Prevention of liver cancer and care of people living with Chronic Hepatitis B. Presenters Dr. Nicole Allard and Vanessa Towell.

Transcription

1 Prevention of liver cancer and care of people living with Chronic Hepatitis B. Presenters Dr. Nicole Allard and Vanessa Towell.

2

3 Pre and post test questionnaire

4 1. In Australia the main burden of Chronic hepatitis B is in people born in Asia True False

5 2. Aboriginal people are one of the priority communities affected by CHB True False

6 3. Hepatitis B causes liver cancer True False

7 4. The majority of people living with CHB do not need ongoing management True False

8 5. The presence of HBsAg in a 40 year old born in China needs a further test at 6 month to confirm CHB infection True False

9 6. CHB patients born in Africa with chronic hepatitis B should be screened for liver cancer from the age of 20. True False

10 7. There is treatment available for chronic hepatitis B True False

11 8. Treatment reduces liver scarring but not risk of cancer True False

12 9. Pregnant women and their children are normal managed and followed up by specialist services True False

13 10. Cancer screening is aimed to detect cancers early rather than prevent cancer True False

14 Declaration Nicole Allard Has received no pharmaceutical company support or sponsorship Advisory COC for ASHM Vanessa Towell Has received no pharmaceutical company support or sponsorship

15 Acknowledgement Slides: presentation adapted from relevant section of Advanced Management of Hepatitis B course for general practitioners developed by ASHM and also includes material from VIDRL presentations and ML mapping project.

16 Objectives include to understand Epidemiology Natural History Who and how to test Role of primary care in care and cancer screening How to develop a GPMP for CHB

17 Global epidemiology Major health issue worldwide ~ 350 million with CHB, 500, ,000 deaths annually most infected perinatally Estimated to be the 10 th leading cause of death worldwide 2 nd most important human carcinogen, after tobacco HCC 5th most common cause of cancer, 3 rd most common cause of cancer related mortality China deaths over 300,000 per year 80% CHB WHO fact sheet, Chen 2011

18 Source: et/index.htm

19 Lavanchy 2004

20 Epidemiology in Australia Most reliable Australian estimate: 218,000 people with chronic hepatitis B, over 2 million ever infected J MacLachlan, ANZJPH 2013

21 Mortality Chronic hepatitis B: 15-25% will die from the complications of cirrhosis or from hepatocellular carcinoma (HCC) without appropriate treatment and care Ref: Fattovich J Hepatol 2008

22 Liver cancer and ATSI Indigenous Australians are 3 times as likely to develop, and 3.3 times as likely to die from liver cancer and had a lower chance of surviving another 1 year (21% compared with 33%). ( Australian Institute of Health and Welfare report 2013) higher prevalence of hepatitis B infection 3.7% in this population group is a contributing factor.

23 HBV vaccination in Australia Vaccine available since 1984 Aboriginal and Torres Strait Islander people in NT since 1990 Adolescent catch up program 1998 Universal infant vaccination 2000.so why is it an ongoing issue? National Immunisation Handbook 2013

24 Australian permanent migration data High >8% Intermediate 2 8% Low <2% 0 Source: Dept of immigration permanent migration data

25 Chronic Hepatitis B in Australia 218,000 living with CHB 112,000 diagnosed 25,000 in care J MacLachlan ANZJPH 2013, NNDSS, Medicare data

26 Viral Load and Incidence of Cirrhosis Cumulative incidence of liver cirrhosis (% subjects) Baseline HBV DNA level, copies/ml 10 6 (n=602) 10 5 <10 6 (n=333) 10 4 <10 5 (n=628) 300 <10 4 (n=1,150) <300 (n=869) Log rank test of trend p< Year of follow up Cumulative Incidence of Liver Cirrhosis All Subjects (n=3,582) 36.2% 23.5% 9.8% 5.9% 4.5% Iloeje UH, et al. Gastroenterology. 2006;130;

27 Viral Load and Incidence of HCC Cumulative incidence of HCC (%) Cumulative Incidence of HCC: All Subjects (n=3,653) Baseline HBV DNA Level, copies/ml < < <10 4 < Year of follow up 14.89% 12.17% 3.57% 1.37% 1.30% Chen CJ, et al. JAMA. 2006;295:65 73.

