Acute hepatitis C The European Experience

Transcription

1 Acute hepatitis C The European Experience Dr Emma Page MBBS MRCP MD(Res) Chelsea and Westminster Hospital, London

2 AHC the European Experience 1. Epidemic 2. CNS sequelae 3. Incidence 4. Re-infection

3 Reports of AHC outbreaks 1,2 5 3, Browne RE, et al. 2nd IAS 2003; Abstract Giraudon I et al. STI 2007;84: , 3. Ghosn et al. STI 2006; 82: ; 4. Gambotti et al. Euro Surveill 2005; 10: ; 5. Gotz et al. AIDS 2005; 19: Vogel M et al. J Viral Hepat 2005; 12: ; 7. Rauch A et al. Clin Infect Dis 2005;41:

4 Reports of AHC outbreaks USA 1,2 : 55 cases Prevalence chronic HCV/HIV %: Canada 23 : ~30 cases Prevalence of chronic HCV/HIV 24 19%: Lebanon 22 : 1 case Prevalence of chronic HCV/HIV 25 49%: Europe: 1068 cases Prevalence chronic HCV/HIV 14,15 25%: UK 3, Germany 5,18, France 6, Netherlands 8, Belgium Swiss Italy Denmark Spain 26 ~8 Taiwan 28 : 28 cases Prevalence of chronic HCV/HIV 29 55%: Australia 11 : 47 cases Prevalence chronic HCV/HIV 16,19 < 1%: :Luetkemeyer JAIDS 2006; 2:Cox Gastroenterology 2008; 3:Giraudon Sex Transm Infect 2008; 4:Ruf Eurosurveill 2008; 5:Vogel CID 2009; 6:Gambotti Euro Surveill 2005; 7:Morin Eur J Gastro Hepat 2011; 8:Urbanus AIDS 2009; 9:Rauch CID 2005; 10:Gallotta 4th Works. HIV & Hep. Coinf. 2008; 11:Matthews CID 2009; 12:Sherman CID 2002; 13:Backus JAIDS 2005; 14:UNAIDS Report 2008; 15:Soriano JID 2008; 16:Matthews CID 2011; 17:Arends Neth J Med 2011; 18:Neukam HIV Med 2011; 19:Pfafferott PLoS One 2011; 20:Bottieau Euro Surveill 2010; 21:Barfod Scand JID 2011; 22:Dionne-Odom Lancet Infect Dis 2009; 23:Hull personal conversation 2011; 24:Remis Public Health Agency of Canada 2002; 25:UNGASS Country progress Report 2010; 26:Soriano personal conversation 2011; 27:Boesecke 18 th CROI Boston 2011 abstract #113; 28:Sun Liver International 2011; 29:Lee J F Med Assoc 2008

5 Phylogenetics UK: initial data 7 genetically distinct clusters (largest n = 43) G1a: 5 clusters G1b: 1 cluster G3a: 1 cluster 1. Multiple clusters: multiple genetically distinct viral variants environment or lifestyle 2. Clusters: common source 3. Sequences from different clinics in same cluster: social networks

6 Phylogenetics France & Netherlands 1. Multiple clusters: G1a & G4d

7 Europe n= 200 Ref sequences = 850 England (107) / Netherlands (58) / Germany (25) / France (12) monophyletic clusters: 1 37: UK, NL 2 34: UK, NL, GE, FR 3 19: UK, NL, GE 4 17: UK, GE 7 6: NL, GE 8 6: UK, FR ¾ HCV strains from Europe circulating in > 1 European country

8 Europe, Australia & USA European cluster 1 (n=38) Australian cluster 1 (n=6) European cluster 3 (n=18) Clusters 94 U.S. cluster 1 (n=10) European 95 U.S. cluster 2 (n=6) Australian 94 European cluster 2 (n=19) U.S. 94 European cluster 5 (n=6) 94 U.S. cluster 5 (n=5) Independent evolution of epidemics in America, Europe & Australia Australian cluster 2 (n=4) U.S. cluster 9 (n=3) U.S. cluster 6 (n=5) U.S. cluster 7 (n=4) 99 U.S. cluster 4 (n=6) 91 European cluster 4 (n=12) 1a U.S. cluster 9 (n=4) U.S. cluster 3 (n=6) Fierer DS et al. CROI 2011 Session 34-Oral Abstracts 1b European cluster 6 (n=4)

9 Origin of the epidemic Lessons from G4d in Amsterdam 2 clusters: Dutch IDU 1960 lenient drug legislation 1990 harm reduction strategy HIV+ MSM 1985 initial transmission event 3 sub-clusters 1992, 1994, % lineage splits after 1996 Similar events are likely to have occurred in Australia & USA

