start

Quantitative HBsAg and its Role in Chronic Hepatitis B Patient Management

so I am a consultant for quest

Diagnostics as my main relevant

disclosure and we are now going to start

the presentation with an outline as

learning objectives we can have a brief

overview of the hepatitis B viral

disease talk about laboratory markers

and their significance and then focus

heavily on the role on s antigen

quantitative assay both in the setting

of interferon therapy nucleotide a

nucleotide analog and also talked about

as managin in drug development there's

many new medications coming out for

hepatitis B we hope in the next five

years and talk about how to integrate

that testing and drug development which

then would enter your practice all right

appetite is B overview this is a virus

with DNA virus that's in terrible that

is surrounded by an antigen and core

antigen score antigen forms a capsid and

surface antigens part of the viral

envelope inside the viral particle is

the viral DNA this is a major component

and of course there's an e antigen which

is related to the core antigen in the

sense that it's a commercial protein

that is also secreted or made by the

hepatitis B virus that's measured

clinically the body of course makes

antibodies the core and to e and to

service management and we measure those

also in clinical practice this is a

diagram of peptides be life cycle it

comes into the cell through attachment

in what's called an tcp receptor goes

into the liver cell unclose goes into

the nucleus form CCC DNA that's why it's

in terrible it moves back to the

cytoplasm with RNA RNA lengths pre

genomic RNA becomes encapsulated then

becomes enveloped and then is secreted

but making this simple there's many many

other complex steps but it is a dating

lifecycle of the hepatitis B virus now

this is a grasp and almost everybody is

seen during their training or during

practice and talking about aq2 then

chronic disease and usually early the

antigen is positive indicating wild-type

infection and then they become e

antibody positive the antigen disappears

either with viral suppression or as the

virus mutates what's called the pre-core

mutant and in that setting there's no e

antigen but there's ongoing viral

replication surface antigen is produced

of course during that life of the virus

as chronic disease is tested and

documented core antibody is also

positive

we'll talk maybe a little bit about core

antibody during this presentation it is

a cure possible yes in the future but

today have to place B is incurable

so you mentioned it's making a antigen

surface antigen both of which modulate

manipulate the immune system in the

nucleus is CC cDNA which is a stable

template you'd have to basically kill

every liver cell to cure the virus and

of course then you wouldn't have a liver

left you would have the patient is alive

so they'd get a liver transplant maybe

there are settings where CC cDNA is

completely cleared with a liver

transplant or maybe they're setting a

fulminant liver disease but the time

being this is an incurable disease and

once a patient has a core antibody they

have core antibody typically for their

lifetime and they always have residual

HTV DNA in their liver cells there's no

such thing as natural immunity which is

found on a variety of different websites

including the CDC website that we

consider that an oxymoron and we talked

about reactivation we put latency talk

about patients don't needing to don't

need vaccine if their core positive now

this is a slide that talks about the

five phases of chronic hepatitis B I'm

not going to read through each one of

these bullets because this is fairly

complicated but there's this early phase

that we call high replication slow

inflammatory normal alt royalty high HPV

DNA we used to call this immune

tolerance that is really not a tolerant

phase there's a training of the immune

system that would have wild-type

infection with

positive we interview control in active

service management carrier no

replication there is a negative with

moderate to high DNA levels and then

finally s clearance it's not a cure it

just means that manager is cleared for

the serum the natural history

chronic hepatitis B is marked by the

surface antigen if it's positive it's

got either used for chronic disease

99.9% of the patients you see will have

chronic hepatitis B disease surface

antigen clearance is our highly

desirable treatment endpoint today

although this rarely happens with either

interferon or nucleoside or concludes at

analogs but when you clear an antigen

there is an improvement in survival

lower rates of liver cancer lower rates

of Liberty compensation and we're using

a term now called a functional cure

patients clear as management and we're

talking about that management natural

clearance occurring at about 0.5 percent

of patients with vertically transmitted

hepatitis B which is specifically asian

population or 2 percent an adult

acquired hepatitis B which you might

find in the US or Western Europe another

diagram on the natural history of

hepatitis B knowing that the majority of

hepatitis B in the world is perinatal e

transmitted from mother to child most

patients that enter this high

replication low inflammation stage

horizontal transmission transmission

usually is the antigen positive

wild-type infection with immune active

disease and then we have these

transitional states to immune control a

negative disease and then as a clearance

now the surface antigen titer has some

correlation to HPV DNA quantification

but I want to highlight here that these

tests are complementary they're to be

used together and you're going to be

using qantas with Kwan HPV DNA ee

