Cirrhosis Of The Liver Definition

>> good afternoon, everyone. thanks for being here for thepublic grand rounds,on the 25th anniversary of thediscovery of the hepatitis cvirus. look back and looking forward.25 years ago, cdc played an integral role in identifyingwhat was then known as non-a, non-b hepatitis and becamehepatitis c virus. since then there have beenreally important public health milestones including thedevelopment of a screening test for hepatitis c, the screeningof blood, making our blood

supply safer and dramaticallyreducing the number of infections, new infections inthis country. and now we have a new milestone,which is effective, better tolerated and shorter durationtreatment for hepatitis c. we have the potential to cure alot of people who are infected with hepatitis c and whootherwise will go on to develop severe disease, cirrhosis, livercancer, and other severe complications.there are significant concerns about both cost and access tomedical treatment for hepatitis

c and i think that we in thepublic health world can't afford to be naive, either about theneed to stand up for what's right in terms of getting accessto lifesaving treatment or about the concerns that are validabout the affordability and profit margins of treatmentsthat are essential that may exist.and i think one of the things that means for us is is that weneed to be extremely careful about any conflict of interestor potentially perceived conflict of interest in any ofour recommendations and actions

particularly when there arelarge economic interests at stake.we'll also need to address the whole cascade of treatment.we've seen this in condition after condition, whether it'shypertension or hiv, going from how many people are out there tohow many people are actually effectively treated.and to do that is going to require our engagement with thehealth care system where we in public health can bring a laserfocus on thinking about denominators, how many people dowe really need.

but it will be the clinicalproviders who need to figure out how to get that proportioneffectively treated up. that cascade has so many pointsof falloff it's not enough to increase testing rates.we have to fig dwrur out how to make sure that the providers andthe systems out there have systems in place to giveconsistently good results and get a very high proportion ofpeople effectively treated. we'll also need to understandthe long-term consequences of treatment and confirm thatsustain virological response

is truly sustained.i want to thank our speakers for today's really important grandrounds and introduce for the introduction dr. thorpe.[ applause ] thank you, dr. frieden, foryour comments. i'm deputy scientific directorof the public health grand rounds and i'd like to welcomeyou to the june 2014 cdc public health grand rounds session onhepatitis c. in addition to joining us here,grand rounds is available on the grand rounds website.also on our website we have a

featured video segment calledbeyond the data, which is posted shortly after the session.continuing education credits for public health grand rounds areavailable for physicians, nurses, pharmacists, healtheducators and others. please see the public healthgrand rounds website for additional information.as part of the continuing education process, we at thepublic health grand rounds and the presenters want to tell youwe have nothing to disclose. we have partnered with the cdcpublic health library and

information center to featurescientific articles relevant to hepatitis c.the full listing is available at cdc.govscienceclips.here is a preview of the upcoming grand rounds sessions.also, as a gentle reminder, please silence your cell phonesand other electronic devices. in addition to today'soutstanding featured speakers i'd like to acknowledge theimportant contributions of the individuals listed here.thank you. now i'd like to introduce thefirst speaker, dr. john ward.

thanks, and good afternoon,everyone. i'm the director of the divisionhere at cdc. hepatitis c virus was firstdiscovered in 1989. we're privileged today two ofthe key leaders in that discovery have joined us,dr. dan bradley, formerly of cdc and the hepatitis range anddr. harvey alter from the national institutes of health.if dan and harvey could please stand and have everyone givethem a round of applause. [ applause ]nay eel be giving a presentation

about their discovery later thisafternoon which will be available as a webcast.you can go to our hepatitis website at cdc to get theinformation about that, and we'll be honoring them in areception later this evening. hepatitis c is an envelope rnavirus. the genome consists of 9,600nuclei sites and polyprotein clinged into structural proteinsand nonstructural proteins. the nonstructural proteinsare the targets for antiviral therapy as you'll hear later onin this session.

