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VIRAL HEPATITIS

July 1996

Volume 5 - Number 1

EDITORIAL

MEETING NEWS

• Viral hepatitis overview

• HAV occurs in cyclical outbreaks
• Strategy for protecting against HAV
• HAV and occupational risk
• Future of HAV vaccination
• Defining occupational risk for HBV
• HBV prevention and management
• Facts on HCV
• HCV a serious threat to public health
• Defining the magnitude of HCV problem
• Breast feeding and HCV
• Understanding HCV transmission
• HCV as an occupational hazard
• Treating HCV infection
• Counselling guidelines for HCV
• Education key to prevention
• Issues surrounding HCV screening

This issue of Viral Hepatitis focuses on the epidemiology and prevention of hepatitis A, B and C. In particular, the public health issues surrounding hepatitis C are emphasised, with a closer look to occupational risks.

Discovered in 1989, hepatitis C represents a major public health problem. The World Health Organization estimates that tens of millions of people are infected with the virus worldwide.

Although the majority will show no symptoms for the major part of the disease, a high percentage - between 50 and 80 percent - will go on to develop chronic disease. This means there is a large hidden population suffering from a potentially life-threatening infection. As no vaccine is available or expected in the immediate future, attention will need to be focused on other means of prevention and treatment regimes.

Hepatitis C has been the subject of extensive biological, clinical, epidemiological research, and considerable progress has been made towards better understanding the disease, its natural history, how it is transmitted, and how it can be prevented. The VHPB, ICOH and invited guests met in Vienna, March 28-29 to discuss these findings, and details of the speeches and study presentations are included in the Meeting News.

What was brought to light at the conference was not only the progress made towards better understanding HCV, but also the questions that remain unanswered. Hepatitis C research is still in its infancy and more work is needed to understand how the virus is transmitted; to improve methods for disease prevention and control; to develop reliable and affordable assays for detection of the infection; to understand the natural history of the disease acquired through different routes; to identify clinical, epidemiological and economic benefits of different therapeutic treatments; and to raise public awareness of the seriousness of HCV infection. These are no small tasks, however, particularly in times global weakening of public health services and economic pressure on health budgets. This recently discovered disease represents a considerable challenge to both the medical community and to society.

Dr Johannes Hallauer

Institute for Health Systems Research

WHO Collaborating Centre on Public Health Research,

Kiel, Germany

This edition of Viral Hepatitis is prepared from material presented at the VHPB/ICOH Hepatitis Challenge Workshop held 28-29 March 1996 in Vienna, Austria.