antigen status ee antibody status alpha

to protein alte elastography

platelet count abdominal imaging there's

at least seven major tests and actually

11 tests that I do on all of my

hepatitis B patients to stage their

disease but I'm putting quant s in that

top tier of tools to stage patients in

their first testing process might see

them in clinic and then I have a

baseline quant asked to look at what's

happening either naturally or with

therapy during treatment that I may

Institute for their care there's another

graph that looks at log hbf AG was done

correlation with HPV DNA but at the

upper and lower boundaries of the HPV

DNA belonged education you can see a

pretty widespread now we're going to

talk a little bit about how we tighten

up our assessment of patients now

cuantas can help us focus on those

patients and provide I think better care

so this slide is very important we've

got our immune trained or tolerance in

the upper left with very high at

managing status so the piece is in a

grey zone you're not quite sure where

they are they're alt may not be healthy

let's say a woman should be less than 19

but our alt s in the twenty six range

you've got a super high as antigen Guan

they're probably in that immune train

stage that low inflammatory high

replication now we move to immune

clearance we're starting to see more and

more patients with lower s Quandt low

replication phase very low as management

qualification and e antigen negative

we're seeing patients in that mid range

so the labs aren't clear the alt is not

absolutely clear you can be looking at

the quant F to help stage those patients

and define where they are and this helps

you decide who to start treatment who

you might want to wait who you might

want to monitor another slide looking at

that baseline quant asked versus

inactive an active disease let's look at

the lower three lines DNA let's say is

800 alts and

healthy rains are just likely above the

healthy range and we're going to be

talking about that patient probably

being an inactive carrier that's the AC

designates now we're looking across this

with higher Kwon soo and they're active

carriers that's the AC designation at

the carrier one active carrier 2 it's a

little higher level of liver disease and

higher level of risk program and you may

want to institute therapy in those

individuals of course this correlates

with DNA level at some level of

correlation there's another slide

talking about HPV disease phases and

looking at contacts and combining that

Quan s good Quan HPV DNA now on this

slide we're just giving you references

and a number of patients sensitivity and

specificity and predictive value for

something such as reactivation the

patient's naturally can suppress the

virus but about 15% per year will

reactivate and that risk of reactivation

correlates would be as an antigen

quantification from one publication now

had 30 patients it's a relatively low

number but this can help you guide

therapy guide monitoring of patients how

frequently you may want to do follow-up

testing so a lot of data on this slide

that just gives references and NPV

negative predictive value positive

predictive value sensitivity and

specificity let's go into a little bit

more detailed laboratory markers and

hepatitis B infection now this is a

slide it has what is s all mine

hepatitis B patients or when I'm in

clinic I don't do tells the testing on

every hepatitis D patient but I'm

thinking about it on anybody who hasn't

old acquired and that's native B or

anybody with advanced liver disease just

just as an example or if I've got

somebody's antigen positive but they're

35 years old

I will check core in pre court as you

can see the qantas has a prominent role

assessing those patients for their

disease stage

and I'm thinking about future risk for

cancer whether I'm going to start

therapy whether I'm going to be doing

surveillance with lab testing every

three or every six months so this slide

is very important for you to come back

to in reference and really keep on your

desktop in your hepatitis B patient

assessment now here we're talking about

application of quantum there's some

proposals Natural History and during

therapy and we're going to get into more

detail in here that pegylated interferon

and nucleoside and D create site analogs

and where is that data application and

benefits are highlighted on this slide

and you might use it as a stopping rule

if you do use interferon in your

practice it's pretty rare or more likely

if I have a patient on a new Chris isn't

active alert in alpha v Rennell pass

which is a new form of tune officer

that's on the market I'll be able to use

want to say whether they're going to

have a chance of clearing as antigen on

that nuke if the advantage enticing now

what about mother-to-child transmission

we brought up initially that that's the

most common way for people to become

infected globally and the higher the

quant

s is what this graph is showing higher

the risk of transmission to the infant

basically we've been using HTV DNA level

we have an absolute cutoff absolute

meaning in the cod lines went to 200,000

i you the quantitative HPV DNA for high

risk versus low risk well that's not a

perfect number it's a simple number but

it's not a perfect number and quant

asked could come into the mix if you

have a patient who's got an HPV DNA

level they have 200,000 but their

antigen negative and if they're quant is

low the risk of transmission is going to

be much much lower and you may not

institute nuclear appease such as

profiteer during the third trimester so

it's a very interesting publication that

came out now patients have good immune

control that means your immune system is

