1. Update on Hepatitis C SSHA Conference 2015
Daniel Bradshaw
Locum Consultant GUM/HIV
Brighton and Sussex University Hospitals NHS Trust

2. Overview Epidemiology Natural history of HCV
Acute HCV in HIV-positive MSM
Diagnostic tests for HCV
Treatments – old and new
Treatment as prevention

3. Global anti-HCV prevalence
230K PLW HCV in UK; around 8K HCV/HIV coinfected

4. Easterbrook et al IAS 2015

5. Natural history of HCV 20 % spontaneous clearance HCV acquisition
80 % chronic infection
20% develop cirrhosis after 20 yr
Add refs – see my intro to MD; indication for liver transplant in UK
1-4% per year risk of hepatocellular cancer
Freeman et al Hepatol. 2001

6. Public Health England website 2015; vertical 2-8%. Increased in HIV
Public Health England website 2015; vertical 2-8% ? Increased in HIV. Mention prevalence in PWID in UK, Scotland, Europe.
Universal screening of blood donors in 1991 – risk is 1 in 2 million

7. Transmission of HCV infection
Route of Exposure
HCV
HIV
HCV transmission compared to HIV
Parenteral
(needlestick)
1.5-3%
0.3%
> x10
Permucosal
(sexual) %
1-5%
< x10
Vertical
2-5%
20-30%
< x6-10
So lest move on to look at those at risk for acute HCV . Certainly the predminant route of transmission for HCV is via parenteral exposure i.e. blood to blood contact traditioanlly through bllod transfusions, injecting drug use , unsafe mediacl injections.
Epithelial target cell not right target unlike hiv

8. HCV transmission: HIV-negative, HCV-discordant heterosexual couples
Study
Type of study
Study population N
Duration
follow-up
Incidence /1000 person years (cases)
Kao 2000
Prospective
Taiwanese
112
46 m
0.23 (1)
Vandelli 2004
Italian
776
120 m
0.37 (3)
Tahan 2005
Turkish
216
36 m
None
Terrault 2013
Cross-sectional
American
500
180 m
0.72 (3)
Despite this sexual transmission has generally been traditionally associated with very low risk – such that guidelines do not recommend condoms in hetersexual relationships . Overall risk is <1% per year
Here a number of cohort studies following discordant couples with very low rates of new infections – a yearly transmission risk of < 1%
Nb 180m is the median time (15 years) of the reported monogamous relationship
Terrault – low transmission risk 1 per 190,000 sex contacts; excluding HIV infected couples and where percutaneous risk identified in both partners. 500 couples
No condom guideline
 1 transmission per 190,000 episodes of sex

9. HCV seroprevalence in high–risk STI groups suggests sexual risk is present
Risk group
Anti-HCV
Associated factors
FSWs 6%
Number of partners, other STIs, sex with trauma, non-use of condoms
STI clinic 4%
Risk for IDU > sexual factors.
In non IDU : number of partners, high-risk sexual contacts, HIV+
MSM
In non IDU : HIV+, number of partners, sexual practices
In fact HCV seroprevalence data in highrisk sexual groups would suggest there is an incraesed risk
This is a USA study – all available seroprevalence figures combined
Retrospective data. Seroprevalence Oz 1-2%
Terrault Hepatology 2002

10. Characteristics of the study population, by hepatitis C virus (HCV) serostatus in EUROSIDA cohort
Characteristics of the study population, by hepatitis C virus (HCV) serostatus at recruitment into the EuroSIDA cohort.
6000 patients
All HIV-positive
33% overall were HCV+
7% acquiring HIV via MSM contact were HCV+ (Ab or RNA)
78% acquiring HIV via IDU were HCV+
Rockstroh et al 2005

11. Acute HCV in HIV-positive MSM

12. Acute HCV in the Swiss HIV Cohort Study
Wandeler et al CID 2012

13. Countries reporting acute HCV in HIV+ MSM
Apers 2015
Browne 2004
Gotz 2005
Vogel 2005
Gambotti 2005
EHSSS 2009
Wandeler 2012
Nishijima 2013
Sanchez 2013
Orsetti 2013
Luetkemeyer 2006
Sun 2012
Chan 2015
Evolving since London
Public Health Agency of Canada, Hep C & STI, surveillance and epi section. Epidemiology of acute hepatitis C infection in Canada: results from the enhanced hepatitis strain surveillance system (EHSSS) 2009.
Characteristics – 30s/40s, MSM, HIV+, well controlled, mostly deny IDU
New – Taiwan, Japan
Matthews 2007

14. Potential factors for increasing permucosal transmission in HIV+ MSM
Behavioural
1. Serosorting1
2. Mucosal trauma2,3,4
3. Mucosally-administered recreational drugs2,3,4
Biological
1. HIV5,6
2. STIs2,3,4,7
Chronic hCV – increased HCV shedding in semen if HIV+
Lattimore et al 2011
Danta et al 2007
Schmidt et al 2011
MMWR Morb Mortal Wkly 2011
Briat et al 2005
Sherman et al 2005
Van de Laar et al 2007

