Bible Class: HCV Infection

Transcription

1 Bible Class: HCV Infection PD Dr. Dr. med. Nasser Semmo UVCM, Hepatology

2 What is the HCV prevalence and incidence? 2

3 HCV Prevalence Worldwide about Mio. infected with HCV, about 9 Mio. in Europe, in CH 3-4 Mio. new HCV infections per year 25-30% of OLTs in Europe due to HCV (EASL conference 1999) 3

4 HCV Prevalence 4

5 What are Hepatitis C Risk Factors? 5

6 Hepatitis C Risk Factors Blood contamination Blood transfusions (HCV: before 1990) IVDU HCV-prevalence in IVDU between 15-90% (Esteban, J Hepatol 2008) Sexual transmission rarely in a stable heterosexual relationship Perinatale transmission rarely (5%) 6

7 HCV-Course HCV-Exposition HCV-Infection 15% 85% No HCV-Infection Symptomatic, acute Infection 50% 50% 20% 80% Asymptomatic, acute Infection Virus elimination Virus persistence 4-20% Cirrhosis 1-4% HCC Puig et al., 2004; CDC; Moradpour et al.,

8 Who to screen for HCV? 8

9 Who to screen for HCV? Elevated Liver enzymes & signs of hepatitis, chronic liver disease with unknown etiology Active or history of IVDU Homosexual men a/o persons with frequently changing sexual contacts Dialysis patients Persons with migration background from regions with high HCV prevalence (Eastern Europe, Mediterranean) 9

10 Who to screen for HCV? Liver cirrhosis HCC HIV-Infected pat. Recipients of solid organ transplants before and after Transplantation Blood- and Organ donors 10

11 How to diagnose HCV infection? 11

12 HCV-Diagnostic Algorithm Screening-Test EIA-2/EIA3 No HCV-Infection HCV-Genotyping when treatment planned Confirmatory Test HCV-RNA-assay HCV positive RIBA-Test HAV-, HBV- & HIV Screening If negative, then vaccination Spontaneous HCV- Elimination EIA false-positive CDC,

13 What is the current standard of care treatment (SoC), what is the new treatment and when to start with treatment? 13

14 HCV Treatment Common Standard of care treatment (SOC) Pegylated Interferon alpha (P) & Ribavirin ( R ) Genotype- & Response guided treatment duration GT2/3: better SVR (80-90%) GT1: weaker SVR (max. 50%) New standard of treatment in HCV GT1 Protease inhibitors Telaprevir or Boceprevir in combination with SOC (PR+ B o. T) GT1: much better SVR Indication in HCV GT 1 Treatment naive HCV patients With SOC pre-treated pat.(relapser, partial Responder or Non-Responder) Compensated liver cirrhosis 14

15 When to start treatment / treatment indication Chronic HCV GT1 Elevated Transaminases, pos. HCV-PCR Fibrosis (min. F2) Chronic HCV GT2/3 Even without fibrosis Wish of the patient Condition: Adherence/Compliance 15

16 What is the dosage of the drugs/prescription in GT1, especially with the new PIs? 16

17 Drug prescription Triple treatment with Telaprevir (Incivo ): Pegylated Interferon 180 ug or 1,5 ug/kg 1x per week Ribavirin 200mg 2(3)-0-3 Incivo 375mg every 8h with fatty meal Telaprevir only for 12 weeks in Triple-combi, then followed by SOC Triple treatment with Boceprevir (Victrelis ) Pegylated Interferon 180 ug or 1,5 ug/kg 1x per week Ribavirin 200mg 2(3)-0-3 Victrelis 200 mg every 8h Start BOC 4 wks after SOC (Lead in) 17

18 PIs dosing tips Protease inhibitor Protease inhibitor Protease inhibitor or or or 7 am 3 pm 8 pm 11 pm Breakfast Ribavirin Dinner Ribavirin 18

19 What is the treatment duration with the Triple Tx? 19

20 Algorithm: Treatment duration with Telaprevir: SASL 2012/SMW

21 Algorithm: Treatment duration with Telaprevir: SASL 2012/SMW

22 Algorithm: Treatment duration with Boceprevir: SASL 2012/SMW

23 Algorithm: Treatment duration with Boceprevir: SASL 2012/SMW

24 Algorithm: Treatment duration with Boceprevir: SASL 2012/SMW

25 What are the common AEs under SOC? 25

26 Common AEs under SoC treatment Hematological changes Anemia (Ribavirin) Leucozytes/Neutrophiles Decrease (IFN) Thrombocytes Decrease (IFN) Psychic-Psychiatric AEs Depression Aggression Fatigue Dermatologic Changes Dry skin 26

27 What are the adverse events under the new PIs? 27

28 Adverse Events under PIs 28

29 Management of adverse events When to reduce IFN, when Ribavirin and when to stop them? 29

30 Pegylated Interferon - Reduce Peg IFN if - Absolute neutrophil count falls below 750/mm 3 - Platelet count falls below 50,000/mm 3 - Stop Peg IFN if - Absolute neutrophil count falls below 500/mm 3 - Platelet count falls below 25,000/mm 3 - or if severe unmanageable depression develops 30

31 Ribavirin - If Hemoglobin <10 g/dl occurs, Ribavirin dose should be adjusted downward by 200 mg at a time - Stop Ribavirin if Hemoglobin falls below 8.5 g/dl - Alternatively, EPO can be used to maintain high Ribavirin dose 31

32 Leukopenia/Neutropenia In general, infection rate during HCV treatment is elevated However, neutropenia alone in patients with compensated HCV infection is not associated with elevated infection risk Patients with neutropenia do not have higher infection rate in comparison to those without neutropenia Dose reduction of IFN does not lead to reduction of susceptibility to infections Therefore dose reduction not necessary if no signs of infection present Thus: IFN-reduction in pat. with co-morbidities, older pat, liver cirrhosis a/o Diabetes if neutrophiles < 750, Filgrastim (Neupogen) if neutrophiles <500 Roomer et al., Hepatology 2010, Antonini et al., Infection

33 Thrombopenia IFN Dose reduction if Tc< Give Eltrombopag (Revolade) if despite IFN reduction no improvement of Tc and if further IFN dose reduction not possible STOP IFN, if Tc<20000, and if no improvement with Revolade Revolade dosage: 1x25 mg daily CAVE: Portal vein thrombosis through Eltrombopag possible (Afdhal et al., NEJM 2012) 33

34 Management of adverse events How to prevent or treat Rash? 34

35 Prophylaxis and treatment of Rash e.g. Elocom cream or Betnovate cream 35

36 Estimating Body Surface Area (BSA) = 1 % skin surface 36

37 Correct dosage of corticosteroid cream 37

38 Prophylaxe und Therapie des Rash 38

39 THANK YOU 39

40 Definitions 40