Dr Johannes Hallauer

Institute for Health Systems Research

WHO Collaborating Centre on Public Health Research

Kiel, Germany

Dr Mark Kane

WHO, Global Programme for Vaccines and Immunization

Geneva, Switzerland

Dr Elizabeth McCloy

Civil Service Occupational Health and Safety Agency

Edinburgh, United Kingdom

Prof André Meheus*

Department of Epidemiology and Community Medicine

University of Antwerp, Belgium

Dr Colette Roure

WHO Regional Office for Europe

Copenhagen, Denmark

Dr Pierre Van Damme

Department of Epidemiology and Community Medicine

University of Antwerp, Belgium

Prof Paolo Bonanni

Public Health Department

University of Florence, Italy

Prof Pietro Crovari*

Institute of Hygiene and Preventive Medicine

University of Genoa, Italy

Dr José de la Torre

Ministry of Health and Consumer Affairs

Madrid, Spain

Prof Alain Goudeau*

Department of Medical and Molecular Microbiology

University of Tours, France

Prof Peter Grob

Department of Medicine

University Hospital Zurich, Switzerland

Prof Wolfgang Jilg*

Institute for Medical Microbiology and Hygiene

University of Regensburg, Germany

Dr Daniel Lavanchy

BVI Unit, Division of Communicable Diseases

World Health Organization

Geneva, Switzerland

Dr Harold Margolis

CDC, Hepatitis Branch

Atlanta, Georgia, United States

Prof Georges Papaevangelou

National Centre for Viral Hepatitis

Athens School of Hygiene, Greece

Dr Rafael Esteban

Department of Internal Medicine, Hepatology

University General Hospital

Barcelona, Spain

Mrs Gabrielle Page

C Positive

Shenfield, Essex, UK

Dr Thierry Poynard

Pitié-Salpêtrière

Paris, France

Dr Arne Wennberg

International Commission on Occupational Health

Stockholm, Sweden

Margaret Van der Elst

Antwerp, Belgium

Mrs Emmy Engelen

Mr Gino Verwimp

Department of Epidemiology and Community Medicine

University of Antwerp, Belgium

*Not present at the meeting

Six distinct viruses causing viral hepatitis have been identified, each differing in the severity of disease they cause, epidemiological characteristics, modes of transmission and recommendations for control. These six viruses are hepatitis A, B, C, D, E and G.

Hepatitis A virus (HAV) is characterised by low mortality, no chronic carrier state and lifelong immunity following infection. Modes of transmission include faecal-oral, person-to-person, and contaminated water and food.

Historically, infection with HAV was a common in young children and not considered a public health problem. With improved hygiene and socio-economic conditions, however, the virus now often strikes at a later age and with more severe consequences. 'Hepatitis A is probably the most important travel-related, vaccine-preventable disease,' says Dr Mark Kane of the World Health Organization.

The outcome of hepatitis B virus (HBV) infection is often severe, with acute HBV infection leading to chronic carrier state, cirrhosis, liver cancer and death. Six to 10 percent of infected adults will become chronic carriers; infection during infancy and early childhood frequently progresses to the chronic carrier state, with 70-90 percent of neonates becoming chronic carriers. Hepatitis B is transmitted through infected blood and body fluids, perinatal transmission, horizontal transmission, sexual transmission and intravenous drug use. Both plasma derived and recombinant vaccines are approved for use in most parts of the world; even so, worldwide one million deaths per year are directly related to HBV infection. To control the disease, the World Health Assembly recommends that 'the most effective strategy is incorporation of universal hepatitis B vaccination into the routine infant or adolescent immunisation schedules'.

Discovered in 1989, the hepatitis C virus (HCV) is a small, single stranded RNA virus. It is estimated that approximately 1% of the world's population have HCV. The virus is blood-borne, and the majority of those infected with HCV show no symptoms initially. Approximately 50% of people infected with HCV become chronic carriers; of these, half develop cirrhosis or liver cancer.

The hepatitis Delta virus (HDV) is associated with hepatitis B. Too small to replicate itself, the Delta virus lives as a parasite on the hepatitis B virus, using the s antigen of HBV to multiply. The Delta virus is relatively rare and is not present with every case of HBV infection. The progression to chronicity is not common. If HBV infection does become chronic, however, the Delta virus speeds the progression to chronic liver disease. Vaccination against HBV protects against Delta infection as well.

Formally known as enterically transmitted NANB hepatitis, hepatitis E virus (HEV) has no chronic carrier state and does not cause chronic liver disease. Hepatitis E infection is highly dangerous, however, for pregnant women, causing up to 20% mortality in women in their third trimester of pregnancy. Largely transmitted through faecal-oral transmission, hepatitis E epidemics are usually waterborne epidemics. The disease can be controlled through the provision of safe water and food. There is no vaccine as yet, though prototype vaccines are in the pipeline.

'Hepatitis E looks like hepatitis A but it has the propensity for killing pregnant women,' says Dr Kane. Even though prevalence rates of HEV are less than one percent in Western Europe and North America 'it is a major pathogen around the world and we'll be hearing quite a bit about hepatitis E in the next few years'.

The hepatitis G virus (HGV) has only recently been identified. Associated with acute and chronic hepatitis, HGV is spread parenterally; the virus can cause persistent infection and is prevalent in volunteer blood donor populations. HGV and HCV infection can be simultaneously transmitted and result in persistent coinfection. It is presently unknown whether a normal carrier state exists for patients infected with HGV. The role of HGV in cirrhosis and hepatocellular carcinoma also remains to be investigated.

