Hepatitis C Disease Burden and Management Strategies for 2006

Hepatitis C: Disease Burden and Management Strategies for 2006 Graham R Foster Professor of Hepatology Queen Marys School of Medicine Barts and The London HCV in 2006 • Who is infected ? • What does it do ? • What should we do about it ? HCV in 2006 • Who is infected ? • What does it do ? • What should we do about it ? HCV in 2006 We are told that • ‘HCV is common in drug users’ • ‘>90% of patients with HCV have a past history of drug use’ HCV in 2006 HCV is common in drug users Find HCV in drug users Only test for HCV in drug users HCV in 2006 We live on planet earth! Prevalence of HCV Infection Among Blood Donors* Anti-HCV Prevalence >5% - High 1.1-5% - Intermediate 0.2-1% - Low 0.1% - Very Low Unknown * Anti-HCV prevalence by EIA-1 or EIA-2 with supplemental testing; based on data available in January, 1995 Prevalence of HCV Infection Among Blood Donors* Anti-HCV Prevalence >5% - High 1.1-5% - Intermediate 0.2-1% - Low 0.1% - Very Low Unknown * Anti-HCV prevalence by EIA-1 or EIA-2 with supplemental testing; based on data available in January, 1995 HCV in 2006 The prevalence of HCV in the Indian Subcontinent is unknown HCV in 2006 The prevalence of HCV in the Indian Subcontinent is unknown • WHO estimates – 3- 5% HCV in 2006 The prevalence of HCV in the Indian Subcontinent is unknown • WHO estimates – 3- 5% • Studies in Bangladesh – 0.9% - 13% HCV in 2006 The prevalence of HCV in the Indian Subcontinent is unknown • WHO estimates – 3- 5% • Studies in Bangladesh – 0.9% - 13% • Studies in Pakistan – 3- 5% HCV in 2006 The prevalence of HCV in the Indian Subcontinent is unknown • • • • WHO estimates – 3- 5% Studies in Bangladesh – 0.9% - 13% Studies in Pakistan – 3- 5% Anecdotes in Pakistan – 20-50% 2002 census Ethnic origin – Largest group 2.3 million (4.0%) of ISC origin • ~ 1 million of Pakistani / Bangladeshi • ~ 1 million of Indian origin Born overseas – Indian (570,000) – Pakistani (336,000) 3% 17100 10080 10% 57000 33000 – Bangladeshi (152,000) 4560 15000 HCV in 2006 There may be a lot of HCV in the ethnic minority groups in the UK HCV in 2006 Whitechapel HCV in 2006 • Pilot community screening project in the East London Mosque Took place at lunchtime prayers Screened exclusively Bangladeshi subjects • • HCV Screening in East London Males 70 60 50 40 30 20 10 0 <19 20-29 30-39 40-49 50-59 60-69 70-79 >80 No of subjects HCV Screening in East London Female 40 No of subjects 30 20 10 0 <19 20-29 30-39 40-49 50-59 60-69 70-79 HCV Screening in East London Males 70 60 50 40 30 20 10 0 <19 20-29 30-39 40-49 50-59 60-69 70-79 >80 No of subjects 1 +ve HCV Screening in East London Female 40 No of subjects 30 20 10 0 <19 1 + ve 20-29 30-39 40-49 50-59 60-69 70-79 HCV Screening in East London • In Bangladeshi patients born in Syllhet the prevalence is low (<1%) • Further studies in Pakistani communities are in progress HCV in 2006 • Who is infected ? • What does it do ? • What should we do about it ? HCV – ‘ancien regime’ • HCV is a mild disease in the majority of patients • Treatment is ineffective and expensive • We should only treat patients with biopsy proven bad disease Natural History of HCV: Patients infected when young who get old ? • What is the natural history of HCV after 50 years ??? • There is very little data HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth Percent of Patients with Cirrhosis 90 80 70 60 50 40 30 20 10 0 