Update on Hepatitis B and C in CEE
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1 4th CEE Meeting on Viral Hepatitis and HIV Update on Hepatitis B and C in CEE Miłosz Parczewski Dept. of Infectious Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Poland
2 Thus: A virus may be considered a self replicating machine in the cellular environment. Biology is a science on the selfreplicating machines Freitas, Merkle, Kinematic Self-Replicating Machines, 2004 Janos von Neumnn,
3 General principles of Von Neumann machines as viruses A construction element Rybosom (human), proteases, structural proteins B replicating element transcriptases, DNA polimerases (human) C controlling elements NS5A? Tat, rev, nef F(ABC) instruction Viral RNA/DNA, copydna, genomicdna, mrna Concept of self-replicating machines Freitas, Merkle, Kinematic Self-Replicating Machines,
4 Von Neumann Machine vs. viruses Infected host cell Messenger viral RNA/DNA, viral proteins, host ribosome, host restiction factors (inhibition of selfreplication) Infecting viron Budding infectious viron Integrated viral RNA/DNA
5 HBV/HCV - global perspective Global hepatitis report, WHO, 2017
6 WHO 2030 targets to stop two key selfreplicating viral machines: HBV and HCV
7 HBV/HCV in the European Region 18.5 mln estimated to live with chronic HBV 15 mln with chronic HCV Annual deaths > cases Expected increase in mortality in the near future Target in context: If 7% of HCV the epidemic in 2016 is cured each year (net), >90% of people infected in 2016 should be cured by 2030.
8 Issues to be addressed for HBV/HCV elimination in CEE. Drug and vaccination rollout and price competition Surveillance over transmission networks and reinfections PWID Viral resistance Treatment of HCV complications (cirrhosis, HCC, OLTx) Diagnostics including the point-of care testing
9 HBV in the European context Global hepatitis report, WHO, 2017
10 HBV in the European context: success of early vaccination programs HBs prevalence among children <5 years Global hepatitis report, WHO, 2017
11 HBV seroprevalence across CEE Global hepatitis report, WHO, 2017
12 Outcome of vaccination programmes: Acute HBV infections across CEE countries
13 Distribution of HBV genotypes in Europe Kmet Lunaček N, Poljak M, Matičič M Acta Dermatovenerol Alp Pannonica Adriat Sep;27(3):
14 HCV in European context
15 Impact of migration on chronic HCV cases % contribution to the total number of HCV cases in Europe
16 Mulitifaceted issue of injecting drugs Large array of behaviour form chemsex/rectreational, homemade or very cheap drugs e.g. kompot (Polish heroine), or pseudoephedrine/manganate concotions Marginalisation, criminalisation stigma Insurance issues, HCV reinfection risk (data gap for CEE, to be addressed in the setting of expanding DAA treatment programms)
17 Top HCV HBV countries among PWID with PWID Grebely at al., Additionan, 2018,
18 Beyond hepatitis in PWID: Commentary on CNS manganosis Pseudoephedrine is oxidated with hipermanganate (mix until cherry smell is obtained) and injected. Cheap, short term drug Manganate deposited in the periventricular area of the brain Occasionally visualised by MRI
19 Elimination of HIV/HBV/HCV among PWID: Harm reduction programms in CEE Opioid substitution widely available except in Russian Federation, Turkmenistan and Uzbekistan. Coverage was low - 5.3% in Belarus, 4.9% in Kyrgyzstan, 3.5% in Ukraine and 0.2% in Kazakhstan. Sterile injecting equipment distribution: needle syringe programmes often insufficient except Kyrgyzstan, where 241 needles were provided per client per year (target is 200) prevention gap report, UNAIDS
20 Next level: test and treat: testing availibility across Euorpean Countries