In countries of low endemicity, hepatitis A virus infection usually occurs in cyclical outbreaks in the general population, according to studies conducted by the United States Centers for Disease Control (CDC). The virus circulates in the population, striking when large numbers of people become susceptible.

A 1989 study in the state of Washington showed that hepatitis A occurs in cyclical epidemics, in much the same pattern as other infectious diseases such as polio and measles. A Butte County, California study lasting from 1980 to 1994 indicated approximately three-year cyclical outbreaks of hepatitis A infection occurring every seven to 10 years. In Denver County, Colorado the patterns were similar. 'We have to look at hepatitis A in the context of outbreaks,' says Dr Harold Margolis of the CDC. 'These outbreaks are not just limited to risk groups. In fact, there aren't many risk groups that are affected differently during outbreaks.'

The Denver County study monitored hepatitis A infections from 1986 to1993. During that time, high-risk populations were not affected differently from the general population in outbreak periods. The largest percentage of the population affected reported either no special risk factors for HAV infection or contact with a hepatitis A carrier as the only risk factor.

This was also the case in a closed, religious community in Monroe, New York monitored from 1983 to 1994. The community had high rates of hepatitis A infection and outbreaks of infection occurred in cyclical patterns. After nearly complete vaccination of the community, virtually no cases of hepatitis A infection were reported, with the few cases reported being among unvaccinated newcomers to the community.

Risk Factors of Patients Reported with Hepatitis A

Denver County, 1986-1993

1986 - 1989 1990 - 1993

Hepatitis A virus infection remains a common infection in many developed countries, with most infections occurring among children, adolescents and young adults. The seriousness of hepatitis A infection should not be minimised. Death rates from HAV in the United States from 1983-1989 showed that infected persons over 40 had a case fatality rate of 1.75%, according to the Viral Hepatitis Surveillance Program of the Centers for Disease Control. 'Conventional wisdom has it that this is a disease of low mortality. It is known that hepatitis B has a high mortality, but hepatitis A does kill. People with chronic liver disease have adverse outcomes,' says Dr Harold Margolis of the CDC.

A highly effective inactivated hepatitis A vaccine - with over 95% immunogenicity rates - was recently made available and could prevent the disease, provided clear immunisation strategies are developed. When deciding appropriate vaccine use it is important to remember that most hepatitis A infection occurs in the context of community-wide outbreaks; that much of the community is affected; and that children play an important role in disease transmission.

Vaccinating risk groups has not been shown to be an effective means of disease control. However, epidemiological studies in the United States indicate that routine infant immunisation combined with catch-up immunisation would be effective in preventing hepatitis A outbreaks. 'Children play a significant role in the spread of HAV, serving as a silent reservoir for the disease. Rapid vaccination of children can stop these epidemics,' says Dr Margolis. 'In the US we want to eradicate HAV transmission. That's going to take fairly aggressive immunisation and catch-up immunisation.'

To prevent community-wide epidemics of hepatitis A, the CDC recommendations for the United States are:

• rapid vaccination of children, focusing on children under 10 years of age;

• completion of the vaccination programme over a five-year period;
• integration of hepatitis A into routine immunisation schedules; and
• possible vaccination of adolescent and adult risk groups.

When deciding how best to protect workers from the occupational risk of HAV infection, it is necessary to weigh the risk of exposure versus the risk of infection says Dr Harold Margolis of the CDC. Workers generally considered to have some occupational risk for HAV include healthcare workers, workers in day care centres, waste water workers and food handlers. Yet, all have low infection rates and low transmission rates. Sewage workers, however, do have high rates of exposure to HAV. 'Data in the US indicates that exposure for healthcare workers is quite low and we feel - at least in the US - that we would not be vaccinating healthcare workers,' says Dr Margolis. 'Studies show that the risk of infection for healthcare workers is not greater than a matched control population so we do not recommend vaccination. We might, however, readdress the issue of vaccinating waste workers.' The risk of HAV transmission by food handlers - an issue that comes up repeatedly - is also not considered a major source of infection by the CDC.