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Age of Patients D’Souza et al Clin Gastro Hep 2005 HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth Percent of Patients with Cirrhosis 90 80 70 60 50 40 30 20 10 0 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Age of Patients D’Souza et al Clin Gastro Hep 2005 HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth Percent of Patients with Cirrhosis 90 80 70 60 50 40 30 20 10 0 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Age of Patients D’Souza et al Clin Gastro Hep 2005 Odds of end stage liver disease amongst episodes in HCV infected individuals 3 2.5 odds ratio 2 1.5 1 0.5 0 di an es hi ne s -a ix e ki st a In ad k hi k M O th -c N K d ar ni er fr e Bl ac Bl ac Pa Ba ng l C HCV in East London Percent of Patients with Cirrhosis 90 80 70 60 50 40 30 20 10 0 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Caucasians Age of Patients HCV Screening in East London Males 70 60 50 40 30 20 10 0 <19 20-29 30-39 40-49 50-59 60-69 70-79 >80 No of subjects 1 +ve Platelets/WBC dec HCV Screening in East London Female 40 No of subjects 30 20 10 0 <19 1 + ve FBC Normal 20-29 30-39 40-49 50-59 60-69 70-79 Natural History of HCV • Benign in youngsters • Progressive in the elderly • If we wait long enough many patients will develop bad liver disease HCV in 2006 • Who is infected ? • What does it do ? • What should we do about it ? HCV: therapy in 2005 • Standard of care is Peg-IFN plus ribavirin • We are starting to become very sophisticated in the way we use these drugs Sustained Response Rates in HCV Genotype non 1 – 40 KD PEG IFNα2a + Ribavirin 90 80 70 60 50 40 30 20 10 0 78% 78% 73% 77% SVR (%) n=106 n=162 n=111 n=165 PEG IFN PEG IFN RBV 800 RBV 1000/1200 PEG IFN PEG IFN RBV 800 RBV 1000/1200 24 weeks Hadziyannis et al Ann Intern Med 2004:140;346-355 48 weeks Treating the non-1 patient Can we use shorter durations of therapy ? 90 80 70 60 50 40 30 20 10 0 78% 78% 73% 77% SVR (%) n=106 n=162 n=111 n=165 PEG IFN PEG IFN RBV 800 RBV 1000/1200 PEG IFN PEG IFN RBV 800 RBV 1000/1200 24 weeks Hadziyannis et al Ann Intern Med 2004:140;346-355 48 weeks Super-responders Viral load 1 2 3 Time (months) Super-responders Viral load 1 2 3 Time (months) Super-responders Viral load 1 2 3 Time (months) Super-responders Viral load 1 2 3 Time (months) Mangia Study: Formal Study • Randomised 1:3 • Peg-Intron 1 mg/Kg + weight adjusted riba • Patients randomised to:A) Standard 24 weeks B) Variable therapy – EVR = 12 weeks No EVR = 24 weeks Results Mangia Study • Super responders with genotype 2 • SVR – 24 weeks = 89% (n=31) • SVR – 12 weeks = 87% (n=89) Mangia Study • Super responders with genotype 3 • SVR – 24 weeks = 100% (n=10) • SVR – 12 weeks = 77% (n=24) Mangia Study • The data shows that Italian patients with genotype 2 HCV do very well with 12 weeks therapy Mangia Study • There is insufficient data to comment on Italian patients with genotype 3! Short duration for genotype 3 • We have large numbers of genotype 3 patients from Bangladesh and Pakistan • Most have advanced disease • Response rates to 24 weeks therapy are disappointing Short duration for genotype 3 • What I do….. • Young drug users (super responders) get 12 weeks • The rest get 24 weeks Sustained Response Rates in HCV Genotype 1 – 40 KD PEG IFNα2a + Ribavirin 60 50 51% 41% 40% SVR (%) 40 30 20 10 29% n=101 0 PEG IFN RBV 800 n=118 PEG IFN RBV 1000/1200 n=250 n=271 PEG IFN PEG IFN RBV 800 RBV 1000/1200 24 weeks Hadziyannis et al Ann Intern Med 2004:140;346-355 48 weeks Can we improve results for genotype 1 patients ? 