because the rna lacksproofreading activity, millions of viruses with minor geneticchanges in this quasispecies arise in each host.based on major differences in genetic structure, acv isgrouped into seven genotypes which cluster geographicallyglobally. in the united statesapproximately 70% of infected persons have genotype 1,typically difficult to treat. this genetic diversity coupledwith a host relatively weak immune response increases thelikely hood of kro nis ti as

well as poses formidablebarriers for the development of a protective vaccine.globally hepatitis c is a major problem.based on data from the world health organization, anestimated 135 million persons are living with hepatitis c,with the area of coverage in red the highest prevalence.egypt is considered to have the highest prevalence with 1 out ofevery 10 persons chronically infected.it's estimated that approximately a million personsdie each year from complications

of hcv infection.in the united states, an estimated 1% of the civilianpopulation or approximately 2.7 million persons are infectedwith hcv. this estimate is based on thenational health survey which excludes populations such as thehomeless and the incarcerated, which are known to haveincreased prevalence for hepatitis c.adjustment of the estimates for these exclusions increasethis prevalence by upwards of 350,000 to 850,000 persons.before its discovery in what was

then called nonaids non-vhepatitis as mentioned by dr. frieden, ep deem logicstudies had revealed this was a blood-borne disease transferredto persons through injected drugs and that there was anevolution over time as various prevention strategies were putinto place even before the virus was discovered in 1989 such asvarious surrogate markers for non-a, non-b hepatitis into blood banking as well as hivprevention measure which is began to ramp up in the late1980s, particularly those

directed toward injection drugusers. thereafter with the discovery ofthe virus, serelogic tests were developed which improved bloodsafety, the prevision of intervention measures andcoupled again with other measures such as efforts toimprove patient safety have led to decreased incidence asindicated on this line graph to the point where in 2012, afteryears in the '80s where there were hundreds of thousands ofcases of infection, 22,000 cases were reported in the most recentyear.

this incidence is furtherrevealed by this map here between 2007 and 2012, reportsof new infection increased 50% nationally with 17 statesreporting an increase of 200% over that time period asindicated by the red shading. our epidemologic studies todaysay 70% are related to drug which often prebe ginns with theoral prescription of narcotics among older adolescent andyoung adults. and these individuals arepredominantly white and are residing in suburban and ruralareas.

hcv is more transmissable thanhiv through blood contact as evidenced here by this graphlooking at secondary cases of transmission from a primary caseamong an injection drug user. risk factors for hcvtransmission include the duration of injection, frequencyof injection, and the equipment sharing.not just sharing needles but also preparation of equipmentused to prepare the drug for injection.so as a result, intervention such as sing exchange, which hasbeen highly effective in

preventing hiv transmission, areonly moderately so in preventing hcv.so despite declines in hcv incidence, the prevalence of persons range from 27% to 50%.there are other exposures to contaminated blood whichcontribute to incidence. this includes the health caresetting where the risk of hcv transmission from a needle stickis greater than that for hiv in part because of the higher viralconcentration of hcv versus hiv. from 2008 to 2013 cds cdparticipated in the

investigation of 18 health careassociated outbreaks which were linked to 200 new infections inthe notification over 90,000 patients.each transmission occurred in multiple settings in bothinpatients and among outpatients related to syringe reuse, otherpoor infection control, and drug diversion by health careworkers. there is a risk of transmissionfrom mother to child, particularly if the mother ishiv infected. sexual transmission tends to berare except among hiv-infected

men who have sex with men whereincidence has found to be high in both the europe and the u.s.and other exposures which place people in contact withcontaminated blood. once infected with hcv, the riskof chronic infection ranges between 55% to 85%.thereafter, disease progression is typically silent.that's why hepatitis c is often called the silent epidemic,while the hcv infection leads to liver damage progressively overthe years. with over a 20-year period, 15%to 30% of persons develop a

severe fibrosis known ascirrhosis and thereafter 2% to 4% annual risk of developingend-stage liver disease and liver cancer.there's also a risk for other diseases that contribute to thismorbidity. despite the drop in incidence,mortality from hcv increased from 1999 to 2010 by 50% with amean age of 59 years. several decades younger than theaverage life expectancy of americans.black, nonhispanic, american indians and alaskan natives havetwice the mortality as white

americans.these mortality figures are conservative.as the valuation studies indicate, only about a third ofliver-related deaths among hcv infected persons are reported onvital records. further, other studies haveindicated that about 45% to 60% of persons are unaware of theirhcv infection. i showed you the natural historyover a 20-year period, but disease progression does notstop when the study ends. and so we have modeled thelifetime risk of hcv morbidity

