3 rd Grampian Hepatitis C Stakeholders Meeting. Pittodrie Stadium 16 th June 2011

Transcription

1 3 rd Grampian Hepatitis C Stakeholders Meeting Pittodrie Stadium 16 th June 2011

2 Grampian HCV PCR positive cases

3 Numbers starting treatment

4 Grampian Hepatitis B New Diagnoses Acute Chronic

5 What you wanted to know about hepatitis but were too afraid to ask Andrew Fraser Consultant Gastroenterologist Clinical Lead Grampian HCV MCN Pauline Dundas Lead Hepatology Nurse NHS Grampian

6 Case 1 25 year old female with 3 month old baby Referred from maternity found to have genotype 3 hepatitis C infection IDU from age 20, stopped on finding out pregnant Currently on 30 ml methadone Does not drink alcohol Boyfriend previously successfully treated

7 Case 2 50 year old man, works offshore Drinks daily when onshore Found to have deranged LFTs Tested positive for genotype 1 Hepatitis C Admits to dabbling IDU for a few months in late teens, nil since Wife not aware of previous IDU and attends with him

8 Discussion points Who needs treatment? Are there any contraindications to treatment? Is this a good time for treatment? Any special precautions?

9 Case 1 25 year old female with 3 month old baby Referred from maternity found to have genotype 3 hepatitis C infection IDU from age 20, stopped on finding out pregnant Currently on 30 ml methadone Does not drink alcohol Boyfriend previously successfully treated

10 Liver Fibrosis in HCV Risk factors for rapid progression fibrosis score (0-4) male gender infection after age alcohol > 50g/day <10 10 to >40 female gender infection before age alcohol < 50g/day duration of infection (years)

11 Rate of progression of liver disease Correctable Alcohol consumption (esp. > 5 units per day) Obesity Smoking Cannabis Uncontrollable Age at infection Gender Ethnicity Co-infection HBV and HIV Immune deficiency

12 Case 1 25 year old female with 3 month old baby Referred from maternity found to have genotype 3 hepatitis C infection IDU from age 20, stopped on finding out pregnant Currently on 30 ml methadone Does not drink alcohol Boyfriend previously successfully treated

13 Standard therapy SVR (%) Genotype 1 Genotype 2/3 Hadziyannis SJ. Ann Int Med 2004 Grampian HCV Database 2011 (n=296) 78

14 Case 1 25 year old female with 3 month old baby Referred from maternity found to have genotype 3 hepatitis C infection IDU from age 20, stopped on finding out pregnant Currently on 30 ml methadone Does not drink alcohol Boyfriend previously successfully treated

15 Methadone Methadone %

16 Methadone and completion rates 100% 80% 60% 40% Not Completed Completed 20% 0% No Meth Meth

17 Effect on completing treatment - excluding non-responders 100% 80% 60% 40% 20% No SVR Unknown SVR 0% Completed Incomplete

18 Case 1 25 year old female with 3 month old baby Referred from maternity found to have genotype 3 hepatitis C infection IDU from age 20, stopped on finding out pregnant Currently on 30 ml methadone Does not drink alcohol Boyfriend previously successfully treated

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20 Case 2 50 year old man, works offshore Drinks daily when onshore Found to have deranged LFTs Tested positive for genotype 1 Hepatitis C Admits to dabbling IDU for a few months in late teens, nil since Wife not aware of previous IDU and attends with him

21 Liver Fibrosis in HCV Risk factors for rapid progression fibrosis score (0-4) male gender infection after age alcohol > 50g/day <10 10 to >40 female gender infection before age alcohol < 50g/day duration of infection (years)

22 Case 2 50 year old man, works offshore Drinks daily when onshore Found to have deranged LFTs Tested positive for genotype 1 Hepatitis C Admits to dabbling IDU for a few months in late teens, nil since Wife not aware of previous IDU and attends with him

23 Standard therapy SVR (%) Genotype 1 Genotype 2/3 Hadziyannis SJ. Ann Int Med 2004 Grampian HCV Database 2011 (n=296) 78

24 Predictors of poor response Genotype 1 infection Failure to complete therapy Cirrhosis Male Over 50 Obesity Ongoing alcohol excess