60 50 51% 41% 40% SVR (%) 40 30 20 10 29% n=101 0 PEG IFN RBV 800 n=118 PEG IFN RBV 1000/1200 n=250 n=271 PEG IFN PEG IFN RBV 800 RBV 1000/1200 24 weeks Hadziyannis et al Ann Intern Med 2004:140;346-355 48 weeks Identifying patients who only need 24 weeks • Sophisticated virological studies are under way to determine whether viral kinetic studies can identify early responders • Early studies suggests that patients who are PCR negative (<200 IU/ml) at week 4 can stop after 24 weeks Can we improve results for genotype 1 patients ? 60 50 51% 41% 40% SVR (%) 40 30 20 10 29% n=101 0 PEG IFN RBV 800 n=118 PEG IFN RBV 1000/1200 n=250 n=271 PEG IFN PEG IFN RBV 800 RBV 1000/1200 24 weeks Hadziyannis et al Ann Intern Med 2004:140;346-355 48 weeks Extending treatment duration • Increasing the length of therapy increases the response rates in patients who comply* • We now need to identify who will benefit from prolonged therapy *T. Berg et al – data presented at AASLD 2004 Peg-IFN and Ribavirin Today • The standard algorithms are being revised • Within 2 years we will have ‘patient friendly’ treatment regimes Peg-IFN and Ribavirin tomorrow • New direct antivirals are on the way • In 5-10 years time we will have potent new drugs HCV therapy tomorrow BILN 2061 New protease and polymerase inhibitors are on the way HCV therapy today • Therapy is less effective as you get older Effects of age and SVR (Data from patients treated with 40 KD PEG IFNα2a and Ribavirin) 90 Calculated SVR Rate (%) 80 70 60 50 40 30 20 60 55 50 45 40 35 30 25 20 Age (completed life-years) Foster et al AASLD 2003 Effects of age and SVR (Data from patients treated with 40 KD PEG IFNα2a and Ribavirin) 90 Calculated SVR Rate (%) 80 70 60 50 40 30 20 60 55 50 45 40 35 30 25 20 Age (completed life-years) Foster et al AASLD 2003 The Clinicians Dilemma • Treat early ……. • Treat later …….. The Clinicians Dilemma • Treat early ……. • Treat later …….. • Trust your patient – patients respond better when they are in control HCV – Who should we treat? (Opinion based medicine) We should NOT treat active drug users They will not comply They will get reinfected (They are not worth it) HCV in drug users - evidence Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up. Dalgard O, Bjoro K, Hellum K, Myrvang B, Skaug K, Gutigard B, Bell H; The Construct Group. Eur Addict Res 2002 Jan;8(1):45-9 Treatment of hepatitis C infection in injection drug users Markus Backmund, Kirsten Meyer, Michael Von Zielonka, Dieter Eichenlaub Hepatology July 2001 • Volume 34 • p188 to p193 HCV in drug users • Drug users infect others ! • Not treating drug users encourages the spread of HCV Treating the untreatable 27 patients started therapy (13 Genotype 1) Early cessation = 2 Completed = 10 Completed 3 months = 11 ETR = 9 (SVR 3/3) 7 PCR -ve 4 PCR +ve ALL patients have benefited from the attention – two are looking for work! How many patients with HCV should we treat ? Davis GL et al – Projecting future complications of HCV in the US Liver Transplantation 2003;9:331-338 Therapy for HCV Summary (I) • The natural history of HCV is of glacial progression • Many patients will eventually develop cirrhosis • Delaying therapy may reduce response rates Therapy for HCV Summary (II) • We have effective therapies available and these can be given to ALL patients with chronic HCV