18 T4P chi GAN MAT V1$T NAM so 22-2012
Nghien cuoi moi lien quan giua t^i lu-g^ng vi-riit vdi mot so bieu hien lam sang va x6t nghif m & b^nh nhan vi8m gan vi-rut B man tinh
To study the relationship between virus load (HBV-DNA) with some clinical manifestations, laboratory tests; marker HBeAg, AntiHBe in chronic hepatitis B patients
PHAM MINH TUAN*, TRINH THJ XUAN H6A*'
Abstract:
Methods: 65 inpatients and outpatients in National hospital of tropical disease (NHTD) were enrolled in this study from February.20JJ to September.2011. Clinical, laboratory data were collected at admission the patient began.
HBV-DNA quantiative was made by Real-time PCR. Results:
-There was no correlation between virus load with some clinical (fatigue, anorexia, jaundice, hepatomegaly...) and laboratory
Tom tat
Nghien cuu 65 b?nh nhan, tuoi tren 20, dugc chdn dodn viem gan vi-nit B man tinh dieu tri noi, ngoai tni tai Benh vien Benh nhi?t doi Trung uong hi thang 2 nam 2011 den thdng 9 nam 2011 voi myc tieu nghien cuu mdi lien quan giua tdi lugng vi-nit (HBV-DNA) v6i mpt so bieu hien lam sdng, xet n g h i ^ ; marker viem gan HBeAg, AntiHBe d b?nh nhan viem gan B man tinh. Cac du lieu lam sdng vd x6t nghiem dirge thu thgp liic benh nhan bit dau vdo vipn. Tdi lugng vi-nit (HBV-DNA) dugc xac djnh bang phuang phdp Realtime PCR l.Datvande
Tai lugng vi-nit (HBV-DNA) id xet nghipm sinh hpc phan tOr ngdy cdng dugc sir dung pho bien de ddnh gia lugng vi-rut viem gan B trong mau. Viec dinh lugng HBV-DNA r^t c6 gid trj trong thuc hdnh lam sdng va Id mpt tieu chudn de theo doi vd dieu trj thu6c khang vi-nit cua
enzyme ALT. ratio Prothrombin.
- There was relation between virus load with HBeAg and AntiHBe. The highest rate of HBeAg (+) in the group of patients with high- est virus load > Kfcopies/ml (72.2%). The highest rate of AntiHBe (+) in the group of patients with virus load an average of W -
<10^ copies/ml (8L8%) and lowest in the group with highest virus load (33.3%), the sig- nificant difference statistics with p<0.05
Ket qud:
- KhSng thay moi lien quan giira tdi lugng vi-nit v6i mgt so trieu chung lam sdng vd xet nghipm enzym ALT, ty 1? Prothrombin.
- C6 moi lien quan giira tdi lugng vi-rut vai cdc marker cua HBV. Nh6m c6 tdi lugng vi-nit rat cao >10' copies/ml c6 ty Ip HBeAg(+) cao nhat. Ty Ip AntiHBe(+) cao nhdt a nh6m c6 tdi lugng vi-nit trung binh (10^ - <10' copies/ml) vd thap nhat 6 nh6m c6 tdi lugng vi-rut rdt cao sv khdc bipt c6 y nghia thong ke.
bpnh nhan viem gan B m ^ tinh. Tim hieu vai tr6 ciia tdi lugng vi-nit cdc tdc gid Highleyman L, Hloeje UH, Chen CJ n h ^ thdy 6 bpnh nhdn viem gan man tinh, tdi lugng vi nit cao keo ddi Id ^eu to du bdo ton thuong gan, gia tang tien trien tin xa gan, va ung thu gan nguyen phat
*Benh vien Benh nhiet d(3i TW, ** Bpnh vipn 103, Hpc vipn qudn y
Tgip chi GAN MAT VI$T NAM so 22-2012 19
[6] [7] [9].
Chinh vi vdy chiing t5i thirc hipn dh tdi ndy nham tim hieu moi lien quan giua tdi lugng vi- 2. Doi turmig vh phirong phdp nghien c u u
Gom 65 benh nhan, tuoi tren 20, dugc chan dodn viem gan vi-nit B m?m tinh dieu trj npi, ngoai tni tai B$nh vien Benh nhipt d6i Trung uang tCr thdng 2 nam 2011 d^n thdng 9 nam 2011.
2.L Tieu chudn lua chpn bfnh nhan - Lira chpn benh nhan viem gan vi-nit B man tinh: Theo tieu c h u ^ chdn dodn cua Dien- stag- JL va cgng su [8]
Lam sang:
- M?t m 6 i , chdn an, sg mo, roi loan tieu h6a tao b6n. Co the vdng da, nu6c tiSu vdng.
