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DOI: 10.1055/s-0031-1297922
What Is Killing People with Hepatitis C Virus Infection?
Publikationsverlauf
Publikationsdatum:
21. Dezember 2011 (online)

ABSTRACT
The burden of hepatitis C virus (HCV)-related morbidity and mortality continues to rise. Progression to advanced liver disease among HCV-infected individuals generally requires decades, but we are entering an era where those infected with HCV in the 1970s and 1980s are at significant risk of mortality. Liver disease has overtaken drug-related harm as the major cause of mortality in HCV-infected individuals in many settings. Direct-acting antiviral therapies have provided renewed optimism, but HCV treatment uptake will need to increase markedly to reduce liver disease mortality. This review provides updated information on the natural history of HCV, disease-specific causes of mortality among people with HCV, estimates and projections of HCV-related disease burden and mortality and individual and population-level strategies to reduce mortality. The considerable variability in mortality rates within subpopulations of people with HCV will be outlined, such as in people who inject drugs and those with HIV co-infection.
KEYWORDS
Hepatitis C virus - assessment - treatment - care - barriers
REFERENCES
- 1
Thompson A, Patel K, Tillman H, McHutchison J G.
Directly acting antivirals for the treatment of patients with hepatitis C infection:
a clinical development update addressing key future challenges.
J Hepatol.
2009;
50
(1)
184-194
MissingFormLabel
- 2
Omland L H, Jepsen P, Krarup H DANVIR Cohort Study et al.
Increased mortality among persons infected with hepatitis C virus.
Clin Gastroenterol Hepatol.
2011;
9
(1)
71-78
MissingFormLabel
- 3
El-Kamary S S, Jhaveri R, Shardell M D.
All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals
in the general US population.
Clin Infect Dis.
2011;
53
(2)
150-157
MissingFormLabel
- 4
McDonald S A, Hutchinson S J, Bird S M et al..
The growing contribution of hepatitis C virus infection to liver-related mortality
in Scotland.
Euro Surveill.
2010;
15
(18)
19562
MissingFormLabel
- 5
Amin J, Law M G, Bartlett M, Kaldor J M, Dore G J.
Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based
linkage study.
Lancet.
2006;
368
(9539)
938-945
MissingFormLabel
- 6
Duberg A S, Törner A, Davidsdóttir L et al..
Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide
community-based register study.
J Viral Hepat.
2008;
15
(7)
538-550
MissingFormLabel
- 7
McDonald S A, Hutchinson S J, Bird S M et al..
A population-based record linkage study of mortality in hepatitis C-diagnosed persons
with or without HIV coinfection in Scotland.
Stat Methods Med Res.
2009;
18
(3)
271-283
MissingFormLabel
- 8
Walter S R, Thein H H, Amin J et al..
Trends in mortality after diagnosis of hepatitis B or C infection: 1992-2006.
J Hepatol.
2011;
54
(5)
879-886
MissingFormLabel
- 9
Altekruse S F, McGlynn K A, Reichman M E.
Hepatocellular carcinoma incidence, mortality, and survival trends in the United States
from 1975 to 2005.
J Clin Oncol.
2009;
27
(9)
1485-1491
MissingFormLabel
- 10
Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C.
Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004.
Hepatology.
2008;
48
(1)
137-145
MissingFormLabel
- 11
Bosetti C, Levi F, Lucchini F, Zatonski W A, Negri E, La Vecchia C.
Worldwide mortality from cirrhosis: an update to 2002.
J Hepatol.
2007;
46
(5)
827-839
MissingFormLabel
- 12
Volk M L, Tocco R, Saini S, Lok A S.
Public health impact of antiviral therapy for hepatitis C in the United States.
Hepatology.
2009;
50
(6)
1750-1755
MissingFormLabel
- 13 NCHECR .Epidemiological and economic impact of potential increased hepatitis C treatment uptake
in Australia. Sydney, Australia: National Centre in HIV Epidemiology and Clinical Research, The University of New South
Wales; 2010
MissingFormLabel
- 14
Werb D, Wood E, Kerr T, Hershfield N, Palmer R W, Remis R S.
Treatment costs of hepatitis C infection among injection drug users in Canada, 2006–2026.
Int J Drug Policy.
2011;
22
(1)
70-76
MissingFormLabel
- 15
Lettmeier B, Mühlberger N, Schwarzer R et al..
Market uptake of new antiviral drugs for the treatment of hepatitis C.
