Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01533.x/abstract

Response to tenofovir monotherapy in chronic hepatitis B patients with prior

suboptimal response to entecavir

C. Q. Pan1, K.-Q. Hu2, A. S. Yu3, W. Chen4, C. Bunchorntavakul5,6, K. R. Reddy6

Article first published online: 17 OCT 2011

DOI: 10.1111/j.1365-2893.2011.01533.x

© 2011 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

Summary.  Both entecavir (ETV) and tenofovir (TDF) are potent antiviral agents

for hepatitis B virus (HBV). Suboptimal response (SOR) following antiviral

therapy is associated with an increased risk of subsequent treatment failure and

viral resistance. It remains unclear whether switching to TDF is a reasonable

approach in patients with SOR to ETV treatment. This study was aimed to

determine how HBV patients with SOR to ETV respond to TDF monotherapy. Data of

patients with SOR to ETV (failure to achieve >1 log10 HBV-DNA reduction during

the last 24 weeks of ETV treatment) who were switched to TDF monotherapy during

2005 and 2010 were reviewed. Treatment adherence was assessed by pill-count.

Fourteen patients (2.9%) were identified from a total cohort of 482 ETV-treated

patients. All 14 patients were Chinese and were infected with HBV genotype C

(71%) or B (29%). Nine patients were men, and the median age was 41.5 years

(19–64). Twelve were treatment naïve (one lamivudine- and one

peginterferon-experienced patient); 85.7% were HBeAg positive. The median

baseline HBV-DNA was 7.55 (5.30–9.40) log10 copies/mL, and 57% had abnormal

serum alanine aminotransferase (ALT) levels. Precore and/or basal core promoter

mutations were detected in four patients, whereas no genotypic resistance was

detected at baseline and before switching to TDF. The median duration of ETV

treatment was 64.5 (26–126) weeks. The median HBV-DNA at the time of switching

to TDF was 3.69 (3.00–4.90) log10 copies/mL. The median HBV-DNA reduction from

baseline and during the last 6-month observation period prior to switching to

TDF was 4.04 (0.51–6.06) log10 and 0.43 (−0.09–1.13) log10 copies/mL,

respectively. After the switching to TDF, all 14 patients (100%) achieved

undetectable HBV-DNA and ALT normalization within a median duration of 30 weeks.

In 12 patients who were HBeAg positive, HBeAg seroconversion was observed in two

patients after TDF treatment of 75- and 84-weeks duration. There was no

virological breakthrough observed after switching to TDF with a median follow-up

period of 50 (24–160) weeks. TDF treatment was safe and well tolerated. In

conclusion, suboptimal response to ETV is rare (approximately 3%). TDF

monotherapy is safe and very effective in the management of HBV patients with

SOR to ETV.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01533.x/abstract

Response to tenofovir monotherapy in chronic hepatitis B patients with prior

suboptimal response to entecavir

C. Q. Pan1, K.-Q. Hu2, A. S. Yu3, W. Chen4, C. Bunchorntavakul5,6, K. R. Reddy6

Article first published online: 17 OCT 2011

DOI: 10.1111/j.1365-2893.2011.01533.x

© 2011 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

Summary.  Both entecavir (ETV) and tenofovir (TDF) are potent antiviral agents

for hepatitis B virus (HBV). Suboptimal response (SOR) following antiviral

therapy is associated with an increased risk of subsequent treatment failure and

viral resistance. It remains unclear whether switching to TDF is a reasonable

approach in patients with SOR to ETV treatment. This study was aimed to

determine how HBV patients with SOR to ETV respond to TDF monotherapy. Data of

patients with SOR to ETV (failure to achieve >1 log10 HBV-DNA reduction during

the last 24 weeks of ETV treatment) who were switched to TDF monotherapy during

2005 and 2010 were reviewed. Treatment adherence was assessed by pill-count.

Fourteen patients (2.9%) were identified from a total cohort of 482 ETV-treated

patients. All 14 patients were Chinese and were infected with HBV genotype C

(71%) or B (29%). Nine patients were men, and the median age was 41.5 years

(19–64). Twelve were treatment naïve (one lamivudine- and one

peginterferon-experienced patient); 85.7% were HBeAg positive. The median

baseline HBV-DNA was 7.55 (5.30–9.40) log10 copies/mL, and 57% had abnormal

serum alanine aminotransferase (ALT) levels. Precore and/or basal core promoter

mutations were detected in four patients, whereas no genotypic resistance was

detected at baseline and before switching to TDF. The median duration of ETV

treatment was 64.5 (26–126) weeks. The median HBV-DNA at the time of switching

to TDF was 3.69 (3.00–4.90) log10 copies/mL. The median HBV-DNA reduction from

baseline and during the last 6-month observation period prior to switching to

TDF was 4.04 (0.51–6.06) log10 and 0.43 (−0.09–1.13) log10 copies/mL,

respectively. After the switching to TDF, all 14 patients (100%) achieved

undetectable HBV-DNA and ALT normalization within a median duration of 30 weeks.

In 12 patients who were HBeAg positive, HBeAg seroconversion was observed in two

patients after TDF treatment of 75- and 84-weeks duration. There was no

virological breakthrough observed after switching to TDF with a median follow-up

period of 50 (24–160) weeks. TDF treatment was safe and well tolerated. In

conclusion, suboptimal response to ETV is rare (approximately 3%). TDF

monotherapy is safe and very effective in the management of HBV patients with

SOR to ETV.