Dr. Sherman is a Hepatologist practicing in Toronto, Canada. This paper has been submitted as a contribution to the Canadian Hepatitis Education Council.
Testing for hepatitis C virus (HCV) infection became commercially available in 1991. This allowed better differentiation between non-A, non-B hepatitis and chronic hepatitis C, and enabled investigators to define some of the characteristics of this disease. The objective of this article is to highlight the key facts about the epidemiology of hepatitis C infection and disease transmission in Canada.
How Many People Are Infected?
While chronic hepatitis C has become one of the most common liver diseases, the incidence of HCV infection in Canada is unknown. In the United States it is estimated that there are about 150,000 new HCV infections each year.1 Thus, in Canada, with about 10% of the population of the U.S., there may be as many as 15,000 new infections each year. However, this is likely an overestimate, because intravenous drug use (IVDU) is not as common in Canada as in the U.S.
The prevalence of hepatitis C infection in Canada has also not been determined. Measured prevalence depends on several variables, including, the type of test used (first or second generation ELISA or HCV RNA) and the population being studied. First generation tests for hepatitis C (ELISA I) were relatively insensitive and underestimated the true prevalence. Second generation tests (ELISA II) also underestimate prevalence, but to different extents in different populations. In blood donors there may be a 2% false positive rate, whereas in immunosuppressed populations, the false positive rate may be as high as 20%. The following table shows the prevalence of HCV in different countries.
The reported prevalence of HCV varies in different populations. Although ELISA II testing of blood donors reveals a positivity rate of between 20% to 40%, the majority of these turn out to be false positives. In Canada, among blood donors the current prevalence is about 0.05% (P Gill MD, personal communication). However, blood donors are highly selected and are not representative of the normal population. Other Canadian populations which have been studied include several prison populations,23 (prevalence 25% to 40%) and injection drug users attending a methadone clinic in Toronto (82% anti-HCV positive) (L Reib MD, personal communication).
A study in a Toronto Hospital indicated a prevalence of 0.5%4. This number may also not be representative, because of the nature of the population and because the hospital has a liver diseases section.
Prevalence of anti-HCV antibodies in IV drug users varies from about 65% to 80% in various studies in different parts of the world.5-7 These differences reflect the prevalence of needle sharing programs and the population studied (i.e. regular or occasional users). Regular users and severely addicted individuals living on the street have a higher prevalence than occasional users. The Toronto population referred to earlier, in which 82% were anti-HCV positive, were individuals in a methadone program, with a high rate of recidivism.
Prevalence of anti-HCV positivity in occasional IV drug users is not known. This population includes subjects who used IV drugs occasionally many years ago, when it was fashionable in the youth culture. Such patients comprise a large proportion of the current hepatitis C patient population.
Unlike hepatitis B, health care workers appear not to have an increased prevalence of hepatitis C. Even in dialysis units, where HCV prevalence is high in patients, staff do not appear to have an increased prevalence of the disease.8-9 There is about a 5% risk of acquiring hepatitis C from needle stick or other similar injuries. A similar, but smaller risk exists for exposure to blood in other professions, such as police, fire-fighters and mortuary workers.
Hepatitis C prevalence is higher in alcoholics, although not all studies confirm this. Mendenhall et al found 18% of alcoholics to be positive for hepatitis C and showed that the severity of liver disease is similar in alcoholics with and without HCV, but the average age of those with hepatitis C was about 10 years less than those without. This suggests that HCV accelerates the development of hepatic fibrosis in alcoholic liver disease. A Japanese study demonstrated that 31% of alcoholics were infected with HCV.11 In the U.S. one study demonstrated that 13% of alcoholics were positive for anti-HCV.10 In all of these populations the increased prevalence of hepatitis C can be traced to co-existence of other risk factors, such as IVDU.12
There is only one Canadian study which provides data on the prevalence of HCV in a so-called normal population (i.e. chosen for reasons unlikely to introduce bias in hepatitis C testing). Chaudhary et al tested federal civil servants in Ottawa, during routine annual medical exams, and found a prevalence of 1.2%.13
Elsewhere in the world the prevalence of HCV ranges from 1% to 4%14-18 (see Table 1). Higher prevalence is found in Egypt, Italy, Greece, Romania, and the countries of the old Soviet Union. In many of these areas, prevalence increases with age. Although one cannot extrapolate directly to our population, it is likely that a similar prevalence exists in these immigrant populations in Canada. The reason for higher prevalence in these countries is not certain, but probably reflects the practice of using non-disposable injection needles. Increased prevalence with age may be a result of higher likelihood of transfusion or sexual exposure, or longer duration of exposure to other modes of transmission.