The future of hepatitis A vaccination

• vaccination of travellers

• routine vaccination of infants and children
• vaccination to control outbreaks in communities with intermediate rates of infection
• multiple antigen vaccines to include hepatitis A

The risk of acquiring hepatitis B infection occupationally cannot be defined solely by job title or place of work says Dr Elizabeth McCloy of the UK Occupational Health and Safety Agency. 'Instead, the question should be posed: "What does the worker do." It is important to look within population groups at what tasks people actually carry out.'

Hepatitis B virus infection is a major occupational hazard for healthcare workers and others exposed to blood and infected body fluids. Of those infected with HBV through their occupation, between two and 10 percent will develop chronic infection, leading to cirrhosis or liver cancer. Employees considered at occupational risk of HBV infection can be defined as persons whose work activities involve regular physical contact with patients and/or their blood or body substances for the purpose of providing care and investigational and/or therapeutic intervention.

HBV transmission occurs when blood or other contaminated body fluids from an infected person enter the blood stream of an employee. Occupational transmission routes include: a stab injury with a contaminated needle or sharp; a human bite; or contamination through a broken epithelium or mucous membrane.

By looking at what people actually do in their work, it becomes apparent that many other professionals outside the healthcare industry are also routinely exposed to blood and infectious body fluids. Hospital workers in housekeeping, laundry services, sterile supplies services, and maintenance should also be considered at-risk as they may come into accidental contact with contaminated needles and sharps.

Employees working in institutions for the mentally disadvantaged, and in public services such as paramedics, police officers, fire fighters, (particularly if police and fire fighters deliver emergency care), teachers working in institutions, and waste disposal workers may be at increased risk. Other occupational groups including embalmers, prison staff and research scientists may also be at risk if they are regularly in contact with blood/body substances or at risk of injury from contaminated equipment.

When defining occupational risk of HBV infection the question should be posed: 'What does the worker do.' It is important to look within population groups at what tasks people actually carry out.

The hazard of HBV infection cannot be eliminated in many occupational settings.

Therefore, HBV prevention programmes should be based on an understanding of disease transmission, a consistent adherence to safe work practices, the use of protective clothing, vaccination programmes and post-exposure prophylaxis. 'Prevention programmes must be based on the concept of universal precautions which dictates that all people are potentially infected with HBV and therefore present a risk to others', says Dr Elizabeth McCloy of the UK Occupational Health and Safety Agency.

Active vaccination should be the mainstay of any prevention programme. Workers should be apprised of their exposure risk, and those regularly exposed to HBV offered vaccination. When defining regular exposure and instituting worker vaccination programmes, Dr McCloy cautions against setting inflexible guidelines: 'Being rigid can actually be counter-productive'. Instead, she recommends using a 'reasonably anticipated' risk of exposure as the criterion for worker vaccination.

Although HBV vaccinations have a highly effective sero-conversion rate of almost 95% in young adults, there will always be some people who do not respond to vaccination. Vaccine response is influenced by age, obesity, smoking, immuno-competence and gender; a small percentage of people are genetically or immunologically incapable of responding to the vaccine. Therefore, safe work practices remain an important part of the prevention strategy.

Legislation in both Europe (the Biological Agents Directive and Classification Directive) and the United States (OSHA Blood-borne Pathogen Standard) require that employees be made aware of their occupational risks and given instruction on risk prevention.

Body substances capable of transmitting the HB virus include: blood and blood products; cerebrospinal fluid; peritoneal, pleural, pericardial and synovial fluid; amniotic fluid; semen and vaginal secretions; any other body fluid containing blood; saliva in association with dentistry; and unfixed tissues and organs.

According to Dr McCloy, the following are the underlying principles of safe work practice to prevent occupationally acquiring hepatitis B:

• Cover any skin lesions (e.g. abrasions) on exposed parts of the body;
• Use barrier techniques such as gloves or specialist equipment during contact with membranes, wounds, etc.;
• Avoid needles and sharps whenever practicable;
• Do not carry syringes, needles, equipment from the work site;
• Dispose of equipment safely;
• Clear and disinfect blood spillage immediately.

