Professor Gregory Dore, Doctor Jason Grebely
The vast majority of people with hepatitis C virus (HCV) infection progress to development of chronic hepatitis C (1), with associated risk of progressive liver disease, cirrhosis, liver failure or hepatocellular carcinoma (1-3). In developed countries, injecting drug use accounts for the majority of HCV infections (4-9). The impact of the natural history of chronic HCV infection and its long term complications among an ageing population of infected people who inject drugs (PWID) is now reflected in a growing burden of advanced HCV-related liver disease (10-15). Despite two decades of research on the natural history of HCV infection, uncertainty remains on the contribution of chronic HCV to morbidities, mortality risk and the level of life expectancy reduction (without therapeutic intervention) at individual and population levels. Understanding these elements is a crucial key to enhance HCV assessment and treatment uptake, and consequently, to decrease hepatitis C-related liver disease burden in the long term.
A revolution in HCV treatment is fast approaching; by the end of this decade, interferon free regimens with simple dosing (once-daily), high tolerability, short-duration (6-24 weeks), extremely high efficacy (cure rates >90%) and low toxicity should be the norm (21). However, unless the proportion of individuals screened, assessed and treated for HCV is increased significantly, these impressive anticipated advancements in HCV therapy will have little effect on HCV incidence and prevalence at the population level (21). Given the majority of people with chronic HCV infection are, developing strategies for enhanced HCV assessment and treatment must be effective and applicable among this population(20, 21).
Despite guidelines encouraging the inclusion of PWID for HCV assessment and treatment on a case by case basis (22), treatment uptake remains low in this population (23, 24). Barriers to HCV assessment and treatment uptake are multi-factorial and include issues at the level of the patient, practitioner, and system (25). Toxicity of interferon-based therapy (26, 27), lack of knowledge about HCV infection and competing patient health and social priorities(23, 25), health care providers concern about adherence to therapy (28-31) and suboptimal HCV treatment structure (32, 33) have been frequently cited as factors contributing to low HCV assessment and treatment uptake. However, methodological issues, small study samples and inconsistency in assessment tools have brought discrepancies across previous findings, highlighting the need to better understand a broader range of factors associated with HCV assessment and treatment uptake.
Taken together, little is known about the long term impact of chronic HCV infection on morbidities and mortality risk and little is known about factors associated with HCV assessment, treatment uptake and predictors of response to therapy among PWID. This project aims to address these issues as main barriers to enhanced HCV treatment in this population.
This project aims to assess the long term impact of chronic HCV infection on morbidities and mortality risk, as well as investigate factors associated with hepatitis C (HCV) assessment, treatment uptake and predictors of response to therapy among people who inject drugs (PWID). The overall goal is to explore and address the main barriers to enhanced HCV treatment in PWID.
Data from several studies and existing datasets will be analysed including: notifications of cases of HCV made to the NSW Health Department; the national death registry; the Enhanced Treatment of Hepatitis C in Opioid Substitution Settings (ETHOS) cohort; the Community Health and Safety Evaluation (CHASE) data; and the Australian Trial in Acute Hepatitis C (ATAHC).
The direct impact of HCV-related liver disease on life expectancy reduction among people with HCV mono-infection has been estimated.
Primary analysis has been done on the data from the Enhanced Treatment of Hepatitis C in the Opiate Substitution settings (ETHOS) cohort to assess barriers and willingness to receive HCV treatment among PWID as well as factors associated with HCV assessment and treatment.
Data from the Australian Trial in Acute Hepatitis C (ATAHC) were used to assess the impact of treatment on mental health in the setting of early chronic HCV infection, as well as to evaluate mortality following treatment for acute HCV infection.
To estimate trends in HCV treatment uptake and associated factors, data from the Community Health and Safety Evaluation (CHASE) of inner city residents in the Downtown Eastside (DTES) of Vancouver, Canada are being used.