- Gan, lach c6 the to Xet nghipm:
- Enzym - Transaminase > 2 Idn gid trj binh thucmg.
Marker HBV:
- HBsAg(+)> 6 thdng; Anti- HBcIgG(+) - Tdi lugng vi nit cua benh nhdn (HBV- DNA)>102 copies/ml
Cac benh nhan trong nghien cuu deu chua dugc dieu trj thuoc khdng vi-nit.
nit vai mpt so dac diem lam sang vd xet nghipm if bpnh nhan viem gan vi-nit B man tinh.
2.2. Phuffngphdp nghiin cuu - Tiln cuu , mo td cat ngang.
a) Phuang phdp chia nh6m nghien ciiu:
B?nh nhan dugc chia 1dm 3 nh6m d\ra vdo tdi lugng vi-riit
Nh6m 1: Benh nhan c6 tdi lugng vi-nit tu 10^ den <10^ ( copies/ml) ddy Id nh6m c6 tdi lugng vi-nit trung blnh
Nhom 2:Benh nhdn co tdi lugng vi-nit tu louden 10^ (copies/ml) day Id nh6m c6 tdi lugng vi nit cao
Nhom 3: Benh nhan c6 tdi lugng vi-nit >
10* ( copies/ml) ddy Id nh6m c6 tdi lupng vi- nit rat cao
b) NghiSn ciru moi Uen quan giiia tdi lugng vi-nit vdi mpt so dac diem 1dm sdng vd xet nghipm( Hoat dp enzym ALT, ty le Prothrom- bin, marker viem gan HBeAg vd AntiHBe)
c) Cdc x6t nghiem se dugc thyc hien tai khoa xet nghiem vd chan dodn hinh dnh cua Benh vien benh nhiet dai TU*. Dinh lugng HBV- DNA bdng ky thuat realtime PCR tren hp thong may Cobas do hang Roche san xuat.
3 . Ket qua va ban luan
3.1. Bank gia moi lien quan giua tai luffng vi-riit v&i cdc trifu chung lam sdng, hoqt dg enzym ALT vd ty l§ Prothrombin.
Bdng 3.1. Moi lien quan giira tdi lupng vi-rut vd cdc trieu chung lam sdng
~^^HBV-DNA TCLS ^ ^ ^
Vang da M€t moi Chan an Roi loan tieu lioa
Mit ngii Dau viing gan
Gan to
10'-<10s (n=
n 7 11 11 3 6 1 7
copies/ml
=11) Tyle%
63,6 100 100 27,3 54,5 9,1 63,6
10^- 10^ copies/ml (n=36) n 16 31 28 4 22
3 16
Tyl|%
44,4 86,1 77,8 11,1 61,1 8,3 44,4
> 10^ copies/ml (n=18) n 7 17 14 5 5 2 10
Tyl|%
38,9 94,4 77,8 27,8 27,8 11,1 55.6
P
P>0,05
20 Tsp chi GAN MAT V1$T NAM s6 22-2012 Nhan x6t:
- 6 nh6m b$nh nhan c6 t4i lugng vi-rut trung binh (10= - <10' copies/ml) ty 1? b$nh nhan c6 bieu hi?n ving da, gan to chidni 63,6%
cao Hon so v6i cic nh6m c6n l^i. Tri§u chirng met m6i chdn 5n gap d tit c4 c4c b?nh nhan c6 tii lugng vi-nit trung binh ( 10' - <10' copies/ml)
- Trong khi d6 tri?u chiing mat ngii g§p
nhi^u nhit 6 nh6m c6 tdi lugng vi-rit cao (10' - 10« copies/ml) chilm t^-1? li 61,1 %.
- d nh6m c6 tii lugng vi-rut rit cao (> 10' copies/ml) tri§u chiing dau viing gan (11,1%) vi rAi lo?n tiSu h6a(27,8%) chiem ty 1^ cao horn so vdi cic nh6m c6n l^i.
- Tuy nhiSn d6i v6i t4t ci cic tri^u chumg Iim sing ciia b$nh nhan s\r Idiic bi^t giiia cic nh6m li khdng c6 ^ nghTa th6ng ke.