28 Cancer in New South Wales Incidence and Mortality Report 2008

29 J MacLachlan VIDRL 2012

30 Micro epidemiology Consider your own practice and interests Individual practices may not reflect population in LGA Special interests refugee health, HIV medicine, drug and alcohol, student health

31 Task 1 My patients Newly arrived refugees Pakistan, Burma, Afghani, Iran CHB 56% Sudanese, 4% Vietnamese JOSLIN CLINIC Community health Low SES Women s health Mental health Refugees, BVE, Iran, Burma Sudanese from mid 2000 IDU Old Foostcray (union) Shared care MARIBYRNONG Inner western Melb. 50% born overseas 58% Aust. born have both Parents born overseas Low SES and gentrification 44% 2 languages at home Vietnamese 10% Chinese 3% Indian4%

32 Testing

33 Who to test People born in Asia, Africa, Middle East, Pacific Islands, Eastern & Southern Europe Sexual and household contacts and family members of people with hepatitis B Aboriginal and Torres Strait Islanders Pregnant women Men who have sex with men, people who inject drugs, Sex workers, haemodialysis patients, people with another STI, hepatitis C or HIV infection, everyone prior to receiving cytotoxics or immunosuppressive therapy, people with elevated ALT/AST of unknown aetiology ASHM testing portal

34 What tests should we order? If chronic infection HBsAg anti-hbc (= HBcAb) anti-hbs (= HBsAb) DON T order HEPATITIS B SEROLOGY In suspected acute infection IgM anti- HBc

35 Interpretation of HBV serology HBsAg anti HBc anti HBs negative negative negative susceptible HBsAg anti HBc anti HBs negative positive positive resolved HBV infection HBsAg anti HBc anti HBs negative negative positive vaccinated HBsAg anti HBc IgM anti HBc * anti HBs positive positive positive negative (high titre)* acute HBV infection HBsAg anti HBc IgM anti HBc anti HBs positive positive negative negative chronic HBV infection HBsAg anti HBc anti HBs negative positive negative various possibilities Mast 2006

36 A brief note on isolated core anti-hbc Most common associated with low titre anti-hbs <10 IU/ML and person is naturally immune HBV DNA not on Medicare for testing in this setting Occasionally represent occult infection May be a false positive anti-hbc + May be recovering from acute HBV infection Important in HIV, HCV, liver disease person about to undergo chemotherapy

37 Conveying positive results Use an interpreter where appropriate (check translation of virus ) providing information about the legal considerations around disclosure of hepatitis B status and the provision of information about (and referral to) available to support services Deliver information in more than one form (resources HepB help, ASHM, Cancer council, hepatitis organisations) Arrange for follow up appointment to answer questions and to review further testing ASHM website for hbv testing/ conveying hepatitis b test results

38 Disclosure Sexual partners Workplace Family and extended family Patient living with CHB Childcare centre or school Friends & Community Sporting club

39 Negative results If negative and not immune offer vaccination Vaccination recommended for: Household or household like contacts, sexual contacts, men who have sex with men, migrants from endemic countries, ATSI, haemodialysis patients and patient where haemodyalysis is anticipated, transplant recipients, HIV positive adults and other immunocompromised adults, people with liver disease or hepatitis C, person with developmental disabilities attending residential or non residential facilities, People who inject drugs, sex industry workers and other persons at occupational risk, travelers to endemic areas. BUT NOT ALWAYS FREE (check in your state) Ref: The Australian Immunisation handbook 10 th edition 2013

40 Task 2 HBsAg Anti HBc Anti HBs Person immune from exposure to the virus as a child in China Health care worker successfully immunised last year Person living with CHB

41 Task 2 HBsAg Anti HBc Anti HBs Person immune from exposure to the virus as a child in China + + Health care worker successfully immunised last year Person living with CHB + + +

