istovremena zaraza hiv-om i virusima...
TRANSCRIPT
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VIRUSNI HEPATITISI
Dr.Adriana Vince Referentni centar za dijagnostiku i liječenje virusnih hepatitisa RH
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VIRUSNI HEPATITISI
Prof.dr.sc. Adriana Vince
Referentni Centar za dijagnostiku i liječenje virusnih hepatitisa Klinika za infektivne bolesti “Dr. Fran Mihaljević”, Zagreb
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PRIMARNO HEPATOTROPNI VIRUSI
A, B,C, D,E
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Global health problem
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KLINIČKA SLIKA VIRUSNOG HEPATITISA
• AKUTNI • KRONIČNI
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AKUTNI HEPATITIS
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KLINIČKA SLIKA KRONIČNOG HEPATITISA
• 20 GODINA BEZ SIMPTOMA • PRVI SIMPTOMI VEZANI UZ RAZVOJ CIROZE • PROGRESIJA DO CIROZE U 20-30% KRONIČNIH
INFEKCIJA
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KRONIČNI HEPATITIS B I C
• 5 GODIŠNJA KUMULATIVNA INCIDENCIJA RAZVOJA CIROZE 8-10% • DEKOMPENZIRANA CIROZA 5 GODIŠNJE PREŽIVLJENJE 14-35% • GODIŠNJA INCIDENCIJA HCC 2-5% KADA POSTOJI CIROZA
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Faktori koji ubrzavaju razvoj ciroze
• POVEĆANI UNOS ALKOHOLA
• >40 GODINA
• HIV KOINFEKCIJA
• HBV/HCV KOINFEKCIJA
• STEATOZA JETRE
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Ann Intern Med 2012;156:271-8
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U.S.A. 3-4 M
AMERICAS 12-15 M
AFRICA 30-40 M
EAST EUROPE
10 M
SOUTH EAST
ASIA 30-35 M
AUSTRALIA 0.2 M
WEST EUROPE
5 M
FAR EAST ASIA 60 M
170-200 Million Car r iers Wor ldwide
Hepatitis C: A Global Health Problem
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Kronični hepatitis B •350 MIL people chronically infected •1 Million deaths from complications •5-10% liver transplantations
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premalo pacijenata se otkriva i liječi
Asrani SK, et al. Curr Gastroenterol Rep. 2014;16:381.
2.7-3.9 million infected
50% HCV detected
32% to 38% referred for care
7% to 11% treated
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World Health Organization: Global Health Sector Strategy on viral hepatitis
• SVJETSKA ZDRAVSTVENA ORGANIZACIJA PRIPREMA STRATEGIJU O VIRUSNIM HEPATITISIMA KOJA ĆE BITI PRIHVAĆENA 2016. GODINE
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HRVATSKA
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Opća populacija – HAV, HBV, HCV
• N=2052, rutinski i preoperativni pregledi, osobe bez simptoma hepatitisa
• Anti-HAV prevalencija: 40,5% (raste s dobi)
• HBs-Ag prevalencija: 0,7% (raste s dobi)
• Anti-HCV prevalencija: 0,9% (najviša u dobi 30-39 g)
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Prevalencija anti-HCV kod osoba rizičnog spolnog ponašanja (n=821)
• Promiskuitetni (N=378) = 6,3% (CI 3,9 - 8,8%) • MSM (N=205) = 2,9% (CI 0,6 - 5,2%) • PSU i korisnici (N=272) = 4,0% (CI 1,7-6,4%) • Osobe sa SPB (N=199) = 8,5% (CI 4,7-12,4%)
• Ukupno (N=821) = 4,6% (CI 3,2-6,1%)
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Podaci o ovisnicima o opojnim drogama Izvor: Katalinić D, Huskić A, Hemen M. Izvješće o osobama liječenim
zbog zlouporabe psihoaktivnih droga u Hrvatskoj u 2013. godini. HZJZ, 2014.
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• Prevalencija anti-HCV u općoj populaciji slična prevalenciji HBsAg nosilaštva.
• Viša seroprevalencija kod osoba u rizičnim skupinama (osobe sa spolno-prenosivim bolestima i pormiskuitetne) nego u općoj populaciji
• Značajno viša prevalencija anti-HCV i anti-HBc u populaciji i.v. ovisnika
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1
10
100
1000
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013.
Hospitalizacije zbog akutnog hepatitisa B u Hrvatskoj 2000-2013. Dobne skupine 0-29 i 30+ godina
30+
0-29
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Novootkr iveni “C” U Hrvatskoj
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Umrli od HCC u Hrvatskoj Izvor: Registar umrlih HZJZ
0
50
100
150
200
250
300
350
400
450
500
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008.
Umrli od raka jetre (C22.0 i C22)u Hrvatskoj od 1998 do 2008
C22.0 (hepatocelularni) C22 (rak jetre)
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Histologic Progression of HCV Monitored by Liver Biopsy Inflammation Grade Measure of severity and ongoing disease activity
0-4 (METAVIR)
Inflammation leads to scarring/fibrosis
Fibrosis Stage Amount of fibrous scar tissue
0-4 (METAVIR)
Stage 4 = cirrhosis
Indicates long-term disease progression
No fibrosis
Cirrhosis Brunt EM. Hepatology. 2000;31:241-246.