Alavi M, Law MG, Grebely J, Thein HH, Walter S, Amin J, Dore GJ. Impact of hepatitis C virus infection on life expectancy: a population-based linkage study. The 14th International Symposium on Viral Hepatitis and Liver Disease, Shanghai, China, 22-25 June 2012 (Oral Abstract)
Alavi M, Law MG, Grebely J, Thein HH, Walter S, Amin J, Dore GJ. Impact of hepatitis C virus infection on life expectancy: a population-based linkage study. The 8th Australasian Viral Hepatitis Conference, Auckland, New Zealand, 10-12 September 2012 (Oral Abstract)
Alavi M, Grebely J, Gillman AB, Micallef M, Batey R, Honey C, Bath N, Loveday S, Day C, Dunlop A,Wodak A, Balcomb AC, Abbott P, Rodgers C, Weltman MD, Haber P, Dore GJ. Willingness to receive treatment for chronic hepatitis c virus infection among injecting drug users in the opioid substitution setting: the ETHOS study. The 8th Australasian Viral Hepatitis Conference, Auckland, New Zealand, 10-12 September 2012 (Oral-poster Abstract)
Alavi M, Grebely J, Gillman AB, Micallef M, Batey R, Honey C, Bath N, Loveday S, Day C, Dunlop A,Wodak A, Balcomb AC, Abbott P, Rodgers C, Weltman MD, Haber P, Dore GJ. Assessment and treatment of hepatitis c virus infection among injecting drug users in the opioid substitution setting: the ETHOS study. The 8th Australasian Viral Hepatitis Conference, Auckland, New Zealand, 10-12 September 2012 (Oral-poster presentation)
Alavi M, Law MG, Grebely J, Thein HH, Walter S, Amin J, Dore GJ. Impact of hepatitis C virus infection on life expectancy: a population-based linkage study. Lancet 2012 (Submitted November 6, 2012, THELANCET-D-12-07868) (Original Research, IF 38.28)
Alavi M, Grebely J, Matthews GV, Petoumenos K, Yeung B, Day C, Lloyd AR,Van Beek I, Kaldor JM, Hellard M, Dore GJ and Haber PS on behalf of the ATAHC Study Group. Impact of pegylated interferon alfa-2a treatment on mental health during recent hepatitis C virus infection. J Gastroenterol Hepatol. 2012 May;27(5):957-65.
1. Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. [Review] [55 refs]. Journal of Viral Hepatitis. 2006;13(1):34-41.
2. Harris HE, Ramsay ME, Andrews NJ, Group HCVNRS. Survival of a national cohort of hepatitis C virus infected patients, 16 years after exposure. Epidemiology & Infection. 2006;134(3):472-7.
3. Forns X, Ampurdanes S, Sanchez-Tapias JM, Guilera M, Sans M, Sanchez-Fueyo A, et al. Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center. Journal of Hepatology. 2001;35(2):265-71.
4. Balogun MA, Laurichesse H, Ramsay ME, Sellwood J, Westmoreland D, Paver WK, et al. Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance. Communicable Disease & Public Health. 2003;6(1):34-9.
5. Dalgard O, Jeansson S, Skaug K, Raknerud N, Bell H. Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum. Scandinavian Journal of Gastroenterology. 2003;38(8):864-70.
6. Dore GJ, Law M, MacDonald M, Kaldor JM. Epidemiology of hepatitis C virus infection in Australia. [Review] [69 refs]. Journal of Clinical Virology. 2003;26(2):171-84.
7. Mele A, Tosti ME, Marzolini A, Moiraghi A, Ragni P, Gallo G, et al. Prevention of hepatitis C in Italy: lessons from surveillance of type-specific acute viral hepatitis. SEIEVA collaborating Group. Journal of Viral Hepatitis. 2000;7(1):30-5.
8. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. [Review] [143 refs]. The Lancet Infectious Diseases. 2005;5(9):558-67.
9. Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. [Review]. Lancet. 2011;378(9791):571-83.
