Hepatitis C David Mutimer Queen Elizabeth Hospital Liver Unit Birmingham Substance Misuse Treatment in the West Midlands. How can we reduce harm? Birmingham October 19 th 2007
infection HCV Natural History 20% clearance chronic hepatitis
infection HCV Natural History 20% clearance chronic hepatitis cirrhosis
Liver Biopsy Scoring System Ishak et al. J Hepatology 1995;22:696. Grading Periportal hepatitis Confluent necrosis Spotty necrosis Portal inflammation Score 0-4 0-6 0-4 0-4 0-18 Staging (fibrosis) 0-6
liver fibrosis score (degree of scarring) 6 cirrhosis 3 0 10 20 30 60 years
liver fibrosis score (degree of scarring) 6 cirrhosis HCV-pos (median time 30 years) 3 0 10 20 30 60 years
liver fibrosis score (degree of scarring) 6 cirrhosis HCV-pos (median time 30 years) 3 age at infection gender alcohol consumption 0 10 20 30 60 years
liver fibrosis score (degree of scarring) 6 cirrhosis male infected at 50 alcohol XS 3 age at infection gender alcohol consumption 0 10 20 30 60 years
liver fibrosis score (degree of scarring) 6 cirrhosis female infected at 20 teetotal 3 age at infection gender alcohol consumption 0 10 20 30 60 years
infection HCV Natural History 20% clearance chronic hepatitis cirrhosis 20% @ 20 years 50% @ 30 years age at infection gender alcohol consumption
infection HCV Natural History 20% clearance chronic hepatitis cirrhosis 20% @ 20 years 50% @ 30 years age at infection gender alcohol consumption liver cancer liver failure
HCV Genotypes 6 main genotypes Nucleotide diversity > 20% Little effect on natural history Geographical variation Most important determinant of response to treatment
50% 40% 30% 20% 10% 0% geno 1 geno 2 geno 3 80% 70% 60% 50% 40% 30% 20% 10% 0% geno 1 geno 2 geno 3 100% 80% 60% 40% 20% 0% geno 1 geno 2 geno 3
50% 40% 30% 20% 38% 47% 10% 0% 9% geno 1 geno 2 geno 3
Treatment in HCV NICE approved! Treatment can cure sustained virological response, SVR serum HCV negativity 6 months post-treatment Existing best treatment pegylated interferon (weekly injections) ribavirin (daily tablets) Treatment duration 6 months for genotypes 2 and 3 12 months for genotype 1 Most patients have side-effects treatment compliance is a major issue
Peg-IFN & Ribavirin (Birmingham) Tolerability of treatment % remaining on treatment 100% 95% 90% 85% 80% 75% 70% 65% 60% all patients genotype 1 0 4 8 12 16 20 24 28 32 36 40 44 48 weeks
Antiviral Treatment of Hepatitis C pegifn/riba published pegifn/riba QE B'ham 100% 80% 82% 60% 62% 40% 20% 42% 28% 0% type 1 HCV other HCV types
Why are results inferior? Clinical trials include ideal patients Clinical practice deals with whoever walks through the door! difficult, mad and bad
Why are results inferior? Clinical trials include ideal patients Clinical practice deals with whoever walks through the door! difficult, mad and bad Clinical trials have appropriate support clinical trials nurse Clinical practice fumbles with inadequate support hepatitis nurse specialists, pharmacist, etc
Why are results inferior? Clinical trials include ideal patients Clinical practice deals with whoever walks through the door! difficult, mad and bad Clinical trials have appropriate support clinical trials nurse Clinical practice fumbles with inadequate support hepatitis nurse specialist, pharmacist, etc? trials are undertaken by expert units Trend for generalist to offer HCV treatment
QE HCV Patients Year of referral for patients seen in clinic during 2006 200 180 160 140 120 100 80 60 40 20 <1990 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 0
Ethnic origin of HCV patients (2006) QE Hepatitis Database 574, 73% 9, 1% 165, 21% 43, 5% Asian Black Caucasian Chinese
Birmingham BBV Team HBV vaccination of drug users HCV counselling and screening Direct referral of hepatitis-positive patients to QE Liver Unit if they want referral if they are likely to turn up Audit of activity June 2003 to December 2006
Birmingham BBV Team June 2003 to December 2006 141 cases diagnosed 63 patients referred 45 male, mean age 35 years
QE Hepatitis Clinic 50% 40% 30% 20% 38% 47% 10% 0% 9% geno 1 geno 2 geno 3 BBV referrals 70% 60% 50% 40% 30% 20% 10% 0% 62% 33% 5% geno 1 geno 2 geno 3
Birmingham BBV Team June 2003 to December 2006 141 cases diagnosed 63 patients referred 45 male, mean age 35 years 49 attended first consultation 18 subsequently defaulted 31 continued follow-up (attended recent OPA)
QE Hepatitis Clinic BBV referrals (clinic) actuarial survival 1 0.9 0.8 proportion attending 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 4 8 12 16 20 24 28 32 36 40 44 48 months
Birmingham BBV Team June 2003 to December 2006 141 cases diagnosed 63 patients referred 45 male, mean age 35 years 49 attended first consultation 18 subsequently defaulted 31 continued follow-up (attended recent OPA) 11 commenced antiviral therapy 4 currently on treatment
Birmingham BBV Team June 2003 to December 2006 pt geno titre biopsy week response comment 1 3a 3,045,569 no 22* EVR 2 3a 589,061 no 9* - 3 3a 140,000 F2 20 EVR defaulted 4 3a >550,000 no 24 SVR 5 3a 320,000 F2 24 SVR 6 3a >550,000 no 4* - 7 2 86,900 no 24 EOTR defaulted 8 3a 58,400 no 24 SVR 9 3a 992,257 F3 9* - 10 3a 9,800 F1 24 EOTR defaulted 11 3a 64,823 no 24 EOTR < 6 months post-treatment * still on treatment
The Best Location for Treatment of Hepatitis C? Convenience Safety (essential) Efficacy (essential)
The Best Location for Treatment of Hepatitis C? Convenience Safety (essential) Efficacy (essential) HCV treatment is hard to deliver for the patient! Treatment is expensive efficacy is utmost Who can treat HCV? appropriate experience appropriate resources appropriate back-up appropriate results!