hcv
DESCRIPTION
HCV. Frederik Nevens Hepatologie UZ Gasthuisberg KULeuven WKBV september 2004. Levertransplantatie: voornaamste oorzaken. Leverziekte alcoholisme Meest frequente oorzaken - hepatitis C en B : 25% - leverkanker (hepatoom): 20% - ziekten van de galwegen: 15% (PBC, PSC). - PowerPoint PPT PresentationTRANSCRIPT
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HCVFrederik NevensHepatologieUZ Gasthuisberg KULeuven
WKBV september 2004
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United States
World
Despite Public Health Efforts Many Patients are Still Affected
Source: National Health & Nutrition Examination Survey conducted 1988-1994
Source: National Institute of Health Consensus Development Conference Panel, Statement: Management of Hepatitis C. Hepatol 1997; 26S-10S
4 million
170 million
1
however, this does not mean that the public health issue has gone away, the prevalence still remains high - 4 times higher than HIV in some countries
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HCV Related Disease Burden is Projected to Increase Substantially in the Coming Years
Need for liver transplantation
10 year increase from year 1998 (%)
Decompensated liver disease
Liver disease related death
Cirrhosis
Liver cancer
Source: Davis et al, 1998
100
200
300
400
500
600
1998base rate
CHC could potentially be a huge burden on the healthcare system. It is forecast that:the need for liver transplant will increase by some 528%liver related death will increase by 223%decompensated liver disease will increase by 279%hepatocellular carcinoma will increase by 68% Cirrhosis will increase by 61%
John - replace this with your own data if you feel more comfortable with it - we can replace the graphic for you if required
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French Mortality Attributed toPrimary Liver Cancer (INSERM Data)
Source: Deuffic et alLancet 1998; 351: 214-215
Cases per year
Sheet:
In France it has quadrupled in the same time frame
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Levertransplantatie: voornaamste oorzakenLeverziekte alcoholismeMeest frequente oorzaken- hepatitis C en B : 25%- leverkanker (hepatoom): 20%- ziekten van de galwegen: 15% (PBC, PSC)
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Omvang van het probleem van Hepatitis C in VlaanderenOnderzoek 1993-94 (Van Damme e.a.)0,87 % HCV antistoffen2 % allochtonenOnderzoek 2001 (Cidex accident): 0,77 %85 % niet bewust HCV +Subgroepen: HCV + 70% IV druggebruiker90 % hemofilie patienten
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Van Damme et al
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Invloed op de gezondheid door HCV (1)1.Levercirrose en primaire leverkanker (HCC): 20 % na 15-20 jaar (pijnloze evolutie stille doder) mortaliteit tgv HCC laatste 10 jaar: x 2 1/3 van levertransplantaties wegens HCV
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Invloed op de gezondheid door HCV (2)2. Chronisch vermoeidheidssyndroom: bij 50 % interfereert HCV met sociaal leven. bij 40 % interfereert HCV met professionele activiteit.3. Varia: geen / verhoogde premies van verzekering afwijzing job stopzetten job (chirurg, ) besmetting van moeder op kind (2 5 %)
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Chronic Hepatitis C: Patients have a Significantly Reduced Quality of LifeReduction in quality of life vs normalNormalPhysical functioningVitalityGeneral healthBodily painRole-physicalSource: Bayliss et al Quality of Life Research 1998; 7:39-55Bayliss et al 1999 (submitted)Bonkovosky et al Hepatology 1999; 29:264-270Foster et al Hepatology 1998; 27:209-212Ware et al Hepatology 1999; (in press)Ware et al (in preparation) Social functioningRole emotionalMentalhealthSF-36 domain40455055
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An Immediate Quality of Life Improvement is Seen in Virological RespondersPhysical functioningVitalityGeneral healthBodily painRole-physicalSocial functioningRole emotionalMentalHealthChange from baselineBetterWorseNon-mild diseaseMild diseaseSource: Schering-Plough Research Institute: data on file
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Kosten door HCV: jaarlijkse kost per patient (euro)Frankrijk Belgi (Poynard et al) (Nevens et al,Buti et al.)
Chronische hepatitis zonder cirrose100125
Niet gedecompenseerde cirrose1.500250
Gedecompenseerde cirrose11.0008.125
HCC10.00010.000
Levertransplantatie jaar 175.00060.000
jaar 1+ _ 17.500
Geschatte totale kost/jaar Belgi: 700.000.000 BEF
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Marginal Cost-effectiveness
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Wie moet gescreend worden op HCVBloedtransfusies > 1990Voorgeschiedenis intraveneus druggebruikPiercing, tattoos (vooral in vreemde landen)Kinderen van HCV + moedersHIV (evolutie naar cirrose 2x tot 3x)
N.B.: geen SOA
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Poynard et al J Hepatology 2001
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Prof Leroux-Roels
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Welke behandelingSoort therapie- F2 F3 F4 PEG-IFN + ribaverine- F0 F1 IFN + ribaverineDuur en dosis- genotype 1/4/5 : 48 weken / riba 800-1200 mg - genotype 2/3 : 24 weken / riba 800 mgTenzij na 3 m. geen 2 log daling : stop
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Wie behandelenAlle patinten met histologisch chron. Hepatitis C en ALT
tenzij - contraindicatie INF en/of ribaverine - Child B/C cirrose
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Reden van behandelingVoorkomen gecompliceerd leverlijden (=strikte indicatie) = Metavir fibrose score F2,F3,F4
Behandelen van een infectieuze ziekte (= relatieve indicatie)= Metavir fibrose score F0-F1
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Ondersteunende therapieAnorexia : Seroxat 20 mgAsthenie : Serlain 50 mgAnderen en cirrose : Cipramil : 20 mg
