Critical assessment of the global epidemiology of HCV (how reliable is the global HCV prevalence data?)

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1 Critical assessment of the global epidemiology of HCV (how reliable is the global HCV prevalence data?) Prof. Peter Ferenci Medical University of Vienna Austria

2 There are two types of claims: those based on hard numbers and those based on slippery numbers. Simon Sinek

3 How frequent is Hepatitis C virus infection? -2017: Mill. infected worldwide 2018: 70 Mill. infected worldwide Where are the missing100 Mill.? Do they exist? no reliable epidemiology is available worldwide Computer games are presented How realistic it the plan of WHO to eliminate der HCV until 2030?

4 The first estimate Based on 300 publications from the late 80 s Expert meeting in Amsterdam Assumptions for disease progression (linear vs. nonlinear), changes in trend, age at infection DISMOD (computer program used) works best for chronic diseases (e.g., asthma). It is less adapted for infectious disease such as hepatitis C Factors modifying natural history not considered Consistently normal ALT levels. Steatohepatitis Alcohol intake HIV coinfection. HBV coinfection (HBsAg). The Global Burden of Hepatitis C Working Group, J Clin Pharm 2004

5 Precise estimation of the incidence of HCV infection is not possible given available data Estimate: 130 Mill. globally infected The Global Burden of Hepatitis C Working Group, J Clin Pharm 2004

6 Estimated Global seroprevalence: 184 Mill,

7 Global prevalence of HCV The total global prevalence of anti-hcv was estimated to be 1.6% ( %), corresponding to 115 (92-149) million past viraemic infections The majority of these infections, 104 (87-124) million, were among adults (defined as those older than 15 years old) with an anti-hcv infection rate of 2.0% ( %) The viraemic (RNA positive) prevalence was forecasted to be 1.1% ( %), corresponding to 80 (64-103) = million 80 Mill. viraemic HCV-PCR+ infections Again, most of these viraemic infections were among adults who accounted for 75 (62-89) million viraemic infections or a viraemic prevalence of 1.4% ( %) Gower et al, J. Hepatol Razavi H. Lancet 2017

8 Global prevalence and genotype distribution of HCV infection in 2015: a modelling study Estimate: 71 Mill. infected If your experiment needs a statistician, you need a better experiment. Ernest Rutherford Polaris Study, Lancet Gastroenterology Hepatology 2017

9 Global prevalence and genotype distribution of HCV infection in 2015: a modelling study 80%=57 Mill 20%=14 Mill/4 billion people = 3,500/Mill people Estimate: 71 Mill. infected Europe If your experiment needs a statistician, you need a better experiment. Ernest Rutherford Polaris Study, Lancet Gastroenterology Hepatology 2017

10 N Blood+ plasma Spont. clearance 10-30% Liver mortality ~10%/40a

11 Change in the transmission of HCV Blood, blood products, nosocomial Baby boomer iv.drugs Identification of HCV iv.drugs, HIV

12 -~1968 blood,+ plasma N Spont. clearance 10-30% Liver mortality ~10%/40a

13 Blood transfusion associated HCV infection Open heart surgery in the US Open heart surgery became popular in the late 70 ies, before transfusion were mostly used in trauma cases (war! WW2), major abdominal surgery 1996 USA: 600,000; 2006:700,000/year, higher incidence in the age group > 70a Assuming 200,000 blood transfusions in the 70 ies (heart+other) 45% HCV infection= 90,000/year, about 1 million/10 years Most likely none of them are living today The few children and young adults are now in their 60 ies and 70 s 1991 UK: ~ 18,000, 2007: ~ 17, Germany: 91,967 (all with ECC) German Society for Thoracic and Cardiovascular Surgery After 1982: HCV testing for blood donation, thus transfusion associated transmission should be zero

14 Blood transfusions in the USA USA About 11.5 Mill Units blood transfused/year About 3 units / patient =3.9 Mill. Recipients/year/US ~2-3 % PTH = cases of HCV/year until 1992 Use in hospitals since 1947 Peak 1984 UK Surgenor et al, NEJM 2000, Ellingson et al, Transfusion 2017

15 Plasma products F VIII/F IX substitution Fresh frozen plasma Human albumin outbreak of HCV infection of plasma donors in Austria und Germany (about 4,000) pooled plasma 80 s imported plasma from Africa Hämophiliacs died of HIV!

16 Other routes of infection Barbers, dentists important in developing countries, now legally controlled in Western countries Tatoos now regulated in most Western countries Sexual transmission high in MSM,HIV+ Impact on numbers unknown, regional differences

17 Change in the transmission of HCV Blood, blood products, nosocomial Baby boomer iv.drugs Identification of HCV iv.drugs, HIV

18 blood,+ plasma N Spont. clearance 10-30% Liver mortality ~10%/40a

19 The Vietnam war Men who were sent to Vietnam before 1969 found marijuana plentiful but little else in the way of illicit drugs (Stanton, 1976). In 1969, heroin and opium began to arrive on the scene, and by these opiates were very widely available...heroin and opium were relatively cheap and very pure, so pure that the soldiers could get ample effect by smoking heroin in combination with Tobacco or marijuana. This made opiates appealing to men who would have been reluctant to inject them. At the height of the use of opiates, in 1971, almost half the army's enlisted men had tried them; of those who tried them, about half used enough to develop the hallmarks of addictiontolerance and Withdrawal symptoms (Robins et al., 1975). Extracted from Wikipedia

20 Vietnam was veterans are now in their 70 ies (baby boomers) average survival for men in the US 75a Assuming 1,000,000 veterans with an infection rate of 25%= 250,000 with hepatitis C

21 How genotype 3a came to Europe Goa beach Beatles visisting the ashram of Maharishi Mahesh Yogi.

22 N Spont. clearance 10-30% Liver mortality ~10%/40a

23 CDC million people in the US infected with HCV 46% due to drug abuse Infections through the medical system ( ) n=276!

24 UN General Assembly Special Session on the World Drug Problem 4/16 The report found nearly 250 million people between the ages of 15 and 64 used at least one drug in Although this figure has not grown over the past four years in proportion to the global population, the number of people classified as suffering from drug use disorders exceeded 29 million people, compared with 27 million in the previous report. Additionally, around 12 million people inject drugs, with 14 per cent of these living with HIV.

25 Estimated anti- HCV prevalence among PWID. Globally we estimated that 52 3% (95% UI ) of current PWID have been exposed to hepatitis C (anti-hcv positive), equating to 8 2 million ( million) people.. Degenhardt et al. The Lancet Global Health , e ),

26 2013 Introduction of IFN free DAA combinations

27 now N Spont. clearance 10-30%

28 Opioid epidemic USA

29 Epstein et al, ID week 2018

30 ie. Pakistan Compulsory testing of blood transfusions: 2016 No medical infrastructure in rural areas Political instability No hygienic regulations for barbers Mill. people, ~up to 8% of adults anti-hcv + > 7 Mill affected - Action needed!

31 ie. Austria Compulsory testing of blood transfusions: 1992 Many physicians available, Estimated max. n of HCV infected 28,000, about 15,000 SVR, many on treatment Legal hygienic regulations for barbers.. 8 Mill. people, 0.1% of adults anti-hcv pos! Screening of risk groups enough Estimate number of HCV+ subjects outside of risk groups : < 1000

32 Take home message Numbers on HCV-infected persons unreliable, based on limited data High regional variation route of infection availabilty of trained doctors availabilty of treatment