Transcript What is Hepatitis?

Co-infections: Hepatitis C
1
What is Hepatitis?
‘hepat’ = liver
‘itis’ = inflammation
Viral hepatitis….
A
B
C
D
E
Faeco-oral, never chronic
Blood, sexually transmitted, can be chronic
Blood, sexually transmitted, often chronic
Only with B, usually chronic
Faeco-oral, rarely chronic
VACCINE PREVENTABLE
What is hepatitis C (HCV) ?
• Known as ‘non A non-B’ hepatitis before 1989
• ‘Non-A non-B’ transfusion-related hepatitis
• RNA virus that infects liver cells causing inflammation
and, if untreated, liver scarring fibrosis
• Since 1991 all UK blood transfusions have been
screened
Hepatitis A & B
• Hepatitis A: is caught from infected water or food and
although it can be serious, it only lasts for a short time.
• It is advisable to get vaccinated before travelling to
areas such as Asia, the Middle-East, Africa or Eastern
Europe (check with GP/travel clinic)
• Hepatitis B: is not caught from infected water or food
but from infected blood or other body fluids. It often
becomes an ongoing disease that could lead to liver
cancer.
How is HCV transmitted?
• Most infectious fluid is blood
 Predominantly through injecting drug use
 Blood products, unclean surgical/injecting equipment
 Non-injecting drug equipment such as straws, diluents
 Piercing, tattooing (cleans needles AND ink!)
• Or through sex
 Blood > sexual fluids; LOW levels in semen – MSM with
rough sex practices particular risk
 Risk for heterosexual partners of HCV+, 0.07% a year1
• Mother to child but NOT via saliva or breast milk
[1 Terrault NA et al. Hepatology 2013. [2] Bradshaw et al. Current Opinion 2013. [3] Wandeler G et al. CID 2012.
Who is at higher risk of acquiring HCV?
• People undergoing medical procedures in settings
where infection control is poor
• People who inject drugs (PWID) > people who ‘snort’
drugs
• People with tattoos & piercings
• Sexual partners of people living with HCV
• HIV positive people (particularly men who have sex
with men)
• Infants of HCV+ mothers
How widespread is HCV globally? (2014)
Globally: How do HCV & HIV overlap?
HIV
40
million
HCV
10
million
175
million
What is the impact of HIV on HCV?
• More rapid liver fibrosis (scarring of the liver
leading to Cirrhosis)
• Worse at lower CD4
• Effective HIV treatment may negate this
• HCV more infectious (PLWHA typically have higher
HCV viral load in blood and semen)
• Lower response rates to interferon-based
treatment
Liver-related death is a frequent cause of
non-AIDS death in HIV positive people
Deaths (%)
D:A:D Study: Causes of death in n=49,734 HIV-infected patients followed 1999–2011
AIDS
Liver-related
disease
Weber R, et al. AIDS 2012. Washington USA. Oral presentation THAB0304.
Cardio
-vascular or
other heart
disease
Non-AIDS
malignancies
Other
HCV Treatment- Old and New
• Interferon/ Ribavirin was standard treatment for years
• Lots of new drugs available now (DAA = direct acting
antivirals)
• But VERY EXPENSIVE so access is currently limited
• Approaching 100% success rates for many groups,
including those who are more difficult to treat e.g
HIV+
Fatty liver/cirrhosis
Older age
Diabetes
HCV/HIV SVR24 with Pegylated Interferon and
Ribavirin- Poor Response Rates
100
Genotype 1
SVR 14–38%
Genotype 3
SVR 44–73%
SVR (%)
75
Monoinfection
APRICOT
ACTG
RIBAVIC
Laguno et al.
PRESCO
50
25
0
G1
Genotype
G2/3
Adapted from: Fried et al, NEJM 2002;347:975-982, Torriani et al, NEJM 2004;351:438-50, Chung R, et al, NEJM 2004;351:451-9
Carrat F, et al, JAMA 2004;292:2839-42, Laguno et al, AIDS 2004;18:F27-F36, Nunez et al, JAIDS 2007;45:439-44
5’UTR
Core
E1
E2
p7
How do I know which kind of DAA?