J Hepatol.
2008;
49
(4)
528-536
MissingFormLabel
- 16 NCHECR .HIV, viral hepatitis, and sexually transmissible infections in Australia Annual Surveillance
Report. Sydney, Australia: National Centre in HIV Epidemiology and Clinical Research, The University of New South
Wales; 2010
MissingFormLabel
- 17
Mehta S H, Genberg B L, Astemborski J et al..
Limited uptake of hepatitis C treatment among injection drug users.
J Community Health.
2008;
33
(3)
126-133
MissingFormLabel
- 18
Grebely J, Genoway K, Khara M et al..
Treatment uptake and outcomes among current and former injection drug users receiving
directly observed therapy within a multidisciplinary group model for the treatment
of hepatitis C virus infection.
Int J Drug Policy.
2007;
18
(5)
437-443
MissingFormLabel
- 19
Grebely J, Bryant J, Hull P et al..
Factors associated with specialist assessment and treatment for hepatitis C virus
infection in New South Wales, Australia.
J Viral Hepat.
2011;
18
(4)
e104-e116
MissingFormLabel
- 20
Strathdee S A, Latka M, Campbell J Study to Reduce Intravenous Exposures Project et al.
Factors associated with interest in initiating treatment for hepatitis C Virus (HCV)
infection among young HCV-infected injection drug users.
Clin Infect Dis.
2005;
40
(Suppl 5)
S304-S312
MissingFormLabel
- 21
Grebely J, Dore G J.
An expanding role for primary care providers in the treatment of hepatitis C virus
infection in the community.
Hepatology.
2011. In press
MissingFormLabel
- 22
Micallef J M, Kaldor J M, Dore G J.
Spontaneous viral clearance following acute hepatitis C infection: a systematic review
of longitudinal studies.
J Viral Hepat.
2006;
13
(1)
34-41
MissingFormLabel
- 23
Seeff L B.
Natural history of chronic hepatitis C.
Hepatology.
2002;
36
(5, Suppl 1)
S35-S46
MissingFormLabel
- 24
Aitken C K, Lewis J, Tracy S L et al..
High incidence of hepatitis C virus reinfection in a cohort of injecting drug users.
Hepatology.
2008;
48
(6)
1746-1752
MissingFormLabel
- 25
Mehta S H, Cox A, Hoover D R et al..
Protection against persistence of hepatitis C.
Lancet.
2002;
359
(9316)
1478-1483
MissingFormLabel
- 26
Micallef J M, Macdonald V, Jauncey M et al..
High incidence of hepatitis C virus reinfection within a cohort of injecting drug
users.
J Viral Hepat.
2007;
14
(6)
413-418
MissingFormLabel
- 27
Osburn W O, Fisher B E, Dowd K A et al..
Spontaneous control of primary hepatitis C virus infection and immunity against persistent
reinfection.
Gastroenterology.
2010;
138
(1)
315-324
MissingFormLabel
- 28
Page K, Hahn J A, Evans J et al..
Acute hepatitis C virus infection in young adult injection drug users: a prospective
study of incident infection, resolution, and reinfection.
J Infect Dis.
2009;
200
(8)
1216-1226
MissingFormLabel
- 29
Grebely J, Conway B, Raffa J D, Lai C, Krajden M, Tyndall M W.
Hepatitis C virus reinfection in injection drug users.
Hepatology.
2006;
44
(5)
1139-1145
MissingFormLabel
- 30
van de Laar T J, Molenkamp R, van den Berg C et al..
Frequent HCV reinfection and superinfection in a cohort of injecting drug users in
Amsterdam.
J Hepatol.
2009;
51
(4)
667-674
MissingFormLabel
- 31
Seeff L B.
The history of the “natural history” of hepatitis C (1968–2009).
Liver Int.
2009;
29
(Suppl 1)
89-99
MissingFormLabel
- 32
Freeman A J, Dore G J, Law M G et al..
Estimating progression to cirrhosis in chronic hepatitis C virus infection.
Hepatology.
2001;
34
(4 Pt 1)
809-816
MissingFormLabel
- 33
Thein H H, Yi Q, Dore G J, Krahn M D.
Natural history of hepatitis C virus infection in HIV-infected individuals and the
impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis.
AIDS.
2008;
22
(15)
1979-1991
MissingFormLabel
- 34
Thein H H, Yi Q, Dore G J, Krahn M D.
Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus
infection: a meta-analysis and meta-regression.