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Succes behandelingGenotype 1/4/5: 40 50 %Genotype 2 3: 75 80%
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Zeuzem et al NEJM 2000
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Directe Toekomst : non respondersFibrose remmers- E1 therapeutisch vaccin (fase 2a+)- Glycyrrhizin (ALT)Bijkomende immuunstimulatie- Histamine (fase 3 beeindigd)Bijkomend antiviraal effect- Amantadine (mogelijks rand significant effect)
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E1 Therapeutic Vaccination Materials and MethodsC-terminally truncated recombinant form of the E1 proteinExpressed from an HCV subtype 1b strain consensus sequence, purified from mammalian cells20 mg E1 on alum in 0.5 ml single dose vials for IM injection
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E1-induced humoral response
original DB
BARC NRREQ.NR.VISITDOSPAT.NR.INVESTIGATOR9HCVE19HCVRN9GPT37
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0206-212121552991WEEK 5907/06/0203006NEVENS210191 |[DBN
0206-239811588424WEEK 6225/06/0203006NEVENS211157 |[DBN
0207-224291588434WEEK 6516/07/0203006NEVENS334.6159 |[DBN
0208-211681588448WEEK 6912/08/0203006NEVENS395.61946627114
0209-211941588470WEEK 7310/09/0203006NEVENS382.62404315107
0104-208891385006WEEK 010/04/0103007NEVENS1058485227132 |[DBN
0107-230051385064WEEK 1631/07/0103007NEVENS301695359179
0110-246441451887WEEK 2823/10/0103007NEVENS4085023941108
0203-219021451910WEEK 4812/03/0203007NEVENS267.62764650122 |[DBN
0204-211861552960WEEK 5009/04/0203007NEVENS271.84315574128 |[DBN
0204-255011552975WEEK 5330/04/0203007NEVENS436106
0205-232781549144WEEK 5621/05/0203007NEVENS2606.489
0206-216361549151WEEK 5911/06/0203007NEVENS3071180 |[DBN
0207-202401588426WEEK 6202/07/0203007NEVENS318471
0207-233101588437WEEK 6523/07/0203007NEVENS2068.874
0208-218491588452WEEK 6919/08/0203007NEVENS1836.8720823084
0209-221191588468WEEK 7317/09/0203007NEVENS1151.8809484589
0104-208871385008WEEK 010/04/0103008NEVENS163.8671394111 |[DBN
0107-230031385066WEEK 1631/07/0103008NEVENS681.91939360116 |[DBN
0110-246451451885WEEK 2823/10/0103008NEVENS678.8873858105 |[DBN
0203-219041451911WEEK 4812/03/0203008NEVENS330.676942083
0204-224971549130WEEK 5016/04/0203008NEVENS324.254322790
0205-209601549137WEEK 5307/05/0203008NEVENS622104 |[DBN
0205-246291549147WEEK 5628/05/0203008NEVENS1196.891 |[DBN\
0206-227531549155WEEK 5918/06/0203008NEVENS1032.895 |[DBN\
0207-213961588422WEEK 6209/07/0203008NEVENS1227.2101 |[DBN
0207-241031600379WEEK 6530/07/0203008NEVENS100896 |[DBN\
0208-226451588453WEEK 6926/08/0203008NEVENS946.491952286
0209-230581588464WEEK 7324/09/0203008NEVENS733.11192334110 |[DBN
0104-201611385002WEEK 003/04/0103011NEVENS147.8572478346
0107-223071385063WEEK 1624/07/0103011NEVENS187675829446
0110-230411451876WEEK 2816/10/0103011NEVENS188.7630211848
0203-206901451916WEEK 4805/03/0203011NEVENS132.8162636541
0203-245261549132WEEK 5026/03/0203011NEVENS142.3207430740
0204-224941552971WEEK 5316/04/0203011NEVENS106.930
0205-209581552981WEEK 5607/05/0203011NEVENS23533
0205-246321552989WEEK 5928/05/0203011NEVENS265.246
0206-227551588419WEEK 6218/06/0203011NEVENS416.245
0207-213971588432WEEK 6509/07/0203011NEVENS448.444
0208-205801600381WEEK 6906/08/0203011NEVENS670.439919547
0209-201981588461WEEK 7303/09/0203011NEVENS671.9503767251
0104-215151385004WEEK 017/04/0103012NEVENS95.811851125155 |[DBN
0108-207021385070WEEK 1607/08/0103012NEVENS106.6609878134 |[DBN
0110-230381451878WEEK 2816/10/0103012NEVENS105.5167838187 |[DBN
0203-206871451917WEEK 4805/03/0203012NEVENS94.47780166139 |[DBN
0203-231951549128WEEK 5019/03/0203012NEVENS92.92381762127 |[DBN
0204-211901552969WEEK 5309/04/0203012NEVENS101.7195 |[DBN
0204-255031552978WEEK 5630/04/0203012NEVENS95.59130 |[DBN
0205-232791552986WEEK 5921/05/0203012NEVENS113.7163 |[DBN
0206-216391588416WEEK 6211/06/0203012NEVENS144.1171 |[DBN
0207-202381588436WEEK 6502/07/0203012NEVENS183.3150 |[DBN
0207-241051588447WEEK 6930/07/0203012NEVENS204.91118328132 |[DBN
0208-228931600385WEEK 7327/08/0203012NEVENS211.11291758126 |[DBN
0104-213971385005WEEK 017/04/0103013NEVENS438.827469186
0108-207011385068WEEK 1607/08/0103013NEVENS360.448169244
0110-230361451877WEEK 2816/10/0103013NEVENS31569750041
0203-206881451915WEEK 4805/03/0203013NEVENS311.141554147
0203-231961549127WEEK 5019/03/0203013NEVENS306.214840437
0204-211911552968WEEK 5309/04/0203013NEVENS309.448
0204-255021552977WEEK 5630/04/0203013NEVENS286.149
0205-232761552987WEEK 5921/05/0203013NEVENS268.738
0206-216381588417WEEK 6211/06/0203013NEVENS299.941
0207-202371588435WEEK 6502/07/0203013NEVENS393.549
0207-241071588446WEEK 6930/07/0203013NEVENS434.847468849
0208-228921600386WEEK 7327/08/0203013NEVENS393.3117621142
0104-201601385001WEEK 003/04/0103015NEVENS107.658712473
0107-223061385061WEEK 1624/07/0103015NEVENS10240196545
0110-230631451881WEEK 2816/10/0103015NEVENS107.715718353
0203-206921451918WEEK 4805/03/0203015NEVENS100.719725146
0203-245271549131WEEK 5026/03/0203015NEVENS93.5233615541
0204-224951552972WEEK 5316/04/0203015NEVENS72.433
0205-209591552980WEEK 5607/05/0203015NEVENS66.3747
0205-246331552988WEEK 5928/05/0203015NEVENS55.1240
0206-227541588418WEEK 6218/06/0203015NEVENS84.7949
0207-213981588433WEEK 6509/07/0203015NEVENS106.446
0208-205791600382WEEK 6906/08/0203015NEVENS114.3112868747
0209-201971600387WEEK 7303/09/0203015NEVENS96.1344632951
0104-210281385009WEEK 011/04/0103018NEVENS< 18.75121181198
0107-230041385067WEEK 1631/07/0103018NEVENS< 18.75322400096
0110-246461451886WEEK 2823/10/0103018NEVENS< 18.751402445124 |[DBN
0203-219061451913WEEK 4812/03/0203018NEVENS< 18.751366359217 |[DBN
0204-224981552962WEEK 5016/04/0203018NEVENS< 18.751365698129 |[DBN
0205-209561549138WEEK 5307/05/0203018NEVENS< 18.75155 |[DBN
0205-246301549146WEEK 5628/05/0203018NEVENS36.4170 |[DBN
0206-227561549153WEEK 5918/06/0203018NEVENS54.43173 |[DBN
