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!