controlling that virus they may have a

low level of s

the s antigen may be declining over time

if that is managed it is declining on

its own without intervention without a

therapy you may decide that you're not

going to start there if you're going to

see if that patient is going to ask

clear on their own actually there's

another F antigen quantal as an

indication of immune control then talks

about the different log levels of that

immune control status both are on that

and Kwan HPV DNA and then again back to

risk reactivation and this number around

3 log iu thousand range it's an

interesting cutoff for that level of

really saying somebody's got a good

immune control they may not need therapy

at that time now what about patients who

change their s management but the data

on this slide shows is that here the F

management goes down by one log in e

antigen negative patients that patient

may actually undergo natural antigen

walls there's a lot of data on this

slide but look at the right graph and

looking at that increasing chance of s

loss that is an indication that was a

log reduction over time long-term

follow-up that patient may clear that

antigen on their own so that dynamic

naturally can help describe that

patients future events letter supplied a

natural history of HPV linking a quant X

looking at Kuantan combined with HPV DNA

level more data more references for your

future review with that Kwan test level

can help describe the natural history of

your patient and your connect decisions

about whether to start therapy and

frequency of monitoring D antigen

seroconversion

so we want our patients who have the

antigen positive disease to lose the

antigen that could be naturally or with

therapy now lower the s antigen and when

patients lose

e antigen their liver cancer risk is

lower that's basically what this data is

showing in the right graph on this table

so you like the DNA level to be under

two thousand like the alt T to be less

than forty that's not healthy that's

normal at a number of labs and here we

have a cut-off that managin less than a

thousand you can see a very very

substantial decrement in decreased

future liver cancer risk now you want

ask on its own doesn't always decrease

when places lose key antigen so it

really is an individualized patient

status when patients lose the antigen I

can indicate moving to immune control

and that immune clearance or they can be

converting to e negative disease so

you're going to be combining contacts

with monitoring your qualitative D

antigen status we don't have it all want

the antigen test in the United States at

least not yet now this is looking at a

antigen negative patients followed up

for eight years now will somebody remain

inactive and the cancer remain inactive

is even better when they're as antigen

as less than 100 less than a hundred

extremely low risk reactivation an

antigen over a thousand very high risk

of reactivation to monitor that patient

potentially every three months they

reactivate again this is the one

patients not on therapy then you would

consider instituting a new depending on

their alt and looking at their liver

disease status by lab testing or by

imaging this is a Taiwanese study and e-

patients with HPV DNA levels low under

2000 followed for over thirteen years

when you combine as managing levels with

HPV DNA quant and alte you can help

predict the risk of deep disease

progression in those locations so let's

take on a patient with an HPV DNA level

of a hundred and their alt is just above

the effort

healthy let's say for a man 30 to 35

you're not sure what to do with that

patient

you start nuke or not in the guidelines

would say no but the a management level

was over a thousand and let's say

imaging suggested hepatocellular disease

then I would Institute a new so I'm

praying quant asset especially for your

gray zone patients to decide what to do

with those individuals you start therapy

or not let's to risk a progressive liver

disease back to the sadness western

adults the chance of patient naturally

clearing s on their own as we mentioned

earlier is in the two percent range some

that's even lower but if you can sees in

the Alaska data it's in the 1 percent to

half a percent range that's because in

Alaska most individuals historically had

vertically acquired hepatitis B it

followed more of an Asian pattern also

there were some horizontal transmission

in Canada as well you move to Brazil

that's going to be mostly adult acquired

or horizontally acquired hepatitis B and

here we have a 2% range but there are

other patients that clear on their own

especially we have higher alts lower

Quan DNA levels that want s trajectories

going to help define what direction they

go where they're going

Asian adults but slower chance events

clearance but there is there a chance

that that's clearance and we had a paper

recently at least an abstract from our

practice in San Jose and largely

Vietnamese population where we had a 5%

chance of s loss and there are different

predictors of that s loss and we'll be

looking at quantis in that population

and the Vietnamese population helps

define that's role in that special group

spontaneous zero-clearance and

asymptomatic carriers in highly endemic

areas when does that s clearance usually

take place and here we have a peak

between age 40 and age 55 if you're

younger than that we don't see much s

clearance you're older than that if you

have cleared s you probably won't clear

s so if there is an age

distribution of clearance predictive

factors that has clearance again we're

going to highlight the quantitative F

antigen declining or low levels with as

management our part of that predictive