42 Natural history, monitoring and cancer screening

43 ASHM resource

44 Initial Assessment of patients with CHB 1. History, Family History esp. history of liver cancer and physical examination 2. Viral markers hepatitis B surface antigen (HBsAg) hepatitis B e-antigen (HBeAg); anti-hbe serum hepatitis B virus (HBV) DNA testing for anti-hav, anti-hcv, anti-hdv and anti-hiv 3. Markers of liver disease liver enzymes ALT and AST markers of liver function Serum bilirubin, albumin, INR, AFP, FBC (platelets) Imaging (usually ultrasound) 4. Evaluation for co-morbidities Alcohol, drug abuse, diabetes

45 ALT VALUES and significance Laboratories will vary in reporting of abnormal range >50 FOR women ALT > 20 FOR men ALT > 30 On diagnosis order more than once before deciding on phase e.g. 2-3 times over 3 month period

46 FibroScan Available in most large hepatitis clinics portable units Procedure well validated and reproducible Takes approximately 5 minutes Can be easily repeated on serial basis Can accurately determine if someone has minimal fibrosis or severe fibrosis/cirrhosis ASHM 2012

47 Cancer screening Cancer screening is part of routine monitoring for specific groups African men and women from >20 Asian men for the age of >40 Asian women from the age of >50 Aboriginal and Torres Strait Islander people >50* Patients with cirrhosis Patients with a family history of HCC Ref:

48 Cancer screening participation in established supported programs Cervical cancer 57% Breast 56% Bowel 38% Participation affected by remoteness, SES, CALD& ATSI AIHW 2013, Breast Screen

49 Cancer screening Ultrasound and AFP 6 monthly A new lesion need further assessment with quadruple phase CT and specialist review US report can vary in quality EARLY DETECTION NOT PREVENTION

50 Cancer screening Diagnoses smaller cancers better characteristics less vascular invasion Increases median survival 977 vs 253 days Higher proportion can be treated with curative intent (68% vs 30%) Wong et al. Internal Med Journal 2012

51 Anti viral treatment

52 Progression to Chronic HBV Infection Acute (6 months) HBeAg Chronic (Years) anti HBe HBsAg Titre Total anti HBc IgM anti HBc Years Weeks after exposure

53 HBeAg Positive High HBV DNA Elevated ALT Abnormal Liver Biopsy HBeAg Negative High HBV DNA Elevated ALT Abnormal Liver Biopsy

54 Anti Viral treatment Treatment can reverse fibrosis in the liver and prevent further damage Reduces the risk of cancer up to 75% over 5 years Reduces infectivity and mother to child transmission Reduces mortality May result in HBeAg seroconversion or rarely HBsAg Is cost effective as HCC prevention Papatheodoridis 2010, Kim 2012, Kumada 2012, Hosaka 2013, Robotin 2009

55 Treatment Treatment-Naïve patients PegIFN alfa 2a consider Phase 2 HBeAg Entecavir (well tolerated, low resistance at 5 years) Tenofovir (women of childbearing age, HIV co infection, renal function testing, low/no resistance at 5 years) Lamivudine-Resistant patients Tenofovir ± Lamivudine

56 Definitions of Response in CHB Suppression of HBV DNA and normalisation of ALT Achievable and Effective Endpoint HBeAg loss HBeAg seroconversion HBsAg loss HBsAg seroconversion Major trial endpoint Optimal endpoint

57 All patients All patients need yearly viral load and liver function tests done 6 monthly Should be assessed for cirrhosis using FibroScan specialist referral There is no such thing as a HEALTHY CARRIER

58 Pregnancy High viral load > 10,000,000 IU/ml is associated with increased risk of transmission to newborn Pregnancy is a relatively immune tolerant state All women need HBV DNA during pregnancy and referral for assessment This is not always done by specialist services Glies 2013, Gurguis

59 .so how well are we doing that? 2 Sydney Hospitals 14,857 Births 295 CHB antenatal patients 98% born overseas 3 Victorian hospitals 46,855 Births 398 CHB antenatal patients 87% born overseas HBeAg 65% DNA 3.5% Specialist care 7% HBeAg 33% DNA 20% Specialist care 18% Ref: Guirgis, M JGHF 2009 and Giles et al ANZJOG 2013