0207-213991588420WEEK 6209/07/0203018NEVENS63.43213 |[DBN
0207-241061600377WEEK 6530/07/0203018NEVENS89.13156 |[DBN
0208-228911588454WEEK 6927/08/0203018NEVENS131.12455657216 |[DBN
0209-230571588465WEEK 7324/09/0203018NEVENS111.22909635190 |[DBN
0104-216981385012WEEK 019/04/0103020NEVENS2755.2357200138 |[DBN
0108-207001385073WEEK 1607/08/0103020NEVENS2798.123188498 |[DBN\
0110-246431451884WEEK 2823/10/0103020NEVENS3124.815938981
0203-219031451912WEEK 4812/03/0203020NEVENS3811.211812585
0203-245251549129WEEK 5026/03/0203020NEVENS347220404683
0204-224961552970WEEK 5316/04/0203020NEVENS4323.2106 |[DBN
0205-209571552979WEEK 5607/05/0203020NEVENS3622.4109 |[DBN
0205-246281552990WEEK 5928/05/0203020NEVENS4188.898 |[DBN\
0206-227511588421WEEK 6218/06/0203020NEVENS4460.896 |[DBN\
0207-213951588431WEEK 6509/07/0203020NEVENS5020.873
0208-211691600383WEEK 6912/08/0203020NEVENS4300.825750999 |[DBN\
0209-201991588469WEEK 7303/09/0203020NEVENS3795.264141670
0104-216971385013WEEK 019/04/0103021NEVENS21.544825631131 |[DBN
0108-206991385072WEEK 1607/08/0103021NEVENS57.342048696133 |[DBN
0110-246471451889WEEK 2823/10/0103021NEVENS55.171110833127 |[DBN
0203-219081451919WEEK 4812/03/0203021NEVENS32.111541237169 |[DBN
0204-224991552965WEEK 5016/04/0203021NEVENS31.522059439162 |[DBN
0205-209551549139WEEK 5307/05/0203021NEVENS75.7144 |[DBN
0205-246311552984WEEK 5628/05/0203021NEVENS117.9151 |[DBN
0206-227521549154WEEK 5918/06/0203021NEVENS20496
0207-213941588423WEEK 6209/07/0203021NEVENS297138 |[DBN
0207-241041600378WEEK 6530/07/0203021NEVENS345.4122 |[DBN
0208-226441588455WEEK 6926/08/0203021NEVENS331.22030252132 |[DBN
0209-230591588463WEEK 7324/09/0203021NEVENS393.21563257166 |[DBN
0104-213981385010WEEK 017/04/0103025NEVENS3926.414421269
0108-206971385069WEEK 1607/08/0103025NEVENS3609.622200977
0110-246481451888WEEK 2823/10/0103025NEVENS4471.730507169
0203-219071451908WEEK 4812/03/0203025NEVENS2459.218600077
0204-211871552963WEEK 5009/04/0203025NEVENS4083.238450373
0204-255061549135WEEK 5330/04/0203025NEVENS319281
0205-232771549143WEEK 5621/05/0203025NEVENS3516.886
0206-216351549152WEEK 5911/06/0203025NEVENS3792104 |[DBN
0207-202361588427WEEK 6202/07/0203025NEVENS3203.285
0207-233071588440WEEK 6523/07/0203025NEVENS3590.479
0208-218481588450WEEK 6919/08/0203025NEVENS3737.619769191 |[DBN\
0209-221181588466WEEK 7317/09/0203025NEVENS2944.337728694 |[DBN\
0104-213991385011WEEK 017/04/0103026NEVENS133.84544056191 |[DBN
0108-206981385071WEEK 1607/08/0103026NEVENS117.86803039282 |[DBN
0110-230621451880WEEK 2816/10/0103026NEVENS117.11470757215 |[DBN
0203-206911451909WEEK 4805/03/0203026NEVENS1341071429283 |[DBN
0204-211891552961WEEK 5009/04/0203026NEVENS129.63185526255 |[DBN
0204-255051549136WEEK 5330/04/0203026NEVENS120.2231 |[DBN
0205-232751552983WEEK 5621/05/0203026NEVENS127.3258 |[DBN
0206-216371552992WEEK 5911/06/0203026NEVENS176.6236 |[DBN
0207-202391588428WEEK 6202/07/0203026NEVENS206.8191 |[DBN
0207-233081588439WEEK 6523/07/0203026NEVENS411.6185 |[DBN
0208-220141588449WEEK 6920/08/0203026NEVENS4743543072197 |[DBN
0209-230561588462WEEK 7324/09/0203026NEVENS437.62304506284 |[DBN
0104-210221400565WEEK 011/04/0104002ELEWAUT39.312328431158 |[DBN
0108-201271400573WEEK 1601/08/0104002ELEWAUT267.61367543264 |[DBN
0110-250101451968WEEK 2824/10/0104002ELEWAUT165.31128240135 |[DBN
0203-221741451988WEEK 4813/03/0204002ELEWAUT68.632001295120 |[DBN
0204-215151559332WEEK 5010/04/0204002ELEWAUT82.48270733799
0204-255271559335WEEK 5330/04/0204002ELEWAUT94.8483
0205-236001559338WEEK 5622/05/0204002ELEWAUT112.297
0206-218941559341WEEK 5912/06/0204002ELEWAUT124.192
0207-204801559344WEEK 6203/07/0204002ELEWAUT160.4124 |[DBN
0207-234711559347WEEK 6524/07/0204002ELEWAUT168.6166 |[DBN
0208-221721559350WEEK 6921/08/0204002ELEWAUT154.61245233100
0209-223161559353WEEK 7318/09/0204002ELEWAUT154.5801862125 |[DBN
0104-212901390536WEEK 013/04/0105001SPRENGERS42.24446561169 |[DBN
0108-211481390571WEEK 1610/08/0105001SPRENGERS41.4935650085
0110-260091451935WEEK 2829/10/0105001SPRENGERS35.03465701109
0203-209451451948WEEK 4806/03/0205001SPRENGERS34.49617271114
0204-222731549165WEEK 5015/04/0205001SPRENGERS37.51113943100
0204-252351549173WEEK 5329/04/0205001SPRENGERS38.7298
0205-255201549181WEEK 5631/05/0205001SPRENGERS59.1561
0206-235861549189WEEK 5921/06/0205001SPRENGERS483.6112
0207-222311589465WEEK 6215/07/0205001SPRENGERS267.2117
0208-204331589471WEEK 6505/08/0205001SPRENGERS222.459
0209-200251589477WEEK 6902/09/0205001SPRENGERS208110733369
0209-228251589483WEEK 7323/09/0205001SPRENGERS140.495726855
0104-212911390537WEEK 013/04/0105002SPRENGERS37.24142327390
0108-204501390569WEEK 1603/08/0105002SPRENGERS360.8115142997
0110-257601496921WEEK 2826/10/0105002SPRENGERS323.8120912997
0203-214751451950WEEK 4808/03/0205002SPRENGERS210.3135075996
0203-251851549164WEEK 5029/03/0205002SPRENGERS188.8268855990
0204-235841549172WEEK 5319/04/0205002SPRENGERS1333.497
0205-217311549179WEEK 5610/05/0205002SPRENGERS198499
0205-255181549188WEEK 5931/05/0205002SPRENGERS2059.290
0206-235871589463WEEK 6221/06/0205002SPRENGERS252076
0207-229961589469WEEK 6519/07/0205002SPRENGERS2308.878
0208-217571589475WEEK 6916/08/0205002SPRENGERS2413.1208117468
0209-208771589480WEEK 7306/09/0205002SPRENGERS1820.8341277560
0104-215281390539WEEK 018/04/0105004SPRENGERS< 18.75890331132 |[DBN
0108-205561390570WEEK 1606/08/0105004SPRENGERS326.8242017599
0110-260101451936WEEK 2829/10/0105004SPRENGERS308.361070055
0203-212471451949WEEK 4807/03/0205004SPRENGERS153.6622059132 |[DBN
0203-242991549163WEEK 5025/03/0205004SPRENGERS138.7496063122 |[DBN
0204-222741549170WEEK 5315/04/0205004SPRENGERS550.8123 |[DBN
0205-207431549178WEEK 5606/05/0205004SPRENGERS1589.6109
0205-243391549186WEEK 5927/05/0205004SPRENGERS1636.878
0206-237511589464WEEK 6224/06/0205004SPRENGERS1511.2120 |[DBN
0207-222331589470WEEK 6515/07/0205004SPRENGERS1511.278