matrix that grid that you're going to

put together for your patience in quant

as levels predict spontaneous at zero

clearance this is from after YC Chen

published in 2012 and again cut-offs a

200 or 100 had a both be good positive

and negative predictive value so your

over 100 or 200 better negative

predictive value your under 200 100 that

are positive predictive value on as

levels here is zero clearance and

Asian's

and we're looking at a hundred cutoff

and a thousand cutoff lower the s

antigen levels the higher the chance of

natural s clearance here's what's called

the Albatross study as a clearance in

adult acquired hepatitis b then we can

use this in both vertically transmitted

and adult acquired appetize be and the

quant s level here they're talking about

a five thousand cutoff looking at

different chances yes no clearance and

the results of some influenced by

genotype that pad to do this and of

course low HPV DNA levels but the

quantex at the prediction the p-value is

less than point zero zero one okay

naturally clearing test managing this is

a negative patients just to highlight

that part spontaneous as clearance and

development of HPV so this is bringing

us back not just to you the quantex

number but why we want and managing to

disappear it still has emphasized be in

their liver of course this is incurable

but when you get to dysfunctional terror

your chance of liver cancer drops

dramatically so this is just basically

the homerun and hepatitis b management

let's talk now a little bit more about

monitoring during treatment then lots

and lots of

Natural History discussions here and we

can move through this next section

briefly talking about interferon therapy

if you use interferon which isn't used

much in the United States if you lose

their ease interferon you can lose

advantage and I usually quote to my

patients and the 15% chance but there

are some studies including studies that

were done in Italy or that s clearance

rate was much higher than with controls

who are untreated the difference

sometimes the twofold change and

sometimes it's a three or fourfold

change unfortunately people just don't

like injection therapy with the side

effects interferon in the u.s. we

haven't had Qantas available and Quandt

acid three months into treatment can

help define who's going to respond and

who's not whether you continue or you

stop treatment called stopping rules so

now that we have qua ness the Pharaon

therapy use may increase slightly here

is data from UN from Hong Kong and Lin

from Taiwan showing that even in Asian

patients you can go from this point five

percent of the three percent to get as a

clearance but it's a lot of work for a

low rate of functional cure this is

recent data 2010 from dr. chu Nani

antigen positive and you can see in

responders beautiful decline against

antigen you can follow those patients

about long term and show the advantage

and decline or clearance here on the

percent side on the right side a loss

and s loss you're looking at an

advantage and tighter at week 12 a 1500

so three months and interferon therapy

you can basically say yes or no they're

going to clear e but better yet yes or

no that they're going to clear s this is

by Sonnen velde and hepatology this is a

Western European study mostly adult

acquired for those P but some vertical

transmission

here's more antigen positive data with

PEG interferon defining non-response

relapse and patients with sustained

virologic response loss as managin at

three months you really want to see a

multi vlog decline in these engine

positive patients on interferon just say

they have a chance of losing s more on e

antigen positive patients pegylated

interferon you see this change in the

spread that starts dumb widening between

three and six months with HPV DNA but

it's not as profound as you see in the

right box we're looking at log s

reduction three months really separates

out patients whether they're going to

get s loss or not what about end of

treatment outcomes as clearance with

taken or here on there look basically

here at the top box as antigen level at

week 48 that patient has reached ten I

use remember the sensitivity of the qual

and quant amps is down to point zero

five I use that's 0.05 I use if you're

under ten even have this very very high

chance of losing a Sana's about 50% so I

would be checking quant asset three

months and quantum at week 48 then help

describes this patient what's going to

happen to them long term whether I want

to say come in with a nuke or not if

they're not having a desta Cline in off

of here this is really one of our top

first-line drugs and basically this is

just talking about the non severe and

what's happening to the probability of s

loss on treatment this is not along this

is just saying yes or no

we're following out patients almost in

400 weeks we're getting up to about a

13% chance for those loss until once a

day minimal side effects with this

medication though still isn't a great

number that's why we're developing new

drugs for hepatitis B we want this to be

50% but at least with our oral therapy

there's a chance and in this study the

go on as antigen level at baseline help

predict who is going to clear a rabid s

decline

Deanna's incisions on Sonam premier

predicted who is going to clear you've

got somebody on standoff near you're

monitoring their advantage and status

it's much better as you can see in the

left which is Quan s from the right

craft which HPV DNA levels because

basically everybody on sand off of your

suppresses HPV DNA both nations clear

HPV DNA but only in subset of F decline

which would then predict s clearance a

little bit more here in terms of the