As an educated estimate, the prevalence of hepatitis C infection in Canada is probably somewhere between 0.5% to -1.0%, therefore, 135,000 to 270,000 individuals may be infected.
What Happens to Hepatitis C Carriers?
It is clear that HCV causes cirrhosis and hepatocellular carcinoma (HCC), although the rate at which these conditions develop, and the rate at which they cause death or the need for liver transplantation is unknown. In the U.S., it is estimated that 8,000 to 10,000 patients die annually of complications of HCV infection. Thus in Canada, we might expect, at maximum a death rate of about 800 to 1,000. There are various estimates of the rate of development of cirrhosis, ranging from about 10% of hepatitis C carriers developing cirrhosis each decade, to an alternate estimate that about half of all HCV-infected patients will develop cirrhosis. Tong et al 19 have calculated that cirrhosis develops after a mean of about 20 years (SD 10 to 30 yrs) from initial infection via blood transfusion, and HCC develops a mean of eight years later. However, the population studied was highly selected, being those referred to a tertiary referral center with an interest in liver disease. It is likely that in the overall hepatitis C infected population, the mean rate of progression to cirrhosis and HCC is much lower.
Hepatocellular carcinoma is a recognized complication of hepatitis C. However, unlike hepatitis B, HCC rarely develops in the absence of cirrhosis in HCV-positive patients. The risk of HCC developing in chronic hepatitis C is variable in different studies. Hadziyannis et at 20 calculated odds ratios ranging between 6.3 and 13.7 in different study populations. In a Japanese study the cumulative risk of a hepatitis C carrier developing HCC was 28% for males over 50 years of age and 6% for females over 50.21 Unfortunately, all data on the risk of HCC were obtained from retrospective studies. There are no prospective studies which can provide accurate estimates of the risk of HCC.
There is a pressing need for more accurate data on the prevalence of hepatitis C and on the mortality and morbidity of this disease. In particular studies are needed to obtain Canadian data.
Is Hepatitis C Sexually Transmitted?
Studies in sexually promiscuous populations have demonstrated that the prevalence of anti-HCV is anywhere between 1% and 19%26-29.
Some of these studies have not adequately controlled for other sources of infection, but even in studies of sexually promiscuous populations not using drugs, there is a slightly higher than expected prevalence of anti-HCV positivity. Non-drug using spouses of IV drug users also have an increased prevalence of hepatitis C.30 A Japanese study has demonstrated that in spouses of anti-HCV-positive individuals the prevalence in hepatitis C seems to increase with duration of marriage.31 However, this study did not control for the increase in the prevalence that occurs with increasing age. Overall, in non-promiscuous populations (e.g. monogamous spouses) the risk of sexual transmission is less than 5%.27, 32-34
Sexual practices involving trauma (anal intercourse, “fisting”) have been shown to enhance the risk of being positive for anti-HCV.35
Studies looking at the presence of the hepatitis C virus in sexual secretions have provided conflicting results. One study was unable to identify HCV RNA in either semen or vaginal secretions, despite using polymerise chain reaction technology,35 whereas in another study there were correlations between HCV RNA in serum, and the presence of HCV RNA in saliva (48%), seminal fluid (24%), and urine (7%)36
Sexual transmission has been documented in HIV positive individuals, and overall transmission in this setting appears to be more likely than in those who are HIV negative.27
The data suggest that sexual transmission occurs, but is an uncommon event. The risk of sexual transmission may be increased by sexual practices involving trauma, by sexual intercourse during menstruation, and by the co-existence of HIV infection.
How is the Hepatitis C Virus Transmitted?
