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La gestione del paziente con HCV
nella “nuova” pratica clinica
Congresso Nazionale Malattie Infettive e Tropicali
Catania 8-11 novembre 2015
Massimo Andreoni
Cattedra di Malattie Infettive
Disclosures
I have received funding for membership of Advisory Boards, for
the preparation of educational materials, for research and
educational grants, for membership of speaker panels and for
support for travel to conferences from the following companies:
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Gilead Sciences
Bristol-Myers Squibb
Janssen-Cilag
Viiv Healthcare
Merck Sharp and Dohme
AbbVie
Astra Zeneca
Boheringer Ingelheim
Pfizer
Worldwide deaths from HCV, HBV, HIV,
Tuberculosis and Malaria in 2013
Lancet 2015; 385: 117–171.
HCV and Liver Disease
Taiwan: 23.820 adults
aged 30–65 years old
enrolled during 1991–92
19.636 HBsAg-neg,
18.541 anti-HCV-neg
1.095 anti- HCV-pos
(69,4% had detectable
HCV-RNA).
The REVEAL HCV cohort study
Lee et Al. 2012; 206: 469-477
The REVEAL HCV cohort study
Lee et Al. 2012; 206: 469-477
HCV is a Systemic Disease Affecting Multiple
Body Systems Beyond the Liver
Nervous
system
Immune
system
Musculoskeletal
system
Circulatory
system
Digestive
system
Lymphatic
system
Integumentary
system
Endocrine
system
Respiratory
system
Urinary
system
Reproductive
system
Cacoub P, et al. Dig Liver Dis 2014; 46(Suppl 5):S165–S73;
Soriano V & Berenguer J. Curr Opin HIV AIDS 2015; 10:309–315.
Endocrine
Thyroid disease
Diabetes mellitus
Ocular
Corneal ulcers
Sjögren syndrome
Vascular
Systemic vasculitis
Hematologic
Mixed cryoglobulinemia
Lymphoproliferative disorders
Thrombocytopenia
Renal
Membranoproliferative
glomerulonephritis
Musculoskeletal
Arthralgia
Myalgia
Peripheral neuropathy
Inflammatory polyarthritis
Dermatologic
Lichen planus
Porphyria cutanea tarda
Extrahepatic manifestations of chronic
hepatitis C virus infection
P. Cacoub, 2014, 46:S165–S173
NHL, non-Hodgkin’s lymphoma; SS, Sjögren’s syndrome; PM/DM, polymyositis/dermatomyositis; PAN, polyarteritis nodosa.
The prevalences of coronary artery calcium, any plaque and calcified
plaque were significantly higher among men with an HCV RNA load of
≥2 × 106 IU/mL, compared to men without chronic HCV infection.
McKibben, August 31, 2015
Risk of coronary artery disease (CAD) in HCV–
infected and HCV-uninfected subjects
P <.0001
N° 89,582
N° 82,083
82,083 HCV-infected and 89,582 HCV-uninfected subjects in Veteran Affairs Cohort
Butt AA et sl., Clin Infect Dis. 2009 Jul 15;49(2):225-32
Cumulative mortality from circulatory diseases by serostatus of antibodies
against hepatitis C virus (anti-HCV) and serum HCV RNA level at study
Lee et Al. 2012; 206: 469-477
entry.
Participants with undetectable or low HCV-RNA had similar odds of
progressive CKD as HCV seronegative, while participants with HCV-RNA
800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90).
Mocroft A et al., PLoSOne 2012; 7(7):e40245
Cumulative mortality from nephritis, nephrotic syndrome, and nephrosis by
serostatus of antibodies against hepatitis C virus (anti-HCV) and serum
HCV RNA level at study entry.
Lee et Al. 2012; 206: 469-477
HCV Infection is Associated with Multiple
Neuropsychiatric Comorbidities
General population
HCV patients
Fatigue
Drug abuse
Alcohol abuse
Schizophrenia
Bipolar disorder
0
Anxiety disorder
50
Major depression
Prevalence (%)
100
Prevalence rates of psychiatric diseases in HCV infected patients were obtained
from several publications and mean and standard deviation for prevalence rates
were calculated for each disease.
Schaefer M, et al. J Hepatol 2012; 57:1379–1390.
Kaplan–Meier curves of cumulative event rate of
dementia in the groups with and without HCV
infection from matched 11-year HCV cohorts
Cumulative event rate (%)
Matched Cohort
HCV –
HCV+
Logrank P < 0.001.
58.570 pairs of HCVinfected and HCV noninfected, matched with
a 1:1 ratio by:
sex, age, income,
urbanization, diabetes,
Hypertension,
hypercholesterolemia,
chronic obstructive
pulmonary disease and
depressive disorder.
