Hepatitis Vaccination and Therapy

Transcription

1 Hepatitis Vaccination and Therapy Christoph Jochum Department of Gastroenterology & Hepatology University Hospital Essen, Germany Hepatitis B: Prevalence 1995 High Morbidity and Mortality worldwide HBsAg Prevalence (%) 8: high 2-7: middle <2: low Center of Disease Control (CDC) USA

2 Hepatitis B: Prevalence 2005 High Morbidity and Mortality worldwide Locarnini, S et al, J Hepatol 2015 Hepatitis B: Natural Course Yun-Fan Liaw, Chia-Ming Chu The Lancet Volume 373, Issue

3 Aims of Prevention and Therapy of HBV- Infection Prevention of Cirrhosis and HCC! Erradication of HBV Replicationcycle of HBV HBsAg Virus HBsAg complete viruses ER / Golgi viral genome nucleus ER/Golgi integrated DNA cccdna Reverse Transcription Hepatocyt Adaptiert nach Liaw et al., Hepatology Jun;53(6):

4 Vaccination: Structure of HBV-Surface Antigen Conformational determinants: group specific: a ; d, y w and r for subtypes. Antibodies against a provide cross immunity against allgenotypes Michel, M-L., et al. Pathologie & Biologie 58 (2010) Licenced Vaccines and Mode of Action. Vaccine Antigen adjuvant Cells Recombivax non-glycolisated S alum yeast Engerix non-glycolisated S alum yeast GenHevac B non-glycolisated and glycolisated pres-s and S alum CHO-cells Response-rate: 90-95% in immuno-competent adults Michel, M-L., et al. Pathologie & Biologie 58 (2010) 4

5 Mass-Vaccination of Infants: a Success! Chen, DS: J. Hepatol 2009 Mass-Vaccination of Infants: a Success Even in Patients with High Risk Behavior. (Taiwan) Sun, H.Y.. et al. PLoS One

6 Hepatitis B Vaccination: German Recommendations Baseline Immunization of all infants month of age 2. HIV-positive, Hepatitis-C-positive, patients on dialysis 3. Persons with an elevated non-professional risk of infection: Close contact with HBsAg-carriers in family/living, high risk sexual behavior, iv. drug abuse, prisoners, some patients in psychiatric clinics. 4. Persons with an elevated professional risk of infection, personnel in medical facilities (including students, lab and cleaning services), emergency staff, policemen, personnel in facilities with higher prevalence of Hepatitis B (for example prisons, refugee camps, facility for people with disabilities) 5. For travelers with individual risks. Treatment of Hepatitis B Acute hepatitis B: no treatment recommended Exception: fulminant hepatitis B with acute liver failure: entecavir or tenofovir Chronic hepatitis B: Treatment depending on status of liver disease and viral load. Treatment options: Pegylated Interferon Nucles(t)ides (NUC) 6

7 HBV-DNA as Prognostic Parameter Cumulative incidence of HCC depending on baseline HBV-DNA All patients (n=3653) Patients with normal transaminases (n=2925) Reveal study Chen CJ et al. JAMA 2006; 295: 65 Current Therapeutic Options Alfa Interferons: pegylated Interferon alfa 2a Interferon alfa 2a (Roferon ) Interferon alfa 2b (Intron A ) Nukleosid-Analogoues: Lamivudine (Zeffix ) Entecavir (Baraclude ) Telbivudine (Sebivo ) Nukleotid-Analogoues: Adefovir dipivoxil (Hepsera ) Tenofovir disoproxil (Viread ) 7

8 Indications for Therapy of Hepatitis B (German Guidelines 2011) HBsAg-positive Acute Hepatitis B? No Yes Impaired Liver function? Yes No Therapy no Therapy Chronic Hepatitis B? No Cirrhosis? Yes No HBV-DNA >2 x 10 3 IU/ml? Yes Yes HBV-DNA positive? No No Therapy, Control every 6-12 Months ALT repeatedly elevated or Histology >A1/F1? Yes Therapy Control every 3-6 Months No No Extrahepatic Manifestations or high risk of HCC Yes Update Konsensuskonferenz M. Cornberg, M.P. Manns, Pharm. Unserer Zeit 2011; 40: Drug Therapy in Chronic Hepatitis B Virus Infection Resistance Development of Nukleos(t)id-Analogues Years Lamivudin 24% 38% 70% Adefovir Entecavir 0% 3% 29% <1% <1% 1,2 %? Telbivudin 3-4% 9-22% Tenofovir 0% 0% 0% 8