15. Detection of HCV in semen
Check alignments of words etc and colours
Bradshaw et al JID 2015

16. Serosorting behaviour amongst MSM
Prevalence, correlates and trends in seroadaptive behaviours among men who have sex with men from serial cross-sectional surveillance in San Francisco, 2004–2011
Jonathan M Snowden1,
Lattimore 2011, london
Lattimore et al STD 2011

17. Changing patterns of drug use in MSM
2005
2012
Crystal meth 0%
40%
GBL/GHB
3.2%
27%
Mephedrone
18%
Ref via GUM/A&E/statutory drugs services 8%
63%
Mention ASTRA study
Daskalopoulou M et al.Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV-diagnosed men who have sex with men in the United Kingdom: results from the ASTRA study. J Int AIDS Soc17(Suppl 3):19630, 2014.
David Stuart 2013

18. Mechanism of sexual transmission of HCV in HIV-infected MSM
High-risk practices
Shared implements
Sexual practices
Drug practices
Group Sex
Sexual transmission
of HCV
Internet
‘Club drugs’
STI
Permucosal NOT parenteral transmission

19. HCV reinfection in HIV-infected MSM
200 individuals of survival free from reinfection for patients previous treated for their HCV infection, shown in light gray, and individuals who spontaneously cleared their first HCV infection. As you can see, there is a trend to a higher reinfection rate among individuals treated but this did not reach significance. One startling point to take from this graph is that, as you can see, approximately 25% of individuals treated for HCV infection were reinfected within 2 years.
144 patients
Martin AIDS 2013
Martin et al AIDS 2013

20. Incidence of HCV in HIV-positive MSM in Amsterdam
HCV IR among 761 HIV+MSM (observed and fitted)
HCV IR by age in 2008
Vanhommerig et al, JAIDS, 2014 2

21. Acute HCV in HIV-negative MSM
44 patients identified
35 of 44 patients had subsequent HIV testing within the department and remain negative
Median time since last HIV test until now=
5.6 months (range months)
9 patients had no further HIV tests
20% were on PREP ***************
McFaul et al J Viral Hep 2015

22. Diagnostic tests for HCV infection
Anti-HCV antibody
HCV antigen
HCV RNA
Antigen days before Ab;
Fibroscan assessment of liver fibrosis

23. When to test for HCV in HIV-positive MSM?
1) After very high risk (high risk sex with HCV+ partner)
OR if liver enzymes abnormal
HCV Ab and PCR
Repeat PCR at 4 weeks.
2) After high risk (but normal liver enzymes)
HCV Ab
Repeat Ab at 12 weeks.
3) Repeat testing (Ab and PCR) at 3-6 monthly intervals if ongoing high risk
4) Annual HCV Ab testing if not high risk
Ref the DS HCV testing survey – see boesecke rockstroh for REF
BHIVA Guidelines on Viral Hepatitis 2013

24. HCV treatments

25. Reasons for treatment of HCV in HIV-infected individuals
Transmission
Stigma
More rapid progression of liver disease
Increase in HIV related comorbidities
Increase in HAART toxicity

26. Multiple organ dysfunction in HCV/HIV coinfection

27. Cult Health Sex. 2008 Aug;10(6):601-10. doi: 10.1080/13691050802061673.
An 'elephant in the room'? Stigma and hepatitis C transmission among HIV-positive 'serosorting' gay men.
Owen G.
Sex Health Jul;10(3): doi: /SH12179.
Perceptions and deflections: associations between attitudes towards people with hepatitis C and testing for hepatitis C among Australian gay and bisexual men.
Brener L1, Ellard J, Murphy D, Callander D.
“An 'elephant in the room'?” Stigma and hepatitis C transmission among HIV-positive 'serosorting' gay men
Owen G Cult Health Sex 2008

28. New anti-HCV therapies

29. HCV SVR rates between 1990 - 2014 Webster et al Lancet 2015 Figure 1
Changes in standard of care for HCV, and improvements in numbers of sustained virological responses
Data from references 9–12. PI=protease inhibitor.
Webster et al Lancet 2015
The Lancet  , DOI: ( /S (14) )

30. Cost in India, Egypt - chart

31. MODELLING PROJECTIONS: EDINBURGH
Martin NK, et al. Hepatology 2013

32. Salazar-Vizcaya et al CROI 2015
CROI 2015 poster 675 rauch Behavioural and Treatment Interventions to Reduce HCV Transmissions in HIV+ MSM
Author(s): 
Luisa Salazar-Vizcaya1, Roger Kouyos2, Cindy Zahnd1, Manuel Battegay3, Katharine Darling4, Alexandra Calmy5, Pietro L. Vernazza6, Olivia Keiser1, Andri Rauch
Salazar-Vizcaya et al CROI 2015

33. Two-mode social network diagrams of
HIV+ MSM with acute HCV and venues used for sourcing sexual partners
Melbourne
Sydney
Bradshaw et al AASLD 2013

35. Summary
Epidemic of acute HCV in HIV+ MSM with mostly sexual acquisition
High levels of reinfection in this cohort
New HCV therapies equally effective in both HIV+ and HIV- individuals
In the UK, new HCV therapies are currently only available to cirrhotic patients
Reducing the epidemic will require increases in levels of testing, treatment and effective behavioural interventions

36. Acknowledgements
Professor Mark Nelson

37. THANK YOU