Hepatology.
2008;
48
(2)
418-431
MissingFormLabel
- 35
Kenny-Walsh E. Irish Hepatology Research Group .
Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin.
N Engl J Med.
1999;
340
(16)
1228-1233
MissingFormLabel
- 36
Wiese M, Berr F, Lafrenz M, Porst H, Oesen U.
Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in
Germany: a 20-year multicenter study.
Hepatology.
2000;
32
(1)
91-96
MissingFormLabel
- 37
Poynard T, Bedossa P, Opolon P.
Natural history of liver fibrosis progression in patients with chronic hepatitis C.
The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.
Lancet.
1997;
349
(9055)
825-832
MissingFormLabel
- 38
Wiley T E, Brown J, Chan J.
Hepatitis C infection in African Americans: its natural history and histological progression.
Am J Gastroenterol.
2002;
97
(3)
700-706
MissingFormLabel
- 39
Sterling R K, Stravitz R T, Luketic V A et al..
A comparison of the spectrum of chronic hepatitis C virus between Caucasians and African
Americans.
Clin Gastroenterol Hepatol.
2004;
2
(6)
469-473
MissingFormLabel
- 40
Vogt M, Lang T, Frösner G et al..
Prevalence and clinical outcome of hepatitis C infection in children who underwent
cardiac surgery before the implementation of blood-donor screening.
N Engl J Med.
1999;
341
(12)
866-870
MissingFormLabel
- 41
Casiraghi M A, De Paschale M, Romanò L et al..
Long-term outcome (35 years) of hepatitis C after acquisition of infection through
mini transfusions of blood given at birth.
Hepatology.
2004;
39
(1)
90-96
MissingFormLabel
- 42
Minola E, Prati D, Suter F et al..
Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis
C.
Blood.
2002;
99
(12)
4588-4591
MissingFormLabel
- 43
Ostapowicz G, Watson K J, Locarnini S A, Desmond P V.
Role of alcohol in the progression of liver disease caused by hepatitis C virus infection.
Hepatology.
1998;
27
(6)
1730-1735
MissingFormLabel
- 44
Harris D R, Gonin R, Alter H J National Heart, Lung, and Blood Institute Study Group et al.
The relationship of acute transfusion-associated hepatitis to the development of cirrhosis
in the presence of alcohol abuse.
Ann Intern Med.
2001;
134
(2)
120-124
MissingFormLabel
- 45
Hutchinson S J, Bird S M, Goldberg D J.
Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis.
Clin Gastroenterol Hepatol.
2005;
3
(11)
1150-1159
MissingFormLabel
- 46
Graham C S, Baden L R, Yu E et al..
Influence of human immunodeficiency virus infection on the course of hepatitis C virus
infection: a meta-analysis.
Clin Infect Dis.
2001;
33
(4)
562-569
MissingFormLabel
- 47
Ragni M V, Belle S H.
Impact of human immunodeficiency virus infection on progression to end-stage liver
disease in individuals with hemophilia and hepatitis C virus infection.
J Infect Dis.
2001;
183
(7)
1112-1115
MissingFormLabel
- 48
Thomas D L, Shih J W, Alter H J et al..
Effect of human immunodeficiency virus on hepatitis C virus infection among injecting
drug users.
J Infect Dis.
1996;
174
(4)
690-695
MissingFormLabel
- 49
Grebely J, Raffa J D, Lai C 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.
J Viral Hepat.
2011;
18
(1)
32-41
MissingFormLabel
- 50
Pontisso P, Gerotto M, Benvegnù L, Chemello L, Alberti A.
Coinfection by hepatitis B virus and hepatitis C virus.
Antivir Ther.
1998;
3
(Suppl 3)
137-142
MissingFormLabel
- 51
Gaeta G B, Stornaiuolo G, Precone D F et al..
Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus
infection. A multicenter Italian study.
J Hepatol.
2003;
39
(6)
1036-1041
MissingFormLabel
- 52
Monto A, Alonzo J, Watson J J, Grunfeld C, Wright T L.
Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus,
and alcohol.
Hepatology.
2002;
36
(3)
729-736
MissingFormLabel
- 53
Ratziu V, Munteanu M, Charlotte F, Bonyhay L, Poynard T. LIDO Study Group .
Fibrogenic impact of high serum glucose in chronic hepatitis C.
J Hepatol.
2003;
39
(6)
1049-1055
MissingFormLabel
- 54
Hourigan L F, Macdonald G A, Purdie D et al..