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Hepatitis A Virus
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HEPATITIS A
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Concentration of Hepatitis A Virus in Various Body Fluids
Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890
Feces
Serum
Saliva
Urine
100 102 104 106 108 1010
Bod
y Fl
uids
Infectious Doses per mL
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Hepatitis A
• Feko-oralni put prijenosa, neopranim rukama
• Najčešće kontakt s malim djetetom koje nema nikakve simptome bolesti
• Zaražene osobe izlučuju virus nekoliko tkedana u stolici
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Hepatitis A – Clinical Features
• Incubation period:
• Jaundice by age group: < 6 yrs 6 – 14 yrs > 14 yrs
• Rare Complications:
• Chronic sequelae:
Average 30 days Range 15-50 days <10%
40%-50% 70%-80%
Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis
None
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Hepatitis A cjepivo
Group Age No.
Doses EL.U.* (ml) Schedule (months)
Children and adolescents 2-18 years 3 360 (0.5) 0, 1, 6-12
Adults >18 years 2 1,440 (1.0) 0, 6-12
Doses
HAVRIX�
*ELISA units
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Osobama s povećanim rizikom infekcije:
travelers MSM injecting drug users People with chronic liver disease
Cjepljenje se preporuča
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Hepatitis E Virus
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Kamar et al. Lancet 2012; 379: 2477-88.
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Kamar et al. Lancet 2012; 379: 2477-88. Kamar et al. Lancet 2012; 379: 2477-88
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Emerg Infect Dis 2011; 17: 2309-2312
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Incubation period: Average 40 days Range 15-60 days Case-fatality rate: Overall, 1%-3%
Pregnant women, 15%-25%
Illness severity: Increased with age
Chronic sequelae: liver tranplant patients
Hepatitis E – Clinical Features
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Hoofnagle JH et al. N Engl J Med 2012;367:1237-44.
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Hepatitis B Virus
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Hepatitis B virus 350 millions people with chronic infection
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Hepatitis B – “serology markers”
HBsAg
anti-HBs
anti-HBc total antibodies
anti-HBc IgM
HBeAg
anti-HBe
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Concentration in body fluids
High Moderate Low/Not
Detectable
blood semen urine serum vaginal fluid feces
wound exudates saliva sweat tears
breastmilk
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• Spolni
• Krvlju
• Perinatalno
Putevi prijenosa
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• Incubation period: Average 60-90 days Range 45-180 days
• Clinical illness <5 yrs, <10% (jaundice): >5 yrs, 30%-50%
• Acute case-fatality rate: 0.5%-1%
• Chronic infection: <5 yrs, 30%-90% >5 yrs, 2%-10%
• Premature mortality from chronic liver disease: 15%-25%
Hepatitis B – Clinical Features
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IgM anti-HBc
Total anti-HBc HBsAg
Acute (6 months)
HBeAg
Chronic (Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52
Weeks after Exposure
Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course
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Prevencija HBV infekcije
• rekombinantno cjepivo (HBsAg) • 3 doze u razmaku 0,1,6 mjeseci • Provjera titra anti-HBs protutijela 6 tjedana po
zadnjoj dozi za zdravstvene radnike
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Od 1986. godine rekombinantno cjepivo proizvedeno na kvasnicama
Hepatitis B preventabilna bolest
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Dose Infants** Teens and Adults***
1 16%-40% 20%-30%
2 80%-95% 75%-80%
3 98%-100% 90%-95%
Protection* by Age Group and Dose
* Anti-HBs antibody titer of 10 mIU/mL or higher
*** Factors that may lower vaccine response rates are age >40 years, male gender, smoking, obesity, and immune
deficiency
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• Administered to over 12 million infants and children in the United
States – side effects rare
• Anaphylaxis estimated to occur in
1/600,000 doses given
• No scientific data to link hepatitis B vaccine with multiple sclerosis
(MS), other autoimmune diseases, autism
Hepatitis B Vaccine Safety
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Iloeje UH et al. Gastroenterology 2006; 130: 678-86.