• Elimination

• Substitution
• Risk control
• Vaccination
• Education
• Training
• Evaluation

Hepatitis C usually has an incubation period of six to 12 weeks, but this can last up to six months. The most common symptoms of hepatitis C infection are fatigue and jaundice; although the vast majority of infected persons (up to 90%) show no abnormal physical signs, even those with chronic disease. Fulminant disease with hepatitis C infection is rare.

Of those exposed to hepatitis C, between 50-80% will develop chronic disease, defined as more than six months of continuous viraemia. About 50% of chronic carriers progress to cirrhosis or liver cancer. The severity of disease outcome is influenced by the age at infection, gender, alcohol intake and whether the individual is infected with any sexually transmitted diseases.

The genotype of the infecting hepatitis C virus (there are six known varieties) and the means of infection also play a role in determining the severity of disease and the response to treatment. Carriers infected through blood transfusions appear to have poorer outcomes than those infected by other means. Treatment with alfa interferon is successful in eliminating the virus in approximately 20-25% patients; though those infected with genotypes 1a, 1b and 4 respond poorly to treatment. Studies focusing on different therapy regimens and combinations of antiviral agents are currently underway in an effort to improve treatment outcomes in patients infected with genotypes 1a, 1b and 4.

Detection of HCV infection is based on second and third generation ELISA antibody tests. False positives are common, and confirmation can be done with RIBA tests.

The hepatitis C virus has a 'high propensity to induce a chronic carrier state (50-80%) leading to serious long-term sequelae,' says Dr Daniel Lavanchy of the World Health Organization. 'This places it among the pathogens of primary concern to humanity.'

According to the World Health Organization, 1% of the world's population is infected with the hepatitis C virus. In Europe and North America, the prevalence of hepatitis C is between 0.5 and 2.0%; in parts of Africa prevalence is over 4%. Hepatitis C cannot be easily monitored or controlled; and it is difficult to estimate the annual incidence of hepatitis C infection because even acute infection is most often asymptomatic. At present, there is no effective vaccine or wholly effective treatment.

Because the hepatitis C virus mutates extensively, developing a vaccine has been problematic. 'Vaccination is unfortunately not an immediate issue,' says Dr Lavanchy.

Without a vaccine, emphasis must be placed on other means of disease prevention. HCV is usually spread through unscreened blood and blood products; through medical and dental procedures with reused, unsterile equipment; and through needle sharing among intravenous drug users. Sexual transmission is possible, but is not a particularly efficient means of transmission.

The World Health Organization recommends prevention of HCV transmission through the screening of blood and blood products, and through education programmes about the risks of using unsterile medical materials. More work is also needed to learn how the disease is transmitted in order to establish better methods for prevention. In addition, diagnostic tests that give a true confirmation and meet international quality control standards are still lacking. At present, there is still a problem of a high rate of false positives.

In terms of treatment, 'one in five patients is treated with alfa interferon successfully - a good rate for a viral disease,' says Dr Lavanchy. Still, 90% of patients who need treatment cannot afford the high cost. And, for the remaining 80% who do not respond to treatment with interferon, international research efforts should focus on developing a combined antiviral therapy. The best hope for treatment lies in a combination of drugs that engender mutual exclusive resistance: 'We would not consider treating HIV with one drug; an oncologist would not treat cancer with just one chemotherapy,' says Dr Lavanchy.

Raising public awareness about the seriousness of HCV infection, and finding support for prevention and treatment research looks to be an uphill battle. 'HCV represents a major public health problem today. Butwe are in a world of deteriorating conditions of public health and it will probably be left to the scientists to carry the message that HCV is a serious global issue in terms of economics and human suffering,' says Dr Lavanchy.

Hepatitis C infection is a slowly progressive disease. The development of cirrhosis may take more than 20 years from the time of exposure if this occurs after 40 years of age, and over 40 years in individuals who contract the infection at a younger age. 'We are seeing epidemics of disease, 20, 30, 40 years after exposure to hepatitis C,' says Dr Mark Kane of the World Health Organization. 'We are seeing cases in Japan from contaminated blood in World War Two and after.' Because infection is usually asymptomatic, accurately estimating the prevalence and impact of the disease is problematic.