Bang 3.2. Moi lien quan giiia Idi lu(mg vi-nit vd hoift dd enzym ALT
^ s H B V - D N A ALT ^ \ ^
TSng nhe (80 -200 U/1) Tang vira (201-
400U/1) Ting cao (>40DU/1)
copies/ml (Nh6nil) n 6 1 4
TJl^Vo 54,5
9,1 36,4
10»- 10»
copies/ml (Nhdm 2) n 10 7 19
n 27,8 19,4 52,8
>W
copies/ml (Nh6m 3) n 6 2 10Ty 1? % 33,3
11,1 55,6
P
p>0,05
Nhdn xet:
- Hogt dp enzym ALT tang a miic 2-5 lan binh thuang chiem ty Ip cao nhat (54,5%) ij nhom CO tdi lugng vi-nit trung binh. Hoat dp enzym ALT tdng a miic >10 lan binh thucmg chiem ty le cao nhdt (55,6%) a nh6m c6 tdi lugng vi-nit rdt cao, su khac biet ve miic dp tang enzym ALT tdng trong 3 nh6m nghien cuu Id khong CO y nghTa thong ke.
- Cdc ket qud nghien cuu ciia cdc tac gid trong nuac vd tren the gidi dira ra nhieu ket qua khdc nhau nhu Sakugawa H [11] ( Nhdt Bdn) nghien cuu boat dp enzym ALT a 3 nh6m benh nhdn VGVRB man, HBeAg(+)
(Nhom CO tdi lugng vi nit < 10* copies/ml.
tir 10' - 10'copies/ml, > 10'copies/ml) cho tfiay enzym ALT tang cao nhat g bpnh nhdn c6 tdi lugng vi-nit > 10' copies/ml nhung khong co su khdc biet c6 y nghTa thong ke giiia 3 nhom.
Theo tdc gid Hodng Tien Tuyen [5] a nh6m bpnh nhdn c6 HBeAg(+), boat dp enzym ALT dnh6m c6 tdi lugng vi-nit > lO'copies/mlthap han nh6m c6 tdi lugng vi-nit < 10''copies/ml trong khi d6 ket qua hogt dp enzym ALT o nh6m c6 HBeAg(-) thi ngugc Igi, tuy nliien tat cd sy khdc bipt ndy deu khong c6 y nghTa thong ke.
Nhu vay c6 the ket lugn rdng khong co moi lien quan giua tai lugng vi-nit voi hogt dp enzym ALT.
Bdng 3.3. Moi lien quan giua tdi lupmg vi-nit vd xet nghiem ty 14 Prothrombin
^ ^ H B V - D N A PT(%) ^ \ ^
Binh thirfmg Giam nhf (50-70%) Giam nang
(<50%)
W - <10' copies/ml n
7 2 2
T ^ l | % 63,6 18,2 18,2
10' - <10' copies/ml n
25 10 1
Ty 1« % 69,4 27,8 2,8
>10«
copies/ml n 11
5 2
T y l ? % 61,1 27,8 11,1
P
p>0,05
T?;p chi GAN MAT VIET NAM so 22-2012 21 Nhdn xet:
T;^ l^ Prothrombin chu ySu biSu hi?n hoat tinh dong mdu cua cac yeu to tham gia trong con du6fng dong mdu ngogi sinh (II, V, VII, X, fibrinogen...) binh thuang ndm trong khodng 70-140%. Hau hit cac yeu t6 dong mdu dugc t6ng hgp tai gan, cho nen m0t khi te bdo gan bj ton thuang qud trinh tdng hgp cdc yeu t6 d6ng mdu bj gidm siit, ddn den gidm nong dp cac yeu t6 ddng mau trong huyet tuang. Nhu vdy khi benh nhdn c6 ty le Prothrombin gidm th6 hi^n muc dp ton thuang cua tk bdo gan vd d6 ciing
3.2. Ddnh gid moi lien quan giira tdi lupng vi-rut vdi cdc marker HBeAg, AntiHBe.
Bdng 3,4. Moi lien quan giua cdc muc dp tdi lupng vi-rut vd HBeAg Id mOt trong nhirng can cii bieu hi?n vd tien lugng bpnh [2]
Hipn chua co nghien ciiru ndo trong nude v6 moi lien quan giiia tdi lugng vi nit va ty Ip Pro- thrombin. Theo tac gid Dinh Diic Thdng [3]
khong c6 su khdc biet ve gidm ty le Prothrom- bin giua hai nh6m nghien cihi HBeAg (+) vd HBcAg (-). Trong nghien ciiu cua chiing toi nh^n thdy khong c6 su khdc bi$t thuc sy v8 tj/
1$ Prothrombin giua cdc nh6m c6 tdi lugng vi nit khdc nhau.