10. Omland LH, Jepsen P, Krarup H, Schonning K, Lind B, Kromann-Andersen H, et al. Increased mortality among persons infected with hepatitis C virus. Clinical Gastroenterology & Hepatology. 2011;9(1):71-8.
11. El-Kamary SS, Jhaveri R, Shardell MD. All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population. Clinical Infectious Diseases. 2011;53(2):150-7.
12. Amin J, Law MG, Bartlett M, Kaldor JM, Dore GJ. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study. Lancet. 2006;368(9539):938-45.
13. Duberg AS, Torner A, Davidsdottir L, Aleman S, Blaxhult A, Svensson A, et al. Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community-based register study. Journal of Viral Hepatitis. 2008;15(7):538-50.
14. McDonald SA, Hutchinson SJ, Bird SM, Mills PR, Dillon J, Bloor M, et al. A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland. Statistical Methods in Medical Research. 2009;18(3):271-83.
15. Grebely J, Raffa JD, Lai C, Kerr T, Fischer B, Krajden M, et al. Impact of hepatitis C virus infection on all-cause and liver-related mortality in a large community-based cohort of inner city residents. Journal of Viral Hepatitis. 2011;18(1):32-41.
21. Dore GJ. The changing therapeutic landscape for hepatitis C. The Medical Journal of Australia. 2012 June 4;196(10):629-32.
22. Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver D. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-74.
23. Grebely J, Raffa JD, Lai C, Krajden M, Kerr T, Fischer B, et al. Low uptake of treatment for hepatitis C virus infection in a large community-based study of inner city residents. Journal of Viral Hepatitis. 2009;16(5):352-8.
24. Mehta SH, Genberg BL, Astemborski J, Kavasery R, Kirk GD, Vlahov D, et al. Limited uptake of hepatitis C treatment among injection drug users. Journal of Community Health. 2008;33(3):126-33.
25. Grebely J, Petoumenos K, Matthews GV, Haber P, Marks P, Lloyd AR, et al. Factors associated with uptake of treatment for recent hepatitis C virus infection in a predominantly injecting drug user cohort: The ATAHC Study. Drug & Alcohol Dependence. 2010;107(2-3):244-9.
26. Maddrey WC. Safety of combination interferon alfa-2b/ribavirin therapy in chronic hepatitis C-relapsed and treatment-naive patients. Seminars in Liver Disease. 1999;1:67-75.
27. Janssen HL, Brouwer JT, van der Mast RC, Schalm SW. Suicide associated with alfa-interferon therapy for chronic viral hepatitis. Journal of Hepatology. 1994;21(2):241-3.
28. McHutchison JG, Fried MW. Current therapy for hepatitis C: pegylated interferon and ribavirin. [Review] [14 refs]. Clinics in Liver Disease. 2003;7(1):149-61.
29. Sylvestre DL, Clements BJ. Adherence to hepatitis C treatment in recovering heroin users maintained on methadone. European Journal of Gastroenterology & Hepatology. 2007;19(9):741-7.
30. Calleri G, Cariti G, Gaiottino F, De Rosa FG, Bargiacchi O, Audagnotto S, et al. A short course of pegylated interferon-alpha in acute HCV hepatitis. Journal of Viral Hepatitis. 2007;14(2):116-21.
31. Dore GJ, Hellard M, Matthews GV, Grebely J, Haber PS, Petoumenos K, et al. Effective treatment of injecting drug users with recently acquired hepatitis C virus infection. Gastroenterology. 2010;138(1):123-35.
32. Lerner BH, Gulick RM, Dubler NN. Rethinking nonadherence: historical perspectives on triple-drug therapy for HIV disease. [Review] [92 refs]. Annals of Internal Medicine. 1998;129(7):573-8.
33. Bamberger JD, Unick J, Klein P, Fraser M, Chesney M, Katz MH. Helping the urban poor stay with antiretroviral HIV drug therapy. American Journal of Public Health. 2000;90(5):699-701.
For more information relating to this project, please contact Maryam Alavi: