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The threat to public health of hepatitis C
0 INSTITUT PASTEMELSEVIER
Res. Virol.
Paris 1997
1997, 148, 143-145
The threat to public health of hepatitis C D. Lavanchy WHO, Division
of Emerging and other Communicable Diseases CH-1211 Geneva (Switzerland)
Surveillance
and Control (EMC),
Introduction
Pathophysiological
Viral hepatitis C is a major global public health problem. The isolation of the hepatitis C virus (HCV) in 1989 (Choo et al., 1989) ended a period of intensive international research efforts aimed at the discovery of the elusive, parenterally transmitted, non-A, non-B virus, well known as the major cause of post-transfusion hepatitis (Alter, 1994). Although HCV infection is not as easily transmitted as hepatitis B or HIV virus infections (Brackmann et al., 1993; Kiene et al., 1994), its high propensity to induce a chronic carrier state (50-80%) leading to serious long-term clinical sequelae places it among the pathogens of primary public health concern (Ohkoshi et al., 1993). As it is a recently discovered infectious agent, a consensus has still to be reached within the international scientific community in regard to prevalence, incidence, long-term pathobiological implications, socioeconomic burden and management of acute and chronic hepatitis C. Prevalence rates of 0 % to 72 % have been published in different countries worldwide. WHO estimates that 3% of the world’s population has been infected with the hepatitis C virus and that more than 170 million persons are chronic carriers (WHO, in preparation). The annual incidence of hepatitis C on a global scale is largely unknown, partially due to the fact that over 50% of the infections are asymptomatic (Ohkoshi et al., 1993; Shimoyama et al., 1993). Thus, the clinical spectrum of the acute infection is still a matter of uncertainty. Preliminary evidence suggests that in areas of high endemicity for viral hepatitis, symptomatic acute hepatitis C infection represents a significant cause of acute liver disease (Bortolotti et al., 1994; Coursaget et al., 1995; Tassopoulos et al., 1992).
Chronic hepatitis C poses a serious threat to health even in the absence of overt symptoms. Cirrhosis develops in up to 50 % of chronically infected individuals, and liver cancer has been shown to occur at an annual rate of l-4 %, after a long period of time, generally exceeding 30 years (Di Bisceglie et al., 1991 ; Kiyosawa et al., 1994a; Sherlock, 1994; Yano et al., 1993). Even in asymptomatic carriers, a decrease in quality of life has been reported (Davis et al., 1994). In contradiction to these findings, a study has reported no excess mortality after follow-up of 18 years in a population with a history of clinical non-A, non-B post-transfusion hepatitis (Seeff et al., 1992). Thus, it is not yet known whether the status of the “healthy carrier” exists in the longer term.
Received November 5, 1996.
Socioeconomic
implications
burden
The costs of chronic hepatitis C (e.g. medical interventions, work loss) imposed upon the community have not been fully assessed. From studies dealing with the consequences of chronic hepatitis B (Ascione and De Luca, 1995 ; Kerleau et al., 1995 ; Van Damme et al., 1995), it can be anticipated that these costs are sufficiently high for the community to consider treatment and (if available) global immunization as cost-saving measures. Management
The HCV genome mutates extensively in the structurally important envelope region, which is accessible to the immune defence system, as well as
144
D. LA VANCHY
in other non-structural regions. Most probably these spontaneous mutations represent efficient viral escape mechanisms,responsible for the high rate of chronicity observed. Treatment with interferon alpha (and possibly beta) effectively eradicates circulating HCV in ~20% of patients, leading to a reduction of the inflammatory process in the liver (Fried and Hoofnagle, 1995). Currently the follow-up period is insufficiently long, so that the permanent elimination of HCV and the long-term benefits of interferon therapy remain to be demonstrated. For the remaining ~80% of non-responders, international research effort should focus on combined antiviral therapy using currently available and newly developed antiviral drugs. Of patients who are in need of treatment, 90% live in areas with poor economic standards, and there is concern that they will not have accessto expensive antiviral therapy. The current state of vaccine research implies that no candidate will be available in the foreseeable future; therefore, emphasismust be placed on available preventive measures. Horizontal (intra-familial), sexual and perinatal transmission have been reported, but are so uncommon that they cannot explain the high HCV prevalence found worldwide. On the other hand, transmission of HCV through parenteral routes such as transfusion of unscreened blood and blood products, injections and other percutaneous medical or dental procedures with reused unsterilized equipment, and needle-sharing among drug abusersis well documented and a major cause of HCV dissemination (Hayashi et al., 1995; Kiyosawa et al., 1994b; Shimoyama et al., 1993). Conclusion Effective monitoring and diseasecontrol of HCV representsa significant challenge to the medical and public health community. To addressthese problems on a global scale, we need to deal with the following issues. (1) Development of guidelines for the diagnosis, control, and treatment of HCV based on an intemational consensus. (2) Improvement of global surveillance in order to assessthe impact of HCV upon the community at the local, regional and global level. The majority of HCV prevalence data are based on studies of blood donors, which are not necessarily representative of the general population. Consequently, caution is necessary in interpreting existing data, and the epidemiology should be refined.
HCV
=
hepatitis
C virus.
(3) Assessmentof the economic consequencesof HCV in communities. (4) Prevention through screening of all blood and blood products worldwide. (5) Promotion of prevention through use of universal precautions, which are the only effective preventive methods available today. Disposable medical material should not be reused, and reusable medical material should be appropriately sterilized. Education about the risks of using unsterilized material should be promoted. (6) Investigation of the significance of different mechanismsof transmissionin communities in order to establish more effective prevention strategies. Studies designed for the detection of alternate transmission modes involving unique social, cultural, paramedical and behavioural practices (e.g. earpiercing, circumcision, tattooing, scarification) should be performed. (7) Standardization of diagnostic procedures and reagents. True confirmatory tests combined with internationally recognized quality controls are needed. Diagnostic tools capable of differentiating between recovery, healthy carrier state or chronic agressive diseaseshould be explored. (8) Investigation of immunopathological complications and susceptibility to treatment; systematic sequencing of HCV isolates and investigation of immune responsemechanisms. In these times of weakening of traditional public health activities in many countries, especially surveillance, and of deteriorating conditions in public health laboratories which perform the basic work, the challenge of a new disease (among others) places extensive pressureon the medical community and additional financial burden upon society. The careful assessmentof the consequencesof HCV is needed to mobilize resources and to ensure their effective use. WHO will encourage and facilitate efforts to achieve better understanding and control of hepatitis C. Key-words: HCV, Hepatitis C, Public health.
References Alter, H.J. (1994), Transfusion transmitted hepatitis C and non-A, non-B, non-C. VOX Sang, 67, Suppl. 3, 19-24. Ascione, A. 8z De. Luca, M. (1995), Costo-beneficio delle terapie con interferone nelle ma&tie epatiche croniche virali. Miner-vu Gustroenterol. Dietol., 41(l), 123-125.
THE THREAT
TO PUBLIC
Bortolotti, F., Crivellaro, C., Carretta, M., Tagger, A., Ribero, M., Bertolini, A., Barbierato, E., Noventa, F. & Cadrobbi, P. (1994), Acute non-A, non-B hepatitis in Italy : a 1Byear prospective epidemiological study. The possible role of hepatitis C virus. Infection, 22(5),321-325.