quantum let's look at the third green

box from the left go down to the bottom

says s antigen greater than four point

five logs this is kind of interesting

because this is the patient population

who had a high class at baseline for

some reason higher than quantized

baseline the higher the chance of

answered clearance

long-term this is different than what we

saw with interferon data where the lower

the s antigen at baseline I didn't show

the state of put the lower the s antigen

at baseline help predict interferon

induced s antigen loss and why it's

discrepant between interferon and nuke

we don't know but here's the fact but

here higher inflammatory score HPV DNA

levels and genotypes also help predict s

loss at clearance that year for

treatment now let's look at the kinetics

this is what we call it spaghetti graph

as you can see that the patients who

clear as antigen typically had a

significant decline in s antigen early

or moderately early in this treatment

course now this was an interesting study

because it subset of patients were on a

depth of here a drug that we don't use

anymore for hepatitis B management and

when you switch from a depth of here to

turn off here you can see that you pick

up another group of patients in the

orange lines who are going to clear as

antigen so patients and providers often

ask me am i using lividity they have

somebody on limiting or somebody on a

deaf ear what do I do I switch everybody

to first line therapy because the rates

that have clearance with

or dismal at least Woodsen on foreign

tech and off of here or in texture we

have a chance this is a discussion about

long term antiviral therapy for

hepatitis B in a real-world setting

we like real-world data and we published

this paper in an abstract looking at

about a thousand patients in a GI based

practice in Northern California and it

was almost 99% Asian and had about 87

month follow-up we did have significant

s loss in this patient population and

the cohort characteristics are

highlighted on the right side baseline

information 62 percent of these patients

were cirrhotic so what did we show in

this abstract that we could get as long

as I mentioned earlier at a 5% rate in

our Asian patient population alt

normalization also occurred undetectable

HPV DNA in most patients what's

interesting here is is that about 10% of

patients lost s but still had detectable

HPV DNA

it's just highlight that you need to be

looking at your patients from their

advantage n't on as antigen perspective

and monitoring DNA if their DNA remains

positive but they lose s you need to

continue to monitor those patients more

closely now this is talking again about

what groups higher the alt higher the

chance of s loss cirrhotic patients

could lose s but the patients without

cirrhosis did better and interestingly

older age had a slightly higher rate of

s loss and then had a slightly higher

rate of s loss predictors of s

management loss now in new treated

patients this is a combined table from

three different studies now we're going

to drop down now to the orange bars or

the higher want s levels as we mentioned

earlier now predict that's loss but more

importantly it's the dynamic you need

about 1/2 log reduction that

12 or 24 or a antigen negative by week

24 and it's an offer group to say that

they had a higher chance of s loss so

it's really hard to lose XA if you're a

antigen to remaining positive so we have

a matrix we have a series of lab tests

baseline and on treatment that we're

going to use for monitoring our patients

because it's an offer dear study where

they combine turn off here with

pegylated interferon in patients with

significant liver disease I'm not going

to go into all the different parts of

the study design they're just going to

say that there is a hint that

combination therapy resulted in a higher

rate of s loss that you really have to

look at patient characteristics and here

we're going to basically say the

baseline predictors of HPV DNA decline

square the p-value point zero zero one

included a low want s level at baseline

so what predicted quant asks decline

genotype a interesting P here highest

engine and high HPV DNA levels of

baseline so you look at this you have to

look at your therapy and you have to

look at the dynamic on treatment to

define who's likely to lose s managing

so what about risk of liver cancer

during treatment this is kind of

interesting study higher the advantage n

over 2000 much higher risk of HCC look

at the difference here s engine less

than 2000 negligible risk as antigen

over 2000 during this study we're

talking about a higher risk

now we're combining that with HPV DNA

levels so if you've got a low s antigen

doesn't really matter what your HPV DNA

level is if you have a high x antigen

higher the DNA level higher the risk of

HCC what about alt flares sort of an

interesting study alt flares here did

help predict a decrease in s antigen so

if you

see an alt increase during your patient

management you should really continue

whatever you're doing the fielder tells

the patient there's a higher chance of

having F loss of an S decline during

that Flair advantage will often be

positive and a negative patient this is

just reviewing what happens left cluster

is our new right cluster is pegylated

interferon and we have five to ten

percent chance with nukes and we have an

eight to fifteen percent chance of s

loss with interferon therapy and even

combination therapy may be slightly

higher although that's still not golden

what about drug development as we

mentioned earlier there's many many new

medications being developed for

hepatitis B we're looking for hepatitis

B cure like we have with hepatitis C but

