TCNCYH 70 (SJ - 2010

T A I L IEU T H A M K H A O 2. D6 Nho Hon, Nguyin Chi Dung, Hans

1. Nguyin Chi Dung, Vu Qudc LOdng (1997): Limberg (2008): Danh gia nhanh mu Ida cd the

Djch t l bpc benh mat hot d tre em dfldi 15 tudi phdng tranh dflpc ta i l 6 tinh thanh Viet Nam.

tai 1 sd vung Viet Nam hien nay. Tap chf Nghien Cdng trinh NCKH cap Bp, Benh vien Mat

cflu Y hpe. Volume 3. Sd 3,1997, tr 8 - 1 4 . Trung fldng.

Summary

RAPID ASSESSMENT OF ACTIVE TRACHOMA, TRICHIASIS AND BLINDNESS

PREVALENCE IN THE COMMUNITY OF NAM DINH, THAI BINH, HAI DUONG PROVINCES

Assessment of active trachoma and TT prevalences is necessary for Trachoma Control planning.

Objectives: (1). To evaluate active trachoma prevalence in under 16 children and TT prevalence in 40

years and older population. (2). To assess Blindness prevalence and causes in 40 years old and over popu­

lation in the community. Method: Cross - sectional prescriptive study on 5201 children and 9554 persons

of 40 years old and over. Results: Active trachoma prevalence in children in 3 provinces is 0%, TT preva­

lence in ThaiBinh is 4.48%, in NamDinh is 1.44% and in HaiDuong is 1.28% in the population of 40

years old and over, but mainly found in the group of 70 and over. Prevalence cf blindness in the popula­

tion of 40 years old and over is 4.17% in ThaiBinh, 2.52% in NamDinh and 1.24% in HaiDuong. Main

cause of blindness is still cataract (3.3% in ThaiBinh, 2.3% in NamDjnh, 0.9% in HaiDuong), trachoma

blindness is 0.1 %(ThaiBinh), 0.03% (NamDinh) and 0% (HaiDuong). Conclusion: To control of Blinding

trachoma, promotion of TT surgery, especially in the population under 70 years old is necessary and feasi­

ble target in some years.

Keywords: assessment of active trachoma and TT

THONG BAO DAU TIEN VE NGHIEN CL/U GIA TRj PIVKA - II

TRONG CHAN DOAN UNG THU GAN 6 BENH NHAN VIET NAM

NHIEM VIRUS VIEM GAN B

Bui Xuan TrOdng, Nguyin Khanh Trach

Benh vien Bach Mai

Ung thd gan (UTC) rat pho bien vi cd ty Id td vong cao Alpha - fetoprotein (AFP) li dau an sinh hoc duy

nhat ddac sd ddng de chin doin UTC tai Viet Nam, nghien cdu cic dau an sinh hoc khac nhu PIVKA - II

(protein t^o ra do sU thieu hut vitamin K) cdn rat han chi. Muc tieu: budc diu dinh gia vai trd cua PIVKA - II

trong chin doin ung thd gan d benh nhin Viet Nam nhiim virus viem gan B. Ddi ttfgng va phuang phap:

nghien cdu bao gom 104 bdnh nhin nhiim virus viem gan B (HBV) ddac chia lam bdn nhdm, ngddi lanh

mang virus (NLMVR), viem gan man tinh (VGM), xa gan (XG) va UTC. AFP ddac xic dinh bing ELISA, PIVKA - II

duac xic djnh bing Eitest PIVKA - II cua cdng ty Eisai, Nhat Ban. Ndng do HBV - DNA vi kiiu gen cua HBV

duac xic djnh tdang dng bang real - time PCR va PCR - RFLP. Chin doan UTG ddac xic djnh bang md bdnh

hoc Ket qua: PIVKA - II cd dd nhay cao han va dd die hieu thip han AFP d tat ca cic mde ning dd phan

88

TCNCYH 70 (SJ - 2010

tich. Ket hap hai dau an cd do die hi$u cao ban va ty Id chan doin dung tdt ban. Nong do PIVKA - II va AFP

deu ting din td nhdm NLMVR ddn VGM, XC va cao nhat d nhdm UTC, sd khic bidt la cd y nghTa thdng ke

(p < 0,05). Phan tich dan bien cho thi'y tuoi (> 50), kieu gen C cua HBV, AFP (> 20ng/mL) va PIVKA - II (> 40

mAU/mL) la nhOng ye'u td nguy ca cd f nghTa thdng ke ddi vdi XG va UTG. Tuy nhien, phin tieh da bien cho

thiy chi cd tuoi (> 50), kiSu gen C cua HBV va PIVKA - II (> 40 mAU/mL) la nhdng ydu td nguy ca cd y nghTa

thdng ki ddi vdi XC va UTG. Kit luan: PIVKA - II la diu in sinh hgc, cd gii trj va cd vai trd hd tra tdt AFP

trong chan doin UTC.

TO khoa: ung thO gan, virus vi€m gan B

I. DAT VAN DE Ung thu gan la mdt trong sau loai ung thU phd

bi ln nhat tren the gidi, d nam gidi ung thU gan

dflng hang thd ba sau ung thU phdi va ung thU da

day. Virus viem gan B (HBV: hepatitis B virus),

virus viem gan C (HCV: hepatitis C virus) va rUdu

la nhflng nguyen nhan hang dau gay xd gan (XG)

va ung thu gan (UTG). D i n nay, mac du nh i lu

loai t h i he thude thupe nhdm chat tUdng ddng

nucleotide (nucleot/side analogue) dfldc p h l t trien

thanh cdng, cung nhfl viee trien khai ap dung

dieu trj bang Peg - interferon (Pegasys, Pegintron)

rpng rai hPn, nhflng hieu q u i dieu trj viem gan B

man tfnh van chfla dfldc nhfl mong ddi. Chung ta

v in ehUa dat dUpc khai niem lam sach HBV trong

dieu trj viem gan B man tinh, HBV va benh ly do

HBV gay nen van la mpt g i nh nang cho nhan

loai, ddng thdi cung la mpt thaeh thflc cho y hpe.