25 Case 2 50 year old man, works offshore Drinks daily when onshore Found to have deranged LFTs Tested positive for genotype 1 Hepatitis C Admits to dabbling IDU for a few months in late teens, nil since Wife not aware of previous IDU and attends with him

26 Contraindications to antiviral therapy Chaotic drug misuse Alcohol, heroin, crack Untreated severe psychiatric disorder Pregnancy / breast feeding Severe epilepsy Uncontrolled hypertension Active malignancy Renal failure (ribavirin) Recent severe cardiac disease

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28 Case 3 35 year old female originally from Indonesia. Married and moved to Aberdeen with 15 year old son and new husband. Currently pregnant and found to have chronic Hepatitis B infection on routine antenatal screening eag negative, eab positive, core IgM negative Works as a nurse in private nursing home

29 Discussion Why does she have infection Why is there antenatal testing Does she need further investigation Does she need treatment What about the rest of the family What about her job

30 Case 3 35 year old female originally from Indonesia. Married and moved to Aberdeen with 15 year old son and new husband 5 years ago. Currently pregnant and found to have chronic Hepatitis B infection on routine antenatal screening eag negative, eab positive, core IgM negative Works as a nurse in private nursing home

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32 HBV Endemic Regions Up to 30% of population infected Vertical transmission at time of birth Chronic infection in >90% Fibrosis, cirrhosis and hepatoma

33 HBV Nonendemic Infection usually in adulthood IDU Sexual transmission Up to 30% jaundiced especially IDU Virus cleared in 95%

34 Case 3 35 year old female originally from Indonesia. Married and moved to Aberdeen with 15 year old son and new husband. Currently pregnant and found to have chronic Hepatitis B infection on routine antenatal screening eag negative, eab positive, core IgM negative Works as a nurse in private nursing home

35 Stages of CHB disease Immune tolerance HBeAg + Immune clearance HBeAg + Low replicative phase Reactivation phase HBeAg - HBeAg - HBV-DNA cp/ml cp/ml <10 5 cp/ml >10 5 cp/ml ALT Normal/ mild CH Moderate/severe CH Cirrhosis Normal/mild CH Inactive cirrhosis Moderate/severe CH Cirrhosis HBeAg + CHB HBeAg + CHB Inactive-carrier state HBeAg CHB Adapted from Fattovich. Sem Liver Dis 2003

36 Case 3 35 year old female originally from Indonesia. Married and moved to Aberdeen with 15 year old son and new husband 5 years ago. Currently pregnant and found to have chronic Hepatitis B infection on routine antenatal screening eag negative, eab positive, core IgM negative Works as a nurse in private nursing home

37 HBV INFECTION Infant subclinical 95% chronic carrier Cirrhosis HCC (up to 40%)

38 HBV is preventable - Immunisation >95% protection from vertical transmission if immunised at birth Consider addition of antiviral drugs in last trimester in mother if viral load high >90% protection for adults in at risk categories WHO recommends universal HBV vaccination UK has adopted selective

39 Adult HBV INFECTION Infant 80% subclinical 20% acute hepatitis 1% fulminant hepatitis subclinical 95% recovery 5% carriers Cirrhosis HCC (0.5%) 95% chronic carrier Cirrhosis HCC (up to 40%)

40 HBV - vaccination - Who? Babies of chronic carriers of HBV IDU Multiple sexual partners Chronic liver disease Family contacts Haemophiliacs Chronic renal failure Healthcare workers Staff and residents in mental handicap inst. Emergency services Prison staff and inmates Travellers to endemic areas

41 HBV and EPP EPP When part of the healthcare workers hands not fully visible and could come into contact with sharp object within patients body eag +ve - EPP not allowed eag ve HBV DNA > 1000 cp/ml EPP not allowed HBV DNA cp/ml EPP only allowed if < 1000 cp/ml on treatment.

