HBV Rebound Common for Some Patients

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HBV Rebound Common for Some Patients

By , North American Correspondent, MedPage Today

Published: April 28, 2011

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco.

Action Points

--------------------------------------------------------------------------------

”Explain that in clinical practice, the hepatitis B virus often rebounds in

patients taking nucleoside or nucleotide analogues.

”Note that drug resistance is the most common cause of such a rebound but that

in nearly 40% of patients who experience rebound, there is no sign of genetic

resistance to the drugs.

In clinical practice, the hepatitis B virus often rebounds in patients taking

nucleoside or nucleotide analogues, researchers reported.

Drug resistance is the most common cause of such a rebound, but not the only

one, according to Lok, MD, and colleagues at the University of Michigan

Medical School in Ann Arbor.

Indeed, in nearly two of every five patients who experience rebound there is no

sign of genetic resistance, Lok and colleagues said online in Hepatology.

In those cases, they speculated, the cause of the rebound may be poor drug

adherence.

" This study underscores the need for patients to take their medicines regularly

to derive optimal response, " Lok said in a statement.

For doctors, she added, the results are a warning not to tinker with drug

regimens on the assumption that all treatment failure is caused by resistance.

" There is a danger of misdiagnosis of drug resistance and unnecessary

modifications to treatment regimen when it could be patients not adhering to

their drug regimen, " Lok said.

So-called virological breakthrough is the first manifestation of antiviral drug

resistance during nucleoside or nucleotide analogue therapy of chronic hepatitis

B, she and her colleagues noted.

But clinical trials suggest that not all virological breakthrough is associated

with resistance mutations, they added.

To help clarify the issue, they conducted a retrospective analysis of 148

patients treated with the drugs in the University of Michigan Health System

between January 2000 and July 2010.

Of those, 39 patients (26%) had at least one incident of virological

breakthrough, defined either as an increase in serum hepatitis B DNA by more

than a factor of 10 from its lowest point or redetection of serum viral DNA at

levels at least 10 times the lower limit of detection of an assay after a

previous undetectable result.

However, on retesting, 38% of those patients no longer had a breakthrough and 10

of the 39 (also 38%) showed no sign of drug resistance mutations.

Overall, the cumulative probability of virological breakthrough at five years

was 46%, Lok and colleagues reported.

But the probability of confirmed virological breakthrough -- two consecutive

tests meeting the definition -- was only 30% at five years and the probability

of genotypic resistance was 34%.

A multivariate analysis found that the only factor that was significantly

associated with virological breakthrough was serum viral DNA level that was

detectable even at its lowest point (HR 5.5, 95% CI 2.49 to 12.28, P˜0.001).

Among the 10 patients with breakthrough but no resistance, continuing the same

regimen resulted in serum viral DNA decreases, to the point of undetectability

in nine of them, Lok and colleagues found.

They cautioned that because of the retrospective nature of the analysis there

was no direct data on adherence to medication.

They added that it's also possible that more sensitive methods might have found

resistance mutations in some of the 10 apparently nonresistant patients,

although the follow-up data showing viral suppression suggests that adherence,

rather than resistance, was the cause of the original breakthrough.

The authors did not report external support for the study. Lok reported

financial links with Gilead Sciences, Roche, Bristol-Myers Squibb,

GlaxoKline, and Schering-Plough.

Primary source: Hepatology

Source reference:

Hongthanakorn C, et al " Virological breakthrough and resistance in patients with

chronic hepatitis B receiving nucleos(t)ide analogs in clinical practice "

Hepatology 2011; 53(5): DOI:10.1002/hep.24318

[Guest guest]

http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26177?utm_content= & utm_m\

edium=email & utm_campaign=DailyHeadlines & utm_source=WC & userid=23283

HBV Rebound Common for Some Patients

By , North American Correspondent, MedPage Today

Published: April 28, 2011

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco.

Action Points

--------------------------------------------------------------------------------

”Explain that in clinical practice, the hepatitis B virus often rebounds in

patients taking nucleoside or nucleotide analogues.

”Note that drug resistance is the most common cause of such a rebound but that

in nearly 40% of patients who experience rebound, there is no sign of genetic

resistance to the drugs.

In clinical practice, the hepatitis B virus often rebounds in patients taking

nucleoside or nucleotide analogues, researchers reported.

Drug resistance is the most common cause of such a rebound, but not the only

one, according to Lok, MD, and colleagues at the University of Michigan

Medical School in Ann Arbor.

Indeed, in nearly two of every five patients who experience rebound there is no

sign of genetic resistance, Lok and colleagues said online in Hepatology.

In those cases, they speculated, the cause of the rebound may be poor drug

adherence.

" This study underscores the need for patients to take their medicines regularly

to derive optimal response, " Lok said in a statement.

For doctors, she added, the results are a warning not to tinker with drug

regimens on the assumption that all treatment failure is caused by resistance.

" There is a danger of misdiagnosis of drug resistance and unnecessary

modifications to treatment regimen when it could be patients not adhering to

their drug regimen, " Lok said.

So-called virological breakthrough is the first manifestation of antiviral drug

resistance during nucleoside or nucleotide analogue therapy of chronic hepatitis

B, she and her colleagues noted.

But clinical trials suggest that not all virological breakthrough is associated

with resistance mutations, they added.

To help clarify the issue, they conducted a retrospective analysis of 148

patients treated with the drugs in the University of Michigan Health System

between January 2000 and July 2010.

Of those, 39 patients (26%) had at least one incident of virological

breakthrough, defined either as an increase in serum hepatitis B DNA by more

than a factor of 10 from its lowest point or redetection of serum viral DNA at

levels at least 10 times the lower limit of detection of an assay after a

previous undetectable result.

However, on retesting, 38% of those patients no longer had a breakthrough and 10

of the 39 (also 38%) showed no sign of drug resistance mutations.

Overall, the cumulative probability of virological breakthrough at five years

was 46%, Lok and colleagues reported.

But the probability of confirmed virological breakthrough -- two consecutive

tests meeting the definition -- was only 30% at five years and the probability

of genotypic resistance was 34%.

A multivariate analysis found that the only factor that was significantly

associated with virological breakthrough was serum viral DNA level that was

detectable even at its lowest point (HR 5.5, 95% CI 2.49 to 12.28, P˜0.001).

Among the 10 patients with breakthrough but no resistance, continuing the same

regimen resulted in serum viral DNA decreases, to the point of undetectability

in nine of them, Lok and colleagues found.

They cautioned that because of the retrospective nature of the analysis there

was no direct data on adherence to medication.

They added that it's also possible that more sensitive methods might have found

resistance mutations in some of the 10 apparently nonresistant patients,

although the follow-up data showing viral suppression suggests that adherence,

rather than resistance, was the cause of the original breakthrough.

The authors did not report external support for the study. Lok reported

financial links with Gilead Sciences, Roche, Bristol-Myers Squibb,

GlaxoKline, and Schering-Plough.

Primary source: Hepatology

Source reference:

Hongthanakorn C, et al " Virological breakthrough and resistance in patients with

chronic hepatitis B receiving nucleos(t)ide analogs in clinical practice "

Hepatology 2011; 53(5): DOI:10.1002/hep.24318