La storia clinica del paziente con infezione cronica da HCV: focus epidemiologico. Monica Schiavini

Transcription

1

2 La storia clinica del paziente con infezione cronica da HCV: focus epidemiologico Monica Schiavini

3 105/185 million people anti-hcv positive worldwide Global anti HCV prevalence in adults: 2% 3/4 million new cases of HCV infection emerge every years Chronic HCV infection causes almost half million deaths annualy Chronic HCV infection is the 25th leading cause of death worldwide

4 Epidemiology of HCV in Europe <0,5 % 0,5 1% 1,1 1,5% 1,6 2,5% 0,2% 0,2% 0,1% 1,3% 2,7% 2,6 3,5% > 3,6% 1% 2,5% 1% 0,2% 1% 0,2% 2% 1% 0,6% 1% 4% 1,3% 1% 1% 0,5% 0,8% 3% 2% 6% 3,5% 2% 2% 1,5% 2,5% 3% 1,5% 3% 2% Esteban J Hepatol 2008; 48: 148

5 Category Iatrogenic Intravenous drug use Sexual Specific modes of transmission Blood transfusion of unscreened products Transfusion of clotting factors or other blood products Organ transplantation Reuse of medical instruments used in invasive settings (eg, needles, infusion sets, syringes, catheters) Hemodialysis Endoscopy Reuse of syringes and needles Use of cookers (drug-solution containers, such as a spoon), filters (cotton), water used to mix the drug, and alcohol swabs (rarely) Controversial Risk may increase when favoring conditions exist, such as sexually transmitted infections, frequency and type of sexual activity Mother to child Occupational Typically occurs at delivery, but in utero transmission is not infrequent Risk factors include higher maternal HCV RNA level, HIV coinfection Factors not shown to increase transmission risk: vaginal vs Cesarean section delivery, amniocentesis (limited data), and breast-feeding Via skin injury Typically occur in operating rooms and emergency departments May occur during routine procedures such as blood draws in medical wards

6 Cases of acute hepatitis C by symptom onset date grouped by quarter and risk factor. Barcelona city,

7 Trend in number of acute hepatitis C cases per 100,000 inhabitants and incidence rate ratio of hepatitis C by sex and age, Barcelona city residents,

8 Genotype distribution

9 Genotype 1 is by far the most frequent genotype in chronically infected patients worldwide Hajarizadeh et al., Nat Rev 2013

10 Genotype distribution varies by the route of transmission GENOTYPE 1 GENOTYPE 2 GENOTYPE 3 GENOTYPE 4 TRANSFUSION, SURGERY AND DENTAL PROCEDURE NOSOCOMIAL TRANSMISSION AND PRIOR DENTAL TREATMENT INTRAVENOUS DRUG USER, HISTORY OF TATTOOING AND PIERCING HIGH RISK SEXUAL PRACTICE AND INTRAVENOUS DRUG USE

11 Casisisica I Divisione Malattie Infettive ASST- FBF- Sacco, Milano Distribuzione genotipi Popolazione generale % 4 altro 1a Coinfezione HIV-HCV 3 % 4 2 1b 1a 3 2 1b

12 30 yearsafter infection Female sex, young age Decompensation (~20%) Normal liver Acute infection Chronic infection (80%) Chronic hepatitis Cirrhosis (20%) HCC (1 4% per year) Infection resolves spontaneously (20%) Stable hepatitis (80%) Slowly progressive (~75%) < 20 years after infection Alcohol use, co-infection with HIV or hepatitis B virus

13 Evolution of HCV Markers After Acute Infection ALT Infection Acute hepatitis HCV RNA il sommerso ovvero la Anti-HCV popolazione con infezione non nota è stata e rimane una delle tematiche più importanti HCV RNA Anti-HCV ALT Infection Acute Chronic hepatitis

14 Spontaneous HCV Clearance From Serum of Patients with Symptomatic Acute Hepatitis C Gerlach JT et al Gastroenterology 2003;125:80-88

15 Viral clearance % Factors that Contribute to Spontaneous Viral Clearance in Acute Hepatitis C n. patients <20 yr >20 yr Males Females Blacks Whites Present Absent Neg Pos Age Gender Race Jaundice HIV Alter et al, NEJM1999. Bakr et al, Gut Gerlach et al, Gastroenterology Thomas et al, JAMA 2000