and mortality, and it's shownhere on this slide where we take the population of approximately2.7 million persons within haines from the civilianpopulation and over the course of their lifetime we estimateabout 1.5 million will progress on to cirrhosis, 350,000developing primary liver cancer, and 900,000 dying of anhcv-related complication in the absence of diagnosis, care, andtreatment. given the rising morbidity andmortality, given the large number of persons currentlyunaware of their status, we

began to look for other optionsfor intervention beginning with testing, looking at the datawhere it revealed that the wave of incidence that was observedin the '70s and '80s and early '90s persist as a wave ofprevalence with infection among young adults in those earlieryears now persisting as infection among middle age andolder adults currently. and indeed the birth co-hor, apersons born between 1945 through 1965, or the so-calledbaby boom population, has the highest prevalence by birth yearcompared to other adults.

indeed, a six-fold higherprevalence than other dulls representing 81% of all personsliving with hcv in the u.s. and 3 out of every 4 persons dyingof this condition. because a cohort has been silentlicariing hcv and the risk of liver failure and liver cancergrows, there's an immediate need to identify them through testingso that they can receive treatment and care and adoptprevention strategies to avoid the harmful e effects of hcvinfection. accordingly, we proceeded to anevidence-based process of

developing a new recommendationfor a one-time test for all persons born in 1945 through1965. this recommendation was releasedby cdc in august of 2012 and was incorporated into therecommendations released by the u.s. preventive services taskforce in june of 2013. this recommendation is basedsolely on the year of birth and does not require a riskassessment in part because risk assessment is found to beinadequate, particularly for the birth cohort where the riskexposures happen decades ago and

may not be relevant to person'scurrent life circumstances. this birth cohort recommendationhas been joined with the risk-based recommendations manyof these listed here were first issued by cdc in 1998 and thenwere also adopted by the u.s. preventative services task forcein june of 2013 when they issued their recommendation for birthcohort testing. the benefits of cohort testingand linkage to care and treatment is that it reduces therisk of all causes of mortality by 50% and the risk of livercancer by 70% and the risk of

all types of liver disease by90%. we estimate that this willresult in tens of thousands if not over 120,000 deaths with afull adoption and successful implementation of the birthcohort strategy. we also did cost effectivemodeling at the time of gathering and evaluatingevidence for the birth cohort recommendation by cdc.and that's reflected in the blue bar graph labeled 2012, where welooked at the agents recommended for hcv therapy in that year andthen judged what was the cost

for quality adjusted life yearsof testing links to that recommended care and treatmentand in the analysis which was published we found that about$35,000 per quality was the outcome of testing and treatmentin 2012. and in comparison verycomparable to other prevention services considered to be goodpreventive practice in the united states.we're now in the process of looking at the new agents whichhave recently been licensed over the last four to five months.to see how this cost per quality

changes.and that's represented in the blue bar labeled 2014, which ispreliminary data, but it suggests that hcv testing linkedto treatment, particularly for patients that have some evidenceof liver disease, continues to be a cost-effective approach,very comparable to other preventative services.we're continuing to look at this population of patients as wellas other hcv-infected patient populations so that we can addcost-effectiveness data to this discussion about the cost andbenefits of hcv therapy.

as you'll be hearing from davein just a moment, we've entered into a whole new highlyeffective era for hcv therapy, but we're not going to besuccessful if we don't link the patients who need testing, care,and treatment to those interventions.and as was published by cdc authors and our partners lastyear, the care cap date for hcv is absolutely dismal with only50% of persons aware of their status, only a little over athird getting some type of care for their staging of theircurrent infection, staging of

their liver disease, only asmall fraction have been placed on treatment and only even asmaller proportion have successfully completed treatmentand achieved what was called a sustained virologic response,another term for care of their hcv infection.so where are we now? the burden of hcv-relateddisease is large. reports of new hcv infectionsare increasing. cdc and u.s. preventive servicestask force have issued new recommendations calling for hcvtesting for persons born during

1945 through 1965 or person whoinject drugs and others at risk. at least half of hcv infectedpersons are unaware of their status and access to hcv careand treatment must improve for patients to benefit fromtherapy. now i'll turn it over to davidthomas to describe the evolution of hcv therapy and the arrivalof the curative era for hcv. thank you.>> thanks very much, john. pleasure to be here, honor tospeak about hcv treatment, arguably one of the most rapidlychanging fields of medicine.