9 HBV-DNA below limit of detection Endpoints of Nukleos(t)id-analogue Therapy HBeAg-positive patients HBeAg-negative patients Seroconversion HBeAg anti-hbe No Seroconversion HBeAg anti-hbe termination 12 months after Seroconversion Continue therapy Long term therapy End of therapy when HBsAg-Seroconversion occurs: (HBsAg negative, anti-hbs >100 U/l) Antiviral Efficacy of HBV-drugs No head to head studies 9

10 Results at week 48 [%] Response: Peg-Interferon vs. Entecavir PegIFN (n = 61) ETV (n = 33) P < P = HBV DNA HBeAg loss < 400 copies/ml 9 P = HBeAg Seroconversion P = HBsAg loss P = HBsAg Seroconversion P = ALT normal Reijnders JG, et al. J Hepatol. 2011;54: Treatment as Prevention Sufficient treatment reduces the infection rate. In HIV-patients a sufficient treatment (= HIV viral load below 40copies/ml) brings infectivity to zero. There no single case documented were a HIV infection took place from a patient with an viral load below 40 copies/ml for more than 6 months. In HBV: A viral load below 1000 IU/ml makes accidental infections a very rare event. Effective antiviral therapy prevents vertical transmission. 10

11 HCV-RNA (log 10 IU/ml) Hepatitis C - Prevention There is no vaccination available! There is no vaccine candidate in clinical phase III Prevention: Therapy of infected persons and reduction of risk behavior. Successful treatment cures hepatitis C! Response to Antiviral Therapy PegInterferon-alfa and Ribavirin Null-Response* Partial Response* Relapse unverifiable RVR EVR ETR SVR Weeks after start of therapy * Subset of non-responder SVR: HCV-RNA non detectable 12 weeks (SVR12) or 24 weeks (SVR24) after end of treatment = cure of hepatitis C. Ghany MG et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatol. 2009;49:

12 Classical Therapy for HCV-GT Infection: Pegylated Interferon-α + Ribavirin PegIFN/RBV represented the standard therapy for HCV-infection until 2011 In May 2011 two Direct Acting Antivirals were licensed by EMA. PegIFN/RBV is still the backbone of this therapy 1 ( tripple therapy). IFN is a cytokine, stimulating the immune response and represents a nonvirus specific anti-viral effectivity. Ribavirin is an oral nukleosid analogon with a wide activity against different viruses. Registered trade name manufacturer Pegyliertes IFN - PegIFN-α 2b - PegIFN-α 2a Ribavirin (RBV) - PEG-Intron - Pegasys - Rebetol - Copegus - Generika - Merck - Roche - Merck - Roche - several 1. Sarrazin C, et al. [Expert opinion on boceprevir- and telaprevir-based triple therapies of chronic hepatitis C]. Z. Für Gastroenterol. 2012;50: Development in HCV-Therapy Discovery of HCV Interferon Interferon Ribavirin Peg-Interferon Alpha 2b Ribavirin Peg-Interferon Alpha 2a Ribavirin Direct acting Antivirals (DAA): Telaprevir Boceprevir DAA: Sofosbuvir (Sovaldi ) Simeprevir (Olysio ) Daclatasvir (Daklinza ) Sofosbuvir+ Ledipasvir FDC (Harvoni ) / 2015 DAA: Ombitasvir + Paritaprevir/r FDC (Viekirax ) und Dasabuvir (Exviera )+/- RBV 12

13 HCV Life Cycle and Targets of DAA s Binding to receptor and endocytosis Transport and release Fusion and Uncoating (+) RNA LD ER lumen LD Translation and polyproteinprocessing Virusassembly NS3/4 Proteaseinhibitors ER lumen LD NS5B Polymerase- RNA replication inhibitors Nukleoside/Nukleotide Non-nukleosidic -previr NS5A* Inhibitors *Blockade of replication complex, Assembly -asvir -buvir Adaptiert von CCO nach Manns MP, et al. Nat Rev Drug Discov. 2007;6: ,. Therapy of HCV-Infection The Good News 100 PegIFN DAAs Standard IFN 1991 RBV IFN 6 mos IFN 12 mos IFN/RBV 6 mos IFN/RBV 12 mos PegIFN 12 mos PegIFN/ RBV 12 mos PegIFN/ RBV/ DAA DAA + RBV ± PegIFN Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring, MD. 13

