Chronic Hepatitis B Diagnosis When to refer

1. Chronic Hepatitis BDiagnosis When to refer Dr Yeung Yat Wah 楊日華醫生

2. Screening for HBV • Persons born in hyperendemic areas • Men who have sex with men • Injection drug users • Patients on dialysis • HIV patients • Pregnant women • Family, household, and sexual contacts

3. Prevention of infection • Have sexual contacts vaccinated • Use barrier method • Not share toothbrushes or razors • Cover open cuts and scratches • Clean blood spills with detergent or bleach • Not donate blood or sperms • Safe: • Contact sports, sharing food, utensils • Kiss

4. Natural HistorySelecting patient to treat • Immune tolerance phase • First 3 decades • Very high viral load with normal ALT • Immune clearance phase • Liver damage with high ALT, can be asymp • HBeAg seroconversion • Quiescent phase

5. Evaluation • Hx and P/E • FHx of liver ds, Hepatitis B, HCC • Lab tests • CBP, PI • HBeAg/Ab HBVDNA • USG • Fibroscan • Liver Bx

6. Fibroscan – How it works • Fibroscan is non-invasive, good reproductivity, and easy operations • Patients need to • lay down and • put his right • arm during the • examination

7. Fibroscan – How it works • The probe is placed at the intercostal space of the rib bones • Shear (mechanical) wave is triggered by pressing the button at the probe • The ultrasound will track the • speed of the shear wave • The harder the liver and faster • the speed higher stiffness(LSM); • softer the liver and slower the • speed  lower stiffness(LSM)

8. LSM is highly reproducible Overall interobserver agreement ICC: 0.98 Intraobserver agreement ICC: 0.98 Intraobserver agreement ICC: 0.98 • Study population: 200 patients with chronic liver diseases • 800 LSMs were performed • Intraobserver and interobserver agreement were analyzed using the intraclass • correlation coefficient (ICC) LSM is a highly reproducible and user-friendly technique for assessing liver fibrosis in patients with chronic liver diseases Fraquelli et al. Gut. 2007

9. Factors Associated with LSM Failure 60 LSM failure rate(%) 41.7% 40 24.9% 20 16.9% BMI (kg/m2) 12.4% 8.1% N=4172 N=3089 N=1568 N=967 N=225 N=48 1.0% Factors associated with LSM failure: 0 • BMI (>30 kg/m2) • Operator experience (<500 examinations) • Age(>52y) • Type 2 diabetes • Time of examination <25 ≥25 ≥28 ≥30 ≥35 ≥40 Castera et al. Hepatology. 2010

10. LSM in CHC: Treatment Effects LSM decreases in sustained responders following IFN-based therapy in patients with chronic HCV Wang et al. J Gastroenterol Hepatol. 2010

11. LSM in CHB: Treatment Effects 100% 25% F4 (≥11.0 kPa) F3 (8.1-10.9 kPa) F0/F1 (<7.2 kPa) 53% 75% F2 (7.3-8.0 kPa) • Study population: 53 patients with cirrhosis; 13 patients with advanced fibrosis • Median treatment duration: • 50.5 months • Transient elastography examinations demonstrate that prolonged treatment with NUCs in patients with CHB results in low liver stiffness 100% 100% 12% 50% 58% 17% 35% 25% 0 Before After Before After Advanced fibrosis before treatment Cirrhosis before treatment Andersen et al., Scand J Gastroenterol. 2011

12. Treatment • Aims: sustained suppression • Prevent cirrhosis, hepatic failure, and HCC • Assess treatment response • ALT • Decrease in serum HBVDNA • Loss of HBeAg with + HBeAb • Improvement in histology

13. Candidates for Referral • Cirrhosis • Chronic Hepatitis B • ALT above 2x and HBVDNA 5 log copies • Any ALT elevations with HBVDNA 5 log • Above 40 • Liver bx showing active disease or sig fibrosis

14. Monitoring for those who do not need treatment • HBeAg+ with normal ALT • LFT every 3-6 months • More frequent if ALT elevated • For persistent slightly high ALT, consider liver biopsy esp above 40 years of age • In young patients (below 30) liver biopsy is usually not necessary if ALT is persistently normal • HBeAg status every 6-12 months

15. Monitoring for those who do not need treatment • HBeAg negative • Monitor LFT every 3 months during the first year to verify that they are truly inactive • Then every 6-12 months

16. Case sharing (1) • HKU student, 20 years old • Normal LFT • Normal USG • No need to check HBVDNA • HBeAg status

17. Case sharing (2) • Young man, 22 years old • Normal LFT • Normal USG • HBVDNA 9 logs • HBeAg + • Started on oral drugs and referred to HA

18. Case sharing (3) • Male 65 years old • Known HB years ago during regular blood check • No regular follow up and monitoring • Recently seen by his family physician and LFT showed ALT 200+, so referred to Medical

19. Case sharing (3) • As his ALT was high an early appointment was given (2 weeks) • New case assessment: P/E normal • Taking his age and deranged LFT into account, an early USG was arranged in a week which showed a 3 cm mass • Confirmed HCC with surgery done and received treatment for his HB

20. Case sharing (4) • 44 gentleman seen by GP for years • Known Hepatitis B for years • In recent 3-4 years noted a slightly high ALT around 40+ to 50+ • USG showed fatty liver • Continue to monitor

21. Case sharing (4) • Came to seek a second opinion • USG showed moderate coarsening suggesting cirrhosis. Spleen was also enlarged to 11.5 cm. Platelet count was low at 100+ • HBVDNA was 3 logs • Treated with oral drugs

22. Case sharing (5) • Male 55 years old • Known HB during pre-marital check up • No regular follow up • Taking herbs for eczema for a year • Noted ankle and scrotal oedema, seen by GP, noted deranged LFT with ALT 300+, RFT also abn with creatinine 130+, USG showed a few nodules below 1 cm • Adm PWH due to dizziness

23. Case sharing (5) • While waiting for hepatologist assessment came to see me • USG showed a vague large mass 6 cm but PV was patent, Alb normal • ? HCC but some element due to herbs? • CT scan confirmed several masses and extensive IVC infiltration and LN involvement

24. HCC screening • LFT AFP and USG every 6 months • Male HB patients over 40 • Female HB over 50 • Any Cirrhosis • FHx of HCC in HB patients

25. Cumulative Risk Scores and Projected HCC Risk

26. ROC Curves for Model Validation Cut-off risk score: 12 Sensitivity: 0.84 Specificity: 0.73

27. Thank You