to understand hepatitis ctreatment you need to think about three terms defined bywhat happens after -- to the hcv virus lode after treatment.in some individuals, treatment is given and there's little tono reduction in the hcv viral lode, a condition referred to asnonresponse. in others hcv rna is suppressedbelow the level of detection, but then after treatment isdiscontinued the infection rebounds and those persons arecalled relapsers. and a third group ofindividuals, hcv rna is pressed

below the level of what can be detected in the blood and evenafter therapy is discontinued remains undetectable.the fda has decided that the goal of successful therapy isbeing undetectable 12 weeks after therapy is discontinued,so-called svr-12. we refer to an svr as a cure forone of three reasons. one of them dr. frieden actuallybrought up, which is the durability.scr is considered a cure because it's curable and thousands ofindividuals, more than a

thousand shown on this slidealone, followed after successful treatment, after svr-12 or 24,there's few to no individuals in whom infection is detected againin the blood. and in some, in whom it is, it'simpossible to rule out that they were reinfected rather than thattheir original infection relapsed.so first of all, svr is considered cure because it'sdurable. secondly, it's considered a curebecause it most importantly reduces the incidence of hardclinical outcomes.

there's been a number of waysthat this has been shown in a number of different studies but,for example, this study follows 530 individuals, 8.4 years afterthey achooefd an svr-24. 36% of the individuals hadachieved that svr, and you can see that the incidence of liverfailure is lower in those with svr compared to those withoutsvr. likewise, the incidence ofcarcinoma was lower, as was all cause mortality.so svr is considered a cure first of all because it'sdurable and secondly because it

reduces the incidence of hardclinical outcomes, including mortality.third, hcv sustained virologic response is considered a curebecause as dr. copman will emphasize later it reduces therisk and actually eliminates the risk of the virus beingtransmitted to another person. now, we've been able to achievethat cure with a variety of different approaches over theyears beginning in 1991 with the approval of interferon.we've had progressive improvements in the frequencywith which cure can be produced

by changing to long-actinginterferon and most importantly by adding to the interferon andother drug molecules that directly interfere with variousnonstructural proteins as john mentioned in his first talk.in particular, the hcv protease has been drug targeted withmolecules approved by the fda for use in clinical practice.so this progress is remarkable, especially when you look at thepast few years. an example are these data thati'll show where i'm demonstrating the sustainedvirologic response, curates

across a variety of patientgroups including historically difficult to treat patientgroups such as those with cirrhosis and african-americanindividuals. and you can see that with just12 weeks high sustained virologic cure rates wereachieved. taking that further and evenmore exciting is looking to regimens that are not yet fdaapproved but which have been filed with the fda.an example is this, the combination of that samenucleotide inhibitor with an

agent.those two co-frm lated as one pill that can be taken once aday, and you can see that with as brief as eight weeks oftreatment with one pill once a day, high curates have beenpublished with this combination including a person withcirrhosis and those who failed prior treatment.taking that a step further, that same combination, to those havebeen added an additional direct acting agent and therapy hasbeen abbreviated from eight weeks to six weeks with highsustained virologic response

rates.and one study recently presented but not yet published by -- notyet published. now, these are not fda approvedbut represent part of the excitement, part of the futurefor hcv treatment. as exciting as the improvementsand efficacy are, we've also experienced substantialimprovements in the safety of treatment.this slide represents on treatment, if you will,real-world experience post approval of hcv proteaseinhibitors when used with

interferon.you can see high rates of adverse events and low toleralertollerab tollerableity.i don't have this the experiments for some, but thepublished experience of those from the phase we studiedsuggests that they'll be much, much safer than what we'veexperienced with protease inhibitors.fortunately, although i've only had the opportunity tounderscore this point with the example of sufostazere andrelated products, there are a

large cases filed with expeditedreview approved by the u.s. fda and some interferon-bearingregimens that are already fda approved for use in the unitedstates. with each of these, many ofwhich have already been published, have already had thephase three data published, there are high rates ofsustained virologic response, in other words, high curates andvery high toleraability as what i've shown you.well, in this rapidly changing era, typical methods ofestablishing guidelines, if you

will, for how to use medicationsreally are insufficient. accordingly, the centers fordisease control has co-sponsored, along with theamerican association for the study of liver disease and theinfectious disease society of america in partnership with theinternational antiviral society of the usa, guidance for how touse these medications and other aspects of hepatitis cmanagement. there's information on testing.there's information on linkage to care.and there's information on what

regimens are recommended forparticular situations. in addition, the all-importantquestion of which patients should be treated and when willsoon be addressed by this group probably in the forthcomingmonth. now, it used to be that weanswered that question when we had medications with lots ofside effects by weighing the risks of treatment over andagainst the potential benefits. and often times the balancefavored the use of medications only for persons with advancedliver disease.