14 Therapeutical Options in June 2015 Interferon-based Pegylated Interferon + Ribavirin (PR) (All genotypes) Telaprevir (TPV) + PR (Genotype 1) Boceprevir (BOC) + PR (Genotype 1) Simeprevir (SMV) + PR (Genotype 1+4) Sofosbuvir (SOF) + PR (All genotypes) Interferon-free Sofosbuvir(SOF) + Ribavirin (RBV) (all Genotypes) Simeprevir (SMV) + Sofosbuvir (SOF) +/- Ribavirin (RBV) (Genotype 1 +4) Daclatasvir (DCV) + Sofosbuvir (SOF) +/- Ribavirin (RBV) (Genotype 1-4) Sofosbuvir (SOF) + Ledipasvir (LDV) FDC +/-Ribavirin (RBV) (Genotype 1-4) Paritaprevir(PTV)/R+Ombitasvir(OMV) +/- Dasabuvir (DSV)+/-Ribavirin (RBV) (Genotype1+4), 2015 European HCV Guidelines (EASL) 14

15 EASL 2015 HCV*: Tx-Naive or PR-Exp d, GT1, 4, 5, or 6, Without Cirrhosis Regimen HCV Genotype 1a 1b 4 5 or 6 SOF + PR 12 wks 12 wks 12 wks SMV + PR 12 wks (naive or relapse) 24 wks (partial/null) 12 wks (naive or relapse) 24 wks (partial/null) Not recommended LDV/SOF 8-12 wks, no RBV 12 wks, no RBV 12 wks, no RBV OBV/PTV/RTV + DSV 12 wks + RBV 12 wks, no RBV Not recommended Not recommended OBV/PTV/RTV Not recommended 12 wks + RBV Not recommended SOF + SMV 12 wks, no RBV 12 wks, no RBV Not recommended SOF + DCV 12 wks, no RBV 12 wks, no RBV 12 wks, no RBV *Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts. 8 wks may be used in treatmentnaive pts without cirrhosis if baseline HCV RNA < 6 million IU/mL, but should be done with caution, especially in pts with F3 fibrosis. EASL HCV Guidelines. April EASL 2015 HCV*: Tx-Naive or PR-Exp d, GT1, 4, 5, or 6, Compensated Cirrhosis Regimen HCV Genotype 1a 1b 4 5 or 6 SOF + PR 12 wks 12 wks 12 wks SMV + PR LDV/SOF OBV/PTV/RTV + DSV 12 wks (naive or relapse) 24 wks (partial/null) 12 wks + RBV or 24 wks, no RBV or 24 wks + RBV if negative predictors 24 wks + RBV 12 wks + RBV 12 wks (naive or relapse) 24 wks (partial/null) 12 wks + RBV or 24 wks, no RBV or 24 wks + RBV if negative predictors Not recommended *Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts. Not recommended 12 wks + RBV or 24 wks, no RBV or 24 wks + RBV if negative predictors Not recommended OBV/PTV/RTV Not recommended 24 wks + RBV Not recommended SOF + SMV SOF + DCV 12 wks + RBV or 24 wks, no RBV 12 wks + RBV or 24 wks, no RBV 12 wks + RBV or 24 wks, no RBV 12 wks + RBV or 24 wks, no RBV Not recommended 12 wks + RBV or 24 wks, no RBV EASL HCV Guidelines. April

16 EASL 2015 HCV*: Tx-Naive & PR-Exp d, GT2 or 3 Regimen No Cirrhosis Compensated Cirrhosis (Child-Pugh A) GT2 GT3 GT2 GT3 SOF + PR 12 wks 12 wks 12 wks 12 wks SOF + RBV 12 wks 24 wks wks Not recommended SOF + DCV 12 wks, no RBV 12 wks, no RBV 12 wks, no RBV 24 wks + RBV *Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts. Best first-line option for genotype 2 HCV; other options may be useful in pts with GT 2 HCV who experience tx failure on sofosbuvir plus ribavirin. Suboptimal for genotype 3 HCV, particularly in pts with cirrhosis and previous failure of PR. EASL HCV Guidelines. April No Longer Recomended Combinations: Combination Treatment duration SVR Side effects Pegylated Interferon+ Ribavirin (PR) Wo 45-55% Fatigue, anemia, aeutropenia, thrombocytopenia, weakness, nausea, loss of appetite, weight loss, muscle pain, depression, hashimoto thyreoditis, cough, pneumonitis, retinitis, rash, ikterus, and many more Telaprevir + PR Wo 75% Boceprevir + PR Wo 69% Additional: Anemia, rash, anorectal dyscomfort Additional: Anemia dysgeusia, neutropenia 16

