis and the
fact that HAV shares some common risk factors for transmission with HBV and
HCV. It is also readily vaccine preventable.
The current issue of The Canadian Journal of Infectious Diseases
contains multiple articles reporting on the prevalence, incidence and impact
of hepatitis A, B and C in Canada (Wu et al, pages 341-344; Zhang et al,
pages 345-350; Minuk and Uhanova, pages 351-356; Zou et al, pages 357-363).
These articles highlight significant limitations in our surveillance systems
and the lack of standardized measurement tools to monitor the true burden of
these infectious diseases in our population. Proper resource planning
requires detailed information on the natural history of hepatitis, utility
of preventive interventions and a better assessment of treatment cost and
effectiveness. Garnet et al (18) recently highlighted how a combination of
both prevention and treatment is required to minimize ongoing transmission
of HIV in the population effectively. Developing best practice models for
prevention and treatment requires sensitive surveillance systems. Incident
cases need to be detected to define current risk factors for transmission,
whereas prevalent cases need to be identified so that treatment or
monitoring can be initiated. Given the fact that approximately 0.5% to 1.0%
of Canada's population is infected with either HBV or HCV, and the plethora
of new effective and expensive drugs in the pharmaceutical pipeline, it
behooves us to develop cost effective care management strategies. Although
the articles in the current issue provide the best available information on
the status of hepatitis in Canada and outline interventions to improve
outcomes, the articles illustrate the difficulty in obtaining reliable
incidence, prevalence and burden of disease information.
British Columbia has recently developed an integrated viral hepatitis
program, details of which are available at
<http://www.bccdc.org/hepatitis/index.shtml> (19). This program attempts to
integrate hepatitis services across the continuum of prevention,
surveillance, care management, education and support, information management
and research. Part of the conceptual model is illustrated in the following
paragraphs. For example, Figure 1 illustrates the population infected with
or at risk for hepatitis, as well as the component activities relating to
prevention and care management.
Typically, hepatitis-infected individuals are identified after
serological testing by physicians, because they presented with risk factors
or illness, or were identified during blood donor testing, during insurance
testing or after maternal screening to identify HBV carriers to prevent
perinatal HBV transmission. Because most cases of hepatitis remain
asymptomatic, it is estimated that only one- to two-thirds of infected
individuals have been diagnosed. The identification of incident cases is
important to determine whether the acute infection resolves or the
individual becomes chronically infected (HBV and HCV). Risk factor
information for incident infections is necessary to evaluate prevention
strategy effectiveness, including vaccine efficacy for HBV and HAV. This
information is also important for the quality assurance of infection con |
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