but now, as i'm starting to --as i'm showing, we're looking at medications with few to nomeasurable adverse event, and that shifts its dynamic andopens up the opportunity for treatment for far moreindividuals. that also raises the question ofhow that expanded access to treatment if you will will bepaid for. as dr. freiden mentioned thecost of hepatitis c care has become an important issue toconsider. now, hepatitis c treatmentsalways been expensive.

the regimens that were standardof care from 2011 to 2013 could be $50,000 to $100,000.but as john mentioned, there's already been studies that haveshown that meditations in that price range and with thatefficacy would be consistent with what we usually consider tobe cost effective in the unit states.the new regimens are more expensive, but they're also moreefficacious, and as john showed preliminary observation suggeststhat there's incremal cost effectiveness achieved that, inother words, the increase in

efficacy counterbalances theincrease in cost from a cost perspective, that is.nonetheless, the issue of cost has clearly come into thehepatitis c treatment discussion and has entered in and shiftedthe dynamic, whereas we once talked about essentially whatwas the advisability, if you will, of treatment or theadvisability for a given patient determined by risk and benefit,we're now concerned with this broadest perspective, and aphysician's not only thinking about the advisability but insome instances having to defend

the necessity of treatment,something that we haven't had to do in the past.i won't have time to sufficiently discuss thiscrucial question, but i will mention that david rind, who hasdone some of this original work, will be presenting a full talkon this in the next symposium. so there's no question --there's no question that we've experienced since harvey and danfirst got into this field remarkable progress on this --on the efficacy of hepatitis c treatments, beginning withinterferon and now with the

all-oral regimens, reallyrealistically being able to achieve a cure in more than 90%of the persons who come in for care.it's tremendous progress that we need to celebrate and applaud.however, when we take a broader perspective, consider thatprogress on the y axis, if you will, the percent who are cured,over and against the percent of the 135 million people aroundthe world that know they have hepatitis c and have had anopportunity to be treated, not to mention be cured, we get avery different perspective, and

this stars to show us what thechallenge is for the next 25 years, whereas we've been ableto move up the y axis because of the progress in virology,clinical testing and the progress brought about withclinical trials and the innovations from that work, inthe next 25 years, we're really going to have to make progresson this x axis, expanding the percentage of persons who knowthey have infection and somehow giving treatment to them andpaying for it. so what i've done in my talk isestablish that hepatitis c can

be cured.i've used the word cure because the sustained vir logic responseis durable because it reduces hard clinical outcomes includingimproving mortality because it prevents transmission from oneperson to another. i've also emphasized that theefficacy of hepatitis c treatment has risen considerablyin association with improvements in the safety of hepatitis ctreatment. but then i've also pointed tochallenges that remain. and when we think about the next25 years, the kinds of science,

the kinds of implementationscience that will be necessary to have the same sort of impactthat we're celebrating today. thanks very much for yourattention. thank you.so as we've heard so far we've entered an rather where we havethe tools to end hepatitis c in the united states.there are two major goals to achieve this.the first is to treat those already infected, and the otheris to prevent new infections from occurring.the new screening guidelines

targeting those with mostadvanced liver disease, particularly baby boomer, canallow us to cure a substantial proportion of the population andlead to enormous reduction in the morbidity and mortality fromchronic hepatitis c. to prevent new infections, weneed to implement ways to interrupt transmission amongthose who are most at risk. in particular, people who injectdrugs. those are multiple risk groups,these two groups represent the bulk of established incidentcases of hepatitis c.