At present, most information about the nature and transmission of the hepatitis C virus in the general population is based on studies of volunteer blood donors. Among blood donors in Europe, the prevalence of anti-HCV ranges from a low of .23% in Scandinavia to a high of 1.15% in Italy. By extrapolating from studies of the prevalence of seropositivity among blood donors in different European countries, it can be estimated that approximately 1.2 million individuals in Europe are HCV positive; 70% of them will develop some degree of chronic liver disease, according to Dr Rafael Esteban of University General Hospital in Barcelona. These are conservative estimates and probably not representative, however, as blood donors undergo strict pre-screening and will often self-exclude themselves if they have any risk factors.

By comparing blood donor statistics with infection rates among risk group populations a clearer picture of the magnitude of HCV infection emerges. In Europe and the United States, for instance, between 50 and 90% of all haemophiliacs are infected with HCV. Without active screening of the general population, however, it is virtually impossible to calculate the number of HCV-infected people in Europe who have progressive chronic liver disease.

Studies aimed at better defining and understanding the modes of HCV transmission are needed to help check the spread of the virus. It is known that parenteral transmission through infected blood and blood products appears to be the most efficient method of HCV transmission. Sexual transmission, whether homosexual or heterosexual, occurs but is not particularly efficient. A study by Dr Esteban, for example, indicated that only 8% of HCV positive patients' spouses were also HCV positive. In addition, a large percentage of HCV positive patients indicated no apparent risk factors and the mode of transmission was unknown, indicating a need for more research into how the disease is transmitted.

Other priorities for research include developing inexpensive, simple-to-use but valid tests for HCV infection; defining the natural history of the infection in patients acquiring infection by different routes; better establishing prevalence, risk and control strategies for occupationally acquired and nosocomial infection; and identifying the clinical, epidemiological and economic benefits of therapeutic interventions.

Although perinatal transmission of HCV from mother to baby may occur, it is not common. Furthermore, breast feeding does not appear to increase or contribute to perinatal transmission, and it is considered safe for HCV-positive mothers to breast feed their infants. 'Breast feeding carries no further risk of HCV infection,' says Dr Esteban of University General Hospital in Barcelona. 'This is an important issue in the developing world.'

Although the primary route of HCV transmission is through infected blood, in up to 50% of cases no obvious transmission factor could be found. About 25% of infected patients worldwide have a history of blood transfusion, but since the early 1990s procedures designed to exclude infected donors or infected blood products have produced a detectable fall in HCV prevalence in some countries.

Groups at high risk of exposure to HCV include recipients of blood or blood products, dialysis patients, and intravenous drug users. Intravenous drug abuse involving the use of shared needles appears to be an efficient route of transmission. Unlike hepatitis B, however, HCV is not readily transmitted by sexual contact, either heterosexual or homosexual, although contact with many sexual partners appears to increase the risk of infection. In addition, the presence of sexually transmitted diseases may facilitate transmission.

Transmission from mother to baby may occur, with up to 10% of infants born to HCV- positive mothers infected. Those living in the household with an HCV-positive person may be at slightly raised risk of infection, although whether this is due to contact or to some shared aspect of lifestyle is not clear. Occupationally, workers who are involved either inevitably or accidentally with contaminated blood are at potentially higher risk than the general population.

Hepatitis C infection is not a new disease. It is a disease that has remained silent for many years and now presents itself as a new epidemic. When assessing the occupational risk of hepatitis C infection, it is important to establish the prevalence of infection in the general population and in high-risk groups; to understand disease transmission and disease profile; and to formulate appropriate prevention strategies in line with national health and safety regulations based on this information.

In an occupational setting, transmission of HCV infection requires entry of contaminated blood or body fluids from an infected person into the bloodstream of an employee. Patients who have received blood transfusions and blood products, dialysis patients and intravenous drug users (IVDU) have significantly higher prevalence rates than the general population.

'In Europe and North America markers of HCV infection are more common than HBV markers in patients presenting with liver disease,' says Dr Elizabeth McCloy of the UK Occupational Health and Safety Agency. 'It is these "silent" cases of unknown aetiology who will present the greatest occupational hazard to healthcare workers.'

