CHIN LC IU TR VIM GAN B MN GIAI ON HIN NAY
TS.BS. Phm Th L HoaBM Nhim, HYD TP HCM
20/12/2014
NI DUNG
I. TNH HNH IU TR NHIM HBV HIN NAY
II. MC TIU V NHNG THCH THC CA IU TR
III. CHIN LC IU TR V CC BIN PHP TR LIU MI
TRONG THP NIN TI
IV. NHNG IM ANG THAY I TRONG TR LIU
400 triu ngi nhim HBV, 750.000 cht hng nm do bnh l lin quan vi HBV.
>60% nc ang pht trin
2 chin lc iu tr chnh:
iu tr c thi hn bng IF hay PEG-IFN
iu tr lu di vi NAs
nh gi p ng iu tr? Ngng thuc? HBeAg m?
Cc phc kt hp tr liu? D bo p ng?
THUC IU TR C HIU C T 1992 (LAM 4 NHM NAs nhiu NAs mi
IU TR KHI cn l thch thc. cccDNA tn lu ko di trong gan.
TI HOT; TI PHT; X GAN; VIM GAN BNG PHT... CN L MI E DA
TNH HNH CHUNG V IU TR VIM GAN B MN
YU T NH HNG N DIN TIN T NHIN
Liaw et al, Liver Int 2006:26, 472-489Fattovich et al. J Hepatol 48, 2008:335-352
Kao JH, Hepatol Int 2007
VIRUS HBV
t bin1762/1764, PreS
Genotype C>B D>ATi lng virus
HBsAg nh lng
K CH
Nam, Tui >40Gim min dch
(nng, a c hiu)Tng ALT nhiu tHot tnh vim trn
m hc
YU T KHC
Ru bia, Thuc lTip xc Aflatoxin
ng nhimHIV/HCV
Tiu ngBMI cao
Tng tin trin bnh l gan do HBV
X GAN/UNG TH GAN
YU T K CH TRN DIN TIN T NHIN NHIM HBV
Thursz et al. Seminar Liver dis 2011
THI TR NHIM HBV KO DI
Tnh a hnh lin quan
PHN NG CYTOKIN
TNF-863A TNF-238A
TNF-308A
IL-10R K47E
C TNH HLA HLA NHM I: A*0301HLA NHM II:
DRB1*1301
DRB1*1302
HLA NHM I: B*08
HLA NHM II:
DR7 (DRB1*07)
DR3 (DRB1*07)
DQA1* 0310
DQA1* 0510
DRB1* 1201
II. MC TIU V
NHNG THCH THC CA IU TR
MC TIU IU TR CHUNG
AASL 2009C CH KO DI SAO CHP HBV V PHC HI BNH L GAN
EASL 2012C CH LU DI SAO CHP CA HBV.CI THIN CHT LNG SNG/ KH NNG SNG CN QUA:
Phng nga din bin x gan, mt b gan, bnh gan giai on cui, UTG vt vong.
APASL 2012C CH LIN TC SAO CHP HBVT P NG BN VNG (DURABLE)
Phng nga din bin x gan, mt b gan, UTGTng t l , thi gian sng cn
Liaw YF Hepatol Int 2012:6:531-561Lok AS. Hepatol 2009; AASLD practice GuidelinesEASL Jury; J Hepatol 2012:167-185
MC TIU IU TR C TH
TRONG IU TR
Sinh ha: ALT
Chuyn i huyt thanh HBeAg v HBsAg
c ch sao chp (HBVDNA m khng ng ngha thi tr hon ton HBV)
M hc: Ch s phn ng vim (A) v x ha (F)
LU DI:
Ci thin x ha, x gan: Lm sng, Fibroscan, Tiu cu, ...