some parts of public healthmodels that have proven use to feel complement or enhance themanagement of hiv can be applied to form late a public healthresponse to hepatitis c. this continuum starts withprevention, goes to screening, diagnosis, treatment, viralsuppression and hopefully reduction in prevalence andincidence of disease. it's useful not just forimproving clinical outcomes by identifying gaps but also inhelping public health in tracking lab-based outcomes.if we apply it to hepatitis c,

primary prevention includesinterventions like syringe access and access to otherinjection equipment, safer sex, particularly among hiv positivemen who have sex with men, and improved access to disordertreatment, medication assisted therapies.screening in this setting could be tracked by health caresystems which have access to both positive and negative testresults. electronic health records can beused by establishing automated alerts, reminders to screenbased on public health

recommendations by both riskfactor and birth cohort. screening would optimally bedesigned as opt out as it should be for hiv.and local and health systems would need to develop guidelinesin terms of how frequently you need to screen those who are atongoing risk of transmission. diagnosis still unfortunatelyrequires a screening and a subsequent rna test forhepatitis c, a two-step process that can sometimes be confusingand patients oftentimes don't know if they have rna confirmedhepatitis c or simply positive.

there are some movement towardsreflex testing, which would be an automatic confirmatory rnatest with a positive antibody as it's done for hiv and syphilis.this would be a huge benefit as of course would be a paint ofcare rna. public health's role in thissetting could be to track those with a positive antibody havereceived rna testing. however, it would have to changethe required reporting. currently negative rnas are notreportable to public health surveillance systems so there'sno way to track if all hepatitis

c sero positive persons havereceived rn, a confirmatory testing.another role for public health in this setting is to evaluatethe effectiveness of screening interventions like with hiv, ifwe're effectively screening would expect to detect people athigher four counts and hepatitis c we'd expect to detect peoplewith earlier stages of fibrosis. the initial management ofhepatitis c includes screening for infections, hepatitis-a andb, hiv, vaccinating for hepatitis-a and b andpneumococc

pneumococcus, counselingregarding risk reduction and transmission, alcohol -- briefclinician interventions around alcohol have been shown to benoif this setting and you need to assess for treatment both interms of getting a geno type and evaluating liver disease.so the liver evaluation includes a physical exam, liver functiontests, platelets, sometimes imaging and pathologicintervention to estimate degree of fibrosis in the liver.clinically health care systems could do this with simple --could follow this as sort of a

simple laboratory-based proxy oflevels after diagnosis just to ensure people have had eevaluation of their liver and genotypes to be sure patientshave been considered for treatment.additional steps in management are getting patients intodisorder treatment, particularly methadone, agnes treatment, andpsychiatric management, although that is less critical as we moveaway from interferon, which is the primary reason thatpsychiatric disease has historically been acontraindication to hepatitis c

treatment.so the toxicity of interferon, the duration of treatment, thelow likelihood of cure, these are not as relevant moveaway from interferon and the much more challengingtreatments. however, we have new barriers inparticular cost, which we all expect is going to limit accessto hepatitis c treatment for some time to come.interventions to improve uptake of treatment include casemanagement, pharmacy support, however, now effectiveassistance of -- get credit.

the uptick of treatment could betracked by looking for serial rnas in a patient that hasdiagnosed hepatitis c. this unfortunately couldn't yetbe done by surveillance because surveillance doesn't have accessto negative rna results. the proportion cured byhepatitis c treatment with curates over 90% should bepretty close to the proportion that are actually treated.it depends a little bit on which regimen is offered and onadheren adherence, of course.one way to track this in a

health care system once againwould be to look for a series of negative rna results, whichwould represent either viral clearance naturally or -- isthat involved extensive screening recommendation that'squite similar to birth cohort screening.on this graph, the y axis is the number of hepatitis c-relateddeaths, liver deaths. the solid black line shows thepredicted number of deaths with the old risk factor-basedscreening and the old treatment. the dotted black line is if wetake the new treatment and we

apply them aggressively to thepopulation. the dotted red line is if wehave the old treatment but the new screening recommendations.and the solid red line is if we do everything, aggressivescreening and aggressive treatment with the new regimens.that-in that study the peak number of deaths drops from37,000 to about 20,000, and this might be a great underestimateas dr. ward described, we now believe that there may be fourtimes as many liver-related deaths from hepatitis c thanthis model estimates.