0208-210791589474WEEK 6909/08/0205004SPRENGERS1382.445022990
0209-210351589481WEEK 7309/09/0205004SPRENGERS978.486678885
0104-212921390538WEEK 013/04/0105006SPRENGERS54.3132910782
0108-204511390568WEEK 1603/08/0105006SPRENGERS61.1959846772
0110-240981462206WEEK 2819/10/0105006SPRENGERS64.0534772568
0203-202251451947WEEK 4801/03/0205006SPRENGERS61.4425408282
0203-251841549162WEEK 5029/03/0205006SPRENGERS62.0142923175
0204-235851549171WEEK 5319/04/0205006SPRENGERS58.4179
0205-217301549180WEEK 5610/05/0205006SPRENGERS60.7178
0205-255191549187WEEK 5931/05/0205006SPRENGERS12783
0206-235881589462WEEK 6221/06/0205006SPRENGERS374.686
0207-222321589468WEEK 6515/07/0205006SPRENGERS597.685
0208-217561589476WEEK 6916/08/0205006SPRENGERS701.142443271
0209-218091589482WEEK 7313/09/0205006SPRENGERS624.830955074
ind graphs
&L&F
ind graphs
95.87
98.26
87.85
85.96
85.39
81.67
96.03
117
138
370
530.4
458.4
pat 01-006
DB fig
305.5
348.5
315.4
312.6
286
327
337.1
422.8
403.6
448
461.2
402
pat 01-009
median PLC
1440.8
1368.6
1412
1327.2
1377.4
1256.5
1269
1401.8
1418.7
1509.4
1641.6
1506.4
pat 01-010
median E1
95.27
319.5
318.8
205.4
216
223.6
249.3
277.6
312
332.5
313.8
347.8
pat 01-011
graphs median profile
178
163
179.7
61.36
67.36
93.1
121.3
134.3
163.7
157.2
154
103.1
pat 01-012
DB change
104.1
109.9
110.4
112.1
123.6
120.9
157.9
177.6
217.4
219
233.6
228
pat 01-015
change analysis
50.4
574.2
1251.5
367.5
297.3
822.4
1082.4
1215.2
1046.4
916
835.2
689.8
pat 01-016
batch1vs2
0
195
513.4
163
135.6
353.4
508.4
967.4
1611.2
2361.6
1032
815.2
pat 01-017
101.2
103.8
106.3
108.2
102.5
93.43
123.8
154.4
274.4
452.4
855.2
667.7
pat 02-002
44.24
70.58
102.2
50.05
43.87
76.86
164
229
340.1
378.3
435.2
415.2
pat 02-009
93.12
108.1
124.1
88.36
82.91
73.19
91.68
115.5
135.8
197.1
397.2
324.6
pat 02-010
53.13
56.03
53.92
49.51
52.27
54.47
72.48
85.02
85.45
76.75
78.34
74.13
pat 02-011
0
18.76
0
0
0
0
25.08
45.22
58.38
64.94
76.99
55.01
pat 02-012
23.05
50.22
51.56
35.26
34.24
69.89
295.2
222.2
311.2
520.8
643.6
593.6
pat 02-013
316.4
446.2
382.6
290.4
314.8
383.7
410.4
507.2
487.6
492.4
590.8
483.2
pat 02-014
25.17
266.4
152.6
48.9
44.5
148.2
522.4
598.4
1016
1261.6
1553.6
1670.4
pat 03-002
67.88
116.8
137.1
99.98
83.76
105.4
140.4
210
211
334.6
395.6
382.6
pat 03-006
105
301
408
267.6
271.8
436
2606.4
3071
3184
2068.8
1836.8
1151.8
pat 03-007
163.8
681.9
678.8
330.6
324.2
622
1196.8
1032.8
1227.2
1008
946.4
733.1
pat 03-008
147.8
187
188.7
132.8
142.3
106.9
235
265.2
416.2
448.4
670.4
671.9
pat 03-011
95.81
106.6
105.5
94.47
92.92
101.7
95.59
113.7
144.1
183.3
204.9
211.1
pat 03-012
438.8
360.4
315
311.1
306.2
309.4
286.1
268.7
299.9
393.5
434.8
393.3
pat 03-013
107.6
102
107.7
100.7
93.52
72.4
66.37
55.12
84.79
106.4
114.3
96.13
pat 03-015
0
0
0
0
0
0
36.4
54.43
63.43
89.13
131.1
111.2
pat 03-018
2755.2
2798.1
3124.8
3811.2
3472
4323.2
3622.4
4188.8
4460.8
5020.8
4300.8
3795.2
pat 03-020
21.54
57.34
55.17
32.11
31.52
75.7
117.9
204
297
345.4
331.2
393.2
pat 03-021
3926.4
3609.6
4471.7
2459.2
4083.2
3192
3516.8
3792
3203.2
3590.4
3737.6
2944.3
pat 03-025
39.31
267.6
165.3
68.63
82.48
94.84
112.2
124.1
160.4
168.6
154.6
154.5
pat 04-002
42.24
41.49
35.03
34.49
37.5
38.72
59.15
483.6
267.2
222.4
208
140.4
pat 05-001
37.24
360.8
323.8
210.3
188.8
1333.4
1984
2059.2
2520
2308.8
2413.1
1820.8
pat 05-002
0
326.8
308.3
153.6
138.7
550.8
1589.6
1636.8
1511.2
1511.2
1382.4
978.4
pat 05-004
54.31
61.19
64.05
61.44
62.01
58.41
60.71
127
374.6
597.6
701.1
624.8
pat 05-006
133.8
117.8
117.1
134
129.6
120.2
127.3
176.6
206.8
411.6
474
437.6
pat 03-026
BARC NRREQ.NR.VISITDOSPAT.NR.INVESTIGATOR9HCVE19HCVRN9GPT37
0103-219931384876WEEK 019/03/0101006DE VOS95.872360130173 |[DBN
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0203-243021549094WEEK 5025/03/0202011HORSMANS52.2759411286
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0204-240641552973WEEK 5323/04/0203006NEVENS105.4121 |[DBN
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0209-211941588470WEEK 7310/09/0203006NEVENS382.62404315107
0104-208891385006WEEK 010/04/0103007NEVENS1058485227132 |[DBN
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0203-219021451910WEEK 4812/03/0203007NEVENS267.62764650122 |[DBN
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0205-232781549144WEEK 5621/05/0203007NEVENS2606.489
0206-216361549151WEEK 5911/06/0203007NEVENS3071180 |[DBN
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0205-209601549137WEEK 5307/05/0203008NEVENS622104 |[DBN
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0104-215151385004WEEK 017/04/0103012NEVENS95.811851125155 |[DBN
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0207-241071588446WEEK 6930/07/0203013NEVENS434.847468849
0208-228921600386WEEK 7327/08/0203013NEVENS393.3117621142
0104-201601385001WEEK 003/04/0103015NEVENS107.658712473
0107-223061385061WEEK 1624/07/0103015NEVENS10240196545
0110-230631451881WEEK 2816/10/0103015NEVENS107.715718353
0203-206921451918WEEK 4805/03/0203015NEVENS100.719725146
0203-245271549131WEEK 5026/03/0203015NEVENS93.5233615541
0204-224951552972WEEK 5316/04/0203015NEVENS72.433
0205-209591552980WEEK 5607/05/0203015NEVENS66.3747
0205-246331552988WEEK 5928/05/0203015NEVENS55.1240
0206-227541588418WEEK 6218/06/0203015NEVENS84.7949
0207-213981588433WEEK 6509/07/0203015NEVENS106.446
0208-205791600382WEEK 6906/08/0203015NEVENS114.3112868747
0209-201971600387WEEK 7303/09/0203015NEVENS96.1344632951
0104-210281385009WEEK 011/04/0103018NEVENS0121181198
0107-230041385067WEEK 1631/07/0103018NEVENS0322400096
0110-246461451886WEEK 2823/10/0103018NEVENS01402445124 |[DBN
0203-219061451913WEEK 4812/03/0203018NEVENS01366359217 |[DBN
0204-224981552962WEEK 5016/04/0203018NEVENS01365698129 |[DBN
0205-209561549138WEEK 5307/05/0203018NEVENS0155 |[DBN
0205-246301549146WEEK 5628/05/0203018NEVENS36.4170 |[DBN
0206-227561549153WEEK 5918/06/0203018NEVENS54.43173 |[DBN