21 AIDS 2018 DAA treatment uptake across Eurosida cohorts (HIV/HCV coinfected)
22 Restrictions to DAA use in EEA ( ) Marshall AD et al. The removal of DAA restrictions in Europe ( J. Hepatol 2018)
23 Reported restriction to DAA care across Europe
24 HCV treatment disparities net cures 5:1 (5x more people reach SVR than are new infections) 1:1 the same number of SVR ads new infections 1:5 5x less people acheive SVR than get infected
25 Transmission networks as the issue which may negatively affect hepatitis elimination targets
26 Acute HCV infections and shift in G1 patterns Acute HCV; n (%) Chronic HCV; n (%) P value Gender Male 66 (100) 45 (71.4) <0.001 Female 0 18 (28.6) Reported HCV infection route Intravenous drug use (IDU) 0 53 (84.1) <0.001 G1A Heterosexual tended partners to of IDUs be more prevalent 0 compared 4 (6.4) to G1B Men-who-have-sex-with-men 66 (100) 9 (9.5) HCV genotype among 1a vs. 1bmen-having-sex-with-men (MSM) Genotype 1a 24 (36.4) 19 (30.2) n.s [34/52(65.38%) vs. 48/96(50.0%), p=0.07] and Genotype 1b 42 (63.6) 44 (69.8) patients with a history of syphilis [18/34 (52.94%) History of syphilis during follow-up Yes vs. 15/56(26.79%),p=0.01]. 27 (77.2) 4 (8.0) No 8 (22.8) 46 (92.0) <0.001 History of HBV coinfection HBs antigen positive 1 (1.9) 1 (2.9) n.s HBs antigen negative 52 (98.1) 54 (97.1) Parczewski et al., EACS 2017, Milan, PS3/3
27 HCV intercity transmission clusters are driven by MSM Parczewski et al., JAIDS, 2018
28 Genotype 1a acute HCV clusters CLADE I CLADE II Q80K RAS transmission was observed among six G1A individuals. Parczewski et al., EACS 2017, Milan, PS3/3
29 Gentotype 1b acute HCV clusters Part of the Genotype 1b tree 37 sequence G1B cluster containing sequences from 5 cities (mean intercity distance 370 km). (sampling timeline ) Parczewski et al., EACS 2017, Milan, PS3/3
30 HCV re-infections are expected to be more commonly revealed in CEE Chemsex
31 HCV resitance which may potentially affect DAA treatment response
32 Baseline NS3 RAVs prevalence (n=384) 30,0% 27,8% 25,0% 20,0% 15,0% 10,0% 1a 1b 5,0% 0,0% 1,9% 1,9% 1,9% 0,3% 0,7% 0,3% 0,3% 0,3% 0,3% 36L 54S 55A 55A, 80K 80K 80L 80R 156T 168E 170A G1a G1b Total Parczewski at al., CMI, 2018
33 30,0% Baseline NS5A RAVs prevalence (n=384) 25,0% 20,0% 15,0% G1A G1B 10,0% 5,0% 0,0% 5,1% 3,7% 3,3% 1,9% 0,3% 0,6% 28T 30R 31F 31I 31M 93H G1a G1b Total Parczewski at wl., CMI, 2018
34 NS5A RAVs at baseline 25,00% p=0.004 p=0.019 p=0.003 p= ,00% 20,34% 15,00% 12,50% 10,00% 7,07% 6,56% 5,00% 0,00% F0/1 F2 F3 F4 Fibrosis stage Present Absent Total Parczewski at al., CMI, 2018
35 Y93H NS5A RAVs at baseline p=0.04 p=0.009 p=0.008 p= ,00% 20,00% 15,00% 10,00% 10,00% 11,86% 5,00% 2,72% 1,64% 0,00% F0/1 F2 F3 F4 Present 5 Fibrosis stage Absent Total Parczewski at al., CMI, 2018
36 NS3A RAVs at baseline p=ns p=ns 25,00% p=ns 20,00% p=ns 15,00% 10,00% 5,00% 8,00% 9,43% 3,03% 5,36% 0,00% F0/1 F2 F3 Fibrosis stage F4 Present Absent Total Parczewski at al., CMI, 2018
37 No clustering of NS5A RAVs neither in G1 nor in G1b which suggest de novo selection of NS5A variants in the course of long-term chronic HCV
38 Real life: DAA resistance among experienced patients (unpublished) NS5A failure and RAS NS3 falure and RAS N=41 N=52 100,00% 80,00% 60,00% 40,00% 20,00% NS5A RAS Y93H 100,00% 80,00% 60,00% 40,00% 20,00% 0,00% NS5A RAS Y93H 0,00% NS3 RAS significant trend (p=0.01) Insignificant trend NS3 variant decay ater treatment termination NS5A decay ater treatment termination
39 Thank you If you want to get somewhere else, you must run at least twice as fast as that! ) - Lewis Carroll (Comment: viruses run faster, anyway)
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