42 Hepatitis B and C in Scotland Hepatitis C Predominantly IDU Indigenous Curable 6 to 12 months of therapy High incidence of side effects Prevention Prevention of IDU Safe injecting practices Hepatitis B Predominantly vertical Immigrants Treatable Life-long therapy? Low incidence of side effects Prevention Vaccination Condoms

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46 Stages of CHB disease Immune tolerance HBeAg + Immune clearance HBeAg + Low replicative phase Reactivation phase HBeAg - HBeAg - HBV-DNA cp/ml cp/ml <10 5 cp/ml >10 5 cp/ml ALT Normal/ mild CH Moderate/severe CH Cirrhosis Normal/mild CH Inactive cirrhosis Moderate/severe CH Cirrhosis HBeAg + CHB HBeAg + CHB Inactive-carrier state HBeAg CHB Adapted from Fattovich. Sem Liver Dis 2003

47 Predictors of poor response Genotype 1 infection Failure to complete therapy Cirrhosis Male Over 50 Obesity Ongoing alcohol excess

48 Discussion points Does she need treatment? Are there any contraindications to treatment? Is this a good time for treatment? Any special precautions? What are her chances of cure?

49 Liver Fibrosis in HCV Risk factors for rapid progression fibrosis score (0-4) male gender infection after age alcohol > 50g/day <10 10 to >40 female gender infection before age alcohol < 50g/day duration of infection (years)

50 Discussion points Does she need treatment Likely mild disease Young female, short duration of infection, no alcohol Are there any contraindications to treatment Not obvious Is this a good time for treatment Side effects Small child, methadone Teratogenicity of treatment

51 HCV Infection Virus cleared No liver disease 15-20% 80-85% Ongoing viraemia Minimal liver disease Ongoing mild hepatitis Liver fibrosis cirrhosis Liver failure hepatoma

52 Age at first positive HCV test

53 Available treatments Weekly subcutaneous injection of Pegylated interferon Self-administered plus Daily Ribavirin tablets Between 4 and 7 tablets per day Treatment normally 6 or 12 months

54 Numbers starting treatment

55 Numbers starting treatment

56 Methadone Methadone %

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58 What about treatment?

59 Progress in HCV Therapy SVR % IFN 6m IFN 12m IFN/RBV 6m IFN/RBV 12m PEG-IFN 12m PEG-IFN /RBV 12m

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61 Standard therapy SVR (%) Genotype 1 Genotype 2/3 Hadziyannis SJ. Ann Int Med 2004 Grampian HCV Database 2011 (n=296) 78

62 Protease Inhibitors Treatment naïve Genotype PROVE 1 PROVE 2 SPRINT 1* SOC Combination

63 Protease Inhibitors Previously treated Genotype PROVE 3 RESPOND 2* SOC for 48 weeks Combination

64 AEs Occurring in 25% of Patients During any Treatment Phase Patients, n (%) T12/PR48 (N=266) Pbo/PR48 (N=132) Fatigue 145 (55) 53 (40) Pruritus 138 (52) 36 (27) Headache 112 (42) 49 (37) Rash 99 (37) 25 (19) Nausea 94 (35) 31 (23) Influenza-like illness 85 (32) 33 (25) Anaemia 79 (30) 20 (15) Anorectal symptoms 75 (28) 10 (8) Insomnia 68 (26) 34 (26) Diarrhoea 66 (25) 18 (14) Pyrexia 60 (23) 36 (27) Cough 62 (23) 26 (20) Asthenia 51 (19) 38 (29) Shading indicates AEs with an incidence >10% greater in the T12/PR48 arm compared with Pbo/PR48

65 Why do patients stop treatment Non-response Disappear / Drug and alcohol use Side-effects Anaemia Erythropoeitin Reduced White Cells GCSF Mental health issues Antidepressants Sleeping tablets

66 Adherence to planned treatment 100% 80% 60% 40% 20% 0% Incomplete On Treatment Complete

67 Patients who come to clinic have a high chance of starting antiviral therapy 80% of people completing prescribed course will cure their Hepatitis C infection

68 Hepatitis C conclusion There is a lot of it about (1%) Majority are males of working age Without treatment large percentage will progress to cirrhosis There is a cure Treatment is arduous but time limited Support through therapy Alteration of work pattern Psychological Financial

69 Hepatitis B

70 5% prevalence = 1600 cases of chronic HBV infection

71 Source of HBV infection 2004

72 Source of HBV infection 2010?

73 Stages of HBV infection sag sab eag eab cab cab IgM DNA ALT cccdna Acute infection present Immunotolerant N present Immune reactive present Low replicative /- N present Late reactivation present Previous infection N present