The majority of occupational HCV infections can be attributed to needle stick injuries, although studies in Europe and the United States indicate that the prevalence of HCV in healthcare workers is not greater than in the general population. Transmission from healthcare worker to patient appears to be extremely rare.

Like the risk of HBV infection, occupational risk of HCV infection cannot be determined solely by job title, but rather by what the worker actually does. Using this method, it becomes clear that many other professionals outside the healthcare profession could be at risk of HCV infection. These include: workers in hospital housekeeping, laundry services, sterile supplies services, and maintenance; public service employees such as paramedics, police officers, fire fighters, teachers, workers in long-stay residential institutions, and waste disposal workers; and embalmers, prison staff and research scientists.

Programmes to prevent occupational HCV infection must be based on screening and treatment of blood products, standard precautions, use of disposable equipment and sterilisation of reusable medical equipment. 'It's all part of good working practice and it's not reinventing the wheel,' says Dr McCloy. 'We also need to continually assess whether the control measures we put in place are appropriate.'

Prevention programmes must include a clear policy for managing exposure accidents. These include: attending to the wound immediately; reporting the accident; obtaining blood samples from the patient and worker; establishing the patient's disease status; establishing the worker's baseline; offering counselling; and monitoring the worker for 12 months.

Guidelines for managing exposure accidents:

• Attend to the wound immediately.

• Report the accident.
• Obtain blood samples from both patient and worker.
• Establish the patient's disease status.
• Establish the worker's baseline.
• Offer counselling.
• Monitor the worker for 12 months.

Treating hepatitis C

The only approved treatment for hepatitis C infection is alfa interferon. Clinical trials in Europe and North America show that approximately 50% of patients treated for six months with alfa interferon have a clinically favourable response; however, up to 50% of initial responders relapse when treatment stops, yielding a long term response rate of 20 to 25 percent. There is some evidence to suggest that those who do not relapse by this time may remain disease-free for years. More observation is needed, however, to confirm this.

Response to therapy is influenced by duration of therapy, dosage, infecting viral load and disease stage. Some studies suggest that patients with early-stage hepatitis respond better to interferon therapy than those with later-stage hepatitis. The strain of the infecting virus may also affect the clinical response.

Currently, efforts to improve response to treatment with interferon include prolonging treatment to 12 - 18 months; focusing on patients more likely to respond (younger patients with no cirrhosis); prolonging low-dose treatment; and combining interferon treatment with other drugs, in particular, ribavirin.

The cost of interferon treatment makes it prohibitively expensive in the majority of cases, and treatment with interferon is associated with significant side effects. 'Interferon is an effective treatment, but a treatment with many side effects - not dangerous ones - but many side effects,' says Dr Thierry Poynard of Pitié-Salpêtrière in Paris. The most common side effects are flu-like symptoms, alopecia, leucopenia, thrombopenia and depression. Even so, most patients are able to complete therapy. In rare cases adverse events may be severe, including fatal liver failure and bone marrow suppression.

The impact of a diagnosis of hepatitis C should not be underestimated; and counselling services need to be an integral part of treatment for individuals who receive positive diagnoses for HCV. Patients are presented with an illness which may run the course of a lifetime and face a 20 percent chance of developing chronic liver disease.

The key to effective counselling is honest information about disease progression and treatment options; it must also be stressed to patients that hepatitis C infection is not a short-term illness. 'It will be a long-term relationship [between physician and patient] so both sides need to get it right,' says Gabrielle Page of the UK patient support group C Positive.

HCV infected persons should be advised about lifestyle modifications, including alcohol intake, the risk of sexual transmission and the possibility of transmission to others in the household. The implications of coming forward for testing in terms of employment prospects and social stigma also need to be addressed.

Families of HCV-infected individuals benefit from counselling as well, and should be made aware of the facts about HCV, the risks of transmission and their role in supporting the patient. During drug therapy for hepatitis C - which exacts a heavy toll - support services should also be made available to the patient.

