Viral Hepatitis Prof. MUDr. Petr Husa, CSc. Klinika infekčních chorob, FN Brno C:\Users\33550\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.IE5\9H6TIIOV\Virus-Vaccinia[1].jpg Viral Hepatitis 1.Enterically transmitted – no chronic stage •VH A •VH E –rare (immunosuppressed pts.) 2.Parenterally transmitted – possible chronic stage •VH B •VH C •VH D Healthy liver Healthy Liver small Drawn Liver prezenční listina květen0011 Liver fibrosis Fibrosis small Drawn Fibrosis prezenční listina květen0009 prezenční listina květen0010 Liver cirrhosis Drawn Cirrhosis Cirrhosis prezenční listina květen0013 CIH-VHC-caput medusae varixy6 varixy5 prezenční listina květen0014 cirhotik1 cirhotik5 Hepatocellular carcinoma small Drawn Cancer Carcinoma 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 VH A 132 128 1648 1104 862 264 284 348 673 723 VH B 307 307 306 247 244 192 154 133 105 90 VH C 1022 980 974 836 709 812 794 873 867 945 VH E 35 43 65 99 72 163 258 218 299 409 j0178242 Viral Hepatitis in CR 2006-2015 hepatitis a virus Hepatitis A virus (HAV) family Picornaviridae, genus Hepatovirus – non-enveloped RNA, 27 nm Global_HepA_ITHRiskMap Hepatitis A Epidemiology •Fecal –oral route of transmission üContaminated hands or daily used instruments üContaminated drinking water üContaminated food • •Vaccination available, recommended especially fore travelers to countries with lower standard of hygiene dlane Concentration of Hepatitis A Virus graph hepatitis a virus infection graph Hepatisi B Virus Hepatitis B Virus (HBV) family Hepadnaviridae, enveloped DNA virus, 42 nm Global significance of HEP B •One of the biggest global health problems üMore than 2 billions of infections during the life ü350-400 million chronic carriers - China (125 million), Brazil (3,7 million), South Korea (2,6 million), Japan (1,7 million), USA (more than 1 million), Italy (900 thousand). ü25-40 % chronic carriers have LC or HCC, 0,5-1,0 million deaths due to decompensated LC or HCC ü50 thousand death annually due to fulminant hepatitis üGlobal vaccination in 177 countries (2008) • • j0186004 Hepatitis B slide08.jpg slide06.png Hepatitis B in Czech Republic •Still important infection but incidence and prevalence are gradually decreasing üPrevalence of chronic carriers was 0.56 % (2001) üPrevalence of historical antibodies anti-HBc total was 5,59% (2001) üDecrease of prevalence and incidence due to vaccination of high-risk persons (health care workers, newborns of HBsAg-positive mothers, before hemodialysis) üGlobal vaccination of all newborns and 12-years old children since 2001 • • Epidemiology of HBV •Transmission ü blood and blood products ü sexual intercourse ü organ and tissue transplant recipients ü vertically from mother to newborn •Who is in the highest risk in well-developed countries? ü intravenous drug abusers ü persons with multiple sexual partners • HM00316_ playmate_01 Clinical pictures of acute HEP B •IP: 30–180 days (mostly 2–3 months) •Prodromal stage - flu-like syndrome •Fulminant hepatitis: < 1 % •Chronic HBV infection mortality: 15 – 25 % j0136801 C:\Documents and Settings\admin\Desktop\slide_lib\png\Slide10.jpg Outcome of Hepatitis B Virus Infection by Age at Infection (graph) C:\Documents and Settings\admin\Desktop\slide_lib\png\Slide11.jpg C:\Documents and Settings\admin\Desktop\slide_lib\png\Slide12.jpg Hepatitis C virus (HCV) family Flaviviridae, genus Hepacivirus, enveloped RNA virus 60 nm http://upload.wikimedia.org/wikipedia/commons/3/3b/HCV_EM_picture_2.png • Hepatitis C World Health Organization. Wkly Epid Rec .1999;74:425-427. World Health Organization. Hepatitis C: Global Prevalence: Update. 2003. Farci P, et al. Semin Liver Dis. 2000;20:103-126. Wasley A, et al. Semin Liver Dis. 2000;20:1-16. Europe 8.9 million (1.03%) Americas 13.1 million (1.7%) Africa 31.9 million (5.3%) Western Pacific 62.2 million (3.9%) Eastern Mediterranean 21.3 million (4.6%) Southeast Asia 32.3 million (2.15%) HCV, hepatitis C virus. The World Health Organization has estimated that approximately 170 million persons are infected with HCV worldwide. The distribution of HCV infection is not uniform around the world. In most places, approximately 1% to 2% of the population is infected with HCV, but some regions, such as Egypt, are burdened with rates that range from 10% to 20%. HCV screening is the first step in identifying the 170 million HCV-infected persons worldwide. Distribution of HCV genotypes Hepatitis C •Significant global health problem üabout 3 % of the world population are chronically infected with HCV üIn well-developed countries about 20 % of all acute hepatitis, 70 % chronic hepatitis, 40 % cirrhosis, 60 % HCC and indication to 30 % liver transplantations •In Czech Republic üprevalence 0,2 % (2001) •No vaccine, no hyper-immune immunoglobulin j0286672 Epidemiology of HEP C •Transmission: ü blood and blood products ü sharing of used injection needles and syringes ü sexually (rare) ü vertically (rare) •Who is in the highest risk of HCV infection at present? ü intravenous drug abusers •Infection is frequently diagnosed in chronic stage • j0281051 Patients with higher risk of HCV infection PIntravenous drug abusers (sharing of injection needles and syringes) PRecipients of blood transfusions before the year 1992 (especially hemophiliacs) PPersons with tattoo or piercing Clinical course of HEP C •Acute hepatitis is mostly asymptomatic •Probability of chronicity is high (40-50% till 90-100%). •Higher probability of chronicity: aOlder persons aHigher initial infection dose (transfusion versus needles) aHBV, HIV co-infection aabusus of alcohol aimmunodeficiency Clinical course of HEP C •LC in about 20 % patients with chronic HCV infection •HCC annually in 1-4 % patients with LC •Progression to HCC depends on: üage (more rapid progression in older persons) üalcohol abuse üHIV co-infection üHBV co-infection j0084356 Anti-HCV are total antibodies against HCV – not division into IgM and IgG class ! Serologic Pattern of Acute HCV Infection w/ Recovery Diagnosis of HCV infection Hepatitis D (Delta) Virus (photo and diagram) Hepatitis D Virus (HDV) Satelite virus, family Deltaviridae, enveloped RNA, 40 nm Hepatitis D •Ability of replication only in presence of HBV infection üCo-infection (better prognosis) üSuper-infection (worse prognosis) •Endemic in South America, Mediterranean Region, Romania, Central Africa •Very low prevalence in CR Anti-HDV prevalence in HBsAg-positive (approximately 5%) Rizzetto M. EASL 2009 • Drug addicts Rizzetto M. EASL 2009 Diapositiva1 2010s : • immigrants 2009 Rizzetto M. EASL 2009 Hepatitis E Virus (photo) Family Hepeviridae, genus Hepevirus, non-enveloped RNA virus, 27-34 nm HEV0002 HEV genotypes Purcell RH, Emerson SU. J Hepatol 48 (2008) 494-503 Hepatitis E in Southern Moravia Hepatitis E •Travel-related disease (G-1+2 – faecely contaminated water) •Infection is currently more frequently acquired in CR (G-3 - pork, game meat) •Extremely serious clinical course in late pregnancy (mortality above 20 %) and in patients with alcoholic liver cirrhosis (mortality 60-70%) •Repeated infection may be possible •Rare cases of chronic hepatitis E in seriously immunosuppressed patients (organ recipients…) • • Covance 7 Figatellu – sausage with raw pork liver Kliknutím na obrázek zavřete okno HEV Serology (graph) Covance 7 Rapid progression of chronic hepatitis E Treatment of acute hepatitis (all types) •Symptomatic for all types ü physical and mental rest ü diet ü no alcohol, no hepatoxic drugs ü supportive treatment (silymarin, essential phosholipids) • j0318804 Current possibilities of treatment of HBV infection •pegylated interferon alfa-2a – 48 weeks •lamivudine - only in severe acute HEP B or protection of reactivation or recurence •entecavir – for naive patients •tenofovir – both for naive and lamivudine-resistant patients • HBV resistance during therapy Drugs for hepatitis C therapy üPEG-IFN alfa-2a, -2b üRibavirin üBoceprevir (BOC) – protease inhibitor of the 1st generation üTelaprevir (TVR) – protease inhibitor of the 1st generation ü üSofosbuvir (SOF) – since January 2014 – nucleotide inhibitor of NS5B polymerase üSimeprevir (SMV) – since May 2014 – new wave of protease inhibitor of the 1st generation üDaclatasvir (DCV) – since August 2014 – NS5A inhibitor üLedipasvir (LDV) – since November 2014 – NS5A inhibitor – only fixed combination with SOF ü3D kombinace – since January 2015 - paritaprevir/ritonavir – PI, ombitasvir - NS5A, dasabuvir – non-nucleoside polymerase inhibitor ü IFN-free regimens for HCV infection •Very probably the future of HCV therapy •Combination of oral drugs •High efficacy •Almost no adverse events •Short duration of therapy – 12-24 weeks • • Hepatitis D therapy •very problematic – low efficacy •PEG-IFN long-term (more than 1 year) •TDV, TDV – not effective • Chronic hepatitis E therapy •Still unknown • •Only case reports with ribavirin in various therapeutic regimens • husa-tenisky Thank you for your attention! phusa@fnbrno.cz