Brackmann, S.A., Gerritzen, A., Oldenburg, J., Brackmann, H.H. & Schneweis, K.E. (1993), Search for intrafamilial transmission of hepatitis C virus in hemophilia patients. Blood, 81(4), 1077-1082. Choo, Q.L., Kuo, G., Weiner, A.J., Overby, L.R., Bradley, D.W. & Houghton, M. (1989), Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244(4902), 359-362. Coursaget, P., Leboulleux, D., Gharbi, Y., Enogat, N., Ndao, M.A., Co11 Se& A.M. & Kastally, R. (1995), Etiology of acute sporadic hepatitis in adults in Senegal and Tunisia. Scar&. J. Infect. Dis., 27(l), 9-11. Davis, G.L., Balart, L.A., Schiff, E.R., Lindsay, K., Bodenheimer, H.C., Jr., Perrillo, R.P., Carey, W., Jacobson, I.M., Payne, J., Dienstag, J.L. et al. (1994), Assessing health-related quality of life in chronic hepatitis C using the Sickness Impact Profile. Clin. Ther., 16(2), 334-343. Di Bisceglie, A.M., Goodman, Z.D., Ishak, K.G., Hoofnagle, J.H., Melpolder, J.J. & Alter, H.J. (1991), Longterm clinical and histopathological follow-up of chronic posttransfusion hepatitis. Heputology, 14(6), 969-974.
Fried, M.W. & Hoofnagle, J.H. (1995), Therapy of hepatitis C. Semin. Liver Dis., 15(l), 82-91. Hayashi, J., Kishihara, Y., Yamaji, K., Yoshimura, E., Kawakami, Y., Akazawa, K. & Kashiwagi, S. (1995), Transmission of hepatitis C virus by health care workers in a rural area of Japan. Am. J. Gastroenterol., 90(5), 794-799. Kerleau, M., Flori, Y.A., Nalpas, B., Lanoe, J.L., Berthelot, P. & Fardeau Gamier, M. (1995), Analyse coutavantage dune politique de prevention vaccinale de l’hepatite virale B. Rev. Epidemiol. Sante Publique, 43(1),48&I
HEALTH
OF HEPATITIS
C
145
Kiene, K., Hsu, B., Rowe, D. & Carruthers, A. (1994), Hepatitis, HIV, and the dermatologist: a risk review. J. Am. Acad. Dermatol., 30(l), 108-115. Kiyosawa, K., Tanaka, E., Sodeyama, T. & Furuta, S. (1994a), Natural history of hepatitis C. Intervirology, 37(2), 101-107. Kiyosawa, K., Tanaka, E., Sodeyama, T., Yoshizawa, K., Yabu, K., Furuta, K., Imai, H., Nakano, Y., Usuda, S., Uemura, K. et al. (1994b), Transmission of hepatitis C in an isolated area in Japan: community-acquired infection. The South Kiso Hepatitis Study Group. Gastroenterology, 106(6), 15961602. Ohkoshi, S., Watanabe, M., Kuwana, K., Tawaraya, H., Kamimura, T. & Asakura, H. (1993), Clinical evaluation of the antibody against core protein of hepatitis C virus. Gastroenterol. Jpn, 28, Suppl. 5, 80-83. Seeff, L.B., Buskell, B.Z., Wright, E.C., Durako, S.J., Alter, H.J. & Iber, F.L. (1992), Long-term mortality after transfusion-associated non-A, non-B hepatitis. N. Engl. J. Med., 327, 1906-1911. Sherlock, D.S. (1994), Chronic hepatitis C. Dis. Mon., 40(3), 117-196. Shimoyama, R., Sekiguchi, S., Suga, M., Sakamoto, S. & Yachi, A. (1993), The epidemiology and infection route of asymptomatic HCV carriers detected through blood donations. Gastroenterol. Jpn, 28, Suppl. 5, l-5. Tassopoulos, NC., Hatzakis, A., Delladetsima, I., Koutelou, M.G., Todoulos, A. & Miriagou, V. (1992), Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: a 5-year prospective study. Gastroenterology, 102(3), 969-972. Van Damme, P., Tormans, G., Beutels, P. & Van Doorslaer, E. (1995), Hepatitis B prevention in Europe: a preliminary economic evaluation. Vaccine, 13, s54-s57.
Yano,
M., Yatsuhashi, H., Inoue, O., Inokuchi, K. & Koga, M. (1993). Epidemiology and long term prognosis of hepatitis C virus infection in Japan. Gut, 34, S13-S16.