Fibrosis in chronic hepatitis C correlates significantly with body mass index and
steatosis.
Hepatology.
1999;
29
(4)
1215-1219
MissingFormLabel
- 55
Ortiz V, Berenguer M, Rayón J M, Carrasco D, Berenguer J.
Contribution of obesity to hepatitis C-related fibrosis progression.
Am J Gastroenterol.
2002;
97
(9)
2408-2414
MissingFormLabel
- 56
Leandro G, Mangia A, Hui J HCV Meta-Analysis (on) Individual Patients' Data Study Group et al.
Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C:
a meta-analysis of individual patient data.
Gastroenterology.
2006;
130
(6)
1636-1642
MissingFormLabel
- 57
Adinolfi L E, Gambardella M, Andreana A, Tripodi M F, Utili R, Ruggiero G.
Steatosis accelerates the progression of liver damage of chronic hepatitis C patients
and correlates with specific HCV genotype and visceral obesity.
Hepatology.
2001;
33
(6)
1358-1364
MissingFormLabel
- 58
Singal A G, Volk M L, Jensen D, Di Bisceglie A M, Schoenfeld P S.
A sustained viral response is associated with reduced liver-related morbidity and
mortality in patients with hepatitis C virus.
Clin Gastroenterol Hepatol.
2010;
8
(3)
280-288, 288, e1
MissingFormLabel
- 59
Hézode C, Roudot-Thoraval F, Nguyen S et al..
Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis
C.
Hepatology.
2005;
42
(1)
63-71
MissingFormLabel
- 60
Hsu P C, Federico C A, Krajden M et al..
Health utilities and psychometric quality of life in patients with early- and late-stage
hepatitis C virus infection.
J Gastroenterol Hepatol.
2011;
Epub ahead of print
MissingFormLabel
- 61
Nelson P K, Mathers B M, Cowie B et al..
Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results
of systematic reviews.
Lancet.
2011;
378
(9791)
571-583
MissingFormLabel
- 62
Degenhardt L, Hall W, Warner-Smith M.
Using cohort studies to estimate mortality among injecting drug users that is not
attributable to AIDS.
Sex Transm Infect.
2006;
82
(Suppl 3)
iii56-iii63
MissingFormLabel
- 63
Degenhardt L, Bucello C, Mathers B et al..
Mortality among regular or dependent users of heroin and other opioids: a systematic
review and meta-analysis of cohort studies.
Addiction.
2011;
106
(1)
32-51
MissingFormLabel
- 64
Gibson A, Degenhardt L, Mattick R P, Ali R, White J, O'Brien S.
Exposure to opioid maintenance treatment reduces long-term mortality.
Addiction.
2008;
103
(3)
462-468
MissingFormLabel
- 65
Degenhardt L, Randall D, Hall W, Law M, Butler T, Burns L.
Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years:
risk factors and lives saved.
Drug Alcohol Depend.
2009;
105
(1-2)
9-15
MissingFormLabel
- 66
Gibson A, Randall D, Degenhardt L.
The increasing mortality burden of liver disease among opioid-dependent people: cohort
study.
Addiction.
2011;
106
(12)
2186-2192
MissingFormLabel
- 67
Darke S, Kaye S, Duflou J.
Comparative cardiac pathology among deaths due to cocaine toxicity, opioid toxicity
and non-drug-related causes.
Addiction.
2006;
101
(12)
1771-1777
MissingFormLabel
- 68
Harris H E, Ramsay M E, Andrews N J. HCV National Register Steering Group .
Survival of a national cohort of hepatitis C virus infected patients, 16 years after
exposure.
Epidemiol Infect.
2006;
134
(3)
472-477
MissingFormLabel
- 69
Iloeje U H, Yang H I, Jen C L Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis
B Virus Study Group et al.
Risk and predictors of mortality associated with chronic hepatitis B infection.
Clin Gastroenterol Hepatol.
2007;
5
(8)
921-931
MissingFormLabel
- 70 Yang H I, Chen C J, Jen C L et al.. Causes of death associated with hepatitis B or hepatitis C virus infections in a long-term
population-based cohort study. Paper presented at: Digestive Disease Week 2007; May 19–24, 2007; Washington, DC
MissingFormLabel
- 71
Thomas D L, Leoutsakas D, Zabransky T, Kumar M S.
Hepatitis C in HIV-infected individuals: cure and control, right now.
J Int AIDS Soc.
