1. TELBIVUDINE FOR THE TREATMENT OF CHRONIC HEPATITIS B: A CASE SERIES N.K. Gatselis, K. Zachou, E.I. Rigopoulou, G. Papadamou, K. Galanis G.N. Dalekos Department of Medicine & Research Lab of Internal Medicine University of Thessaly Medical School Larissa, Greece

2. Disclosure For the current presentation NONE Grant/Research Support: Investigator in International/Greek Protocols: GILEAD, JANSSEN, BAYERN, ROCHE

3. Background (I) Entecavir (ETV) and Tenofovir (TDF) are potent HBV inhibitors with a high barrier to resistance and therefore, can be used as first-line monotherapies in HBV infection Telbivudine (TBV) is a potent inhibitor of HBV replication, but lower barrier to resistance has been observed in patients with high baseline HBV DNA levels and in those with detectable HBV DNA after 6 months of therapy EASL & KEELPNO CPG 2012

4. Background (II) Resistance rates to TBV are relatively low in patients with low baseline viraemia (<2 X 10 8 IU/ml in HBeAg-pos & <2 X 10 6 IU/ml in HBeAg-neg) who achieve undetectable HBV DNA at 6 months of therapy Chronic kidney disease is frequent in patients with CHB (15- 30%) Renal impairment at low percentages with all antivirals except for TBV which seems to improve the creatinine clearance EASL & KEELPNO CPG 2012 Mauss, J Hepatol 2001. Gane et al, Gastroenterology 2014 However…

5. Background (III) After transplantation for CHB, oral antiviral therapy is administered for a long term to prevent HBV recurrence. These patients are at increased risk for CKD due to the concomitant use of calcineurin inhibitors and because of the high prevalence of diabetes and hypertension. TBV appears to be safe and effective in this population. Pregnancy: Category Β (with TDF) TBV can be used HBV/HIV co-infected not candidates for HIV antiretroviral therapy EASL & KEELPNO CPG 2012 Cholongitas, J Viral Hepat 2014 However…

6. Aim To assess the long-term antiviral efficacy and safety of telbivudine in patients followed in the Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School

7. Patients and Methods 19 HBeAg (-) CHB patients treated with TBV (600 mg/d) 7 females / 12 males Median (IQR) age at baseline: 44 (23) years Median (IQR) duration of infection: 46.7 (31.5) years 3/19 (15.8%) cirrhotic at baseline

8. Previous treatment

9. Reasons for TBV choice previous treatment with TDF inactive carriers

10. HBV DNA baseline change from TDF to TBV due to ˅CrCl inactive carrier receiving immunosuppression

11. Biochemical Response Median (IQR) TBV treatment duration: 25 (26) months

12. Virological Response Median (IQR) TBV treatment duration: 25 (26) months Patient 1 Patient 2 Patient 3

13. L180 / M204 Wild type L180 / M204 Wild type PATIENT 1 PATIENT 2 Compliance issues?

14. L180M / M204V Resistance mutations L180M / M204V Resistance mutations PATIENT 3

15. Creatinine clearance alteration Cockcroft-Gault for eGFR (ml/min) Mean CrCl (±SD): 103±23 → 104±26 ml/min mean ΔGFR: 0.66 ± 28 ml/min p=0.67 Median (IQR) TBV treatment duration: 25 (26) months

16. Creatinine clearance alteration MDRD for eGFR (ml/min/1.73 m 2 ) Mean CrCl (±SD): 91.5±19.4 → 98.2±30.9 ml/min/1.73 m 2 mean ΔGFR: 6.4±34.1 ml/min/1.73 m 2 p=0.756 Median (IQR) TBV treatment duration: 25 (26) months

17. CPK alteration Median (IQR) TBV treatment duration: 25 (26) months

18. Current treatment - Outcome 1 patient changed to TDF because of: -ALT 46 U/L and HBV DNA increased (3.162 IU/ml) 3.5 years after TBV initiation -resistance mutations developed (L180M/M204V) 2 patients discontinued TBV -lack of insurance coverage -immunosuppression cessation 16 patients are still on TBV treatment with virological and biochemical response Median (IQR) TBV treatment duration: 25 (26) months

19. Conclusions This uncontrolled real-life study showed that TBV administration in HBeAg (-) CHB patients with low baseline viraemia had a safe profile Renal function was preserved in all patients CK elevations is common AE while myopathy is rare So far, treatment efficacy in these patients was excellent as attested by the achievement of virological and biochemical response in almost all compliant patients

21. The economic burden