Res. Virol.
Paris 1997
1997, 148, 143-145
The threat to public health of hepatitis C D. Lavanchy WHO, Division
of Emerging and other Communicable Diseases CH-1211 Geneva (Switzerland)
Surveillance
and Control (EMC),
Introduction
Pathophysiological
Viral hepatitis C is a major global public health problem. The isolation of the hepatitis C virus (HCV) in 1989 (Choo et al., 1989) ended a period of intensive international research efforts aimed at the discovery of the elusive, parenterally transmitted, non-A, non-B virus, well known as the major cause of post-transfusion hepatitis (Alter, 1994). Although HCV infection is not as easily transmitted as hepatitis B or HIV virus infections (Brackmann et al., 1993; Kiene et al., 1994), its high propensity to induce a chronic carrier state (50-80%) leading to serious long-term clinical sequelae places it among the pathogens of primary public health concern (Ohkoshi et al., 1993). As it is a recently discovered infectious agent, a consensus has still to be reached within the international scientific community in regard to prevalence, incidence, long-term pathobiological implications, socioeconomic burden and management of acute and chronic hepatitis C. Prevalence rates of 0 % to 72 % have been published in different countries worldwide. WHO estimates that 3% of the world’s population has been infected with the hepatitis C virus and that more than 170 million persons are chronic carriers (WHO, in preparation). The annual incidence of hepatitis C on a global scale is largely unknown, partially due to the fact that over 50% of the infections are asymptomatic (Ohkoshi et al., 1993; Shimoyama et al., 1993). Thus, the clinical spectrum of the acute infection is still a matter of uncertainty. Preliminary evidence suggests that in areas of high endemicity for viral hepatitis, symptomatic acute hepatitis C infection represents a significant cause of acute liver disease (Bortolotti et al., 1994; Coursaget et al., 1995; Tassopoulos et al., 1992).
Chronic hepatitis C poses a serious threat to health even in the absence of overt symptoms. Cirrhosis develops in up to 50 % of chronically infected individuals, and liver cancer has been shown to occur at an annual rate of l-4 %, after a long period of time, generally exceeding 30 years (Di Bisceglie et al., 1991 ; Kiyosawa et al., 1994a; Sherlock, 1994; Yano et al., 1993). Even in asymptomatic carriers, a decrease in quality of life has been reported (Davis et al., 1994). In contradiction to these findings, a study has reported no excess mortality after follow-up of 18 years in a population with a history of clinical non-A, non-B post-transfusion hepatitis (Seeff et al., 1992). Thus, it is not yet known whether the status of the “healthy carrier” exists in the longer term.
Received November 5, 1996.
Socioeconomic
implications
burden
The costs of chronic hepatitis C (e.g. medical interventions, work loss) imposed upon the community have not been fully assessed. From studies dealing with the consequences of chronic hepatitis B (Ascione and De Luca, 1995 ; Kerleau et al., 1995 ; Van Damme et al., 1995), it can be anticipated that these costs are sufficiently high for the community to consider treatment and (if available) global immunization as cost-saving measures. Management
The HCV genome mutates extensively in the structurally important envelope region, which is accessible to the immune defence system, as well as
144
D. LA VANCHY
in other non-structural regions. Most probably these spontaneous mutations represent efficient viral escape mechanisms,responsible for the high rate of chronicity observed. Treatment with interferon alpha (and possibly beta) effectively eradicates circulating HCV in ~20% of patients, leading to a reduction of the inflammatory process in the liver (Fried and Hoofnagle, 1995). Currently the follow-up period is insufficiently long, so that the permanent elimination of HCV and the long-term benefits of interferon therapy remain to be demonstrated. For the remaining ~80% of non-responders, international research effort should focus on combined antiviral therapy using currently available and newly developed antiviral drugs. Of patients who are in need of treatment, 90% live in areas with poor economic standards, and there is concern that they will not have accessto expensive antiviral therapy. The current state of vaccine research implies that no candidate will be available in the foreseeable future; therefore, emphasismust be placed on available preventive measures. Horizontal (intra-familial), sexual and perinatal transmission have been reported, but are so uncommon that they cannot explain the high HCV prevalence found worldwide. On the other hand, transmission of HCV through parenteral routes such as transfusion of unscreened blood and blood products, injections and other percutaneous medical or dental procedures with reused unsterilized equipment, and needle-sharing among drug abusersis well documented and a major cause of HCV dissemination (Hayashi et al., 1995; Kiyosawa et al., 1994b; Shimoyama et al., 1993). Conclusion Effective monitoring and diseasecontrol of HCV representsa significant challenge to the medical and public health community. To addressthese problems on a global scale, we need to deal with the following issues. (1) Development of guidelines for the diagnosis, control, and treatment of HCV based on an intemational consensus. (2) Improvement of global surveillance in order to assessthe impact of HCV upon the community at the local, regional and global level. The majority of HCV prevalence data are based on studies of blood donors, which are not necessarily representative of the general population. Consequently, caution is necessary in interpreting existing data, and the epidemiology should be refined.