Hien nay, tren toan the gidi, mdi nam ed khoing

0,5 trieu benh nhan UTG mdi dUde p h l t hien.

Mpt so' nha nghien edu y hpe nhan djnh, so' benh

nhan UTG v i n t i l p tuc gia tang trong mpt vai

th|p k'y tdi.

Khoang 85 - 90% benh nhan UTG cd kem

theo XG d cac mfle dp khae nhau. Hieu qua d i l u

trj UTG phu thupe vao giai doan p h l t trien eua

khdi U, benh ly gan va toan than, ed di can hay

chUa ed di can. UTG dflpc phat hien sdm, dac

biet tren benh nhan tdn thfldng XG chfla nang, ed

tien Iflpng tdt va cd k h i nang keo dai eupc sdng

tren 5 nam rat cao. Day ehinh la ly do nh i lu nha

y hpe di sau t im h i l u nghien cdu va dUa ra cae

g i i i p h l p ehan dean UTG giai doan sdm. Cung

vdi sU phat trien cua chuyen nganh ehan do ln

hinh I n h , chup cat Idp vi tinh (CT) va cpng hudng

tfl hat nhan (MRI), y hpe ngay cang cd kh i nang

chan do ln ung thfl gan d giai doan sdm va giai

doan rat sdm. Tuy nhien, d CT va MRI deu cd

g i l thanh d i u tUdng dd'i cao, hdn nfla v l mat trang

th i l t bj cung khd trien khai lam cdng tac sang Ipe

trong cpng ddng. Do vay hien nay, sieu am

thudng qui k i t hpp vdi xet nghiem alpha - fetopro­

tein (AFP), vdi UU diem g i l thanh re va d l trien

khai van la phUPng p h l p chu y l u dUdc I p dung

tren the gidi de sang Ipe v l phat hien benh nhan

UTG giai doan sdm. NhUng nhUpe diem cua sieu

am la phu thudc vao nang Iflc cua ngUdi lam, thdi

diem tie'n hanh lam trong ngay va the trang benh

nhan, do vay sieu am cd dp nhay dao ddng cao.

AFP cho d i n thdi diem hien tai van la mpt dau an

(marker) sinh hpe chUa the thay the trong chan

do ln va theo ddi hieu q u i d i l u trj UTG. Tuy

nhien trong chan do ln UTG, viec sfl dung AFP cd

the bd sdt tdi 40% benh nhan, ben canh dd nh i lu

benb nhan viem gan v l xd gan cung ed tang ndng

dp AFP tUdng ddi cao va ndng dp AFP khdng cd

md'i tUPng quan chat che vdi kich thUde khd'i U

gan [4, 5, 7].

Trong mpt vai thap k"/ g i n day, viec tim ra

mpt marker sinh hpe ed kha nang thay the hoae

hd trp cung AFP trcng chan doan sdm va theo doi

hieu qu i d i l u UTG dUdc d e nha y hpe khdng

ngOng quan tam nghien cdu. D i n nay cd hang

chuc marker sinh hpe da dUdc tim ra, nhUng chi

cd khoang hdn 10 marker trong sd dd dupe danh

89

TCNCYH 70 (SJ - 2010

g i l la cd trieri vpng kha quan trong thflc hanh lam

sang [7]. Mpt trong d c marker dd la PIVKA - 11,

mpt protein dUdc tac ra do sU tieu hut vitamin K,

hay edn dupe gpi la des - gamma - carboxy

prothrombin (DCP). Vai trd cua PIVKA - II trong

chan doln va theo ddi hieu qua d i l u trj UTG ngay

cang duoc quan tam nghien eflu d cpng ddng

benh nhan thupe eac khu vfle khac nhau tren the

gidi. Mpt so' nghien edu nhan thI'y PIVKA - II ed

g i l trj cao hdn AFP trong chan doan va tien lUpng

d benh nhan UTG [3, 9, 10]. Tuy vay, nhieu nha

nghien edu ddng nhat quan diem PIVKA,- II va r'

AFP cd tac dung hd trp nhau, PIVKA - II ehUa thflc

sfl cd kh i nang vflpt trdi hoan to ln d l ed t h i loai

bd dflpe AFP trong thflc hanh lam sang.

La nflde thupe vung tay T h i i Binh DUPng, mpt

trong nhflng khu vfle ed ty le nh i lm HBV eao nha't

t h i gidi vdi dfldng lay truyen chu y l u tfl me sang

con, ty le nh i lm HBV tai mpt sd tinh - thanh d

Viet Nam ed the Idn hdn 1 5% dan sd [2, 8]. HBV

la nguyen nhan hang d i u gay viem gan man

(VGM), XG va UTG. Tai Viet Nam, UTG cung la

mpt trong nhflng ung thU phd b i l n nha't va ed ty le

tfl vong cao. Vdi khoing 75% dan sd sd'ng tai

ndng thdn va d i l u kien cham sdc y t l edn chUa

ddng deu gifla ndng thdn va thanh thj, do vay rat

nhi lu benh nhan UTG tai Viet Nam khi di kham

d giai doan benh da mudn hoae rat mudn. D i l u

nay ly giai tai sao ty le benh nhan UTG ed ddi

sd'ng keo dai tren 5 nam edn kha thap. Viec sang

Ipc benh nhan UTG tai Viet Nam v l can ban

cung dUa chu y l u vao sieu am va cd hay khdng

ed k i t hdp vdi xet nghiem AFP (do nh i lu benh

vien nhd va phdng kham chUa ed kha nang trien

khai lam AFP). Nhflng den nay, tai Viet Nam viec

nghien edu eac da'u a'n sinh hpe thay the hay hd

trp eung AFP trong thflc hanh lam sang edn rat

han c h i , chfla cd nghien edu di sau tim hieu gia

trj cua PIVKA - II trong ehan doan va theo ddi tien

lupng hieu qu i d i l u benh nhan UTG. Do vay

nghien cflu nay dUdc t i l n hanh vdi muc tieu:

Budc diu danh gia vai tro cua PIVKA - ll trong

chan doan ung thtf gan d benh nhan Viet Nam

nhiem virus viem gan B.