0207-213991588420WEEK 6209/07/0203018NEVENS63.43213 |[DBN
0207-241061600377WEEK 6530/07/0203018NEVENS89.13156 |[DBN
0208-228911588454WEEK 6927/08/0203018NEVENS131.12455657216 |[DBN
0209-230571588465WEEK 7324/09/0203018NEVENS111.22909635190 |[DBN
0104-216981385012WEEK 019/04/0103020NEVENS2755.2357200138 |[DBN
0108-207001385073WEEK 1607/08/0103020NEVENS2798.123188498 |[DBN\
0110-246431451884WEEK 2823/10/0103020NEVENS3124.815938981
0203-219031451912WEEK 4812/03/0203020NEVENS3811.211812585
0203-245251549129WEEK 5026/03/0203020NEVENS347220404683
0204-224961552970WEEK 5316/04/0203020NEVENS4323.2106 |[DBN
0205-209571552979WEEK 5607/05/0203020NEVENS3622.4109 |[DBN
0205-246281552990WEEK 5928/05/0203020NEVENS4188.898 |[DBN\
0206-227511588421WEEK 6218/06/0203020NEVENS4460.896 |[DBN\
0207-213951588431WEEK 6509/07/0203020NEVENS5020.873
0208-211691600383WEEK 6912/08/0203020NEVENS4300.825750999 |[DBN\
0209-201991588469WEEK 7303/09/0203020NEVENS3795.264141670
0104-216971385013WEEK 019/04/0103021NEVENS21.544825631131 |[DBN
0108-206991385072WEEK 1607/08/0103021NEVENS57.342048696133 |[DBN
0110-246471451889WEEK 2823/10/0103021NEVENS55.171110833127 |[DBN
0203-219081451919WEEK 4812/03/0203021NEVENS32.111541237169 |[DBN
0204-224991552965WEEK 5016/04/0203021NEVENS31.522059439162 |[DBN
0205-209551549139WEEK 5307/05/0203021NEVENS75.7144 |[DBN
0205-246311552984WEEK 5628/05/0203021NEVENS117.9151 |[DBN
0206-227521549154WEEK 5918/06/0203021NEVENS20496
0207-213941588423WEEK 6209/07/0203021NEVENS297138 |[DBN
0207-241041600378WEEK 6530/07/0203021NEVENS345.4122 |[DBN
0208-226441588455WEEK 6926/08/0203021NEVENS331.22030252132 |[DBN
0209-230591588463WEEK 7324/09/0203021NEVENS393.21563257166 |[DBN
0104-213981385010WEEK 017/04/0103025NEVENS3926.414421269
0108-206971385069WEEK 1607/08/0103025NEVENS3609.622200977
0110-246481451888WEEK 2823/10/0103025NEVENS4471.730507169
0203-219071451908WEEK 4812/03/0203025NEVENS2459.218600077
0204-211871552963WEEK 5009/04/0203025NEVENS4083.238450373
0204-255061549135WEEK 5330/04/0203025NEVENS319281
0205-232771549143WEEK 5621/05/0203025NEVENS3516.886
0206-216351549152WEEK 5911/06/0203025NEVENS3792104 |[DBN
0207-202361588427WEEK 6202/07/0203025NEVENS3203.285
0207-233071588440WEEK 6523/07/0203025NEVENS3590.479
0208-218481588450WEEK 6919/08/0203025NEVENS3737.619769191 |[DBN\
0209-221181588466WEEK 7317/09/0203025NEVENS2944.337728694 |[DBN\
0104-213991385011WEEK 017/04/0103026NEVENS133.84544056191 |[DBN
0108-206981385071WEEK 1607/08/0103026NEVENS117.86803039282 |[DBN
0110-230621451880WEEK 2816/10/0103026NEVENS117.11470757215 |[DBN
0203-206911451909WEEK 4805/03/0203026NEVENS1341071429283 |[DBN
0204-211891552961WEEK 5009/04/0203026NEVENS129.63185526255 |[DBN
0204-255051549136WEEK 5330/04/0203026NEVENS120.2231 |[DBN
0205-232751552983WEEK 5621/05/0203026NEVENS127.3258 |[DBN
0206-216371552992WEEK 5911/06/0203026NEVENS176.6236 |[DBN
0207-202391588428WEEK 6202/07/0203026NEVENS206.8191 |[DBN
0207-233081588439WEEK 6523/07/0203026NEVENS411.6185 |[DBN
0208-220141588449WEEK 6920/08/0203026NEVENS4743543072197 |[DBN
0209-230561588462WEEK 7324/09/0203026NEVENS437.62304506284 |[DBN
0104-210221400565WEEK 011/04/0104002ELEWAUT39.312328431158 |[DBN
0108-201271400573WEEK 1601/08/0104002ELEWAUT267.61367543264 |[DBN
0110-250101451968WEEK 2824/10/0104002ELEWAUT165.31128240135 |[DBN
0203-221741451988WEEK 4813/03/0204002ELEWAUT68.632001295120 |[DBN
0204-215151559332WEEK 5010/04/0204002ELEWAUT82.48270733799
0204-255271559335WEEK 5330/04/0204002ELEWAUT94.8483
0205-236001559338WEEK 5622/05/0204002ELEWAUT112.297
0206-218941559341WEEK 5912/06/0204002ELEWAUT124.192
0207-204801559344WEEK 6203/07/0204002ELEWAUT160.4124 |[DBN
0207-234711559347WEEK 6524/07/0204002ELEWAUT168.6166 |[DBN
0208-221721559350WEEK 6921/08/0204002ELEWAUT154.61245233100
0209-223161559353WEEK 7318/09/0204002ELEWAUT154.5801862125 |[DBN
0104-212901390536WEEK 013/04/0105001SPRENGERS42.24446561169 |[DBN
0108-211481390571WEEK 1610/08/0105001SPRENGERS41.4935650085
0110-260091451935WEEK 2829/10/0105001SPRENGERS35.03465701109
0203-209451451948WEEK 4806/03/0205001SPRENGERS34.49617271114
0204-222731549165WEEK 5015/04/0205001SPRENGERS37.51113943100
0204-252351549173WEEK 5329/04/0205001SPRENGERS38.7298
0205-255201549181WEEK 5631/05/0205001SPRENGERS59.1561
0206-235861549189WEEK 5921/06/0205001SPRENGERS483.6112
0207-222311589465WEEK 6215/07/0205001SPRENGERS267.2117
0208-204331589471WEEK 6505/08/0205001SPRENGERS222.459
0209-200251589477WEEK 6902/09/0205001SPRENGERS208110733369
0209-228251589483WEEK 7323/09/0205001SPRENGERS140.495726855
0104-212911390537WEEK 013/04/0105002SPRENGERS37.24142327390
0108-204501390569WEEK 1603/08/0105002SPRENGERS360.8115142997
0110-257601496921WEEK 2826/10/0105002SPRENGERS323.8120912997
0203-214751451950WEEK 4808/03/0205002SPRENGERS210.3135075996
0203-251851549164WEEK 5029/03/0205002SPRENGERS188.8268855990
0204-235841549172WEEK 5319/04/0205002SPRENGERS1333.497
0205-217311549179WEEK 5610/05/0205002SPRENGERS198499
0205-255181549188WEEK 5931/05/0205002SPRENGERS2059.290
0206-235871589463WEEK 6221/06/0205002SPRENGERS252076
0207-229961589469WEEK 6519/07/0205002SPRENGERS2308.878
0208-217571589475WEEK 6916/08/0205002SPRENGERS2413.1208117468
0209-208771589480WEEK 7306/09/0205002SPRENGERS1820.8341277560
0104-215281390539WEEK 018/04/0105004SPRENGERS0890331132 |[DBN
0108-205561390570WEEK 1606/08/0105004SPRENGERS326.8242017599
0110-260101451936WEEK 2829/10/0105004SPRENGERS308.361070055
0203-212471451949WEEK 4807/03/0205004SPRENGERS153.6622059132 |[DBN
0203-242991549163WEEK 5025/03/0205004SPRENGERS138.7496063122 |[DBN
0204-222741549170WEEK 5315/04/0205004SPRENGERS550.8123 |[DBN
0205-207431549178WEEK 5606/05/0205004SPRENGERS1589.6109
0205-243391549186WEEK 5927/05/0205004SPRENGERS1636.878
0206-237511589464WEEK 6224/06/0205004SPRENGERS1511.2120 |[DBN
0207-222331589470WEEK 6515/07/0205004SPRENGERS1511.278
0208-210791589474WEEK 6909/08/0205004SPRENGERS1382.445022990
