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 •VH A – only acute •VH E – posibble chronic (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 C:\Users\33550\Pictures\Image Library One\My Images\Lékařské\Cirhotici\IMG_0717.JPG cirhotik1 cirhotik5 Hepatocellular carcinoma small Drawn Cancer Carcinoma 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 VH A 128 1648 1104 862 264 284 348 673 724 930 VH B 307 306 247 244 192 154 133 105 89 73 VH C 980 974 836 709 812 794 873 867 956 1104 VH E 43 65 99 72 163 258 218 299 412 339 j0178242 •Viral hepatitis in CR 2007-2016 hepatitis a virus •Hepatitis A virus (HAV) •family Picornaviridae, genus Hepatovirus – non-enveloped RNA, 27 nm http://gamapserver.who.int/mapLibrary/Files/Maps/Global_HepA_ITHRiskMap.png 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 ü240 million chronic carriers ü686 000 deaths anualy due to LC or HCC (2013, increase about one third since 1990) üIndication for 5-10 % liver transplantations globally ü50 thousand death annually due to fulminant hepatitis üGlobal vaccination in 177 countries (2008) • • j0186004 •Chronic HBV infection (CDC 2017) •Zdroj: WHO 2008 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) …0,064 %(2013) 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 2001-2013, now only newborns (hexavaccine) • • Epidemiology of HBV •Transmission ü blood and blood products ü sexual intercourse ü organ and tissue transplant recipients ü vertically from mother to newborn • 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\Slide12.jpg C:\Documents and Settings\admin\Desktop\slide_lib\png\Slide11.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 Chronic HCV infection (CDC 2017) • Global HCV distribution •Messina JP, et al. Hepatol. 2014; doi: 10.1002/hep.27259 •ttp://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index4.html#incidence • •Estimates 2014: 115 millions anti-HCV+, 80 millions of them HCV RNA+ Původce hepatitidy C •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 • Matavir 3.. 00000010Ramonet ABA78158: ch 00000010Ramonet ABA78158: fig82x.jpg 00000010Ramonet ABA78158: •Acute • infection •Chronic • infection •80% •Chronic •hepatitis •80% • Cirrhosis •20% •Fibrosis •0...........1........2.......3......4 • HCC •1-5%/year > 30 years •Alcohol, co-infection (HBV,HIV), < 20 years WERWER 00000010Ramonet ABA78158: Clinical course of HBV infection • •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 (vaccination against HBV is potent against HDV as well) üCo-infection (better prognosis) üSuper-infection (worse prognosis) •Globally gradually decreasing HDV prevalence due to massive vaccination against HBV •Very low prevalence in CR • •Drug addicts •Rizzetto M. EASL 2009 Diapositiva1 • 2010s • •: • immigrants 2009 •Rizzetto M. EASL 2009 •Significant incidence and prevalence •(since 2006) •PAKISTANI1 •INDIA2 •MONGOLIA3 •IRAN4 •VIETNAM5 •TAJIKISTAN6 •TUNISIA7 •MAURETANIA8 •1. Zuberi BF, 2006; 2. Acharya SK, 2006; 3.Tsatsralt-Od B, 2006; 4. Roshandel G, 2007; 5. Nguyen VT, 2007; 6. Khan A, 2008; 7. Djebbi A, 2009; 8. Lunel F, personal communication 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 •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 •tenofovir disoproxil or alafenamide – both for naive and lamivudine-resistant patients •entecavir – for naive patients •pegylated interferon alfa-2a – 48 weeks • • IFN-free regimens for HCV infection •Current standard of HCV therapy •Combination of oral drugs •High efficacy •Almost no adverse events •Short duration of therapy – 8-24 weeks • • HCV infection is curable in majority of patients •SVR – sustained virological response = the definite eradication of HCV infection •1. Pawlotsky JM. J Hepatol 2006;44:S10–3; 2. Siliciano JD, et al. J Antimicrob Chemother 2004;54:6–9; 3. Lucas GM. J Antimicrob Chemother 2005;55:413–6; 4. van der Meer AJ, et al. JAMA 2014;312:1927–8; 5. Burki T. Lancet Infect Dis 2014;14:452–3 •Long-life suppression •Long-life suppressione •Vymizení HCV •Vyléčení • “Vzhľadom k tomu, že neexistuje účinná vakcína, optimálna liečba chronickej HCV infekcie sa dnes považuje za ‘nutnú’ jednak z hľadiska stratégie verejného zdravotníctva, jednak z hľadiska klinického vývoja jednotlivých pacientov.” od Yu a Chuang J Gastro Hep 2009 Popis obrázku: Hostiteľská bunka cccDNA Hostiteľská DNA Jadro Liečba Provírusová DNA Liečba Vírusová RNA Liečba Direct Acting Antivirals against HCV Lék zkratka třída Glecaprevir GLE NS3/4A protease inhibitor Pibrentasvir PIP NS5A inhibitor Voxilaprevir VOX NS3/4A protease inhibitor Ruzasvir* RZV NS5A inhibitor Uprifosbuvir* UPR Nucleotide NS5B polymerase inhibitor Daclatasvir DCV NS5A inhibitor Dasabuvir DSV Non-nucleoside NS5B polymerase inhibitorázy Elbasvir EBR NS5A inhibitor Grazoprevir GZR NS3/4A protease inhibitor Ledipasvir LDV NS5A inhibitor Ombitasvir OBV NS5A inhibitor Paritaprevir PTV NS3/4A protease inhibitor Simeprevir SMV NS3/4A protease inhibitor Sofosbuvir SOF Nucleotide NS5B polymerase inhibitor Velpatasvir VEL NS5A inhibitor •* Before approvement Hepatitis D therapy •very problematic – low efficacy •PEG-IFN long-term (more than 1 year) •ETV, TDF, TAF – not effective (absence of target enzyme – reverse transcriptase) 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