Guidelines for counselling anti-HCV positive persons

• All anti-HCV positive individuals are considered potentially infectious.

• Individuals should refrain from donating blood, body organs, other tissue, or semen.
• Household articles such as toothbrushes and razors should not be shared, and cuts or skin lesions should be covered.
• When seeking medical or dental care, anti-HCV-positive individuals should inform those responsible for their care of their status.
• Anti-HCV-positive individuals should be informed of the potential for sexual transmission.
• For persons with a steady sexual partner, changes in current sexual practices are not recommended.
• For persons with multiple sexual partners, safer sex should be practised.
• Consideration may be given to testing exposed partners and, if positive, evaluating them for chronic liver disease.
• No evidence supports advising against pregnancy based on anti-HCV status alone, or advising special treatments or precautions for pregnant women or their offspring.

Post-exposure prophylaxis with immune globulin is not effective in preventing hepatitis C infection. Preventing exposure to HCV is the only way to prevent infection. It is therefore necessary to educate those at occupational risk of the importance of adhering to strict aseptic techniques and standard precautions, including appropriate use of barrier techniques, personal protective devices, and care in the use and disposal of needles and other sharp instruments.

The groundwork has already been laid with prevention programmes for hepatitis B. 'Even before vaccination for hepatitis B was available, we drastically reduced hepatitis B transmissions through standard precautions and education about transmission. We should be able to do the same with HCV,' says Dr Harold Margolis of the CDC. 'In terms of occupational risk, HCV is much lower than HBV. Yes, it's higher than HIV. And that's an important message for those of you in education to be getting out.'

Information instructing workers on how to protect themselves against HBV and HIV infection should include information on HCV. Institutions should formulate exact procedures about what to do to prevent occupational HCV exposure and infection. These include procedures detailing: correct waste collection, storage and disposal; the use of protective clothing such as masks, gloves, aprons and goggles; the use of inactivated blood products; and the use of sterile or one-treatment disposable equipment.

Workers who are accidentally exposed to HCV should be offered occupational counselling on the disease, its outcomes, and the treatment options.

It is estimated that almost two percent of the US population is infected with HCV; and although hepatitis C infection is dropping in the US, it still represents 100,000 plus infections per year. Dr Margolis warns that the message about HCV prevention is not reaching physicians: 'We still need to get to the level where caregivers and policy makers are aware of the disease, and how it is transmitted and prevented.'

No consensus has been reached among physicians and the health community as to whether the general population or even those at increased risk of hepatitis C exposure should be systematically screened for HCV infection. Routine screening would not appear to be cost effective and it is therefore difficult to justify systematic screening programmes among high risk individuals unless they present with symptoms. 'Routine screening is expensive and not recommended if there is no counselling in place,' says Dr Daniel Lavanchy of WHO. Furthermore, screening of the general population is not recommended until a consensus on treatment and prevention of transmission has been reached.

For now, the recommendation for standard screening is limited to blood donors and donors of tissue products. Effective serological assays are available to prevent HCV transmission from blood, blood products and other human tissues, but at a cost of more than $5.00 US per test, these tests are unaffordable in some developing countries. Further work is needed to develop cheap screening tests and implement affordable screening programmes in blood banks of all countries. This will require negotiations with manufacturers.

The Viral Hepatitis Prevention Board works under the auspices of the Society of Occupational Medicine and the European Public Health Association. The Board is supported by grants from the pharmaceutical industry (SmithKline Beecham Biologicals, Pasteur Mérieux MSD, Merck Vaccine Division) but has strict scientific independence. The organisers are grateful to Schering-Plough Pharmaceuticals for sponsoring The Hepatitis Challenge meeting.

Viral Hepatitis is published and produced by the VHPB, and printed by Jacqmain Ltd., Edegem, Belgium.

For further information please contact the VHPB Executive Secretariat at:

The VHPB Executive Secretariat

Epidemiology and Community Medicine

University of Antwerp

Universiteitsplein 1

B-2610 Antwerp, Belgium

Tel 32 (0)3 820 25 23 Fax 32 (0)3 820 26 40