16 Main issues about HCV and DAAs in Italy Large population of patients with chronic HCV infection, > 70% > 60 years HCV-related deaths 10,000/year 60-80,000 known patients with F4 fibrosis 2-3,000 currently decompensated 500 OLT/yr ,000 estimated patients with F0-F3

17 Disease Burden Deaths associated with different diseases in Italy Comparison of the number of deaths associated with selected diseases compared to liver diseases based on death certificates (age-standardized) in Italy (population 59,6 millions) Disease n. deaths/yr Colon and rectum cancers 20,269 Breast cancers 13,222 Chronic obstructive pulmonary disease 21,527 Nephritis and nephrosis 8744 Liver cancer 9753 Cirrhosis of the liver % related to HCV Blachier M, J Hepatol 2013;58(3):593

18 Number of deaths due to cirrhosis (ICD IX 571) or viral hepatitis (ICD IX 070), Sicily Death rates for cirrhosis and hepatitis, Sicily

19 ETA ANNO > 25 Totale , 0 16,0 4, 0 5, ,0 10,0 4,0 4, ,5 8,0 3,0 3, ,0 9,0 2,0 3, ,0 8,0 2,0 3, ,0 6,0 2,0 2, ,0 5,0 2,0 2, ,0 4,0 2,0 2, ,0 3,0 1,0 2, ,0 3,0 2,0 2, ,0 2,0 2,0 2, ,0 2,0 1,0 1, ,0 1,0 1,0 1, ,0 1,0 1,0 1, ,2 1,0 1,0 1, ,1 0,7 0,7 0, ,4 1,0 1,0 0, ,1 1,0 1,0 0, ,1 0,6 0,9 0, ,1 0,4 0,7 0, ,0 0,6 0,6 0, ,1 0,5 0,6 0, ,0 0,4 0,6 0, ,0 0,4 0,5 0, ,0 0,2 0,2 0, ,0 0,4 0,2 0, ,0 0,3 0,3 0, ,1 0,3 0,3 0, ,0 0,3 0,3 0, ,0 0,2 0,3 0,2 Tassi di incidenza (x ) dell'epatite C* per età ed anno di notifica. SEIEVA

20

21 Anti-HCV % Geographical and Age-Related Distribution of Anti-HCV Carriers in Italy ( ) ~ 1 million carriers Age (years) > 60 SEIEVA 2002

22 Age and Gender Distribution of HCV in Italy HCV prevalence by age & gender (2001) HCV infected population (2015) Ansaldi F, et al. J Med Virol 2015; 76:

23 Casistisica I Divisione Malattie Infettive ASST-FBF- Sacco, Milano PZ TOT PZ MONOINFETTI PZ COINFETTI HIV+ N. PZ ETA MEDIA (SD) 58.4 (12.7) 60.6 (13.7) 53 (6.5) SESSO M (%) 710 (55.4) 447 (47.7) 263 (76)

24 Estimating the incidence, prevalence and clinical burden of hepatitis C over time in Italy Wave 1: the elders There is a marked age-specific prevalence distribution and evidence that > 60% of HCV positive subjects are currently older than 65 years Birth cohort before 1950 Gt 1b predominant and 2a/c present Gt 3 and Gt 4 uncommon Strong South-North gradient Iatrogenic due to glass syringes Iatrogenic due to transfusion Mariano A, et al. Scand J Infect Dis. 2009;41:689-99

25 Wave 2 is most apparent in urban areas of northern and central Italy and is related to a worse disease course, likely due to HIV coinfection and alcohol abuse Estimating the incidence, prevalence and clinical burden of hepatitis C over time in Italy Wave 2: the IVDUs Birth cohort Gt 1b still predominant Gt 3 and Gt 4 increasing Reduced South-North gradient HIV confection Associated to alcohol abuse Mainly IDU Transfusion prior 1992 Healthcare associated Mariano A, et al. Scand J Infect Dis. 2009;41:689-99

26 Estimating the incidence, prevalence and clinical burden of hepatitis C over time in Italy Wave 3: new cases Wave 3 is a non-wave, but a constant background. New incident cases occur as consequence of sexual exposure, IVDU, inappropriate healthcare and cosmetic interventions. Birth cohort after 1970 Gt 1b still predominant Gt 2a/c decreasing Gt 3 and Gt 4 increasing Mariano A, et al. Scand J Infect Dis. 2009;41: Spada E, et al. J Med Virol. 2013;85:433-40