17 SVR (%) Sofosbuvir + PegIFN/RBV: NEUTRINO Phase III Study Design Wk Sofosbuvir + PegIFN/RBV (N = 327) SVR12 Open label Sofosbuvir 400 mg QD + pegifn alfa-2a 180 µg/wk + RBV mg/day for 12 wks (no response-guided therapy) Treatment-naive, genotype 1, 4, 5, and 6 HCV-infected patients 89% of patients had genotype 1 HCV 17% of patients with cirrhosis Lawitz E, et al. N Engl J Med. 2013;368: NEUTRINO Study: Virologic Response Sofosbuvir + PegIFN/RBV x 12 Wks ITT SVR12 GT1 Cirrhosis n = 327 n = Lawitz E, et al. N Engl J Med. 2013;368:

18 SVR (%) Simeprevir + P/R in GT1, Tx-Naive Patients: QUEST- 1/2 Phase III Trial Design Response-Guided Treatment (RGT) N = 521 * SMV 150 mg QD + P/R P/R P/R N = 264 Placebo + P/R P/R P/R Wk RGT in simeprevir arm: if HCV RNA < 25 IU/mL at Wk 4 and undetectable at Wk 12, complete treatment at Wk 24; otherwise, continue treatment to Wk 48 Stopping rules If HCV RNA > 1000 IU/mL Wk 4, stop SMV/placebo If HCV RNA < 2 log 10 IU/mL reduction at Wk 12, or confirmed > 25 IU/mL at Wk 24 or 36, stop all treatment *QUEST-1: n = 264; QUEST-2: n = 257. QUEST-1: n = 130; QUEST-2: n = 134. Jacobson I, et al. EASL Abstract Manns M, et al. EASL Abstract Simeprevir + P/R: Phase III QUEST-1: Impact of Subtype & Fibrosis Stage in GT Overall GT1a GT1b F0-F2 F3 F Simeprevir P/R Simeprevir P/R SVR: GT1b > GT1a SVR: F0-F2 > F4 SVR is lowest for patients with GT1a and baseline Q80K mutation Jacobson I, et al. EASL Abstract

19 SVR12 (%) OPTIMIST-1: SMV + SOF for 8 vs 12 Wks in Noncirrhotic Tx-Naive & Tx-Exp d GT1 Pts Multicenter, randomized, open-label phase III trial Key baseline characteristics: 75% GT1a (41% with Q80K), 73% IL28B non-cc, 18% black, 15% Hispanic, 30% treatment experienced, median HCV RNA: log 10 IU/mL Stratified by HCV subgenotype and Q80K in GT1a; treatment history; IL28B GT GT1 HCV infected non-cirrhotic pts with HCV RNA > 10,000 IU/mL (N = 310) Simeprevir 150 mg QD + Sofosbuvir 400 mg QD (n = 155) 8 Wks Simeprevir 150 mg QD + Sofosbuvir 400 mg QD (n = 155) 12 Wks OPTIMIST-1 83%* 97% SVR12 Historical Control *Not superior to historical control based on lower limit of 95% CI (76.3%) not > historical control rate. Superior to historical control based on lower limit of 95% CI (93.7%) > historical control rate. 83% 87% Kwo P, et al. EASL Abstract LP14. OPTIMIST-1: SVR12 by Pt Subgroup Safety and tolerability consistent with previous reports SMV + SOF 12 wks SMV + SOF 8 wks n/n = 0 112/ 88/ Naive 38/ 40 Treatment History 40/ 52 Exp d 112/ 92/ / 36/ a 1a + Q80K HCV GT 68/ 56/ a no Q80K 38/ 36/ b 43/ 43 38/ 41 83/ 86 72/ 86 24/ 18/ / 46/ CC CT TT < 4 x 10 6 IU/mL IL28B GT 96/ 82/ x 10 6 IU/mL Baseline HCV RNA Kwo P, et al. EASL Abstract LP14. 19

