Chairpersons: Aabha Nagral, Prashanth LK,SK Yachha Talk: Ashish Bavdekar

1. Choice and Monitoring of Drug therapy Chairpersons:Aabha Nagral, Prashanth LK,SK Yachha Talk: Ashish Bavdekar

2. Wilson’s Disease – choice and monitoring of drug therapy Dr. Ashish Bavdekar Associate Professor Consultant Ped. Gastroenterologist K.E.M. Hospital, Pune bavdekar@vsnl.com

3. Wilson’s Disease - therapy 1) Reduce Cu to sub-toxic threshold - takes 6-12 months - DP, Trientine, TAM 2) Maintain slightly negative Cu balance - life long therapy - DP, Trientine, Zn

4. EuroWilson: initial treatment Zn + penicillamine Zn + trientine Why? Zn sulfate penicillamine “Available in our country Cheap Tried and tested What we’ve always used Zn acetate “expensive” trientine transplanted “Not available in our country Kept as second line Not as effective?

5. Treatment depending on severity Tx DP/Trientine + zinc ‘bridge’ • acute liver failure with encephalopathy • acute liver failure without encephalopathy • intermediate severity • Asymptomatic transaminitis • Asymptomatic and normal LFTs • Neonate detected by screening Modified Kings score Tx if >11 DP/Trientine + zinc

6. Modified King’s score A score > 11 = urgent need for transplantation Validated in other centres; better than PELD Dhawan et al, 2005

7. Treatment depending on severity Tx DP/Trientine + zinc ‘bridge’ • acute liver failure with encephalopathy • acute liver failure without encephalopathy • intermediate severity • Asymptomatic transaminitis • Asymptomatic and normal LFTs • Neonate detected by screening Modified Kings score Tx if >11 DP/Trientine + zinc Zinc Zinc – when to start?

8. Treatment depending on severity List for Tx DP/Trientine + zinc ‘bridge’ • acute liver failure with encephalopathy • acute liver failure without encephalopathy • intermediate severity • Asymptomatic transaminitis • Asymptomatic and normal LFTs • Neonate detected by screening Modified Kings score Tx if >11 DP/Trientine + zinc Zinc Zinc – when to start?

11. Monitoring in WD ? • To determine clinical and biochemical improvement/deterioration • Determine effective decoppering • Ensure compliance • To identify adverse effects of medications • To review diagnosis if necessary

12. Monitoring plan (chelators) • Clinical • Liver status, neuro-psychiatric worsening • KF ring annually • Biochemical (USG) • CBC, Urine, LFTs • Initially 5, 10, 15, 30 days initially • Later 3 mo, 6mo, • Urinary Cu, Serum free copper (Serum Cu & Cp) • Initially after a month, 4 times per year • Later 1-2 times per year

13. Monitoring plan (chelators) • Clinical • Liver status, look for side effects • KF ring annually • Biochemical (USG) • CBC, Urine, LFTs • Initially 5, 10, 15, 30 days initially • Later 3 mo, 6mo, • Urinary Cu, Serum free copper (Serum Cu & Cp) • Initially after a month, 4 times per year • Later 1-2 times per year

15. Monitoring plan (chelators) • Clinical • Liver status, neuro-psychiatric worsening • KF ring annually • Biochemical (USG) • CBC, Urine, LFTs • Initially 5, 10, 15, 30 days initially • Later 3 mo, 6mo, • Urinary Cu, Serum free copper (Serum Cu & Cp) • Initially after a month, 4 times per year • Later 1-2 times per year

16. Biochemical improvement • Children on long-term chelation • 20/32 children normalised at variable times • INR - median of 1.8 yrs (0-12.2) • AST – median of 0.97 yrs (0-9) • Bilirubin – median of 0. yrs (0-2.3) • Asymptomatic sibs • 15/17 normalised LFTs • Median 283 days (35days-6.7yrs) Dhawan et al, 2005

17. Monitoring plan (chelators) • Clinical • Liver status, neuro-psychiatric worsening • KF ring annually • Biochemical (USG) • CBC, Urine, LFTs • Initially 5, 10, 15, 30 days initially • Later 3 mo, 6mo, • Urinary Cu, S. free copper (Serum Cu & Cp) • Initially after a month, 4 times per year • Later 1-2 times per year

18. Urinary copper in Wilson’s disease

19. Urinary copper / serum ‘free’ copper

20. Summary • Chelators - mainstay of treatment (hepatic) • Zinc has role in long-term Rx, neurological, co-Rx • Monitoring is crucial • Clinical and improvement in LFTs slow • Monitoring for Cu balance important • Interpretation important • Compliance