Hepatitis

liver411

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