20 Phase III Studies of SOF/LDV FDC ± RBV for 12 or 24 Wks in GT1 Patients ION-1 [1,2] Treatment-naive HCV GT1; cirrhosis in 15% to 17% per arm (N = 865) Wk 12 SOF/LDV (n = 214) SOF/LDV + RBV (n = 217) SOF/LDV (n = 217) SOF/LDV + RBV (n = 217) Wk 12 Wk 24 Wk 24 SVR12, % ION-2 [3] Treatment-experienced HCV GT1; 20% cirrhotics (N = 440) SOF/LDV (n = 109) SOF/LDV + RBV (n = 111) SOF/LDV (n = 109) SOF/LDV + RBV (n = 111) ION-1,2: No difference in the outcome according to cirrhosis status, type of treatment failure 1. Mangia A, et al. EASL Abstract O Afdhal N, et al. N Engl J Med. 2014;370: Afdhal N, et al. N Engl J Med. 2014;370: ION-3: Phase III Study of SOF/LDV FDC ± RBV for 8-12 Wks in Tx-Naive Non-cirrhotic GT1 Patients Wk 8 Wk 12 SVR12, % Treatment-naive, non-cirrhotic pts with HCV GT1 (N = 647) SOF/LDV (n = 215) SOF/LDV + RBV (n = 216) SOF/LDV (n = 216) Kowdley KV, et al. N Engl J Med. 2014;

21 SAPPHIRE I & II: Phase III Studies of PTV/RTV/OMV (NS5A) + DSV (NNI) + RBV in Non-cirrhotic GT1 Pts SAPPHIRE-I Treatment-naive noncirrhotic pts with HCV GT1 [1,2] (N = 631) Wk 12 SVR12, % ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 473) 96 Placebo (n = 158)* SAPPHIRE-II Treatment-experienced non-cirrhotic pts with HCV GT1 [3,4] (N = 394) ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 297) Placebo (n = 97) 96 SAPPHIRE: no difference in the outcome according to 1a/1b subtype, type of treatment failure *Placebo recipients received active treatment regimen at Wk Feld JJ, et al. EASL Abstract O60. Reproduced with permission. 2. Feld JJ, et al. N Engl J Med. 2014;370: Zeuzem S, et al. EASL Abstract O1. 4. Zeuzem S, et al. N Engl J Med. 2014;370: TURQUOISE II: Phase III Study of PTV/RTV/OMV (NS5A) + DSV (NNI) + RBV in Cirrhotic GT1 Patients DAA-naive cirrhotic pts with HCV GT1; 58% of patients were treatment experienced, and 36% were previous null responders (N = 380) ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 208) Wk 12 ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 172) Wk 24 SVR12, % No significant difference in 12 vs 24 wks; high SVR in all subgroups analyzed ABT-450/RTV/ombitasvir 150/100/25 mg once daily; dasabuvir 250 mg twice daily; RBV mg/day. Poordad F, et al. N Engl J Med. 2014;370:

22 Ribavirin-Free Therapy in GT1b PEARL-II [1] GT1b Tx Experienced ABT450/RTV/Ombitasvir + Dasabuvir (n = 95) ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 91) Wk 12 SVR12, % PEARL-III [2] GT1b Tx Naive ABT450/RTV/Ombitasvir + Dasabuvir (n = 209) ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 210) PEARL-IV [2] GT1a Tx Naive ABT450/RTV/Ombitasvir + Dasabuvir (n = 205) ABT450/RTV/Ombitasvir + Dasabuvir + RBV (n = 100) Andreone P, et al. Gastroenterology. 2014;[Epub ahead of print]. 2. Ferenci P, et al. N Engl J Med ;370: PTV/RTV/OMV + DSV + RBV Side Effects Therapy AbbVie-Therapy+ RBV (N=473) Placebo (N=158) P-value All AE s 87,5 % 73,4 % < 0,05 Fatigue 34,7 % 28,5 % NS Headache 33,0 % 26,6 % NS Nausea 23,7 % 13,3 % < 0,05 Itching 16,9 % 3,8 % < 0,05 Insomnia 14,0 % 7,6 % < 0,05 Diarrhea 13,7 % 7,0 % < 0,05 Weakness 12,1 % 3,8 % < 0,05 Rash 10,8 % 5,7 % NS SAPPHIRE-I: Feld JJ et al., N Engl J Med Apr 24; 370(17):