10 Ongoing transmission:? sexual Molecular clock data: expansion mid 1990s HAART, perceived threat HIV & unsafe sex 1,2 Concomitant STIs, denial of IVDU Are high risk sexual practices driving the epidemic? Multivariate analysis: Drug use: non significant Group sex: R/I UPAI & fisting Participation in 2: OR 9 Participation in 3: OR Elford L et al. AIDS 2002;16: Parsons JT et al. AIDS Educ Prev 2006;18:

11 Consequences of AHC? Cerebral disturbance Both HIV and CHC are known to result in cerebral disturbance: HIV associated encephalopathy & CHC associated cognitive decline Chronic HCV: HCV RNA in CSF & brain tissue Microglial cell activation & neuroinflammation? Cerebral disturbance in the acute phase Case control study : HIV+ with AHC vs HIV+ without AHC n=24 n=57

12 Consequences of AHC? Cerebral disturbance

13 Consequences of AHC? Cerebral disturbance

14 Consequences of AHC? Cerebral disturbance

15 Is the epidemic ongoing? CASCADE 1 11 cohorts: 8 Europe countries, 1 Canada Analyses: MSM infected with HIV sexually n = 3014, 92 (3%) acquired AHC HCV incidence estimated using 3 methods 1990: 0.04/100 py 1995: 0.55/100 py 2000: 0.80/100 py 2005: 1.68/100 py 2007: 2.34/100 py 1. Van der Helm JJ et al. AIDS 2011;25:

16 Is the epidemic ongoing? EuroSIDA 1 n = 4296 HIV+ Irrespective route acquisition From Jan 2002 Baseline HCV Ab - 2 HCV Ab results AHC = 150 in 19,178 py Incidence: 0.79/100 py 1. Rockstroh JK et al. 11 th International Congress on Drug Therapy in HIV Infection.

17 Is the epidemic ongoing? EuroSIDA 1 2/3rds MSM BUT IDU highest incidence: 4.2/100 py vs 0.09/100 py MSM incidence highest 2010 at > 2/100 py 1. Rockstroh JK et al. 11 th International Congress on Drug Therapy in HIV Infection.

18 High re-infection rates Lambers et al AIDS :? Incidence rate of HCV re-infection n = 56 with ETR n = 5 relapsed Genotype or clade switch 11/51 re-infected Incidence re-infection: 15.2/100 py cumulative incidence of re- infection was 33% (95% CI 16-50) in 2 years 1. Lambers FA et al. AIDS 2011;25;F21-F27

19 High re-infection rates: Chelsea and Westminster Hospital Acknowledgements: Tom Martin, Mark Nelson, R Everett, Brian Gazzard CWH K Martin, M Hickmann University of Bristol P Vickermann London School of Hygiene and Tropical Medicine Aims: Calculate re-infection rates of sexually acquired AHC Compare re-infection rates of spontaneous vs therapeutic clearers Evaluate spontaneous clearance and treatment success rates in re-infection Re-infection : a change in genotype resurgent HCV RNA after: SVR or SC (at least 24 weeks)

20 Resurgent virus = reinfection: Chelsea and Westminster Hospital Re-infections without change in genotype: 83% (10/12) divergent 17% (2/12) possible re-infection BUT 2.5 & 5 yrs post SVR

21 High re-infection rates: Chelsea and Westminster Hospital Jan 2004 to April HIV+ve MSM with sexually acquired HCV that had SC or TC 145 prior documented negative HCV Ab (394 py fu) Results (n = 145) Median age 41yrs HAART 129 (89%) Genotype G1/4: 97 (79%) G2/3: 7 (5%) Re-infections n=32 rate = 8.1/100py Genotypes G1/4: 24 (75%) G2/3: 1 (3%) SC (n = 32) 4 (13%) SVR (n = 17 awaited n = 11) 13 (76%)

22 Results High re-infection rates: Chelsea and Westminster Hospital (n = 145) Spontaneous Clearance Therapeutic Clearance (n = 31 / 21%) (n = 114) Age 41yrs 38yrs HAART 30 (97%) 104 (91%) Re-infections n = 5 n = /100py 9.6/100py P = 0.15 SC 2 (40%) [n = 5] 2 (7%) [n = 27] P = 0.10 SVR 2 (100%) [n = 2] 11 (73%) [n = 15]

23 Time free from infection: Chelsea and Westminster Hospital Re-infections: SC: n = 5 4.3/100py TC: n = /100py P = ) immune response to HCV in SC 2) Treatment not a deterrent more pronounced with DAA 3) re-infected occurs within 4 yrs

24 Thank you