II. DOI TUONG VA PHUONG PHAP

NGHIEN CLfu

1. Doi tOdng nghien cOu: nghien cflu bac gdm

104 benh nhan nhiem virus viem gan B, 88 nam

va 16 nfl, tudi trung binh 36,6 ± 15,8 (17 - 70

tudi). Dd'i tupng nghien cflu dfldc chia lam bdn

nhdm, 40 ngfldi lanh mang virus (NLMVR), 14

benh nhan viem gan B man tfnh (VGM), 25 benh

nhan xd gan (XG) va 25 benh nhan ung thU gan

(UTG). Tat e l benh nhan deu dfldc kham, dieu tri

va theo ddi djnh ky tai benh vien Bach Mai, Ha

Npi. De xac lap "tieu chuan vang" tfnh dp nhay

va dp dae hieu, ta't d benh nhan UTG d iu dUpe

chan doan x l e djnh bang phan tich md benh hpe

dfla tren manh td ehfle sinh thiet gan hoac chpc

hut t l gan dfldi sfl hfldng d i n cfla sieu am.

2. PhOdng phap nghien cffu: do d i l u kien hien

nay tai Viet Nam chfla trien khai lam xet nghiem

PIVKA - II, de d i m b i o tfnh ddng bp cua k i t qua

xet nghiem, m l u benh nhan trong nhdm nghien

edu sau khi thu thap dUdc quay li tam t i ch bo

thanh phan hflu hinh, p h i n huyet thanh cdn lai

dUdc luu trO d nhiet dp am sau (- 80°C), sau dd

dupe ehuyen qua phan tich tai TrUdng Y, Dai hpe

Kobe, Nhat B i n .

Ndng dp HBV - DNA dupe x l c dinh bang

phUdng phap real - time PCR, kieu gen eua virus

viem gan B dfldc phan Icai bang phfldng phap

PCR - RFLP. Ndng dp alpha - fetoprotein (AFP)

dflpe xae djnh bang phfldng p h l p ELISA vdi kit

cua cdng ty AbboL Hoa Ky; ngfldng g i l tri x lc

djnh gifla binh thfldng va bat thfldng la 20 ng/mL.

Ndng dp PIVKA - II dflde x l e djnh vdi kit Eitest

PIVKA - II cua cdng ty Eisai, Tokyo, Nhat B in ;

ngUdng gia trj xac djnh gifla binh thfldng va bat

thfldng la 40 mAU/mL.

90

TCNCYH 70 (SJ - 2010

3. XO ly sd lifu: cac thuat toan Khi binh phfldng

(X ), Fisher's exact test, Mann - Whitney U test

(Wilcoxon rank sum test), phan tieh ddn bien

(univariate analysis) va phan tich da bien (multivariate

analysis) dfldc sfl dung de xfl ly sd lieu. Q u i trinh dUdc

lam tren may tinh vdi chUdng trinh STATA cua Hoa

Ky. Gia trj p = 0,05 (vdi dp tin cay 95%) la ngudng

x lc djnh sfl khIe biet ed y nghTa thdng ke.

I. KETQUA Bang 1. Dac diem nhom benh nhan nghien ctfu

Dac dien

so sanh

Tong sd

(n = 104)

Chan doan lam sang

NLMVR

(n = 40)

VGM

(n = 14)

XG

(n = 25)

UTG

(n = 25)

Tudi

(nam)

Nam/Nfl

ALT

(UI/37°C/L)

HBeAg (-)

Anti - HBe (-I-)

Kieu gen B

Kieu gen C

H B V - D N A

(logcopies/mL)

AFP

(ng/mL)

36,6 ± 15,8

( 1 7 - 7 0 )

88/1 6

36,0 ± 65,4

(5 - 447)

75 (72,1%)

63 (60,6%)

75 (72,1%)'

29 (27,9%)'

5,3 ± 2,1

(2 ,6 -9 ,7 )

155,9 ± 2 9 5

(0 - 894)

21,5 ± 3 , 9 '

( 19 -41 )

33/7

11,9 ±4,5=- '

(7 - 30)

21 (52,5%)''

17 (42,5%)''' =

32 (80%)'

8 (20%)=

5,6 ±2,3=

(2,6-9,7)

7,5 ± 24,9''

( 0 -155 )

38,1 ± 12,9'"''

(1 7 - 64)

11/3

90,8 ± 83,5'

(38 -279)

14(100%)' '

1 3 (92,9%)''

1 3 (92,9%)=

1 (7,1%)=

3,8 ± 1,6='''

(2,6 - 6,4)

119,1 ±251,9' ' ' =

(2,2 - 824)

47,9 ± 12,8'' =

( 18 -69 )

21/4

26,9 ±28 ,9= ' '

( 5 - 107)

19 (76%)

1 8 (72%)=

1 6 (54%)

9 (35%)

5,5 ± 1,9"

(2,5 - 8,7)

201,3 ±324,2 ' '

(0 - 863)

48,5 ± 11,3' =

(30 - 70)

23/2

53 ± 102,9'

(5 - 447)

1 9 (76%)

1 5 (60%)