HCV
=
hepatitis
C virus.
(3) Assessmentof the economic consequencesof HCV in communities. (4) Prevention through screening of all blood and blood products worldwide. (5) Promotion of prevention through use of universal precautions, which are the only effective preventive methods available today. Disposable medical material should not be reused, and reusable medical material should be appropriately sterilized. Education about the risks of using unsterilized material should be promoted. (6) Investigation of the significance of different mechanismsof transmissionin communities in order to establish more effective prevention strategies. Studies designed for the detection of alternate transmission modes involving unique social, cultural, paramedical and behavioural practices (e.g. earpiercing, circumcision, tattooing, scarification) should be performed. (7) Standardization of diagnostic procedures and reagents. True confirmatory tests combined with internationally recognized quality controls are needed. Diagnostic tools capable of differentiating between recovery, healthy carrier state or chronic agressive diseaseshould be explored. (8) Investigation of immunopathological complications and susceptibility to treatment; systematic sequencing of HCV isolates and investigation of immune responsemechanisms. In these times of weakening of traditional public health activities in many countries, especially surveillance, and of deteriorating conditions in public health laboratories which perform the basic work, the challenge of a new disease (among others) places extensive pressureon the medical community and additional financial burden upon society. The careful assessmentof the consequencesof HCV is needed to mobilize resources and to ensure their effective use. WHO will encourage and facilitate efforts to achieve better understanding and control of hepatitis C. Key-words: HCV, Hepatitis C, Public health.
References Alter, H.J. (1994), Transfusion transmitted hepatitis C and non-A, non-B, non-C. VOX Sang, 67, Suppl. 3, 19-24. Ascione, A. 8z De. Luca, M. (1995), Costo-beneficio delle terapie con interferone nelle ma&tie epatiche croniche virali. Miner-vu Gustroenterol. Dietol., 41(l), 123-125.
THE THREAT
TO PUBLIC
Bortolotti, F., Crivellaro, C., Carretta, M., Tagger, A., Ribero, M., Bertolini, A., Barbierato, E., Noventa, F. & Cadrobbi, P. (1994), Acute non-A, non-B hepatitis in Italy : a 1Byear prospective epidemiological study. The possible role of hepatitis C virus. Infection, 22(5),321-325.