unfortunately, the costs of newtherapeutics is expected to result on restrictions on whocan receive them. a common way to restrict thishas been based on degree of fibrosis.in this graph, the black line again shows old treatment, oldscreenings. the solid red line on the bottomshows new screening and aggressive new treatment.and each line going up shows restrictions by a degree of phibreaux bro' sis. as you can see, as we restrictmore and more based on fibrosis,

we lose a lot of the potentialbenefit of these new treatments. because the cost of managinghepatitis c increases as the disease progresses, the time toimplement aggressive screening and treatment from an economicperspective is now. the new therapies are fairlystraightforward. so primary care provider who iscouldn't offer the old therapies due to complexity of theregimens now potentially could. only 5200 individuals prescribedhepatitis c therapeutics in the first quarter of 2014.if we extend this to primary

care providers and others withexpertise in managing viral infections, we can greatlyincrease the number of providers who can offer treatment and thegeographic distribution. federally qualified health carecenters already care for many help tice c-infected persons.and they are available all over the country.moving on to the second goal, preventing new or incidentinfections, we need to focus on high-risk groups.currently they account for the vast majority of new infections.strategies to reduce risk

include syringe access programs,medication-assisted treatment, treatment as prevention, andprophylactic vaccines. medication-assisted treatment,particularly with agents such as methadone, are well-known toreduce disease incidence, but they're not universallyavailable and are often restricted to detoxificationshort-term treatment regimens that are markedly lesseffective. a prophylactic vaccine would befantastic, but we're unfortunately in the very earlystages of development for that.

syringe access programs, whichoffer clean syringes and other injection equipment and teachhygiene, such as not handling equipment with contaminatedhands, are still not widely available in many pars of theunited states. these charts show the impact ofsyringe access programs on hepatitis c prevalence andincidence. the black dots on the left chartrepresent actual prevalence and prevalence if access had notbeen available. on the chart on the right withincidence, the gray area

represents what it would havebeen without syringe access programs.as you can see, there's an effect, and it's an importanteffect. however, it's simply not enoughto achieve reduction in hepatitis c prevalence andincidence in a timely manner. the ease of novel therapiesmakes the concept of treatment as prevention or tasp feasible.successful programs would interrupt secondary transmissionand lower incidence infections. these programs would have themost impact while focusing on

people who are activelyinjecting drugs in areas of a high prevalence of hepatitis c.but implementing that among injectors may be complicated.concerns about adherence to treatment might lead some towant to limb access to treatment to injectors who are intreatment programs such as methadone programs.that would, of course, lessen the impact because thoseindividuals would be at less risk of transmitting hepatitis cwhile they're in the program. patient navigation programs,conditional cash transfer or

contingency management anddirectly observed therapy may be other approaches we need toconsider for maximizing adherence.these graphs show the expected impact over 15 years of treatedactive injectors based on current prevalence in each city.the darkest columns show the impact of treating 1% ofinjectors annually while the lightest show the impact.in a city with a prevalence of injectinjector, treating 8% of injectors per year would resultin a reduction in hepatitis c

prevalence of 90%.the potential reduction may be greater because this modelassumes that reinfection is identical to initial infectionwhereas all the literature sugs that reinfection rates are threeto tenfold lower than initial infections among injectors.it's critical to remember and i can't joemp emphasize there's nosingle intervention for preventing hiv or hepatitis c.the y axis here is the number of injectors that need to betreated in a tasp initiative in order for it to be successful.as you can see, the broader

availability of opiate treatmentand syringe access, the fewer people you need to treat to havea successful intervention, such that if you reach 60% of peoplewith these other interventions you need to treat half as manypeople in order to effect prevalence and incidence.there are some concerns that would need to be addressedbefore this is a viable intervention.the new therapeutics haven't been evaluated among activeinjectors. they're generally universallyexcluded from clinical trials.

like hiv, hepatitis c involveshigher tithers that may role in skwen infection.we need more research. poor adherence could potentiallylead to treatment failure and resistant viruses.fortunately, resistant mutations haven't proven to limit futuretreatment in the hepatitis c treatment trials.this is because of in part the lack of cross resistance betweenmechanisms of different medications and also because ofthe absence of archiving of mutations like we see with hiv.in contrast, in hepatitis c, the

mutations seem to disappearafter 6 to 12 months. reinfection is of course aconcern, but as i've mentioned the rates seem to be quite low.we need, however, a lot of more research into behavioralintervention that can lower the risk of initial and reinfectionwith hepatitis c. so in summary, there aremultiple very positive signs and array of serious challenges.the public awareness campaigns and community mobilization havegenerated broader recognition that hepatitis c needs to beaddressed now, not tomorrow but