14(55%)=

11 (44%)=

5,5 ± 2 , 1 ' '

(2,6 - 9,5)

417,1 ±

365,2''' =

(0 - 894)

PIVKA-II

mAU/mL)

7255,5 ± 19692,4

(4 - 75000)

30,9 ± 8,2'

( 17 -50 )

130,4 ±256,9=

(4 - 959)

12041,3 ±

27291,8'' = (13-75000)

1 8050,8 ±

25638,1' ' =

(15-75000)

NLMVR: ngUdi lanh mang virus, VGM: viem gan man, XG: xd gan, UTG: ung thU gan

ALT: alanine transaminase, ( - ) : am tfnh, (-n): dUdng tfnh

PIVKA - II: protein dflpc tao ra do thieu hut vitamin K (protein induced by vitamin K absence)

HBeAg: kh ing nguyen hda tan cua virus viem gan B, Anti - HBe: khang the khang lai HBeAg

AFP: alpha - fetoprotein, =p < 0,05; ''p < 0,01; ' p < 0,001

Dae diem ddi tfldng nghien eflu dfldc mc t l

trdng bang 1. K i t q u i cho tha'y, tudi trung binh

cua nhdm NLMVR (21,5 ± 3,9 tudi) thap nhat va

tha'p hdn ban sd vdi d e nhdm khae, p < 0,001.

Khdng ed sfl khac biet gifla tudi trung binh cua

nhdm XG (47,9 ± 1 2,8 tudi) va nhdm UTG (48,5 ±

11,3 tudi), p > 0,05. Tudi trung binh cua nhdm

VGM (38,1 ± 12,9 tudi) tuy eao hdn nhdm

NLMVR, nhUng v i n tha'p hdn cd y nghTa thdng ke

so vdi nhdm XG va UTG, p < 0,05. Trong tdng so'

1 04 dd'i tUdng nghien edu bac gdm 88 nam va 1 6

nfl, ty le ham so vdi nfl gifla d e nhdm la khdng

91

TCNCYH 70 (SJ - 2010

cd sfl khIe biet, p > 0,05. Ndng dp ALT d nhdm

VGM (90,8 ± 83,5 UI/L/37°C) eao hPn ed y nghTa

thdng ke so vdi nhdm NLMVR (11,9 ± 4,5

UI/L/37°C), nhdm XG (25,9 ± 28,9 U1/L/37°C) va

nhdm UTG (53 ± 102,9 UI/L/37°C) vdi p < 0,001.

Tuy ndng dp ALT d nhdm XG ed eao hon d nhdm

UTG, nhflng sfl khIe biet khdng ed y nghTa thd'ng

ke, p > 0,05. Ndng dp ALT d nhdm NLMVR thap

hpn ban so vdi nhdm XG (p < 0,05) va nhdm UTG

(p < 0,001). Ty le HBeAg am tinh eao nha't d

nhdm VGM (100%), tiep sau dd la nhdm XG

(76%), nhdm UTG (76%) va tha'p nha't d nhdm

NLMVR (52,5%). Ty le HBeAg am tinh d nhdm

VGM eao hdn ed y nghTa thd'ng ke so vdi nhdm

NLMVR, p < 0,01. Tuong tfl nhfl v l y , X^ le anti -

HBe (khing the khang lai HBeAg) dfldng tinh

cung eao nhat d nhdm VGM (92,9%) va tha'p nhat

d nhdm NLMVR (42,5%), t^ le nay d nhdm XG,

nhdm UTG l l n Ifldt la 72% va 60%.

Trong nghien cdu, 75 (72,1%) benh nhan cd

kieu gen B va 29 (27,9%) benh nhan ed kieu gen

C, sfl khac biet cd y nghTa thdng ke vdi p < 0,001.

Ty le kieu gen B eao nhat d nhdm VGM (92,9%),

t i lp d in la d nhdm NLMVR (80%), nhdm XG

(64%) va thap nhat d nhdm UTG (56%). Ty le kieu

gen B d nhdm VGM va nhdm NLMVR eao hdn ed

nghTa thdng ke so vdi ty le kieu gen B d nhdm UTG,

p < 0,05. T'/ le kieu gen B gifla nhdm XG va UTG,

sfl khIe biet khdng cd y nghTa thdng ke, p > 0,05.

Ngflpe lai vdi kieu gen B, kieu gen C cd Xy le d

nhdm UTG (44%) cao hdn han so vdi nhdm VGM

(7,1%) va nhdm NLMVR (20%), p < 0,05. Ndng dp

HBV - DNA trung binh d nhdm VGM (3,8 ± 1,5

logcopies/ml) thap nhat thap hdn han so vdi nhdm

NLMVR (5,6 ± 2,3 logcopies/ml) vdi p < 0,05; va so

vdi nhdm XG (5,6 ± 1,9 logcopies/ml), nhdm UTG

(5,5 ± 2,1 logcopies/ml) vdi p < 0,01.

Ndng dp AFP trung binh tang d i n tfl nhdm

NLMVR (7,6 ± 24,9 ng/mL), d i n nhdm VGM

(119,1 ± 251,9 ng/mL), nhdm XG (201,3 ± 324,2

ng/mL) va eao nha't d nhdm UTG (417,1 ± 365,2

ng/mL). Ndng dp AFP trung binh d nhdm NLMVR

la thi 'p hdn ban sd vdi eac nhdm khae, p < 0,01.

Ndng dd AFP trung binh d nhdm VGM tha'p hdn

nhdm UTG, sfl kh Ic biet cd y nghTa thdng ke vdi

p < 0,05. Ndng dp AFP trung binh d nhdm UTG

eao hon d nhdm XG, tuy nhien sfl khac biet khdng

cd y nghTa thd'ng ke, p > 0,05. .