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CILEVI LIJEČENJA:
• Spriječiti virusnu replikaciju • Spriječiti profresiju u cirozu i
hepatocelularni karcinom • Eliminacija HBsAg dogodi se u svega 1-3%
liječenih
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• interferon alfa-2b (1992) • lamivudine (1998) • adefovir dipivoxil (2002) • entecavir (2005) • pegylated interferon alfa-2a (2005) • telbivudine (2006) • tenofovir (2008)
FDA approval
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Hepatitis C
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Hepatitis C virus
•Otkriven (kloniran 1989. godine) •Prvi serološki testovi početkom 90-ih •Testiranje u Hrvatskoj na anti-HCV u travnju 1993
• Uzrok 2/3 transplantacija jetara u svijetu •Nema cjepiva
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Putevi prijenosa HCV
o Zarazna je krv oboljele osobe
o Krv mora prodrijeti kroz kožu ili sluznicu zdrave osobe
o Vjerojatnost infekcije ovisi o količini krvi i količini virusnih čestica u zaraženoj krvi
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• Illegal injection drug use • Transfusion or transplant from infected donor • Healthcare associated infections • Birth to HCV-infected mother • Sexual/household exposure to anti-HCV positive
contact • Multiple sex partners
Faktori rizika za HCV infekciju
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Putevi prijenosa hepatitisa C danas
• Intravenska ovisnost (70%) • Spolni prijenos (10-15%) • Nozokomijalne infekcije 5% (nepridržavanje
standardnih mjera prevencije) • 5-10% nepoznatog puta prijenosa
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Injecting Drug Use and HCV Transmission
• Highly efficient – Contamination of drug paraphernalia, not just needles and syringes
• Rapidly acquired after initiation
– 30% prevalence after 3 years – >50% after 5 years
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Intravenska ovisnost i prijenos HCV
• Vrlo efikasno se prenosi kod iv ovisnika
• Zajedničkom i ponovnom upotrebom kompletnog nesterilnog pribora za pripremu droge: igala, šprica, vode, žlica, vate
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HCV pozitivne osobe
• HCV se ne širi ljubljenjem, kihanjem, kašljanjem, grljenjem, hranom, vodom,ili tzv. socijalnim kontaktom
• HCV pozitivne osobe ne smiju biti isključene iz škole, posla, igre, vrtića itd
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Inkubacija: 6 – 7 tjedana
• Ikterična akutna bolest (≤10%)
Smrtnost Niska
Kronična infekcija 60%-85%
Kronični hepatitis 70%
Ciroza 5%-20%
Hepatitis C – Klinička slika
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Histologic Progression of HCV Monitored by Liver Biopsy Inflammation Grade Measure of severity and ongoing disease activity
0-4 (METAVIR)
Inflammation leads to scarring/fibrosis
Fibrosis Stage Amount of fibrous scar tissue
0-4 (METAVIR)
Stage 4 = cirrhosis
Indicates long-term disease progression
No fibrosis
Cirrhosis Brunt EM. Hepatology. 2000;31:241-246.
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Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, Apr il 27-28, 2011, Silver Spr ing, MD, Clinical Care Options
IFN 6 mos
PegIFN/ RBV
12 mos
IFN 12 mos
IFN/RBV 12 mos
PegIFN 12 mos
2001
1998
2011
Standard IFN
RBV
PegIFN
1991
1st generation DAA telaprevir boceprevir
PegIFN/ RBV/
1st DAA
IFN/RBV 6 mos
6
16
34 42 39
55
70+
0
20
40
60
80
100
2nd DAA + RBV
± PegIFN
>90%
2014
LIJEČENJE HEPATITISA C
2nd generation DAAs
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DVOJNA TERAPIJA: ISTOVREMENA PRIMJENA DVA LIJEKA
+
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Treatment of Chronic HCV Peginterferon and Ribavirin
0
20
40
60
80
100
1 2-3 Genotype
Sust
aine
d Vi
rolo
gic
R
espo
nse
(%)
PegIFN-2a/RBV PegIFN-2b/RBV
Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.
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NOVI LIJEKOVI (KOMBINACIJE +/-INTERFERON)
+
+ +
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NOVE TERAPIJE BEZ INTERFERONA SV
R12,
% P
atie
nts
All Patients
96.2% 95.3% 98.0%
GT1a GT1b
HEPATITISC=IZLIJEČIVA BOLEST
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Dostignuća suvremene medicine na području virusnih hepatitisa
• Hepatitis B-cjepivom preventabilna bolest • Kronična HBV infekcija može se dobro kontrolirati
lijekovima
• Hepatitis C ne može se prevenirati cjepivom • Kronična HCV infekcija izliječiva suvremenim lijekovima
u više od 90% zaraženih
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TIHA BOLEST! TIHI PACIJENTI! STIGMA!
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World Health Organization: Global Health Sector Strategy on viral hepatitis
• SVJETSKA ZDRAVSTVENA ORGANIZACIJA PRIPREMA STRATEGIJU O VIRUSNIM HEPATITISIMA KOJA ĆE BITI PRIHVAĆENA 2016. GODINE
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Aktualnost problema u RH
• Nedovoljna svjesnost o problemu u općoj i medicinskoj javnosti (nedovoljno prepoznavanje rizika)
• Pravovremeno otkrivanje zaraženih • Destigmatizacija zaraženih i omogućavanje
liječenja
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Ciljevi Nacionalne strategije i akcijskog plana
• Redukcija HBV i HCV transmisije (edukacija, redukcija“health-related” rizika)
• Case-finding/screening u rizičnim populacijama (edukacija na prepoznavanju rizika, dostupnost testiranja i savjetovanja u rizičnim populacijama)
• Registar pacijenata • Dostupnost liječenja • Poboljšanje kvalitete života, psihosocijalna
podrška oboljelima, reintegracija u radnu sredinu
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SUVREMENA SKRB ZA OBOLJELE S HEPATITISOM
• Dijagnostika • Liječenje • Psihosocijalna podrška • Suradnja s drugim specijalnostima • Suradnja s udrugama pacijenata
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HVALA NA PAŽNJI!