27 Casistica I Divisione Malattie Infettive ASST- FBF- Sacco, Milano Distribuzione genotipi Popolazione generale % 4 altro 1a Coinfezione HIV-HCV 3 % 4 2 1b 1a 3 2 1b

28 Trend cumulativo dei trattamenti avviati

29 Trattamenti avviati per criterio Criterio N. Trattamenti

30 Coinfezione HIV-HCV una popolazione speciale?

31 Prevalence of hepatitis C virus (HCV) seropositivity and active HCV infection in the cross-sectional studies carried out by Grupo de Estudio del SIDA in 2002, 2009, 2015, and HCV Ab+, presence of antibodies against HCV; HCV-RNA+, detectable HCV-RNA;

32 Principal human immunodeficiency virus transmission categories in the cross-sectional studies carried out by Grupo de Estudio del SIDA in 2002, 2009, 2015, and IDU, injection drug use; MSM, men who have sex with men.

33 Persons at Elevated Risk of HCV Transmission: MSM With High-Risk Sexual Practices HCV Incidence per 1000 Person-Years Estimation of the incidence of HCV in HIVinfected MSM from 1990 to 2007 in the CASCADE Collaboration Estimation Methods Incidence method Alternative incidence method Interval-censored data Dramatic increase in incident HCV infections among HIV-infected MSM (non-idus) Recognition and treatment of HCV may be an important step in preventing subsequent infections van der Helm JJ, et al. AIDS. 2011;25:

34 Estimates of HCV co-infection in PLHIV in Italy from cohorts data Cohort Icona 1 (%) Master 2 % (N) Estimated data in PLHIV linked to care 3 PLHIV tested for HCV 75% (11.203) PLHIV with anti HCV reactivity 29% (11241) 34% (8439) De Luca a et al CROI Motta et al AIDS Res Ther Notiziario ISS 2013

35 Estimates of HCV co-infection in PLHIV in Italy from cohorts data Cohort Icona 1 (%) Master 2 % (N) Estimated data in PLHIV linked to care 3 PLHIV tested for HCV 75% (11.203) PLHIV with anti HCV reactivity PLHIV with HCVRNA reactivity 29% (11241) 34% (8439) % De Luca a et al CROI Motta et al AIDS Res Ther Notiziario ISS 2013

36 Prevalence of HCV-RNA pos in 1515 HCVAb pos patients tested for HCV-RNA in ICONA 1301; 86% 214; 14% Neg Pos Jun 2015 Report

37 Fig 3 Proportion of HCVAb positive ICONA patients according to calendar year of enrolment 60% 50% 55,3% 51,2% 42,3% 40% 35,1% 30% 25,6% 22,9% 22,9% 20% 10% 14,2% 12,4% 8,9% 9,8% 9,8% 7,1% 0% n=1325 n= n= n= n= n= n= n= n= n= n= n= n= n= n= n= n= n= n=27 for 2015, first 6 months Jun 2015 Report

38 Proportion of HCV genotypes in 1586 ICONA+ HepaICONA patients 46 3% % % % 19 1% % % % 3% 12 1% 1a 1b 1 1a/1b 1c Others Jun 2015 Report

39 HCV genotypes according to mode of HIV transmission in ICONA and HepaICONA patients 70% 65,5% 60% 50% 50,2% 52,7% 56,8% 40% 30% 20% 10% 0% 29,9% 5,6% 13,0% Heterosexual contacts 13,4% 10,1% 8,4% 1,3% 2,5% Homo/Bisexual contacts 31,2% 13,9% 1,5% 0,8% IDU 25,8% 11,1% 3,7% 2,6% Other/Unknown Others N=231 N=119 N=104 6 N=190 Jun 2015 Report

40 Coinfezione HIV-HCV una popolazione speciale? HIV+ popolazione a rischio unica per livello elevato di screening per HCV Diversa distribuzione genotipi HCV infettanti Possibile valutazione numero pazienti potenzialmente trattabili :

41 Casistica I Divisione Malattie Infettive ASST-FBF- Sacco, Milano PZ TOT PZ MONOINFETTI PZ COINFETTI HIV+ P SOSPENSIONE PER EA PZ (%) 11 (0.8) 6 (0.6) 5 (1.4) p= 0.1 SVR % ITT p= SVR % PER PROTOCOL p= 0.009

42