Cung tUdng tfl nhfl AFP, ndng dp PIVKA - II

trung binh eung tang dan tO nhdm NLMVR (30,9

± 8,2 mAU/mL), de'n nhdm VGM (1 30,4 ± 256,9

mAU/mL), nhdm XG (12041,3 ± 27291,8. mAU/

mU va eao nha't d nhdm UTG (18060,8 25638,1

mAU). Nhflng khIc vdi AFP, ndng dp PIVKA - II

trung binh d nhdm UTG cao hdn cd y nghTa thdng

ke vdi ca nhdm XG vdi p < 0,05 va ndng dp

PIVKA - II trung binh d nhdm XG cung cao hdn cd

y nghTa thd'ng ke so vdi nhdm VGM vdi p < 0,05.

So vdi nhdm VGM va NLMVR, ndng dp PIVKA - II

trung binh d nhdm UTG eao hdn cd y nghTa thdng

ke vdi p < 0,001.

G i l trj dp nhay va dp dac hieu cua AFP,

PIVKA - II d d c mde ndng dp khIe nhau dupe

trinh bay d bang 2. Cae mfle ndng dp dUpe xay

dflng tang d i n theo mpt ty le tfldng flng ddi vdi c l

AFP va PIVKA - II, mde cd sd la 20 ng/mL vdi AFP

va 40 mAU/mL vdi PIVKA - II, sau dd tang len dan

d d c mfle ndng dp gap 2,5 lan, 5 l l n , 10 lan v l

20 l l n . K i t q u i b i n g 2 cho tha'y, d ta't d e l c mfle

ndng dp PIVKA - II d i u cd dp nhay eao hdn AFP,

tuy nhien sfl khac biet khdng cd y nghTa thdng ke,

p > 0,05. Ngflpe lai, d tat ca d e mde ndng dp

AFP d i u cd dp dac hieu eao hdn PIVKA - II, nhUng

sfl khac biet cung khdng ed y nghTa thdng ke,

p > 0,05. Mpt dac diem cung nh in thay ddi vdi

c l AFP v l PIVKA - II trong nghien cdu la khi elc

mfle ndng dp tang d i n thi dp nhay g i l m xudng va

dp dac hieu tang len, tuy nhien du cd tang den

mde gap 20 lan so vdi mfle eP sd thi dd dac hieu

cung khdng dat dUde 100% dd'i vdi d hai da'u an.

92

TCNCYH 70 (SJ - 2010

AFP (ng/mL)

20

50

100

200

400

AFP: alpha

PIVKA-I I :

- fetop

Drotein

Bang 2. So sanh do nhay va

•Do nhay

(%)'

68

60

60

50

56

otein,

dupe tao ra

Dp ddc hieu

' (%)

72,2

81

86,1

88,6

91,1

do th i l u hut vitarr

do dac hieu giffa AFP va PIVKA - //

Do nhay PIVKA - II (mU/mL) • ^ • '

40 84

100 76

200 76

400 72

800 68

Dq dac hi$u

(%)

lin K (protein induced by vitamin K absence)

63,3

78,5

82,3

87,3

89,9

Ki t hpp hai dau an AFP va PIVKA - II vdi nhau, danh gia sfl ket hdp cd g i l trj cac hdn so vdi tflng dau

an rieng biet khdng. Khi k i t hpp d mfle ndng dp 20 ng/mL ddi vdi AFP va mfle ndng dp 40 mAU/mL dd'i

vdi PIVKA - II, k i t qua bieu dd 1 cho thay sfl k i t hpp cd dp nhay (60%) tha'p hPn so vdi dp nhay cua AFP

ddn thuin (68%) va dp nhay cua PIVKA - 11 ddn thu in (84%), tuy nhien sU khac biet khdng cd y nghTa

thd'ng ke, p > 0,05. NgUdc lai, sU k i t hdp ed dp dac hieu cao hdn ban so vdi dp dac hieu cua PIVKA - II

ddn thuan (83,5% sd vdi 53,3%, p = 0,004) v l cung cac hdn so vdi dp dac hieu dPn thuan cua AFP

(83,5% so vdi 72,2%, p > 0,05). Sfl k i t hpp hai dau an cd gia tri chan doan dung cao hdn so vdi rieng le

tflng y lu td AFP ddn thu in hay PIVKA - II ddn thu in (77,9% so vdi 69,2% va 58,3%), tuy nhien sfl khIc

biet khdng to y nghTa thdng ke, p > 0,05.

Do nhay Dp dac hieu

Bleu do 1. Do nhay va do dac hieu khi kit hgp AFP vdi PIVKA - II

Nham danh g i l mde dp vai trd t i c ddng ddc

lap cua AFP va PIVKA - II dd'i vdi nguy cP XG va

UTG, trong nghien edu da t i l n hanh bUde phan

tfch don bien (univarite analysis) va da b i l n

(multivariate analysis) tUdng quan hdi qui. K i t qua

bang 3 cho thay, trong phan tich ddn bien, tudi

> 50, kieu gen C cua HBV, ndng dp AFP > 20 ng/mL

va ndng dp PIVKA - II > 40 mAU/mL la nhflng yeu

td nguy cd cd y nghTa thdng ke dd'i vdi XG va

UTG. Tuy nhien, trong phan tieh da b i l n eho thay

ehi edn tudi > 50, kieu gen C eua HBV va ndng dp

PIVKA - II > 40 mAU/mL la nhdng y l u td nguy cd

ed y nghTa thdng ke dd'i vdi XG va UTG. Trong

phan tieh da bien, gia trj eua AFP > 20 ng/mL v i n

93

TCNCYH 70 (SJ - 2010

ed mde odds ratio k h i cao (OR = 3,02), tuy nhien

gia trj p = 0,082; do vay so vdi PIVKA - II thi AFP

da khdng cdn la yeu to' nguy cd cd y nghTa thdng

ke ddi vdi XG va UTG trong phan tfch da b i l n .