0209-210351589481WEEK 7309/09/0205004SPRENGERS978.486678885
0104-212921390538WEEK 013/04/0105006SPRENGERS54.3132910782
0108-204511390568WEEK 1603/08/0105006SPRENGERS61.1959846772
0110-240981462206WEEK 2819/10/0105006SPRENGERS64.0534772568
0203-202251451947WEEK 4801/03/0205006SPRENGERS61.4425408282
0203-251841549162WEEK 5029/03/0205006SPRENGERS62.0142923175
0204-235851549171WEEK 5319/04/0205006SPRENGERS58.4179
0205-217301549180WEEK 5610/05/0205006SPRENGERS60.7178
0205-255191549187WEEK 5931/05/0205006SPRENGERS12783
0206-235881589462WEEK 6221/06/0205006SPRENGERS374.686
0207-222321589468WEEK 6515/07/0205006SPRENGERS597.685
0208-217561589476WEEK 6916/08/0205006SPRENGERS701.142443271
0209-218091589482WEEK 7313/09/0205006SPRENGERS624.830955074
147.8101.254.31
187103.861.19
188.7106.364.05
134108.261.44
142.3102.562.01
120.293.4358.41
235123.860.71
268.7176.6127
374.6274.4206.8
452.4411.6370
701.1530.4434.8
667.7458.4393.3
Anti-E1 Ab (mU/ml)
Q3
median
Q1
weeks
Placebo/E1 patients (n=9/9)
107.667.8825.17
348.5195102
382.6165.3105.5
267.6100.750.05
271.893.5252.27
436120.975.7
1082.4249.3112.2
1032.8229124.1
1227.2312160.4
1261.6378.3183.3
1032435.2204.9
815.2402211.1
Q3
median
Q1
weeks
anti-E1 Ab (mU/ml)
median profile of E1/E1 patients
patientprevious trtW0W16W28W48W50W53W56W59W62W65W69W73mean end trtabs change
01628485053565962656973
01006PLC95.8798.2687.8585.9685.3981.6796.03117138370530.4458.4494.4398.53
01010PLC1440.81368.614121327.21377.41256.512691401.81418.71509.41641.61506.41574133.2
02002PLC101.2103.8106.3108.2102.593.43123.8154.4274.4452.4855.2667.7761.45660.25
03011PLC147.8187188.7132.8142.3106.9235265.2416.2448.4670.4671.9671.15523.35
03013PLC438.8360.4315311.1306.2309.4286.1268.7299.9393.5434.8393.3414.05-24.75
03018PLC00000036.454.4363.4389.13131.1111.2121.15121.15
03026PLC133.8117.8117.1134129.6120.2127.3176.6206.8411.6474437.6455.8322
05001PLC42.2441.4935.0334.4937.538.7259.15483.6267.2222.4208140.4174.2131.96
05006PLC54.3161.1964.0561.4462.0158.4160.71127374.6597.6701.1624.8662.95608.64
median101.2103.8106.3108.2102.593.43123.8176.6274.4411.6530.4458.4494.4322
Q154.3161.1964.0561.4462.0158.4160.71127206.8370434.8393.3
Q3147.8187188.7134142.3120.2235268.7374.6452.4701.1667.7
01009vaccine305.5348.5315.4312.6286327337.1422.8403.6448461.2402431.6126.1
01011vaccine95.27319.5318.8205.4216223.6249.3277.6312332.5313.8347.8330.8235.53
01012vaccine178163179.761.3667.3693.1121.3134.3163.7157.2154103.1128.55-49.45
01013vaccine00000000000000
01015vaccine104.1109.9110.4112.1123.6120.9157.9177.6217.4219233.6228230.8126.7
01016vaccine50.4574.21251.5367.5297.3822.41082.41215.21046.4916835.2689.8762.5712.1
01017vaccine0195513.4163135.6353.4508.4967.41611.22361.61032815.2923.6923.6
02009vaccine44.2470.58102.250.0543.8776.86164229340.1378.3435.2415.2425.2380.96
02010vaccine93.12108.1124.188.3682.9173.1991.68115.5135.8197.1397.2324.6360.9267.78
02011vaccine53.1356.0353.9249.5152.2754.4772.4885.0285.4576.7578.3474.1376.23523.105
02012vaccine018.76000025.0845.2258.3864.9476.9955.016666
02013vaccine23.0550.2251.5635.2634.2469.89295.2222.2311.2520.8643.6593.6618.6595.55
02014vaccine316.4446.2382.6290.4314.8383.7410.4507.2487.6492.4590.8483.2537220.6
03002vaccine25.17266.4152.648.944.5148.2522.4598.410161261.61553.61670.416121586.83
03006vaccine67.88116.8137.199.9883.76105.4140.4210211334.6395.6382.6389.1321.22
03007vaccine105301408267.6271.84362606.4307131842068.81836.81151.81494.31389.3
03008vaccine163.8681.9678.8330.6324.26221196.81032.81227.21008946.4733.1839.75675.95
03012vaccine95.81106.6105.594.4792.92101.795.59113.7144.1183.3204.9211.1208112.19
03015vaccine107.6102107.7100.793.5272.466.3755.1284.79106.4114.396.13105.215-2.385
03020vaccine2755.22798.13124.83811.234724323.23622.44188.84460.85020.84300.83795.240481292.8
03021vaccine21.5457.3455.1732.1131.5275.7117.9204297345.4331.2393.2362.2340.66
03025vaccine3926.43609.64471.72459.24083.231923516.837923203.23590.43737.62944.33340.95-585.45
04002vaccine39.31267.6165.368.6382.4894.84112.2124.1160.4168.6154.6154.5154.55115.24
05002vaccine37.24360.8323.8210.3188.81333.419842059.225202308.82413.11820.82116.952079.71
05004vaccine0326.8308.3153.6138.7550.81589.61636.81511.21511.21382.4978.41180.41180.4
median67.88195165.3100.793.52120.9249.3229312378.3435.2402
Q125.17102105.550.0552.2775.7112.2124.1160.4183.3204.9211.1
Q3107.6348.5382.6267.6271.84361082.41032.81227.21261.61032815.2
000
000
000
000
000
000
000
000
000
median
Q1
Q3
weeks
E1 Ab
median profile E1 Ab - PLC
000
000
000
000
median
Q1
Q3
weeks
E1 Ab
median profile E1 Ab - HCV E1
patientprevious trtW0W16W28W48W50W53W56W59W62W65W69W73mean end trtabs changeAb_b (902)diff (W0-Ab_b)
01006PLC95.8798.2687.8585.9685.3981.6796.03117138370530.4458.4494.4398.5396-0.13
01009vaccine305.5348.5315.4312.6286327337.1422.8403.6448461.2402431.6126.1338.9-33.4
01010PLC1440.81368.614121327.21377.41256.512691401.81418.71509.41641.61506.41574133.21851-410.2
01011vaccine95.27319.5318.8205.4216223.6249.3277.6312332.5313.8347.8330.8235.5395.6-0.33
01012vaccine178163179.761.3667.3693.1121.3134.3163.7157.2154103.1128.55-49.45279.9-101.9
01013vaccine0000000000000022.3-22.3
01015vaccine104.1109.9110.4112.1123.6120.9157.9177.6217.4219233.6228230.8126.7110.9-6.8
01016vaccine50.4574.21251.5367.5297.3822.41082.41215.21046.4916835.2689.8762.5712.149.90.5
01017vaccine0195513.4163135.6353.4508.4967.41611.22361.61032815.2923.6923.600
02002PLC101.2103.8106.3108.2102.593.43123.8154.4274.4452.4855.2667.7761.45660.2598.52.7
02009vaccine44.2470.58102.250.0543.8776.86164229340.1378.3435.2415.2425.2380.967.336.94
02010vaccine93.12108.1124.188.3682.9173.1991.68115.5135.8197.1397.2324.6360.9267.78125-31.88
02011vaccine53.1356.0353.9249.5152.2754.4772.4885.0285.4576.7578.3474.1376.23523.10549.63.53
02012vaccine018.76000025.0845.2258.3864.9476.9955.01666600
02013vaccine23.0550.2251.5635.2634.2469.89295.2222.2311.2520.8643.6593.6618.6595.5528-4.95