74 Hepatitis B does not cause the liver damage The Immune system does the damage The aim of treatment is to limit liver damage Timing of treatment is important Aims of treatment need to be clear

75 Stages of HBV infection sag sab eag eab cab cab IgM DNA ALT cccdna Acute infection present Immunotolerant N present Immune reactive present Low replicative /- N present Late reactivation present Previous infection N present

76 Interferon 48 weeks of Rx Absence of resistance Higher rates of HBV eag and sag seroconversion Moderate antiviral effect Poorly tolerated Injection NUC Indefinite duration Risk of resistance Lower rates of eag and sag seroconversion Potent antiviral effect Well tolerated Oral

77 Undetectable HBV DNA at 48 weeks

78 Treatment Around 20% of patients require treatment Some suitable for 1 year of interferon Lifelong treatment Tenofovir, entecavir Cost 3,000 per year Virus suppressed in >90%

79 Hepatitis B Summary Chronic HBV infection is becoming more common in Scotland (imported) Requires specialist referral to stage disease and assess for treatment Treatment is safe and effective HBV infection is preventable Vaccination, Condoms, Universal precautions, Sterile equipment

80 Healthy Liver

81 Cirrhosis

82 Viral Hepatitis Hepatitis A Hepatitis B Hepatitis C Delta agent (Hepatitis D) Hepatitis E Other hepatotrphic viruses EBV, CMV

83 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B Hepatitis C Delta agent (Hepatitis D) Hepatitis E Other viruses EBV, CMV

84 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B - Spread by blood and secretions Hepatitis C Delta agent (Hepatitis D) Hepatitis E Other viruses EBV, CMV

85 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B - Spread by blood and secretions Hepatitis C - Spread by blood contact Delta agent (Hepatitis D) Hepatitis E Other viruses EBV, CMV

86 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B - Spread by blood and secretions Hepatitis C - Spread by blood contact Delta agent (Hepatitis D) Incomplete virus Hepatitis E Other viruses EBV, CMV

87 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B - Spread by blood and secretions Hepatitis C Delta agent (Hepatitis D) Incomplete virus Hepatitis E - Spread by the faecal-oral route Other viruses EBV, CMV

88 Viral Hepatitis Hepatitis A - Spread by the faecal-oral route Hepatitis B - Spread by blood and secretions Hepatitis C - Spread by blood contact Delta agent (Hepatitis D) Incomplete virus Hepatitis E - Spread by the faecal-oral route Other viruses - Droplet spread mainly EBV, CMV

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90 HCV infection can be cured More than half treated are cured You can t be cured unless -you know you have the infection -and receive antiviral therapy

91 Natural History Virus only identified % patients report acute jaundice Rarely causes acute liver failure 80% chronic HCV infection Most asymptomatic until cirrhotic May have normal LFT s

92 Transmission IDU Tattoos Sexual Unknown Blood products UK blood donor screening since 1991 Heat treatment of plasma since mid 80s

93 Source of Infection (Of those attending HCV clinic in Grampian) 8% 6% 3% 2% 1% IDU Unknown Blood Transfusion? Tattoo/piercing HCV+ve partner Vertical transmission 80%

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95 HCV Action Plan Scotland - Target treatment figures 08/ / / / * * And every year for next 20 years

96 HCV Clinic Liver Nurse Specialists Medical staff Substance Misuse Nurse Dietician Citizens Advice Bureau Outreach Peterhead, Fraserburgh, Elgin, Homeless practice, prisons

97 Customised Therapy Measure virus level (PCR) Before Rx 4, 12, 24, 48 (72, 96) weeks of treatment Genotype 1 24 weeks for low viral load rapid responders 72 weeks for slow responders Genotype 2 and 3 16 weeks for rapid responders

98 Grampian Treatment started antiviral therapy 198 (72%) completed planned treatment course 162 (59%) achieved SVR (cure) Success rates as good as clinical trials

99 Adult HBV INFECTION Infant 80% subclinical 20% acute hepatitis 1% fulminant hepatitis subclinical 95% recovery 5% carriers Cirrhosis HCC (0.5%) 95% chronic carrier Cirrhosis HCC (up to 40%)