IV. BAN LUAN

PIVKA - II hay des - gamma - carboxy prothrom­

bin (DCP) la prothrombin bat thUdng do thieu hut

nhdm carboxy (CO2) d vj trf gamma trong 10 phan td

glutamic acid n l m d phfa d iu amin (N - terminus

hay amino terminus) cua prothrombin. Q u i trinh

carboxylation (kit gan nhdm CO2) lai phu thudc vao

sfl cd mat cda vitamin K, do v l y loai prothrombin bat

thfldng nay ed hai ten gpi nhfl tren, tuy theo thdi

quen d c t ie gia cd the sfl dung mot trong hai ten dd.

Do mat nhdm carboxy d 10 phan tfl glutamic acid

nhfl vay da lam giam kha nang ket gan vdi ion Ca "

cua prothrombin, va ed the gay nen dIo Ion qu i

trinh ddng mau binh thfldng. Vai trd cua PIVKA - II

trong UTG dUpc Liebman HA va epng sfl l l n dau tien

cdng bd nam 1 984 [Liebman HA, Furie BC, Tong MJ

et al. (1984). Des - gamma - carboxy (abnormal)

prothrombin as a serum marker of primary hepatocel­

lular carcinoma. N Engl J Med, 310: 1427- 1431].

Tuy vay luc d iu , vai trd cua PIVKA - II trong

chan doan va tien lUdng, danh gia hieu qua d i l u

trj UTG dUde t r i ln khai nghien eflu, cung nhU ap

dung trong lam sang nh i lu nha't tai Nhat B in .

Thdi gian g i n day, vai trd cua PIVKA - II dUde ehu

y nhi lu hdn trong eae nghien cflu cua Hoa Ky,

mpt sd nflde chau Au, cung nhfl tai chau A. Trong

benh ly gan va UTG, qua trinh sinh hpe cua AFP

va PIVKA - II la doe lap vdi nhau. Phin Idn d c

nghien edu d Nhat Ban va chau A nhan thay

PIVKA - II cd vai trd td't hdn AFP, dac biet la mdi

tfldng quan vdi kfch thfldc khd'i U, md'i tfldng quan

vdi hinh thanh huyet khdi hay xam lan maeh

mlu , d inh gia kha nang tai phat sau d i l u trj. Tuy

nhien v l kh i nang ehan d d n UTG sdm thi k i t

qua eua eac nghien cflu tai chau A^chUa ed sfl

ddng thuan [9, 10]. Nham dUa ra mdt d c h nhin

tdng the de danh g i l lai vai trd cua AFP, so sanh

gifla PIVAKA - II va AFP, ddng thdi tao tien de

trien khai nghien cflu e l c dau an sinh hpe mdi

trong tUdng lai; hien nay Hda Ky dang thiet k l va

t i l n hanh d c nghien cflu d i n h g i l toan dien

benh ly gan, UTG k h i qui md v l ehi t i l t . Mpt

nghien edu t i l n cdu dpc theo thdi gian cua Hoa

Ky cho tha'y PIVKA - II ed dp nhay va dp dae hieu

cao hdn AFP, ddng thdi g i l tri AUG (area under

the ROC curve) trong phan tfch ROC (receiver

operating characteristic) cua PIVKA - 11 cung cao

hdn AFP. Tuy vay, k i t qua eua nghien edu nay

cung cho thI'y trong sang lpc UTG sdm thi d AFP

v l PIVKA - II van d n p h i i k i t hdp vdi sieu am,

tuy cd flu viet hdn AFP nhflng PIVKA - II v i n chfla

tao nen sfl khIc biet ed y nghTa thdng ke va nlu

k i t hpp hai yeu td lai se eho k i t qu i tdt hon [6].

Nghien cdu chdng tdi tien hanh la nghien cflu

dau tien danh gia vai trd cua PIVKA - II trong

chan do ln UTG d benh nhan Viet Nam, ddng thdi

t i l n hanh so s inh gifla PIVKA - II va AFP. Nghien

cflu nhan thay PIVKA - II cd dp nhay eao hdn

AFP, dp dae hieu khdng bang AFP, nhflng sfl khac

biet khdng ed y nghTa thdng ke. Bang k i t qui

phan tfch ddn b i l n va da bien eho thay, PIVKA -

II cd kha nang danh gia nguy cd XG va UTG dpc

lap tdt hdn sd vdi AFP. Trong mpt nghien cflu

trflde day d i n h gia mpt sd yeu to' nguy ed ddi vdi

XG va UTG d benh nhan Viet Nam nhan thay

AFP la met yeu td d i n h gia nguy cd doe lap trong

d phan tfch ddn b i l n va phan tfch da b i ln [1].

Tuy nhien trong nghien eflu nay, vdi sfl cd mat

cua PIVKA - II thi AFP chi cd vai trd thflc sfl cd y

nghTa thdng ke trong phan tfch ddn b i l n (OR =

6,07 va p = 0,0001), trong phan tich da b i l n tuy

AFP v i n cd gia tri OR k h i cao (OR = 3,02) nhUng

g i l trj p da thay ddi trd thanh khdng edn thUe sU

cd y nghTa thdng ke (p = 0,082). K i t qu i phan

tfch da b i l n trong nghien eflu eho thay tudi (> 50),

94

TCNCYH 70(SJ-2010

Bang 3. Phan tinh dan biin va da bien ttfang quan hoi quy mgt sd yeu to nguy ca cao

ddi vdfi xagan va ung thtf gan

Yeu td phan tfch Ddn bien (n = 104) Da bi§'n (n = 104)