02014vaccine316.4446.2382.6290.4314.8383.7410.4507.2487.6492.4590.8483.2537220.6447.8-131.4
03002vaccine25.17266.4152.648.944.5148.2522.4598.410161261.61553.61670.416121586.83025.17
03006vaccine67.88116.8137.199.9883.76105.4140.4210211334.6395.6382.6389.1321.2278.9-11.02
03007vaccine105301408267.6271.84362606.4307131842068.81836.81151.81494.31389.3112.5-7.5
03008vaccine163.8681.9678.8330.6324.26221196.81032.81227.21008946.4733.1839.75675.95214.8-51
03011PLC147.8187188.7132.8142.3106.9235265.2416.2448.4670.4671.9671.15523.35154-6.2
03012vaccine95.81106.6105.594.4792.92101.795.59113.7144.1183.3204.9211.1208112.19102.2-6.39
03013PLC438.8360.4315311.1306.2309.4286.1268.7299.9393.5434.8393.3414.05-24.75412.726.1
03015vaccine107.6102107.7100.793.5272.466.3755.1284.79106.4114.396.13105.215-2.385149-41.4
03018PLC00000036.454.4363.4389.13131.1111.2121.15121.1500
03020vaccine2755.22798.13124.83811.234724323.23622.44188.84460.85020.84300.83795.240481292.84148-1392.8
03021vaccine21.5457.3455.1732.1131.5275.7117.9204297345.4331.2393.2362.2340.6623.9-2.36
03025vaccine3926.43609.64471.72459.24083.231923516.837923203.23590.43737.62944.33340.95-585.453497429.4
03026PLC133.8117.8117.1134129.6120.2127.3176.6206.8411.6474437.6455.8322139.3-5.5
04002vaccine39.31267.6165.368.6382.4894.84112.2124.1160.4168.6154.6154.5154.55115.2434.94.41
05001PLC42.2441.4935.0334.4937.538.7259.15483.6267.2222.4208140.4174.2131.9643.9-1.66
05002vaccine37.24360.8323.8210.3188.81333.419842059.225202308.82413.11820.82116.952079.7128.19.14
05004vaccine0326.8308.3153.6138.7550.81589.61636.81511.21511.21382.4978.41180.41180.435-35
05006PLC54.3161.1964.0561.4462.0158.4160.71127374.6597.6701.1624.8662.95608.6454.6-0.29
patientprevious trtW0W16W28W48W50W53W56W59W62W65W69W73mean end trtabs change
01006PLC95.8798.2687.8585.9685.3981.6796.03117138370530.4458.4494.4398.53
01010PLC1440.81368.614121327.21377.41256.512691401.81418.71509.41641.61506.41574133.2
02002PLC101.2103.8106.3108.2102.593.43123.8154.4274.4452.4855.2667.7761.45660.25
03011PLC147.8187188.7132.8142.3106.9235265.2416.2448.4670.4671.9671.15523.35
03013PLC438.8360.4315311.1306.2309.4286.1268.7299.9393.5434.8393.3414.05-24.75
03018PLC00000036.454.4363.4389.13131.1111.2121.15121.15
03026PLC133.8117.8117.1134129.6120.2127.3176.6206.8411.6474437.6455.8322
05001PLC42.2441.4935.0334.4937.538.7259.15483.6267.2222.4208140.4174.2131.96
05006PLC54.3161.1964.0561.4462.0158.4160.71127374.6597.6701.1624.8662.95608.64
PLC Average319.37Confidence Level(95.0%)187.3504195487
PLC StdDev243.7336891979
01009vaccine305.5348.5315.4312.6286327337.1422.8403.6448461.2402431.6126.1
01011vaccine95.27319.5318.8205.4216223.6249.3277.6312332.5313.8347.8330.8235.53
01012vaccine178163179.761.3667.3693.1121.3134.3163.7157.2154103.1128.55-49.45
01013vaccine00000000000000
01015vaccine104.1109.9110.4112.1123.6120.9157.9177.6217.4219233.6228230.8126.7
01016vaccine50.4574.21251.5367.5297.3822.41082.41215.21046.4916835.2689.8762.5712.1
01017vaccine0195513.4163135.6353.4508.4967.41611.22361.61032815.2923.6923.6
02009vaccine44.2470.58102.250.0543.8776.86164229340.1378.3435.2415.2425.2380.96
02010vaccine93.12108.1124.188.3682.9173.1991.68115.5135.8197.1397.2324.6360.9267.78
02011vaccine53.1356.0353.9249.5152.2754.4772.4885.0285.4576.7578.3474.1376.23523.105
02012vaccine018.76000025.0845.2258.3864.9476.9955.016666
02013vaccine23.0550.2251.5635.2634.2469.89295.2222.2311.2520.8643.6593.6618.6595.55
02014vaccine316.4446.2382.6290.4314.8383.7410.4507.2487.6492.4590.8483.2537220.6
03002vaccine25.17266.4152.648.944.5148.2522.4598.410161261.61553.61670.416121586.83
03006vaccine67.88116.8137.199.9883.76105.4140.4210211334.6395.6382.6389.1321.22
03007vaccine105301408267.6271.84362606.4307131842068.81836.81151.81494.31389.3
03008vaccine163.8681.9678.8330.6324.26221196.81032.81227.21008946.4733.1839.75675.95
03012vaccine95.81106.6105.594.4792.92101.795.59113.7144.1183.3204.9211.1208112.19
03015vaccine107.6102107.7100.793.5272.466.3755.1284.79106.4114.396.13105.215-2.385
03020vaccine2755.22798.13124.83811.234724323.23622.44188.84460.85020.84300.83795.240481292.8
03021vaccine21.5457.3455.1732.1131.5275.7117.9204297345.4331.2393.2362.2340.66
03025vaccine3926.43609.64471.72459.24083.231923516.837923203.23590.43737.62944.33340.95-585.45
04002vaccine39.31267.6165.368.6382.4894.84112.2124.1160.4168.6154.6154.5154.55115.24
05002vaccine37.24360.8323.8210.3188.81333.419842059.225202308.82413.11820.82116.952079.71
05004vaccine0326.8308.3153.6138.7550.81589.61636.81511.21511.21382.4978.41180.41180.4
vaccine Average485.4016Confidence Level(95.0%)253.7212494716
vaccine StdDev614.6651449091
Grand Average441.4520588235
Grand StdDev542.8653489728
PAT.NR.TreatmentVISITDOSHCVE1 batch 2HCVE1 batch 1batch2-batch1t-Test: Paired Two Sample for MeansHCVE1 batch 2HCVE1 batch 1
01006PLCWEEK 019/03/0195.8790.415.46Mean385.8573608398470.1227111816
01006PLCWEEK 1606/07/0198.2698.67-0.41HCVE1 batch 2HCVE1 batch 1Variance655424.9375951648.625
01006PLCWEEK 2828/09/0187.8588.78-0.93Mean385.8573529412470.1227205882Observations136136
01006PLCWEEK 4815/02/0285.9698.61-12.65Variance655424.941905534951648.640276247Missing0
01009vaccinWEEK 020/03/01305.50372.8-67.3Observations136136variance of difference113546.359375
01009vaccinWEEK 1610/07/01348.50496-147.5Pearson Correlation0.9455475079Mean of differences-84.2653427124
01009vaccinWEEK 2802/10/01315.40460.2-144.8Hypothesized Mean Difference0Hypothesized Mean Difference0
01009vaccinWEEK 4819/02/02312.60538.4-225.8df135Degrees of Freedom135
01010PLCWEEK 020/03/011440.801707.2-266.4t Stat-2.9162986641t-Statistics-2.9162976742
01010PLCWEEK 1610/07/011368.602027.2-658.6P(T
-
E1-Induced T-Cell ProliferationCourse 1Course 2
Chart1
422
6822
640
88100
E1/E1 (n=26/25)
Placebo/E1 (n=9/9)
% Patients with SI>3
Sheet1
0End0End
E1/E1 (n=26/25)4686488
Placebo/E1 (n=9/9)22220100
Sheet1
E1/E1 (n=26/25)
