The effect of improved HCV diagnosis and treatment on public health The effect of improved HCV diagnosis and treatment on public health P Mathurin Hôpital Claude Huriez Lille

Yoshida H et al., Gut 2004 Gain in hepatocellular carcinoma-free survival by Interferon

Yoshida H et al., Gut 2004 Gain in hepatocellular carcinoma-free survival by Interferon

6 months’ interferon monotherapy was the main protocol with a 7% SVR rate for type 1b genotype high viral load Peginterferon and ribavirin for 48 weeks with a response rate of 40% or better will provide - 5 additional years of gain in HCC-free survival in 40-year old patients with fibrosis stage F4 - 1 additional year of gain in HCC-free survival in 60-year old patients with fibrosis stage F2 Gain in hepatocellular carcinoma-free survival by Interferon Yoshida H et al., Gut 2004

Impact of viral eradication on mortality related to hepatitis C using a modeling approach Deuffic-Burban S, Deltenre P, Louvet A, Canva V, Dharancy S, Hollebecque A, Boitard J, Henrion J, Yazdanpanah Y, Mathurin P J Hepatol 2008

Our first aim: quantify the impact of alcohol abuse, present screening policy and antiviral therapy on HCV mortality Second aim: estimate the impact of viral eradication in terms of lives saved, according to different scenarios of progress in HCV screening and treatment practice Aims

Recovery from infection Liver failure Death from other causes Cirrhosis F4 25% 75% P s,a,i P P P P LF P HCC P DHCC P DLF Infection HCC F3 F2 F1 F0 HCV- related HCC death HCV- related l iver failure death Model simulates HCV progression of infected cohorts with acute hepatitis C

Model assumptions Screening assumptions in % of individuals aware of their function - 5% of HCV individuals aware of their HCV infection in 1991 when antiviral treatment became available - linear increase to 24% in 1994 (Dubois F Hepatology 1997) and to 56% in 2004 (Meffre C et al., Prevalence of hepatitis C in France, EASL 2006) - that, according to the same second linear progression, it will reach 75% (French government objective) Assumption for excessive drinking - excessive alcohol intake starts at 20 years of age

Main assumptions for treatment were: 1)Patients eligible for treatment were those aware of their infection, between 18 and 70 years of age 2)The annual likelihood of treatment was independent of age and sex 3)The annual likelihood of treatment for patients with fibrosis stage F<2 was 80% lower than for patients with fibrosis stage F  2 4)For patients with alcohol abuse, the annual likelihood of treatment was 80% lower than for patients without alcohol abuse 5)Patients achieving SVR were withdrawn from the number of patients in the different stages, except for patients with cirrhosis (F4) who remain at risk of developing complications of cirrhosis Model assumptions

Proportion of treated patientsProportion of sustained viral responder Genotypes 1/4Genotypes 2/3Genotypes 1/4Genotypes 2/3References Naive patients (first treatment)F ≤ 2F > 2F ≤ 2F > % 3%2%20%14%(35, 36) % 7%5%29%21%(35, 36) %42%38%27%64%46%(3, 35, 36) 2002*21%42% 53%38%79%68%(3) 80% lower Annual likelihood of treatment for patients with fibrosis stage F<2 was 80% lower than for patients with fibrosis stage F  2 Annual likelihood of treatment among patients aware of their infection

Year Annual incidence of HCC death Predicted death from HCC for men Observed death from HCC for men Predicted death from HCC for women Observed death from HCC for women Model fits the observed mortality

Year Annual incidence of HCV-related mortality Death from liver failure Death from HCC HCV-related mortality: liver failure vs HCC

37% of individuals recovered from their infection -72% of them spontaneously -28% of them after therapy 63% were HCV-RNA+ -17% of whom were previously treated -38% of whom were aware of their infection but never treated -45% unaware of their HCV status Model prediction in 2006 Virological pattern

Impact of viral eradication on mortality Influence of excessive alcohol intake of whom 13% were decompensated of whom 42% were decompensated 23% 52% 0% 20% 40% 60% 80% 100% % of severe fibrosis (F3-F4) < 50 g/day alcohol > 50 g/day alcohol

Age class 0% 2% 4% 6% 8% 10% 12% Mortality ratio (%) Alcohol < 50g per day Alcohol > 50g per day 4% 0.37 % 11-fold increase In 2001 mean age at death was earlier in alcohol+ patients: 69 vs 58 years Impact of viral eradication on mortality Influence of excessive alcohol intake

In the modeling project mean age at death 69 years for HCV patients without alcohol consumption 58 years for alcohol HCV patients Marcellin J Hepatol 2007 Impact of viral eradication on mortality Influence of excessive alcohol intake

Year Annual incidence of HCV-related mortality In the absence of treatment With current practice of treatment -14% 7000 (6,700-7,300) deaths -32% G1/4 G2/ (7,200-7,700) deaths Impact of current treatment on mortality According to genotypes

In a scenario of new therapeutic guidelines supporting treatment regardless of fibrosis stages (same proportion for patients F<2 as those F  2): (95%CI, ) additional lives would be saved The model predicted that the French government objective of 75% of infected patients aware of their status would be reached in If the efforts of French public health authorities were increased so as to reach 75% in 2010 (4 years earlier) (95% CI, 900-1,000) lives could be saved over the next 20 years Impact of scenarios of progress in HCV screening and treatment practice

A scenario potential availability of new antiviral drug in 2010 (same improvement in SVR for G1/4 as previously obtained with pegylated bitherapy (40% increase in viral eradication) –For naïve G1/4 patients, SVR of 74% in F<2 and 53 % in F  2 –For previously treated G1/4 patient, SVR of 24% in F<2 and 18% in F  2 New molecule will save - 1,500 (95% CI, 1,400-1,600) lives over the next 20 years. If, at the same time, the proportion of screening reached 75%, then the impact upon mortality in the next 20 years times greater than the same new molecule without improved screening corresponding to a total of 2,600 (95%CI, 2,500-2,800) deaths avoided (- 4.5%)

Modeling approach in Greece V. Sypsa, J Viral Hepat 2005

Conclusions In France current antiviral therapy will reduce HCV mortality from by 20% Therapeutic guidelines must take into account their impact on HCV mortality Public health policy is as important as treatment