OR (95%C1) Gia trj p OR (95%CI) Gi l tri p

Tudi > 50

<50

Gidi Nam

Nfl

HBeAg DUdng tinh

Am tfnh

Kieu gen Kieu gen C

Kieu gen B

Ndng dp HBV- DNA>5

(logcopies/mL) < 5

Ndng dp AFP > 20

(ng/mL) < 20

Ndng dp PIVKA-II > 40

(mAU/mL) < 40

15,7(4,3 -

1

1,7(0,55

1

0,52 (0,22

1

3,33 (1,34

1

1,5 (0,69 -

1

6,07 (2,5 -

1

13,9 (5,4-

1

55,9)

-4,9)

-1,24)

-8,3)

3,26)

14,7)

35,5)

0,0001

0,361

0,141

0,01

0,37

0,0001

0,0001

7,4(1,5-36,0)

1

1,3 (0,27-5,3)

1

0,47(0,11 -2,1)

1

5,8(1,3-26,4)

1

1,7(0,45-5,1)

1

3,02 (0,87- 10,6)'

1

14,8(4,3-51,3)

1

0,013

0,732

0,325

0,024

0,448

0,082

0,0001

AFP: alpha - feto protein, HBeAg: khang nguyen hda tan cua virus viem gan B,

PIVKA - II: protein dddc tao ra do thiiu hut vitamin K (protein induced by vitamin K absence)

OR: odds ratio, Cl: confidence interval

kieu gen C eua HBV, PIVKA - II (> 40mAU/mL) la

nhflng y lu to' doe lap danh g i l nguy cd XG va

UTG d benh nhan Vi6t Nam nhi lm' HBV. Mpt dac

churig cho e l PIVKA - II v l AFP la khi tang dan

cac mfle ndng dp danh gia (being 2), c l hai ye'u td

deu cd dp nhay giam xud'ng va dp dae hieu tang

len, tuy nhien khi tang mde ndng dp danh gia len

kha cao (gap 20 lan) thi khdng cd ye'u td nao dat

dupc dp dac hieu 100%. Nghien edu nhan thay,

khi ket hdp PIVKA - II vdi AFP se cd dp dae hieu

cao hOn va t'y" le chan doan dung cao hdn.

Khdng the dat dfldc dd dac hieu 100% mac du

da tang mde ndng dp len kha eao, PIVKA - II ehi

cd dp nhay eao hPn AFP va dd dae hieu khdng

bang AFP la mpt sd diem khac biet gifla k i t qu i

nghien cflu eua ehdng tdi va mpt sd nghien edu

khIe d Nhat B in , chau A va Hoa Ky. Chdng ta

b i l t rang, g i l trj cua d c dau an sinh hpe trong

chan doan UTG phu thudc vao mpt so' y l u td ed

b i n nhu tinh chat chung tpc, cd nhiem virus viem

gan khdng va loai virus viem gan (viem gan B hay

viem gan C), giai doan bdnh ly gan va kich thUde

kho'i U gan cua benh nhan trong nghien cflu.

Nghien edu ehdng tdi tien hanh tren d e ddi

tUdng benh nhan Viet Nam nh i lm HBV, benh

nhan UTG deu cd kich khdi U gan > 3em va ty le

benh nhan cd kich thUde khd'i U > 5em rat eao.

Benh nhan XG trong nghien eflu ehu y l u d giai

doan Child - B, t i l p d i n la Child - C va chi ed

mpt ty le rat nhd d giai doan Child - A, ben canh

dd sd lupng benh nhan UTG (n = 25) chUa that

nh i lu va nghien cdu mdi ddng d mde md ta cat

95

TCNCYH 70 (SJ - 2010

ngang. Dieu n l y gidp ly g i i i tai sao trong nghien

cflu, cd k i t qu i phu hpp vdi d c nghien cflu khae

tren the gidi va cd k i t qua chfla phu hpp.

V. KET LUAN

Kit qua nghien cflu bUde dau cho thI'y PIVKA -11

la dau an sinh hpe ed gia trj, PIVKA - II ed vai trd

hd trd td't ehe AFP trong ehan doan UTG d bgnh

nhan Viet Nam nh i lm HBV. Nham d i n h gia td't

hdn vai trd cua PIVKA - II trcng sang Ipc, chan

do ln va theo ddi dieu trj UTG d benh nhan Viet

Nam; trong tUdng lai ehung ta can t i l n hanh

nhi lu nghien eflu vdi qui md Idn hdn d d e dd'i

tUdng benh nhan khIe nhau.

T A I LIEU THAM KHAO

1. BOI Xuan TrOdng (2009). Nghien edu d i nh

gia mpt sd y l u td nguy eP cao ddi vdi xP gan va

ur>g thu gan d benh nhan nh i lm virus viem gan B

man tinh bang phan tfch dPn bien va phan tfch

da b i l n . Tap chf Nghien eflu Y hpe, 51 (2): 1 - 6.

2. Bui Xuan TrOdng, Nguyin Van Bang

(2009). Ty le nhiem virus viem gan B, virus viem

gan C, ddng nhiem virus viem gan B/C va kieu

gen cua virus viem gan B thupe khu vfle bien gidi

Viet - Trung huyen Bat X l t tinh Lao Cai. Tap chf

Nghien edu Y hpe, 54 (5): 52 - 59.

3. Carr Bl, Kanke F, Wise M and Satomura S.

(2007). Clinical evaluation of lens culinaris agglu­

tinin - reactive I - fetoprotein and de - a - carboxy

prothrombin in histologically proven hepatocellu­

lar carcinoma in the United States. Dig Dis Sci,

5 2 : 7 7 6 - 7 8 2 .

4. Gomaa Al, Khan SA and Leen E et al.

(2009). Diagnosis of hepatocellular carcinoma.

World J Gastroenterol, 1 5: 1 301 - 1 314.