Brackmann, S.A., Gerritzen, A., Oldenburg, J., Brackmann, H.H. & Schneweis, K.E. (1993), Search for intrafamilial transmission of hepatitis C virus in hemophilia patients. Blood, 81(4), 1077-1082. Choo, Q.L., Kuo, G., Weiner, A.J., Overby, L.R., Bradley, D.W. & Houghton, M. (1989), Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244(4902), 359-362. Coursaget, P., Leboulleux, D., Gharbi, Y., Enogat, N., Ndao, M.A., Co11 Se& A.M. & Kastally, R. (1995), Etiology of acute sporadic hepatitis in adults in Senegal and Tunisia. Scar&. J. Infect. Dis., 27(l), 9-11. Davis, G.L., Balart, L.A., Schiff, E.R., Lindsay, K., Bodenheimer, H.C., Jr., Perrillo, R.P., Carey, W., Jacobson, I.M., Payne, J., Dienstag, J.L. et al. (1994), Assessing health-related quality of life in chronic hepatitis C using the Sickness Impact Profile. Clin. Ther., 16(2), 334-343. Di Bisceglie, A.M., Goodman, Z.D., Ishak, K.G., Hoofnagle, J.H., Melpolder, J.J. & Alter, H.J. (1991), Longterm clinical and histopathological follow-up of chronic posttransfusion hepatitis. Heputology, 14(6), 969-974.
Fried, M.W. & Hoofnagle, J.H. (1995), Therapy of hepatitis C. Semin. Liver Dis., 15(l), 82-91. Hayashi, J., Kishihara, Y., Yamaji, K., Yoshimura, E., Kawakami, Y., Akazawa, K. & Kashiwagi, S. (1995), Transmission of hepatitis C virus by health care workers in a rural area of Japan. Am. J. Gastroenterol., 90(5), 794-799. Kerleau, M., Flori, Y.A., Nalpas, B., Lanoe, J.L., Berthelot, P. & Fardeau Gamier, M. (1995), Analyse coutavantage dune politique de prevention vaccinale de l’hepatite virale B. Rev. Epidemiol. Sante Publique, 43(1),48&I
HEALTH
OF HEPATITIS
C
145
Kiene, K., Hsu, B., Rowe, D. & Carruthers, A. (1994), Hepatitis, HIV, and the dermatologist: a risk review. J. Am. Acad. Dermatol., 30(l), 108-115. Kiyosawa, K., Tanaka, E., Sodeyama, T. & Furuta, S. (1994a), Natural history of hepatitis C. Intervirology, 37(2), 101-107. Kiyosawa, K., Tanaka, E., Sodeyama, T., Yoshizawa, K., Yabu, K., Furuta, K., Imai, H., Nakano, Y., Usuda, S., Uemura, K. et al. (1994b), Transmission of hepatitis C in an isolated area in Japan: community-acquired infection. The South Kiso Hepatitis Study Group. Gastroenterology, 106(6), 15961602. Ohkoshi, S., Watanabe, M., Kuwana, K., Tawaraya, H., Kamimura, T. & Asakura, H. (1993), Clinical evaluation of the antibody against core protein of hepatitis C virus. Gastroenterol. Jpn, 28, Suppl. 5, 80-83. Seeff, L.B., Buskell, B.Z., Wright, E.C., Durako, S.J., Alter, H.J. & Iber, F.L. (1992), Long-term mortality after transfusion-associated non-A, non-B hepatitis. N. Engl. J. Med., 327, 1906-1911. Sherlock, D.S. (1994), Chronic hepatitis C. Dis. Mon., 40(3), 117-196. Shimoyama, R., Sekiguchi, S., Suga, M., Sakamoto, S. & Yachi, A. (1993), The epidemiology and infection route of asymptomatic HCV carriers detected through blood donations. Gastroenterol. Jpn, 28, Suppl. 5, l-5. Tassopoulos, NC., Hatzakis, A., Delladetsima, I., Koutelou, M.G., Todoulos, A. & Miriagou, V. (1992), Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: a 5-year prospective study. Gastroenterology, 102(3), 969-972. Van Damme, P., Tormans, G., Beutels, P. & Van Doorslaer, E. (1995), Hepatitis B prevention in Europe: a preliminary economic evaluation. Vaccine, 13, s54-s57.
Yano,
M., Yatsuhashi, H., Inoue, O., Inokuchi, K. & Koga, M. (1993). Epidemiology and long term prognosis of hepatitis C virus infection in Japan. Gut, 34, S13-S16.