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P67 Switch to other nucleos(t)ide analogues therapy in chronic hepatitis B cohort on long-term de-novo combination therapy with lamivudine plus adefovir: efficacy and safety
  1. I Carey,
  2. A Mendes,
  3. D Joshi,
  4. M Bruce,
  5. S Knighton,
  6. A Scalori,
  7. S Hughes,
  8. M Al-Freah,
  9. A Suddle,
  10. P M Harrison,
  11. K Agarwal1
  1. 1Institute of Liver Studies, King's College Hospital NHS Foundation Trust

Abstract

Introduction Long-term de-novo combination therapy with lamivudine (LAM) 100 mg/d + adefovir (ADV) 10 mg/d is highly efficient, with no/minimal drug resistance and good safety profile. Tenofovir (TDF) 245 mg/d or entecavir (ETV) 0.5 mg/d are highly efficacious antivirals with high resistance barrier and provide alternative to LAM + ADV combination therapy.

Aim We aimed to investigate the virological and serological responses and renal/bone safety after switch from LAM + ADV to other antiviral drugs.

Method Patients: Nucleos(t)ide analogues naive 192 CHB patients (78% males, median age 40 y, 35% HBeAg+, 34% cirrhosis) were treated with de-novo LAM+ADV at a single-centre practice (median 36 months). 149 patients from this cohort were switched to other nucleos(t)ide analogues therapy: 101 (68%) to TDF monotherapy, 28 (19%) to TDF plus emctritabine, 14 (9%) patients to ETV monotherapy and 6 (4%) patients to other antivirals. Median duration of therapy after switch was 14 months. Reasons for the switch were following: 33 patients slow-response/non-response, 14 had drug-related renal impairment, 5 due to pregnancy, 2 after liver transplantation and 95 patients were switched for other reasons.

Methods Number of patients achieved HBeAg seroconversion and complete virological response (CR) (HBV DNA<12 IU/ml) was compared (LAM+ADV vs. switch). Differences between serum levels of HBV DNA, creatinine and phosphate and estimated glomerular filtration rates (eGFR) were assessed at each time-point and compared between groups and with baseline. HBV genotypic resistance was tested in all patients with suboptimal response by direct sequencing.

Results Baseline HBV DNA was significantly higher in LAM+ADV vs switch group (median log10 4.6 vs 0.89 IU/ml, p<0.01), there was higher proportion of responses after switch than at time of switch and when compared to LAM+ADV (switch baseline 76% vs m3 switch 91%, p=0.02 vs m3 LAM+ADV 48%, p<0.01). On LAM+ADV therapy 14 patients achieved HBeAg and 3 patients HBsAg seroconversion and additional 3 patients and 1 patient seroconverted HBeAg and HBsAg after switch. No viral mutations associated with drug resistance were detected in LAM+ADV and after switch. There were no significant differences in serum creatinine or eGFR between groups at each time-point, but comparing to baseline there was significant decrease in eGFR from M18 onwards in LAM+ADV group (82.2 vs76.2 ml/s, p=0.04). The proportion of patients with eGFR <60 ml/s did not changed during LAM+ADV therapy and after switch. Serum phosphate levels [mmol/l] fell on therapy in LAM+ADV from M12 (M12: −0.04, M18: −0.06 and M24: −0.05) and remained unchanged after switch.

Conclusion Switch to other nucleos(t)ide analogues from long-term de-novo combination LAM+ADV therapy was efficient and was not associated with impact on renal/bone safety.

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