Brief Hepatitis B Update from AASLD

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Brief Hepatitis B Update from AASLD

written by Jules Levin

Entecavir vs 3TC Resistance

A more detailed report is forthcoming but here are a

few highlights

from this

meeting. several apparently promisingly drugs for

treating HBV are in

human

development and moving along and had data presented on

them here at

AASLD:

LDT, FTC (not good for 3TC resistance), adefovir, and

entecavir. This

morning

data was presented on entecavir in 3TC resistant

patients. Previous

study

data showed 0.5 mg (highest of 3 doses) dose of ETV

reduced viral load

by

over 4 log in treatment-naive at week 20. The data

this morning was

presented

in oral session. 85% reportedly had YMDD mutation.

Three ETV doses were

used:

0.1mg, 0.5mg and 1.0mg. Mean HBV DNA was about 9 log.

About 40 patients

in

each arm. 79% in the high dose arm (1.0 mg) had

undetectable HBV-DNA at

week

24 by bDNA, and a 4.4 log reduction in HBV-DNA. By PCR

17% had

undetectable

HBV-DNA. 93% had 2 or more log reduction. There was a

dose response.

The

group receiving 3TC 100mg had little HBV-DNA response.

11% in the high

dose

group (n=27) had loss of HBeAg compared to 6% in the

3TC continuation

arm.

There were 67 adverse events in the ETV 1.0 mg arm:

headache (19),

fatigue

(5), abdominal pain (10), rhinitis (7). 5 discontinued

and 5 had

serious AE.

The incidence of AEs was not different than in the 3TC

arm. Although

there

were 2 serious AEs in the 3Tc arm. Several patients

had elevated ALT.

Adefovir

This morning an oral talk was presented on a study for

adefovir (ADV)

for

patients with HBeAg+ chronic HBV. This study looked at

changes in liver

histology. This 48+ week study looks at fibrosis,

Knodell score, and

necroinflammation. HBV-DNA was 8.4 log at baseline ALT

95. About 20%

were

nonresponders to IFN and <1%-3% had prior 3TC. Median

Knodell scores

were

about the same in placebo 10mg and 30mg ADV arms:

9.5-10.0,

necroinflammation

7.0-8.0, fibrosis 1.0. Cirrhosis: 4% in 30mg arm, 7%

in 10mg arm, 8% in

placebo. The 10 and 30 mg arms had about the same

response measured by

Knoedell (Histology): 53-59% showed improvement

compared to 25% in

placebo

arm. 28%-36% showed no improvement in ADV arms

compared to 65% in

placebo

arm. 10-12% of patients across the 3 arms had missing

data. The

difference

between ADV 10 mg and placebo was significant

(p<0.001).

Necroinflammation:

similar results--71-77% showed improvement in ADV arms

vs 41% in

placebo;

12-15% in ADV arms showed no imprivement compared to

26% in placebo.

34% in

placebo showed worsening compared to 10-13% in ADV

arms. Fibrosis: 41%

showed

improvement in 10mg ADV arm, 54% in ADV 30mg arm, and

26% in placebo.

26%

worsened in placebo while 14% worsened in 10mg arm and

19% in 30mg arm.

50%

remained the same in placebo vs 45% in 10mg and 37% in

30 mg arm.

HBV-DNA:

reduced by median 3.52 log in 10 mg arm (n=172) (21%

<400 copies/ml

HBV-DNA),

4.76 in 30 mg arm (n=173) (39% <400 HBV-DNA) and .55

in placebo (0%).

14%

HBeAg seroconverted in 30mg arm, 12% in 10mg arm, and

6% in placebo.

33% exp

erienced HBeAg loss in 30mg arm, 23% in 10mg arm, 17%

in placebo.

Serious

AEs, AEs, and discontinuations were about the same in

all 3 arms (5%

serious

AE, 87-95% AE, 7-8% disct. Dose reduction was 25% in

30mg ADV arm vs 3%

in

10mg arm. 8% in 30 mg arm had confirmed increase 0.5

or more serum

creatinine

increase from baseline. No serum phosphorous confirmed

decreases <1.5

mg/dL

in any arm. Resistance reported later in conference.

ADV 10 mg selected

for

development due to renal lab abnormalities with 30mg

dose.

Data on FTC is also being presented showing viral load

reductions.

Maureen

Myers reported median HBV-DNA reduction of 3.63 log at

week 4 using

highest

dose og 400mg per day. In lower doses 2-3 log

reductions seen. She

reported

no serious adverse events, toxicities.

It seems apparent that combination therapy for HBV

should be the

approach.

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