TELBIVUDINEFOR 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 SchoolLarissa, Greece
Disclosure
For the current presentation
NONE
Grant/Research Support:
Investigator in International/Greek Protocols: GILEAD,
JANSSEN, BAYERN, ROCHE
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
Background (II)
• Resistance rates to TBV are relatively low in patients with low baseline viraemia (<2 X 108 IU/ml in HBeAg-pos & <2 X 106 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 2012Mauss, J Hepatol 2001. Gane et al, Gastroenterology 2014
However…
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 2012Cholongitas, J Viral Hepat 2014
However…
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
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
Previous treatment
Naïve Peg-IFNa TDF
13
3 3
Reasons for TBV choice
Pregnancy
Osteoporosis
Renal impairment
Immunosuppression
Low viremia (< 7log10 IU/ml)
0 2 4 6 8 10 12
1
1
2
4
11
No of patients
previous treatment with TDF
previous treatment with TDF
inactive carriers
HBV DNA baseline
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 190.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
patients
HBV
DN
A (l
og IU
/ml)
chan
ge fr
om T
DF
to T
BV d
ue to
˅Cr
Cl
chan
ge fr
om T
DF
to T
BV d
ue to
˅Cr
Cl
inac
tive
carr
ier r
ecei
ving
imm
unos
uppr
essi
on
inac
tive
carr
ier r
ecei
ving
imm
unos
uppr
essi
on
Biochemical ResponseMedian (IQR) TBV treatment duration: 25 (26) months
Virological ResponseMedian (IQR) TBV treatment duration: 25 (26) months
Patient 1Patient 2
Patient 3
L180 / M204Wild type
PATIENT 1
PATIENT 2 Compliance issues?
L180M / M204VResistance mutations
PATIENT 3
Creatinine clearance alterationMDRD for eGFR (ml/min/1.73 m2)
Mean CrCl (±SD): 91.5±19.4 → 98.2±30.9 ml/min/1.73 m2
mean ΔGFR: 6.4±34.1 ml/min/1.73 m2
p=0.756
Median (IQR) TBV treatment duration: 25 (26) months
CPK alterationMedian (IQR) TBV treatment duration: 25 (26) months
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
ConclusionsThis 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
Thank you for your attention!
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