2011;
14
22
MissingFormLabel
- 72
Thomas D L, Astemborski J, Rai R M et al..
The natural history of hepatitis C virus infection: host, viral, and environmental
factors.
JAMA.
2000;
284
(4)
450-456
MissingFormLabel
- 73
Thomas D L, Astemborski J, Vlahov D et al..
Determinants of the quantity of hepatitis C virus RNA.
J Infect Dis.
2000;
181
(3)
844-851
MissingFormLabel
- 74
Goedert J J, Eyster M E, Lederman M M et al..
End-stage liver disease in persons with hemophilia and transfusion-associated infections.
Blood.
2002;
100
(5)
1584-1589
MissingFormLabel
- 75
Torriani F J, Rodriguez-Torres M, Rockstroh J K APRICOT Study Group et al.
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected
patients.
N Engl J Med.
2004;
351
(5)
438-450
MissingFormLabel
- 76
Hadziyannis S J, Sette Jr H, Morgan T R PEGASYS International Study Group et al.
Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a
randomized study of treatment duration and ribavirin dose.
Ann Intern Med.
2004;
140
(5)
346-355
MissingFormLabel
- 77
Volberding P A, Deeks S G.
Antiretroviral therapy and management of HIV infection.
Lancet.
2010;
376
(9734)
49-62
MissingFormLabel
- 78
Weber R, Sabin C A, Friis-Møller N et al..
Liver-related deaths in persons infected with the human immunodeficiency virus: the
D:A:D study.
Arch Intern Med.
2006;
166
(15)
1632-1641
MissingFormLabel
- 79
Bica I, McGovern B, Dhar R et al..
Increasing mortality due to end-stage liver disease in patients with human immunodeficiency
virus infection.
Clin Infect Dis.
2001;
32
(3)
492-497
MissingFormLabel
- 80
Lohse N, Hansen A B, Pedersen G et al..
Survival of persons with and without HIV infection in Denmark, 1995-2005.
Ann Intern Med.
2007;
146
(2)
87-95
MissingFormLabel
- 81
Gane E J, Roberts S K, Stedman C A et al..
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir
for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind,
placebo-controlled, dose-escalation trial.
Lancet.
2010;
376
(9751)
1467-1475
MissingFormLabel
- 82
Chak E, Talal A H, Sherman K E, Schiff E R, Saab S.
Hepatitis C virus infection in USA: an estimate of true prevalence.
Liver Int.
2011;
Epub ahead of print
MissingFormLabel
- 83 Australian Government Department of Health and Ageing .Hepatitis C Subcommittee of the Ministerial Advisory Committee on AIDS SHH, the Blood
Borne Virus and Sexually Transmissible Infections Subcommittee of the Australian Population
Health Development Committee. National hepatitis C testing policy. Canberra: Australian Government Department of Health and Ageing; 2007
MissingFormLabel
- 84
Treloar C, Newland J, Harris M, Deacon R, Maher L.
A diagnosis of hepatitis C - insights from a study on patients' experiences.
Aust Fam Physician.
2010;
39
(8)
589-592
MissingFormLabel
- 85
Vergniol J, Foucher J, Terrebonne E et al..
Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients
with chronic hepatitis C.
Gastroenterology.
2011;
140
(7)
1970-1979, 1979, e1–e3
MissingFormLabel
- 86
Grebely J, Bryant J, Hull P et al..
Factors associated with specialist assessment and treatment for hepatitis C virus
infection in New South Wales, Australia.
J Viral Hepat.
2011;
18
(4)
e104-e116
MissingFormLabel
- 87
Arora S, Thornton K, Murata G et al..
Outcomes of treatment for hepatitis C virus infection by primary care providers.
N Engl J Med.
2011;
364
(23)
2199-2207
MissingFormLabel
- 88
Shepard C W, Finelli L, Alter M J.
Global epidemiology of hepatitis C virus infection.
Lancet Infect Dis.
2005;
5
(9)
558-567
MissingFormLabel
- 89
Hellard M, Sacks-Davis R, Gold J.
Hepatitis C treatment for injection drug users: a review of the available evidence.
Clin Infect Dis.
2009;
49
(4)
561-573
MissingFormLabel
Professor Gregory J. Dore
The Kirby Institute for Infection and Immunity in Society, University of New South
Wales
CFI Building, Corner of Boundary and West Streets, Sydney NSW 2010, Australia
eMail: gdore@kirby.unsw.edu.au