Chiu WC et al. European J Neurology 2014: 21:1068
Rome, ICAR 2014
Naive HCV patient with irritative feature such as epileptiform
characteristics in form of Intermittent Rhytmic Delta Activity
(IRDA)
Resolution of irritative feature after DAA therapy
Naive HCV
After
DAAs
treatment
Lee et Al. 2012; 206: 469-477
J Pircher, November 24, 2014 1-23
HCV directly promotes activation, adhesion and infiltration of
inflammatory cells into the vessel wall by activation of endothelial
viral receptors. Proinflammatory effects of viral RNA are
specifically mediated by TLR3 and significantly enhanced by
tumor necrosis factor alpha (TNFa).
HCV-related systemic vasculitis is a severe complication of
infection with HCV and causes significant morbidity and mortality.
HCV- associated vasculitis has been described to occur both in
the presence and in the absence of mixed cryoglobulinemia
(MC).
Human microvascular
endothelial cells (HMEC)
were stimulated with different
concentrations of HCV RNA
for 12 hours and mRNA
expression of selected
cytokines and chemokines
IL-6 (A), IL-8 (C), IP-10 (E)
and adhesion molecule
ICAM-1 (G) was analyzed by
RT-PCR.
J Pircher, November 24, 2014 1-23
September 2014 | Volume 5 | Article 428 | 1
Myeloid cells, including monocytes and macrophages, play an
important role in this balance, particularly through the activities
of the arginine-hydrolyzing enzymes nitric oxide synthase 2
(Nos2; iNOS) and arginase 1 (Arg1).
We discuss a variety of viral infections, including HIV, SARSCoV, HCV, RSV, Lymphocitic choriomeningitis virus (LCMV),
and others, where myeloid cells influence the control and
clearance of the virus from the host, as well as the severity and
resolution of tissue damage, via the activities of iNOS and/or
Arg1.
Pathogeneic mechanisms associated with the development of atherosclerosis
in chronic HCV infection
Van Der Meer et Al, JAMA 2012; 308: 2584-93
Cumulative rates of incidence of lymphoma (%)
HCV Elimination Reduces The
Incidence of Malignant Lymphoma
Persistent Infection (n=2161)
SVR (n=1048)
4
3
Log-rank test p=0.0159
1.49%
2
0.36%
1
0
2.56%
0
0%
0%
0%
5
10
15 Years
Follow-up duration
(years)
Kawamura Y, et al. Am J Med 2007;120:1034-1041
Although the primary target of HCV
infection is the liver, extrahepatic
manifestations related to HCV contribute
significantly to morbidity and mortality in
patients with chronic hepatitis C
Improved Awareness of the Extrahepatic
Manifestations of HCV Could Facilitate Early
Diagnosis and Treatment of HCV
Progression of HCV-related liver disease can take several decades
Acute
infection
Chronic
infection
(55–85%)
Mild
fibrosis
Moderate
to severe
fibrosis
Cirrhosis
(15–30%)
Decompensated
cirrhosis
Liver cancer
(2.4%/yr in cirrhosis)
HCV symptoms unrelated to the liver can appear early
Extrahepatic disease can be present in up to
74% of individuals with chronic HCV
Cacoub P, et al. Dig Liver Dis 2014; 46 Suppl 5:S165–S73.
Recommendations
Antiviral treatment is recommended for all patients
with chronic HCV infection, except those with limited
life expectancy due to nonhepatic causes. (I-A)
HEPATOLOGY, Vol. 62, No. 3, 2015
Cure of HCV infection may also reduce
symptoms and mortality from severe
extrahepatic manifestations.
HEPATOLOGY, Vol. 62, No. 3, 2015
Patients achieving an SVR have substantially
improved quality of life, including physical, emotional,
and social health.
HEPATOLOGY, Vol. 62, No. 3, 2015
Obiettivo: Certezza di Cura per Tutti
Certezza della Cura: MAX
Accesso: MIN
Certezza della Cura: MIN
Accesso: MAX
Grande Expertise
Continuità sul Territorio
Centri di Eccellenza
Centri ad elevata Capability
Elevata Specializzazione
Persona/paziente Consapevole
Terapie altamente Efficaci
Paziente Aderente
Il Modello AbbVie Care:
costruire insieme valore per le Persone
L’organizzazione nazionale AbbVie Care HCV:
personale qualificato, servizi e strumenti a supporto del Paziente e
del Medico
G1
G4
Formazione e Informazione per il Paziente
Comunicazione al Medico e al Paziente
Combo at home
La piattaforma nazionale AbbVie Care HCV:
Informazioni organizzate a portata di mano per il Medico e il Paziente
Un portale per il Medico dove
accedere alle informazioni dei
pazienti, anche quando sono a
casa
Portale per il Medico
Un portale per il Paziente
dove seguire il proprio
percorso di cura e
accedere alle
informazioni, materiali e
strumenti
Portale per il Paziente