NS2
NS3
....previr (PI)
....asvir
NS4B
(NS5A)
NS5A
Protease
Ribavirin
NS3
Protease Inhibitors
Telaprevir
Boceprevir
Simeprevir
Asunaprevir
Paritaprevir
Grazoprevir
3’UTR
NS5B
Polymerase
NS5A
Replication Complex
Inhibitors
Daclatasvir
Ledipasvir
Ombitasvir
Elbasvir
GS-5816
*Representative list modified from CCO. *unlicensed
NS5B
NUC Inhibitors
Sofosbuvir
VX-135
IDX21437
ACH-3422
NS5B
Non-NUC
Inhibitors
Dasabuvir
Beclabuvir
....buvir (Pol)
Drug-Drug Interactions between HCV drugs & ART
Charts revised April 2015.
NNRTI = non-nucleoside reverse transcriptase
inhibitor;
NRTI = nucleoside reverse transcriptase inhibitor.
www.hep-druginteractions.org (Accessed August 2015).
Who needs treatment and treatment
prioritization
• IDEALLY recommended for all persons with
chronic HCV infection (WHO, IAS-USA, EASL
guidelines)
• BUT increasingly treatments are prescribed (due
to high cost and country guidelines) by
prioritization
How do EASL Guidelines Prioritise Need?
Treatment ‘should be prioritized’
Treatment ‘justified’
•F3/F4
•F2
•Decomp. Cirrhosis
•HIV or HBV coinfection
•Liver transplant
•Clinically significant extra-hepatic
manifestation
•Debilitating fatigue
•(As of 2015) Individuals at risk of
transmission (Grade B1)
•‘Informed deferral can
be considered’
F0/F1
EASL Guidelines, Journal of Hepatology,
2015
Acute HCV among HIV+ MSM
Canada24: ~30 cases
Prevalence chronic
19%: 11.200
HCV/HIV25
USA1,2: 55 cases
Prevalence chronic HCV/HIV12–14
15 – 30%: 180.000 – 360.000
Europe: 1068 cases
Prevalence chronic
HCV/HIV14,15
25%: 185.500
- UK3,4 552
- Germany5,18, 28
157
- France6,7 126
Netherlands8,17 97
- Belgium20 69
- Swiss9 23
10
- Italy 21
- Denmark21 13
27
- Spain
~8
Lebanon22: 1 case
Prevalence chronic HCV/HIV26
49%: 1.500
Australia11: 47 cases
Prevalence chronic HCV/HIV16,19
< 1%: 1.000
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 2010; 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. Taylor Gastroenterology 2009; 24. Hull personal conversation 2011; 25. Remis 1st Canadian HCV Conference 2001; 26. UNGASS Country progress Report 2010;
27. Soriano personal conversation 2011; 28. Boesecke 18thCROI Boston 2011 abstract #113; 29. Sun Liver International 2011; 30. Lee J F, Med Assoc 2008.
How/Why is HCV transmission continuing
among MSM?
• ‘Bare-backing’
• Rough sex causing bleeding
• Other traumatic practices like piercing during sex, or saline
scrotal inflation
• Accidental or intended needle sharing
• Sharing sex toys
• Lack of testing for HCV
• Sex with those with acute HCV/ seroconverters (ie with high
viral loads)
HCV: Where we are today with
Unmet Treatment Need?
• High burden of disease (80-130M with detectable virus)
• Substantial uncertainty; need better surveillance
• Increasing cause of death (700k deaths/year)
• Highly effective Direct Acting Antiviral HCV therapy, but
expensive and treatment rates extremely low
• Need for informed prioritization strategies –
mathematical modeling can help
• 95% of HCV+ people were not receiving treatment in 2012
were not receiving HCV therapy
Grebely & Dore, Journal of Antivir Ther , 2014
Conclusions
• Liver disease is an important cause of morbidity and
mortality in HIV positive people
• Key issues = ART, HCV and lifestyle
• HCV
–
–
–
–
The era of DAA based therapy has arrived
IFN-sparing and IFN-free therapy a reality
Responses in HIV+ similar to HIVBeware DDIs
• People with HIV are still a ‘Special Population’ despite
similar response – as HCV aggressive, multi-system
disease, urgent need of therapies
• Need for improved cascade of care and access to therapies