Nga Ung th gan
Tit tr HBV (mt HBsAg)
HAI CHIN LC IU TR VIM GAN B MNQUY TC NGNG IU TR
THI GIAN C NH
CHUYN I HBeAg
MT HBsAg
Liaw YF Hepatol Int 2012:6:531-561Lok AS. Hepatol 2009; AASLD practice GuidelinesEASL Jury; J Hepatol 2012:167-185
KHNG P DNG CHO MT B GAN
C CH NH IU TR
3. NAs KO DI
C THI HN
2. NAs NGN HN
1. C THI HNIFN
Chuyni HBeAg
ALTMt
HBeAgGim
HBVDNAm
HBVDNA
VIM GAN B MN HBeAg DNG
DU HIU CH NG CA P NG IU TR
ALTGim
HBVDNAm
HBVDNA
VIM GAN B MN HBeAg M
GimqHBsAg
MtHBsAg
GimqHBsAg
MtHBsAg
MC TIU
NGN NGA: SUY GAN MNB.GAN G CUI
X GANHCC
CI THIN:CHT LNG SNG
T VONG
MC X HA GAN
NGNG IU TR
NAs: C CH VIRUS KHNG IU TR KHI
NHM THUC C CH SAO CHP:
Kim sot virus lu di (ON-TREATMENT EFFECT)
c ch sao chp ca polymerase (gim, m ha HBVDNA)
Rt him chuyn i HBsAg
HN CH:
S DNG KO DI khng thuc HN CH S DNG KO DI
Khng tc dng trn cccDNA KHNG THI TR HON TON
Chng gen: t bin S/PreS T BIN TRN THOT VCCIN (VAMs)
Khng ci thin khim khuyt trong p ng min dch
LAM ADV ETV TDF
PHC IU TR: C TH HA TR LIU
Liaw YF Hepatol Int 2012:6:531-561Lok AS. Hepatol 2009; AASLD practice GuidelinesEASL Jury; J Hepatol 2012:167-185
KHNG P DNG CHO MT B GAN
C CH NH IU TR
3. NAs KO DI
C THI HN
2. NAs NGN HN
1. C THI HNIFN
T L P NG; TD PH
TI PHT, KHNG THUC
THI GIAN C NH
CHUYN I HBeAg
MT HBsAg
QUY TC NGNG IU TR
III. CC TR LIU MI TRONG THP NIN TI
CHIN LC IU TR
CHIN LC HIN NAYN TR HAY PHI HP IU TR ?
C S L LUN:
Chu trnh HBV phc tpMULTI-TARGET ? (Lao, HIV, ...)
PHI HP NAs: Hiu qu tc thi cao, p ng HT ?
PHI HP NAs + IU HA MIN DCH: P NG VIRUS +
CHUYN I HUYT THANH CAO HN
Trnh t phi hp?
NAs no phi hp?
Tnh hung no nn?
CC NAS MI ANG HA HN
NHM THUC TNH TRNG
NAsC CH
POLYMERASE
CLEVUDINE CHA
EMTRICITABINE FDA (HIV)
AMDOXOVIR II(HIV)
LB80380 IIb
TENOFOVIR ALAFENAMIDE (GS 7340) II/III
CC TR LIU ANG HA HN
NHM THUC TNH TRNG
C CH XM NHP MYRCLUDEX-B Ib/IIa
C CH TO V TIT CORE/CAPSID BAY 41-4109 IGLS-4, NVR-1221 TIN LS
HAP: Heteroaryldihydropyrimidines
C CH SN XUT, CHUYN M cccDNA
GS9620 TIN LS
Cc ZFP, DSS, IFN-Lymphotoxin- receptors
C CH PHNG THCH HBsAg Rep 9 AC IINITAZOXANIDE II
IU HA MIN DCHTIT CYTOKIN PEG-IFN LAMDA I
HOT HA TLR-7, TLR-3 GS 9620 TIN LS
P NG LYMPH T CORE ANTIGEN VACCIN I
KCH THCH LYMPH T TIT IFN- ePA-44 II
RNA INTERFERENCE ARC 520 I
HI-8 HBV II
CC TR LIU CA TNG LAI
Tc dng chng xm nhp (entry): (Myrcludex-B): l lipopeptide tng hpca vng pre-S1, nhm vo NTCP (Natri Taurocholate Co-transported
Peptide).
