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P0647
PROACTIVE DOSE ADJUSTMENTS ARE NECESSARY IN MANY ADV EXPERIENCED
PATIENTS TREATED WITH TDF MONOTHERAPY
FOR 5 YEARS: A PROSPECTIVE COHORT STUDY IN 320 PATIENTS
P. Lampertico1, R. Soffredini1, M. Borghi1, M. Vigano` 2, F. Facchetti1,
E. Galmozzi1, F. Invernizzi1, M. Colombo1. 1Division of
Gastroenterology and Hepatology, Fondazione IRCCS C`a Granda
Ospedale Maggiore Policlinico, Universit`a degli Studi di Milano,
2Division of Hepatology, Ospedale San Giuseppe, Universit`a degli Studi
di Milano, Milan, Italy
E-mail: [email protected]
Background and Aims: Tenofovir (TDF) is a popular anti-HBV
strategy for NUC-experienced patients, but its safety profile in field
practice patients previously exposed long-term to Adefovir (ADV) is
under discussion because of recent reports of Fanconi syndrome
Methods: 320 NUC-experienced CHB patients received Tenofovir
(TDF) for 69 months (range 1–106) as a switch from ADV+LAM or
as a rescue therapy for LAM, ADV or ETV. Baseline features were:
age 59 (24–82), 85% HBeAg-negative, 62% cirrhotics, 88% normal
ALT, 74% undetectable HBV-DNA, 86% switched from ADV+LAM.
Virological response was undetectable HBVDNA; safety analysis
focused on glomerular (eGFR) and tubular renal function. Baseline
was defined as the start of TDF.
Results: During 5 years of TDF, 89 patients (28%) had to reduce
TDF dose after 31 months (2–75); 11 additional patients (3.4%) had
to stop TDF because of renal side effects, and 6 (2%) withdrew for
gastrointestinal side effects. TDF dose was reduced in 57 patients
due to eGFR decline, in 30 patients due to phosphate decline and in
2 cases for both events. All patients who had to stop TDF had low
blood phosphate levels. Overall, 106 patients (33%) either required
a dose reduction or withdrew from TDF for side effects, with a
5 year estimated probability of 40%. Most of those patients who
had to stop TDF were successfully rescued by switching to ETV.
Of note, none of the TDF treated patients developed acute renal
failure, or Fanconi syndrome and viral load did not rebound in
any patient who required dose adjustment. Virological response
progressively increased to 100% at year 5 with most patients
achieving normal ALT. 15 patients (5%) cleared HBsAg, 26 additional
patients had qHBsAg <10 and 25 reached qHBsAg between 10 and
100 IU/ml (Overall, 22% of the patients had qHBsAg <100 IU/ml).
HCC attack rates were 1.3%/year in compensated cirrhotics and
0.2%/year in non cirrhotics, which were significantly lower than
those described in untreated and in TDF treated naïve patients.
No cases of clinical decompensation without HCC were recorded
Overall, 7 patients (2%) were transplanted (all for HCC) and 16 (5%)
died (7 for HCC, 7 for non liver causes and 2 for unknown reasons).
Conclusions: To prevent glomerular and tubular damage, proactive
dose adjustments of TDF are necessary in a large proportion of ADV experienced,
TDF treated CHB patients. Current EASL guidelines
on safety management and monitoring of these patients must be
revised.
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发表于 2015-5-23 13:22