today.the cdc and u.s. preventive services task forcerecommendation for baby boomer screening should be implementedsuch that opt-out screening happens.this would both improve screening and reduce the stigmathat has been a barrier to hepatitis c screening and care.hepatitis c screening can be more simple than the currenttwo-step process of diagnosis that is confusing to manypatients and even some providers.policy changes that, for

example, make negative rnasaccessible and reportable to public health agencies couldimprove the availability of surveillance to track how we'redoing and the expansion of hepatitis c treatment primarycare provider is critical in making sure that hepatitis ctreatment is not just available to those who have cirrhosis butavailable to those who have severe fibrosis will be veryimportant. although costs are a majorbarrier, the pipeline for hepatitis c therapeutics is vastand we all hope that these new

therapies will bring competitionand improve the price issue that we're running into currently.thank you very much. we'll open it up forquestions. my question concernsreinfection. could one of the speakers talkabout whether there is protective immunity againstreinfection? if so, is it subtype specific?>> an interesting question. the reinfection rates in thecohort study, people who have naturally cleared, they tend toget reinfected at a rate of

around 4% per year.the reinfection rate from one treatment study of activeinjectors was 2.6% got reinfected after treatment, andthese are individuals who had been cured through treatment.that suggests that even in individuals who aren't naturallyclearing infection, there is still a relatively low rate ofreinfection. i haven't heard any data interms of it being subtype specific.[ inaudible ]. i have a question.do you have a prediction of

whether you have more new peoplewho are -- who give the disease or do you think new prevalence,you know, is being discovered, like a disease how prevalent isbeing found? the infections are describedon that map and on the line graph based on a definition foracute cases, cases that are -- by certain criteria are -- wereinfected just in the last several months rather thanrecent infections that may have happened in some indefinitetime. in contrast, hepatitis-a,hepatitis b, we don't have a

marker for acute infection forhepatitis c so we have to use a case definition that's notperfect but is standardized. so we feel like much of thatincrease is a true rise in the number of new infections.always a possibility of better surveillance and betterreporting. but given persistence of thisfrom one year to the next and the increase of statesreporting, this we think it's a real increase in new infections.>> interested in the news about the sustained viral response andthat notion of do you think that

is eradication from the bodycompletely of the virus or maybe years later withimmunosuppression it would emerge?>> there have been anecdotes of relapse after immunosuppression,but the bulk of the data situations likeliver transplants in individuals that have a transplant picked upthat there is no relapse. and so it's -- the burden of theevidence favors the durability, though there are certainlyinstances in which reinfection is established and whether ornot that's prior infection or

new infection is sometimesdebatable. from our online audiences,what is the current recommendation for testing ofbabies born to hepatitis c positive mothers?>> the recommendation currently is there's not a recommendationfor testing of -- for screening of pregnant women for hcvbecause there's not an intervention to interrupttransmissi transmission.however, persons that have a possible exposure includinghealth care settings which

infected mothers would beincluded should be tested to see if there's an hcv infection.>> [ inaudible ] and also what are the prospects for a countrylike egypt? that's an important question,and the cost of hep c treatments do vary around the world, andi'm aware of the costs, for example, in england being lessthan in the united states but perhaps 80% of what the costsare here. and in egypt there have beenefforts to further reduce the costs down to nearly -- waybeyond a tenth of what we pay

here.so the costs differ. that's for sure.and why they differ and the extent to which they differ ican't really comment on that. what do you think about theprospects that egypt -- i think in egypt -- egypt forthose who don't know has a particular problem withhepatitis c where about 1 in 5 individuals who were born before1980 is infected. and that means that to try --and also a relatively low gdp. and so to try to addresshepatitis c infection where you

have millions of infectedindividuals in a context like that is very challenging.so there have been efforts to -- that i've read about but notpersonally experienced to marketedly reduce the cost ofsome of these new treatments that are effective for thegenotype that's prevalent there to as low as $1,000 to $2,000 acourse so, that's, you know, substantial departure from whatwe pay here. and i think that's the kind ofthing also an effort msf and w.h.o., a very organized effortworldwide to address the cost of

hepatitis c treatment. >> at this time, thank youvery much. and we'll see you in a month.>>> thank you. [ applause ]