23 PTV/RTV/OMV + DSV Side Effects: Contribution of Ribavirin 45 Therapy HCV-Therapy with PTV/RTV/OMV + DSV HCV-Therapy with PTV/RTV/OMV + DSV + RBV Fatigue 26,5 % 29,9 % Headache 25,3 % 24,4 % Nausea 8,4 % 15,7 % Insomnia 5,1 % 12,2 % Itching 6,1 % 12,0 % Diarrhea 11,4 % 8,7 % pooled data from PEARL-II, -III &-IV Lalezari J et al. AASLD 2014, Poster 1961 Daclatasvir + Sofosbuvir +/- Ribavirin in Naive GT1 Patients [%] N A: Sofosbuvir 7 days lead in + 24 Wk. Daclatasvir + Sofosbuvir B: 24 Wk. Daclatasvir + Sofosbuvir C: 24 Wk Daclatasvir + Sofosbuvir + Ribavirin D: 12 Wk Daclatasvir + Sofosbuvir E: 12 Wk Daclatasvir + Sofosbuvir + Ribavirin Asselah T.:J Hepatol Aug;61(2):

24 Daclastasvir + Sofosbuvir +/- Ribavirin in Treatment Experienced GT1 Patients [%] N A: 24 Wk. Daclatasvir + Sofosbuvir B: 24 Wk. Daclatasvir + Sofosbuvir + Ribavirin All patients had failed a previous Telaprevir- or Boceprevir containing treatment Asselah T.:J Hepatol Aug;61(2): Side Effects of DAA s Sofosbuvir [1-3] Mild fatigue Mild headache Simeprevir [4,5] mild, reversible hyperbilirubinemia Due to inhibition of bile transporter, not related to hepatotoxicity Mild photosensitivity Daclatasvir: Mild fatigue Mild headache Mild nausea 1. Lawitz E, et al. N Engl J Med. 2013;368: Jacobson I, et al. AASLD Abstract LB Sofosbuvir [package insert]. 4. Fried MW, et al. Hepatology. 2013;58: Simeprevir [package insert] 6. Sulkowski, M., et al. N eng J Med 2014;370:

25 Hepatitis Carriers Among Health Care Workers Safety precautions Double gloves during surgery Use of safe instruments (like blunt needles) which are constructed to reduce the risk of injury to minimal Use of protective gear glasses, mask and eye peace Use of suitable boxes for used infectious instruments Notification of every injury, contamination of eyes and other mucous membranes with infectious material to the company physician! 25

26 Nosocomial Infections: Hepatitis B ~500 infections from 40 healthcare workers are documented. All of them had a viral load of >10000 IU/ml, most of them more than IU/ml Specialties at risk: thoracic surgeons, dental surgeons and gynecologists, lower risk: visceral surgeons and other surgical disciplines. Special risk for injuries: sharp wires and certain sutures. General recommendation: Health care workers with a viral load <1000 IU/ml: no work restrictions, however frequent controls of viral load Health care workers with viral load of > IU/ml are banned from any risky procedure. Health care workers with viral load between 1000 and may do some risky procedures with special safety precautions, like double gloves etc. Nosocomial Infections: Hepatitis C ~22 infections from 9 healthcare workers are documented. The risk of infection by a HCV-positive health care worker is considered very low. General recommendation: Health care workers are generally allowed to do any medical procedure with special safety precautions, like double gloves with stab indicator etc. 26

27 Hepatitis Postexposition Prophylaxis (PEP) Risk of infection after injury with a blood contaminated needle: Index-person: HBV: HBeAg-positive: 37-62% HBeAg-negative: 23-37% HCV-positive: 1,8% Hepatitis C: no PEP available and recommended, frequent controls of HCV-RNA in injured person, when positive therapy with pegylated interferon for 6 months or DDA therapy for 8-12 weeks. Hepatitis B: dependent on sero-status of injured and index person Hepatitis B: PEP Serostatus of injured Serostatus of index person Diagnostic test Immunization Anti-HBs >100 IU/ml in the last 12 months successful immunization <5 yrs or past HBV-infection any none none Anti HBs negative HBsAg negative none Active unknown unknown Index: HBsAg, injured anti-hbs Active and passive if applicable unknown indeterminate Injured anti-hbs Active and passive if applicable Non responder (no antihbs after 6 vaccinations) No vaccination Anti- Hbc negative HBsAg positive HBsAg positive Active and Passive Active and passive 27

28 Thank you for your attention! 28