\ ^ H B V - D N A Marker ^ ^ ^
HBeAg(+)
10'-<10'copies/ml n
4
Ty If % 36,4
10'-<10'copies/ml n
20
Tylf%
55,6
>10»
copies/ml n 13
Ty 1? % 72,2
P p>0,05 Nhan xet: HBeAg Id mgt protein khong cau
tnic cua HBV. HBeAg dugc tong hpp vugt tr6i trong giai doan nhdn doi ciia vi-nit. HBeAg xudt hipn sau HBsAg, lien quan d6n sy hien dien cua cac virion hodn chinh vd cling la bdng chiing ciia tinh Idy nhiem cao. Ket qud nghien curu cua chiing toi cho thay ty le HBeAg (+) cao nhat trong nhom benh nhdn co tdi lugng vi-nit >10* copies/ml chiem 72,2% dieu ndy cung phii hgp the hien cac bpnh nhdn ndy dang CO sy nhdn len vi-nit, ket qud ndy cao cdc ket
qua nghien ciiu cua Dinh Diic Thang [3] ty le HBeAg (+) trong nhom HBV-DNA >10«
copies/ml la 52,6 %. Trong nh6m co tdi lugng vi-nit trung binh 10^- <10^ copies/ml ty le HBeAg (+) thap nhat so vai hai nhom con lai chiem ty le 36,4 %. Sy khac biet ve ty le HBeAg (+) giixa 3 nhom nghien ciiu Id khong c6 y nghTa thong ke, c6 the nghien cuu cua chiing toi co ca mdu chua dii lan nen chua nhan thay su khac biet ve ty Ip HBeAg (+) trong cdc nhom c6 tdi lugng vi-nit khac nhau.
Bdng 3.5. Lien quan tdi luamg vi-rut v&i HBeAg(+) vd HBeAg(-) Nhom benh
HBeAg(+) HBeAg(-)
So b^nh nhan (n=65)
37 28
HBV-DNA (copies/ml) 4,9x10'±4,8x10' 3,1x10'±4,2x10'
P
p<0,05 Nhgn xet: Kit qud cho thay tdi lugng vi-nit
tren nhom benh nhdn viem gan B man tinh HBeAg (+) (4,9 x 10' ± 4,8 x 10' copies/ml) cao hem c6 y nghia thfing ke so vdi nhdm benh nhan HBeAg(-)(3,l X 10'±4,2x 10'copies/ml)vdi p<0,05
Trong nhdm nghien cdu tren 65 benh nhan VGVRB man, chiing toi thay nong dp tdi lugng
vi-nit tren nhom benh nhdn viem gan B man tinh c6 HBeAg (+) cao hon c6 y nghia thong ke so vdi nhdm HBeAg (-) vdi p<0,05. Ket qud nghien cdu cua chiing toi ciing tuang tu ket qua nghien ciru cua Yao Xie[l2]. Ndng dp HBV- DNA d nhdm HBeAg duong tinh cao hon nhom HBeAg am tinh. Ci Viet Nam nghien cdu ciia Le Thi Nggc Lan[l] ciing cho ket qud tuong tu.
22 Tap chi GAN MAT VI$T NAM s6 22-2012
Bang 3.6. Moi lien quan giira tdi lupng vi- nit vd AntiHbe
"~^^JBV-DNA Marker ^ \ ^ ^
AntiHBe (+)
I0'-<10' copies/ml n 9
Ty 1? % 81,8
I0'-<10' copies/ml n 21
TJ' If % 58,3
>10»
copies/ml n 6
Ti\i%
33,3 P
p(l-5)>0,d5 p(l-3)<0,0S p(2-3)>0,05 Nhgn x6t: Khi AntiHBe xudt hi^n d6ng thdi
vdi viec HBeAg (-) ngudi ta ggi Id chuyen ddo huyet thanh. Khi xuat hipn hi?n tugng ndy Id benh tien trien t6t, vi-nit khdng nhdn len trong ca the. Tuy nhien HBeAg (-)/ AntiHBe (-1) cdn gap trong the dgt bien tien nhan.