we're not there yet

and the a SLD convened a program in

Virginia in 2016 and this was an

interesting study where they

participants basically voted but what

did they expect during drug development

especially for Phase two studies half

the audience stated that they need to

see a one log decline in more than 50%

of patients during a phase two study to

move that drunk forward to say Phase

three some of the participants wanted s

loss also but that's probably not really

realistic in a phase two study

especially if you're looking at early

data it's going to be an epic line

that's going to be so important so every

study that I know of is looking at

that's antigen quantum antigen levels at

one month intervals during drug

development so this is really the

standard for drug development today

again we're talking about phase three

studies now we're going to be moving

just yes we want death decline a really

s loss and we want s loss in over 30

percent of patients in our phase three

studies and we really want our phase

three study treatment duration this is

now my expert opinion to be a year or

less

that's going to really I think in part a

much higher level a patient and provider

engagement so we're coming up here so we

have some time for Q&A I'm going to move

through a summary here

spontaneous s antigen clearance

0.5 to 2 percent 1 to 2 percent that's

really more data for adults acquired

hepatitis B 0.5% in vertically acquired

patients who typically are from the

asia-pacific region now we're going to

talk about s zero clearance with

antiviral therapy Western patients do

better than Asian patients but as I

showed you an Asian patient population

from our group in San Jose

we had a 5% chance of s loss and that's

hopefully going to be going to be

accepted in a peer-reviewed publication

very soon quant s could be determined

and my opinion annually but you've been

looking at it every two to three years

to look at zero clearance in your

patients who are carriers meaning

patients you may not be instituting

therapy specifically now when to clear

advantage and the good news is these

patients have a lower risk of

decompensation and a little risk of

cancer qantas antigen helps you stage

their disease what's veins what state

are they in future risk of liver cancer

probability of viral clearance that's

that functional cure as clearance what's

the response the Dukes do you have a

reason to stop interferon in three

months if they haven't reached specific

threshold what's the risk of HPV

mother-to-child transmission drug

development for an HPV tier is ongoing

and I also like at management during

treatment especially with nukes to

enhance patient compliance if the

decline is taking place you really can

boost that patient's confidence that

they may be clearing s stay on a nuclear

opee conversely if the eff manager is

not clearing but the DNA has cleared

your DNA negative but if management say

is running 2005

thousand then you're going to be saying

oh my gosh we need to keep you on

therapy because if we stop treatment you

have a substantial chance of relapse and

then of course you can have a relapse

you could have a clarity compensation in

a patient so it really works in all

patients to help with compliance it's a

very important issue and I think we're

going to turn it back over to Melissa

and the team at Quest I want to thank

quests for bringing this ldt test to the

setting that we could use in our

practice in the u.s. it is available in

over 70 countries and I think those

really counted 100 countries worldwide

we can get quant

s now we have it available in the US

it's really nice to be heading towards

the engine and not on the caboose of

testing thank you so much for

participating today thank you so much

dr. - we have a number of questions that

have come in through chat and Q&A which

we will jump right to after we let

Michelle review the instructions for

live questions are you there - Michelle

yes in Taunton and plate this appliance

we will now begin the question and

answer session if you would like to have

the question please press Lorenson one

please and meet your phone and record

your name clearly when prompted

your name is needed to present your

question and to cancel your request you

may press pause and then to inlet to

wait a moment for the first question now

while we're waiting to see if any lights

come in dr. Gish we've had a number as I

mentioned come in under start start

giving them to you so the first step is

any prediction when the FDA will approve

in the United States a quant hepatitis B

surface antigen antigen test so this is

a great question in the United States we

have two pathways forward to get tests

to the clinic one is this ldt or

laboratory determined test and this is

typically a test that CLIA approved and

that may depend even on state-by-state

approval but there are many tests that

you and I use every day that aren't FDA

cleared and we're going to use the word

cleared not approve because that's what

the FDA

terminology is but cleared and approved

or probably interchangeable there are

two assays that are used throughout the

world that are say c e marked and both

roshan abbott have those assays we are

hoping that roshan abbot will work and

move forward to get FDA clearance for

their chests in the united states and

then what may happen quest would use

their LD t currently but there's an FDA

cleared test quest may actually

institute one the other or both of those

FDA cleared tests in their labs i would

be able to quest to decide so i'm just

putting in my expert opinion out there

but for the time being we have a very

reliable LD t-test that's available in