The best known mode of transmission is the parenteral route. In the early 1980’s post-transfusion hepatitis was reported in 9% of multiply transfused individuals.22 With screening of donors for HIV risk factors, the incidence of post-transfusion hepatitis fell to 3%. Introduction of HIV testing induced a further reduction in incidence of post-transfusion hepatitis. After the introduction of anti-HCV testing in 1991, post-transfusion hepatitis became rare, and currently it is estimated that 1/7500 donor exposures will lead to post-transfusion hepatitis C infection (Canadian Consensus Conference – Ottawa, December, 1994). This is because new infections may still occur, there is a false negative rate of anti-HCV testing, and because there is a lag between becoming infected and the development of anti-HCV antibodies (4 to 6 weeks). Thus, even in 1995, patients who receive multiple transfusions remain at risk. This includes patients with haemophilia or thalassaemia, patients receiving clotting factor concentrates, etc.
Post-transfusion hepatitis C accounts for a small proportion of all chronic hepatitis C cases in Canada, perhaps as low as 5%. The largest group of infected subjects are those who acquired the disease by IVDU, the most common mode of transmission. Transmission by organ donation has been well documented. About 2.4% of donors in the U.S. are anti-HCV positive.23 Risk of transmission is higher if the donor is also HCV RNA positive.
Nosocomial transmission of hepatitis C is a newly emerging problem. In different studies, prevalence of hepatitis C in dialysis patients ranges from 2% to 3%.9-24 The exact route of transmission in this population is not clear. Nosocomial transmission has also been documented in a haematology unit where hepatitis C RNA sequencing was used to demonstrate transmission from several index patients to previously uninfected patients.25 Again, route of transmission was not clear, but possibilities include multi-dose vials, poor nursing practices, etc.
Is There Maternal-Infant Transmission?
This is an unusual event, occurring at maximum in about 5% of cases. The risk of transmission seems to be related to the titre of virus in the mother. If the titre is greater than 106 transmission occurs at a rate of 36%. If the titre is less than 106 transmission does not occur. Maternal-infant transmission of anti-HCV anti-bodies occurs regularly, because of transplacental transfer. However, these antibodies usually disappear before one year of age.
It is probably not worth testing young children of anti-HCV-positive mothers, because there is no consensus about treatment of very young children, or even of older children.
What is Sporadic Transmission?
The second largest group of individuals infected with hepatitis C (in some populations, the largest group) are those who have acquired hepatitis C by so-called sporadic or inapparent transmission. Poor socio-economic circumstances are associated with an increased prevalence of HCV. Among this group are those who have used IV drugs, or have been imprisoned. However, in many others no risk factor can be identified, other than poor socio-economic conditions. Possible routes of transmission include sharing of personal hygiene items, such as razors and toothbrushes, and transmission between young children via impetigo or scabies.
Although in epidemiological studies the sporadic infection group is large, with close questioning, identifiable risk factors can be found in more than 80% of patients.
Who is at Risk for HCV?
Major risk groups include those who have had a transfusion, or IVDU, including all those who used IV drugs 20 and 30 years ago.
Dialysis patients comprise another high-risk group. Spouses of hepatitis C carriers should also be screened, as they are at risk, albeit at low risk. Individuals with a history of multiple sexual partners, or a history of a sexually transmitted disease are at risk. In particular, the sexual partners of IV drug users are at risk. Individuals who have spent time in prison are also at risk. Patients with other parenterally transmitted diseases, such as HIV or hepatitis B should be tested for HCV, however, this does not apply to those who acquired hepatitis B in childhood (e.g., South East Asians).
When the epidemiology of HIV became apparent, physicians began to ask their patients about their sexual and IVDU activity. This line of questions is now also necessary with hepatitis C. However, in addition to recent drug use (e.g. within the HIV era), we also need to know about IV drug use 20 and more years ago. We need to ask our patients whether they have ever been imprisoned. Such questioning may be difficult to do, and may be awkward for the patient, but it is necessary to try to determine how the patient became infected, and to assess the duration of the infection. These answers are critical from a public health perspective as well as for the management of the patient, and for our understanding of the epidemiology and transmission of this disease.
Thus in practice, all patients at risk for hepatitis C should be offered screening (with pre- and post-test counselling. Testing should also be offered to the spouses or other sexual partners of index cases. Patients with cirrhosis of unknown etiology, patients with hepatocellular carcinoma, as well as patients with other diseases associated with pepatitis C, such as glomerulonephritis, porphyria cutanea tarda, or cryoglobulinemia also should be tested for hepatitis C. It is probably wiser, when in doubt, to test, rather than not to test.
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