5. Gupta S, Bent S and Kohlwes J. (2003). Test

characteristics of a - fetoprotein for detecting

hepatocellular carcinoma in patients with hepatitis

C. Ann Inter Med, 1.39: 46 - 50.

6. Lok AS, Sterling RK and Everhart JE et al.

(2010). Des - gamma - carboxy prothrombin and

alpha - fetoprotein as biomarkers for early

detect ion of hepatocel lu lar carcinoma.

Gastroenterology, 138 (2): 493 - 502.

7. Marrero JA and Lok AS. (2004). Newer

markers for hepatocellular carcinoma. Gastroen­

terology, 127: S113 -S119.

8. Nguyen VT, McLaws ML and Dore GJ.

(2007). Highly endemic hepatitis B infection in

rural Vietnam. J Gastroenterol Hepatol, 22: 2093 -

2100.

9. Wang CS, Lln CL and Lee HC et al. (2005).

Usefulness of serum de - a - carboxy prothrombin

in detection of hepatocellular carcinoma. World j

. Gastroenterol, 1 1 : 5 1 1 5 - 6 1 1 9 .

10. Yamamoto K, Imamura H and Matsuyama

Y et al. (2009). Significance of alpha - fetoprotein

and des - gamma - carboxy prothrombin in

patients with hepatocellular carcinoma undergoing

hepatectomy. Ann Surg Oncol, 16: 2795 - 2804.

Summary

THE FIRST REPORT OF A STUDY ON EXAMINING THE ROLE OF PIVKA - i l IN

DIAGNOSIS OF HEPATOCELLULAR CARCINOMA IN

HEPATITIS B VIRUS INFECTED VIETNAMESE

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer lesions with a high rate of

mortality and morbidity. Alpha - fetoprotein (AFP) is the only marker for diagnosis of HCC in Vietnam and

studies on examining the role of other bio - markers such as PIVKA - II (protein induced by vitamin K

96

TCNCYH 70 (SJ - 2010

absence) are very l imited. Objective: preliminary study to assess the role of PIVKA - II in diagnosis of HCC

in hepatitis B virus (HBV) infected Vietnamese. Methods: a total of 104 HBV infected patients were

enrolled in the study, the population study was categorized into four groups, asymptomatic carriers (ASC),

chronic hepatitis (CH), liver cirrhosis (LC) and HCC. AFP level was examined by ELISA method and

PIVKA - II level was confirmed by PIVKA - II Eitest from Eisai company, Japan. HBV - DNA and HBV

genotype was analyzed by real - time PCR and PCR - RFLP, respectively. The final diagnosis of HCC was

determined by histo - pathologic analysis. Results: comparison to AFP, PIVKA - II had a higher prevalence

of sensitivity but lower prevalence of specificity in all level analysis. The combination of these two

markers showed a higher prevalence of specificity and a better percentage of accurate diagnosis. The level

of both AFP and PIVKA - II were progressively elevated from ASC to CH, LC and having the highest

concentration in HCC group; the difference was significantly observed (p < 0.05). The data of univariate

analysis reported that age (> 50 years), HBV genotype C, AFP (> 20 ng/mL) and PIVKA - II {> 40 mAU/mL)

were the independent factors for prognosis of LC and HCC. However, in multivariate analysis only age

(> 50 years), HBV genotype C and PIVKA - II (> 40 mAU/mL) were the independent factors for prognosis of

LC and HCC. Conclusions: PIVKA - 11 is the valuable cancer bio - marker and it could be complementary

AFP in the detection of HCC.

Keywords: liver cancer, hepatitis B virus

HOI CHL/NG APERT: NHAN MOT TRU^ClNG HOfP « • •

Dl/aC CHAN DOAN T R U 6 C SINH I ran Danh CoOng

TrUdng Dai hoc Y Ha Ndi

Hoi chdng Apert la mot benh ly hiim gap, nd nam trong nhdm nhdng benh ly hep so kem theo dinh

ngdn. Trddc day da sd eac trddng hdp chi dddc chin doin sau khi de, tuy nhien hien nay vdi ky thuat sieu

am hinh thai va vdi nhdng hinh anh sieu am die trdng nhd bien dang xUang so, dinh ngdn chin vi dinh

ngdn tay thi b$nh niy hoan toan cd the chin doan trddc sinh. Nhan mot trUdng hap ddac chin doin trddc

sinh bang sieu am chung tdi cd y djnh thdng bio nham giup cho cic nha sieu im cd them td Hdu de chin

doin trinh bd sdt vl tien Idang ve mat hinh thai cung nhd vi mat chdc nang cua benh ly nay la rat xau.

TO khoa : Hpi chOng Apert

I. DAT VAN DE

Hpi chflng APERT la mpt benh ly hep xfldng

sp cd kem theo dinh d c ngdn chan va ngdn tay

[1]. Day la mpt benh ly h i l m gap, trflde day da

sd cae trfldng hpp chi dope chan dean sau khi d l

qua tham k h l m tre sd sinh va benh thudng d l

lai di chflng nang n l ve hinh thai eung nhfl phat

trien than kinh van ddng va tri tue [4]. Ngay

nay, bang phfldng phap sieu am hinh thai thai

nhi thi hdi chflng n l y hoan toan cd the dflpe

ehan doan trflde sinh bdi d c dau hieu sieu am

k h i dae trflng [2]. Vfla qua chdng tdi ed ehan

do ln dUde mdt trfldng hdp d tudi thai 24 tuan

chfnh vi vay chung tdi thdng bao trfldng hdp nay

vdi muc tieu: M6 ta hinh anh sieu am va hinh

thai thai nhi trtfdc va sau khi sinh de giup cho

nhOng ngtfdi lam sieu am san khoa chu y trong

tbtfc hanh sieu am.

97