the united states 3dd use in your

practice thank you how about

co-infections between hepatitis B and

hepatitis C is the Quandt antigen as

important that's a great question and I

have to say we don't have data on that

co-infection with either delta there's

probably a zero but there's not a lot of

data in Delta I think the contest tends

to run pretty low but that's a good

place for research and one that we can

move forward at our national and

international meetings excellent thought

what proportion of hepatitis D infected

patients naturally clear circulating

hepatitis B surface antigen

qualitatively will they relapse to a

positive hepatitis B surface antigen

state later in life that's a great

question and we're saying 0.5% and

vertically transmitted up to two percent

in adult adult transmitted hepatitis B

naturally clear as antigen the relapse

rate either naturally or post therapy is

very low and I'd close the lifetime risk

of zero reversion with natural clearance

to be under 5% and zero reversion with

nukes to be well under 15% so it's very

low so what you would do once

and clear this antigen is you would

monitor them annually for at least three

years to document they've lost F and a

maintain s loss for three years then

probably you don't need to check again

unless they have an alt increase thank

you healthy people who are persistent

carriers of the surface antigen may have

no laboratory evidence of hepatitis

whereas others have biochemical or

histological filings of chronic liver

disease is this because the surface

antigen is detectable in the serum is

this because it's detectable in the

serum before liver function test

excuse me test abnormal or before

development of clinical features of

hepatitis all right this is a fantastic

question because we're going to change

your terminology today for the rest of

your life

number one we no longer use the word

healthy carrier because that's an

oxymoron if you are carrying hepatitis B

you can't be healthy so we're going to

talk about these different phases of

diseases but we won't use the word

healthy carrier anymore the next

terminology change is the word liver

function test ASCII and alt are not

liver function tests I know many of you

have been using that term for probably

most of your career but the new world

the world is changing as you know alt

and ast are liver enzymes they do not

denote or mark liver function liver

function is denoted by bilirubin albumin

or INR those are liver function tests

Anstey alt GG t alkaline phosphatase or

liver enzymes liver enzymes you might

check right here but remember there's

365 days in the year and you're only

getting an alt on two days of years so

you're missing 363 days or the alt-right

be increased so if you want to determine

if people have liver disease or not you

have to stage their liver disease by

using other tests now when people have

low alts healthy help me being an alt

and a woman lost at 20 alt less than 30

in a band forget with your lab call

normal IQ dorable but it's not healthy

if you need to stage their liver disease

then back in the former times who would

just say get a liver biopsy but we

rarely do liver biopsy and we will

calculate an a3 or fib 4 score those are

scores available online looking at

enzymes and platelet counts but better

yet in people with normal alt and ASD or

healthy alt and ASD you need to image

their liver a liver imaging can be

simple you get a full abdominal

ultrasound ask for a spleen size and

portal vein diameter and it more

sophisticated geographic locations

you're going to get something called

transient Eli's dog Rafi or you may

order through quest or your local lab

something called fibro sure or fibro

test which is a blood test for liver

damage but in people with normal alts

again less than 20 and women less than

30 in man imaging is your best friend

II left ography is the best way to image

the liver which the whole other

discussion but it's basically a way to

stage fibrosis and if you have normally

last ography normal ultrasound and

normal alt healthy alt you can say that

person is an inactive carrier provided

if their DNA is very lower undetectable

and there s antigen quant is low so

remember this major because you need

multiple tests determine stage state

phase of disease for your patient and

whether they have a low risk of

progression or a high risk again banish

that word healthy carrier is an oxymoron

like jumbo shrimp thank you doctor - can

you please somebody just ask could you

repeat those tests that are the liver

function tests again i INR bilirubin and

then the the chatter is asking what the

third albumin is the third liver

function test that you would look at in

your patients in bilirubin is your best

liver function test and the direct

bilirubin is the best of the best

a healthy direct bilirubin in a healthy

a person or a person with minimal liver

disease who's not necessarily healthy

that has a quat answer as antigen

positive the direct bilirubin should be

0.3 or less something above 0.4 you're

worried about liver dysfunction Thank

You operator are there any live

questions oh yes we have question Ln the

queue and the first question comes from

the line of mr. grandidis sir your life

now opened yes how about money to ask

you have any data regarding those who

are immunosuppressed with biologics with

transplant or HIV otherwise

immunosuppressed with that as good

levels that is a great question I don't

know of any data I'm going to

inferentially predict that the quantex

levels would go up with reactivation

like you would see with HPV DNA but that

is room for research and reactivation as

a super hot topic now as you know

especially because we've seen hepatitis