60 213 HBsAg +ve mother followed, 138 infants tested 4 positive All babies received HBIG and birth dose HBV <12 hours Transmission related to viral load Birth dose is as/more important than HBIG Specialist care Lamivudine or Tenofovir until 3 months post partum Wiseman et al MJA 2009

61 Co infection HDV/HIV/HCV or combination Outcomes worse liver disease, HCC and mortality Specialist management as co infection complicates treatment choice

62 Steps for management 1. work out phase of disease 2. arrange appropriate referral or monitoring 3. cancer (HCC) screening if required 4. HAV vaccination (if not immune)

63 Steps for management in GP (2) 5. Lifestyle advice 6. Information about how you can and can not transmit HBV 7. contact tracing and vaccination of contacts and advise testing of the wider family

64 Case study 50 year old Somali man CHB 2003 previously yearly bloods anti- HBe, viral load 1560 IU/ml, ALT 19 BMI 35 Yearly viral load 24,000 ALT 30 Ultrasound new lesion?haemangioma 9mm x 10mm

65 Case study Mr. BK 30 year old born Afghanistan, Entecavir in Pakistan for one year arrived 2012 screened in detention centre VL 560 IU/ml, HBeAg ve, HBeAB +ve, ALT 20, BMI 24, alcohol intake rarely, Platelets 121, Bilirubin 35

66 Case study A. Mr. N 50 year man B. Mr. K 45 year old C. Mr. N 42 year old HBsAg anti HBc anti HBs + < D. Mr. T 22 year old >100

67 Challenges Priority populations are often disadvantaged in terms of access to services Health literacy Stigma and discrimination CALD and ATSI Lower participation rates in cancer screening programs that are supported breast, cervical and bowel

68 Challenges Poor care during pregnancy DNA not performed, timely? birth dose <24 hours Low Rates of follow up of infants born to CHB+ mothers and their families Loss to follow up as child transitions to adult services Contact tracing not done Ref: Giles 2013, Jimenez 2013, Joslin Clinic IHBS, Williams 2011

69 Challenges Improving screening in affected communities Increasing numbers on treatment to prevent mortality and morbidity 3-5% Adherence to long term anti viral medication Monitoring over many years (OPD 30% FTA, Joslin 15%) VIDRL, NDDSS, WRHC, Western Hospital

70 Task 3: Develop a GPMP Mrs A 34 year old Sudanese woman 3 children 10, 4, 2 years CHB dx: on screening 2004 briefly in specialist care at WH after 3 rd pregnancy, BMI 30 no alcohol no family history cancer 6 monthly tests US normal, AFP 20, AST 50, viral load 20,000,000 HBeAg negative

71 Develop a GPMP KD 17 year old Tibetan high school student dx 2011 at screening in paediatric care, father died 40 years Ca on arrival in Australia abdominal cancer, HBeAg positive, viral load 170,000 ALT 18, BMI 21

72 ASHM 2012

73 GPs and prescribing Pilot in NSW with GP prescribing Recognised as part of First National Hepatitis B Strategy general-schedule.pdf Page 537 A general practitioner or non-specialist hospital doctor may only prescribe Highly Specialised Drugs to provide maintenance therapy under the guidance of the treating specialist Prescriptions for Highly Specialised Drugs can be dispensed by an approved private hospital s dispensary or by a community pharmacy

74 Interested in more? ASHM run courses introductory and advanced management Online learning module through GP Learning

75 References and resources The Australian Immunisation handbook 10 th edition 2013 ASHM: National testing policy ASHM 2008 B positive: All you need to know about hepatitis B a guide for primary providers (currently under review) 20positive/b_positive-all_you_wanted_to_know.pdf ASHM Decision making in hepatitis B 20sheets/hbv/decision_making_hbv.pdf Antenatal guidelines (NSW focus)

76 Information and patient resources: Hepatitis Asutralia HepB Help Cancer Council Help Line The Australian Injecting and Illicit Drug Users League (AIVL) Telephone: The Multicultural Health and Support Service

77 Thank you To VIDRL epidemiology unit, Dr B Cowie and J Maclachlan, ASHM, WRHC, Dr Karen Linton Dr Tom Schulz, Integrated Hepatitis B service from RMH Tracey Cabrie and Jacqui Richmond This work supported by APA scholarship