Tc dng trn qu trnh to capsid: HAP: Hetero-Aryldihydro-Pyrimidines: c ch to capsid, to capsid bt
thng, mt n nh v d b hy hoi.
Phenypropenamide: c ch qu trnh kt hp nn virion, hnh thnhcc virion bt thng (virion trng)
Tc dng trn qu trnh tit HBsAg: Nitazoxanide and Tizoxanide: gim HBsAg, HBeAg ngoi bo v HBcAg
ni bo.
Nucleic acid polymer, Amphipathic oligonucleotide (Rep 9AC)
Tc dng trn qu trnh bc v (encapsidation):
Glucosidase inhibitors: c ch glycosyl ha protein v ti li ni bo (ER) nh
hng s hnh thnh v bc, to nn tiu th Dane bt thng, khng c kh
nng gn vo mng t bo khi pht s xm nhp.
Tc dng trn cccDNA (GS-9620 ): cccDNA trong nhn c thi gian bn hy 33-50
ngy, khng b nh hng bi NAs, l cu trc duy tr tnh di truyn ca HBV.
Thuc to cccDNA li, HBV khng thuc, ti hot sau ngng thuc.
Bt hot/ thi tr/ ging ha cccDNA: cc ZFP (Zinc Finger Protein. Ngn cn
chuyn m ca cccDNA.
Ngng biu hin gen cccDNA (Epigenetic Silencing of cccDNA): c ch biu l
v chc nng ca cccDNA
Tc dng trn mRNA
CC TR LIU CA TNG LAI
Tc dng trn k ch:1. Kch hot TLR Agonists: ung, hp thu nhanh gan, c th sn xut vin phi
hp vi NAs. Kch thch sn xut IFN, cytokin tc dng trn qu trnh truyn tnhiu trong t bo. Thuc tc dng chnh ti gan, trnh c phn ng ton thndo hot ha phn ng khng c hiu.
2. Cytokines
CYT107: l IL-7 ngi ti t hp th h 2. phc hi min dch mnh; dngnh ph gia cho vcxin. Tc dng tt cho iu tr truyn t bo.
Recombinant IL-21: l cht iu ha min dch mi ang pha I v II tr liucho bnh nhn ung th. mt thuc phi hp tt vi NAs.
3. Programmed Death-1/PD Ligand-1: Phc hi trng thi kit qu ca lymph T, phc hi min dch thch ng BN vim gan B mn.
4. Vc xin tr liu:
Protein v ti t hp: HBsAg v HBcAg hay vc xin ti t hp khc Adeno-virus-based Therapeutic Vaccine: TG 1050 DNA & T-cell Peptide Epitope
CC TR LIU CA TNG LAI
CHNG XM NHP (MYRCLUDEX):
Nhm vo NTCP (Sodium Taurocholate
co-transported
peptide)
CHNG TO CAPSID: HAP: Heteroaryl-dihydro-pyrimidinesPhenypropenamide
c ch to capsid, to capsid bt thng, KHNG n nh.
TC DNG TRN QU TRNH BC V: Glucosidase inhibitors: c ch glycosyl ha cc protein v, to cc virion khim khuyt khng c kh nng gndnh gy nhim trng
CHNG TIT HBSAG:Nitazoxanide, TizoxanideGim HBsAg, HBeAg ngoi bo
CHNG cccDNA: cccDNA TG bn hy di(3350 ngy), d tr cccu trc gen t bin
TC DNG TRN mRNA v TC DNG TRN K CH kch thch tit IFN, cytokin
TLR Agonist PD-21, GS-9620, CYT107, IL-7, IL-21, Therapeutic Vaccin: TG 1050, DNA & T-cell Peptide Epitope VACCIN
CC V TR TC DNG CA TR LIU HBV
Top Related