B reactivation with hepatitis E

treatment with our new DAA so it sounds

like we've got some good research ideas

out of this presentation today thank you

Zuber thank you and at this point we

have no questions and our nakum you once

again participant if you would like to

ask question you may press bar and then

one you will be prompted to record your

name and to cancel your request you may

press star and thank you thank you okay

we do have many marks on the QA and the

chat doctor dish could you give a

definition of an alt slur fantastic

question

so ale increasing two times baseline or

five times baseline is the window where

you start speaking of an alt flare so

let's say that somebody's baseline is a

hundred and they go to two hundred that

would be considered an alt flare that's

a doubling now the lower your baseline

alt a little higher threshold let's say

that your baseline alt

fifteen a doubling to 30s not going to

get you too excited but going to 75

would be a major change so the lower the

alt the higher the multiple but a 2 to

5x change in your alt would be defined

as a flare

now flares are different you can have a

just an alt increase and no change in

liver function but you're going to want

to monitor anybody with an alt increase

and take a look at their bilirubin and

most importantly their direct bilirubin

level thank you

here's another one thank you for the

great presentation I'm still having a

difficult time deciding wire would want

to use quantitative surface antigen

levels instead of HPV DNA

can you explain once more why I would

want to use the surface antigen levels

when monitoring my patients so this is a

great question and one that we really

want to highlight we're not replacing

HPV DNA HPV DNA is a foundational test

in your initial assessment and your

monitoring of patients so we're not

going to use the word instead of we're

going to use the word complimentary so

in somebody who's got an HDTV DNA level

of 200 or 10,000 or million that want s

antigen at baseline can help you decide

what phase of disease they're in next is

Bo spaces with hepatitis B you're going

to plan to start therapy 60 70 80 % of

patients fit treatment guidelines that

have been published by a SL B or ezel

once you start therapy you need to see

if they have a declining Cuong M how do

you determine if you have a declining

qantas if you don't have a baseline so

right now we've talked about phase of

disease baseline and getting a baseline

so you can see what's happening on

treatment so I think these are two

important complementary tests we're not

replacing HPV DNA we are improving and

refining because

more granular and how we're managing our

hepatitis B patients really

state-of-the-art thank you

one last checks Maisel any live

questions yes we have two questions in

the queue and first one comes from the

line of miss Ruby Kamino

ma'am your line fell open hello hi I

work in a renal dialysis grab spectra

laboratories we have a hemodialysis

patient that had been had hepatitis B

surface antigen positive results in 2013

up to December of 2016 we test this

patient monthly in January 2017 we've

gotten a negative result two times three

times and joy and so the patient was

taken out of the isolation and was

dialyzed however the patient went back

in February under some kind mid-february

to be positive so I they questioned that

negative result so I told the nurse that

the patient is a chronic earlier and

should still be dialyze in isolation and

they want to give is that a correct

answer and plus is there some kind of of

leaflet or something that you can stand

to me so I can send it to the dialysis

unit that this can happen on a roni

courier patient especially with

immunocompromised patients so it's a

great question and my base is that

someone needs to be negative for at

least a year on sequential S antigen

testing and over talked about

qualitative testing before I'm going to

say they really had s clearance and in

the setting of the dialysis they're

going to need to be quat f- and HPD D

and a negative there's a big up to seven

percent of patients who are s n into

negative or HPV DNA positive so I'm

going to need a year at least in a

dialysis patient quantitive HPV DNA

negative before I would move them from

isolation to being in a standard

dialysis unit remember this Qantas

antigen and

all have a sensitivity of point zero

five if the patients at point zero four

it's going to be negative by the lab

testing but would be positive by more

sensitive as an antigen testing and

there are more more sensitive as antigen

tests that are available on a laboratory

basis they're not commercially available

yet so one here advantage a negative and

you have to confirm their HVD DNA

negative to remove them from an

isolation a dialysis center there are

publications on this we could discuss

that through the quest portal and

potentially get you something that you

could use to reference that to your team

thank you thank you and overheads blush

shade comes from the line mr. Foreman

Burgess sir your line is now open

I'm not knowing the source of the

antibody aka the species of the antibody

used in this essay has there been any

data collected on the effect of human

anti-mouse antibodies or heterophile

antibodies in the quantification of the

surface energy that is a great question

that we'll probably need to get back to

because I think we're at the top of the

hour here and it's quite technical so

I'm going to turn that back over to the

medical science team at quest look at

your name and email address and respond

back to with that information very very

good question but we'll probably need

some time to make sure we get to an

accurate answer