Placebo/E1 (n=9/9)
% Patients with SI>3
Sheet2
Sheet3
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Serum ALT% change from baselineSignificant decrease in ALT from baseline from week 16 onwards
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Total Ishak score after 17 months of E1 therapeutic vaccination**At least 6 portal tracts were evaluated for each liver biopsy**Improvement or worsening defined as >= 2 points change from baseline
Improved
n (%)
Stabilized
n (%)
Worsened
n (%)
Total Ishak **
9 (38%)
10 (42%)
5 (21%)
-
Ishak Fibrosis Score Evolutionexpected natural evolution*observed evolution after E1 with 95% CIend of treatment (17 months)baselinechange from baseline0.47*Ryder S. et al. Hepatology 2002;36(4 Pt. 2), 607 Ghany M. et al. Gastroenterology 2003;124:97-104 (age subgroup 46-69 yr)
Chart7
0.600
-0.040.47-0.04
-0.68
Sheet1
0.6-0.04-0.68
0.40.40.4
00.47
00.4
0-0.04
00.4
Sheet1
000
000
0
Sheet2
expected natural evolution
evolution after E1 with 95% CII
Change in Ishak fibrosis score after E1
change from baseline
baselineI
end of treatment (17 months)
Sheet2
0.600
-0.040.47-0.04
-0.68
expected natural evolution
evolution after E1 with 95% CII
Change in Ishak fibrosis score after E1
change from baseline
baselineI
end of treatment (17 months)
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Before E1 Study Treatment After 17 months of E1Liver Fibrosis10 out of 24 patients showed diminished perisinusoidal fibrosis (Sirius Red stain)
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Significant association of the immunological, histological, and biochemical responses
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Addendum: interpretatie HCV testenHCV AS -.
HCV AS +ALT nl.
HCV AS +ALT .
Role Physical measures the degree of physical incapacitationGeneral Health is the patients evaluation of his/her healthVitality assesses the energetic level of the individualLow scores for these modalities resonate the non-specific but common symptoms that most patients with CHC have: Physical weakness, tiredness, lack of drive and asthenia
The public health problem associated with the rising incidence of liver transplant is exacerbated by the fact that there is a growing shortage of donor organs
Results for anti-E1 antibody increase were compared for 25 E1/E1 patients after 4 injections of E1 at 4-week intervals (at week 16) with 9 placebo/E1 patients after 4 injections of E1 at 3-week intervals (at week 62) in their first course of E1. The median changes for anti-E1 antibodies after 4 E1 injections were 44.7 mU/ml for 4-week intervals and 75 mU/ml for 3-week intervals, thus indicating that a 3 week interval regimen induces a somewhat stronger humoral immune response in a shorter period of time.
Levels of anti-E1 antibodies clearly increased further after course 1 in E1/E1 patients, from a median of 165 mU/ml at week 28 to 425 at week 69/73. Especially in those patients showing the highest increase, there was a plateau phase or even a decrease in detectable antibody level which already started after the last injection was administered (week 69). Further research is ongoing to explain this finding This slide shows the percentage of patients with significant T-cell proliferative responses to E1. In yellow the group with 2 E1 courses is depicted, in blue the Placebo/E1 group. In the E1/E1 group, significant proliferative responses were induced in over half of the patients after the first course of injections. These responses were remarkably sustained throughout the injection-free period between wk26 and wk50. Almost all patients showed strong immune responses after the second course of immunizations, including the Placebo/E1 group. It should be noted that these infrequent responses seen at baseline were only borderline positive, while the stimulation indexes at wk 69 were very strong (E1/E1 group median SI 9.6 (1.0-51.9); Pl/E1 group median SI 17.6 (3.4-27.4)).On this slide, you see the relative change from baseline in serum ALT over the 2 courses in both treatment groups. In the E1/E1 patients, serum ALT decreased significantly from baseline from week 16 onwards. This sustained decline continued during the second course and during the treatment interruption period between the 2 E1 courses. No significant changes could be seen in the smaller placebo/E1 treatment group with only 9 patients and large 95% confidence intervals for the mean.On average, our patient population showed no progression to fibrosis as evidenced by a change of -0.04 points (95% CI: -0.68 to +0.60) on the Ishak fibrosis scale. As there was no control group in this study extension, we based ourselves on the literature to determine the expected natural evolution of fibrosis progression. For the Ishak fibrosis score, a 0.47 point mean progression would be expected during the course of our 17-month study based on a 0.33 points/year progression rate as recently reported in an analysis of 221 repeat liver biopsies in patients with predominantly mild untreated hepatitis C, as reported by Ryder et al (ref 1). An identical Ishak fibrosis progression rate of 0.33 points per year was recently reported by Ghany et al (ref 2), for a subgroup of twenty-three untreated patients aged 46 to 59 as well.Lets first look at the bottom of the figure, where you see the relation between the percentage change in ALT as described in the previous slide, and the change in Ishak fibrosis score . Patients on or above plus 1 point score have fibrosis progression. We will now concentrate on those patients who are on or below -1 fibrosis score change. They all have decreased ALT, mostly more than 25%.If we now also look at the third dimension in the figure, showing the change in anti-E1 antibody level, you will see that most patients with fibrosis regression and decreased ALT also have greater increases in antibody level