Ket qud nghiSn cuu ciia chiing tdi cho thdy ty le AntiHBe (+) cao nhat trong nhdm bpnh 3.3. Khdi qudt moi lien quan giira tdi lir^ng vi-rdt v&i cdc d^c diim Idm sdng vd xdt nghiem
Td cdc ket qud tren chiing tdi thdy chua moi lien quan thuc su ndo giiia tdi lugng vi-nit vdi dac diem 1dm sdng vd xet nghiem ALT, Biliru- bin, Ty le Prothrombin. Tuy nhien neu tdi lugng vi-nit tdng cao vd keo dai se Id yeu to du bdo ton thucmg gan, gia tang tiSn triSn tdi xa gan, vd ung thu gan nguyen phat theo nghien cuu cua Highleyman L, Hloeje UH, Chen CJ [6] [7] [ 9 ] . Ddi chieu vdi ket qud mo benh hgc Alam S (Bangladesh) [5] nghien cdu mo hpc d 175 benh nhdn theo thang didm Knodel! va so sdnh tdn thuang mo hgc viem va hoai tu vd ton thuang xa hda gan giiia cdc miic tdi lugng vi riit khdc nhau( <10^copies/ml, >10^ - 10*
copies/ml, > 10* - 10' copies/ml,
>10'copies/ml) cho thay khdng cd mdi lien quan giiia tdn thucmg viem, hoai tii va miic dp xa hda vdi cdc miic tdi lugng vi-nit. Nhu vgy tai lugng vi-nit cao khdng lien quan vdi muc dp ngng nhe cua benh nhan ve 1dm sdng xet nghiem cung nhu md benh hgc tuy nhien neu 5. Kit luan
1. Mdi lien quan giua tdi luptg vi rut v&i mpt so tripu chirng lam sdng vd xit nghiem & b^nh nhdn viem gan B m^n
- Khong thdy mdi lien quan giira tdn suat xudt hi?n mdt sd trieu chung lam sdng (mpt mdi, chdn an, vdng da, gan to...), hoat d$
nhdn cd tdi lugng vi-nit trung blnh HBV-DNA td 10' - <I0*copies/ml chilm 81,8% . Trong nhdm cd tdi lugng vi-nit rat cao > 10' copies/ml ty Iv AntiHBe (+) thdp nhdt so vdi hai nhdm cdn Igi chiem ty Ip 33,3 %. Sy khdc bipt ve ty le AntiHBe (+) gtua hai nhdm ndy Id cd y nghTa th6ng kS p<0,05
bpnh nhdn cd tdi lugng vi-nit tdng cao k6o ddi se Id yeu to dy bdo ton thuang gan, gia tang tien tnen dan tdi x a gan vd ung thu gan. Dieu ndy cung phu hgp vdi c a che bpnh sinh cua bpnh viem gan vi-nit B rage dd chua sdng to nhung hau het cdc nhd khoa hpc deu cho rang ca che bpnh sinh cua bpnh chinh Id ca chd miln djch, hau qud cua bpnh hodn todn phu thupc vdo so lugng, chat lugng, dgng hgc cua dap dng miln djch bdm sinh va mien djch thu nhan[10]. Qud trinh HBV phat tridn trong tfi bdo gan khdng gay phd vd td bdo gan.
Cd mdi lien quan giua tdi lugng vi-nit va HBeAg nhdm bpnh nhdn HBeAg (+) cd tai lugng vi-nit cao han nhdm HBeAg (-) dieu nay cung phu hgp vi nhdm bpnh nhdn HBeAg (+) the hien vi-nit viem gan B dang boat ddng va cd sy nhan len do dd tai lugng vi-nit trong mau se cao. Cd sy khdc bipt ty Ip AntiHBe (+) giiia nhdm cd tdi lugng vi-rut tnmg binh va rat cao, vi sy chuydn ddo huyet thanh thdnh AntiHBe thudng g^p d giai dogn thdi trit mien djch.
enzym ALT vd ty le Prothrombin vdi tai lupng vi-nit d benh nhdn viem gan B man tinh.
2. Moi lien quan giira tdi lu0tg vi-rut v&i cdc marker cua HBV
- Cd moi lien quan giua tdi lugng vi-nit va HBeAg: Ty Ip HBeAg(+) cao nhat trong nhdm
Tap chi GAN MAT VIET NAM so 22-2012 23
bpnh nhdn co tai lugng vi-nit rat cao >10^
copies/ml (72,2%) vd thap nhdt d nhdm cd tdi lugng vi-rut trung binh 10^ - <10^ copies/ml (36,4%). Ndng dp tdi lugng vi-nit tren nhdm bpnh nhdn viem gan B mgn tinh cd HBeAg (+) la 4,9 X lO' ± 4,8 x 10' cao hem cd ^ nghia thdng ke so vdi nhdm HBeAg (-) Id 3,1 x 10' ±
4 , 2 x l 0 ' v d i p < 0 , 0 5 .
- Cd moi lien quan giua tdi lugng vi-nit vd AntiHBe: Nhdm benh nhdn cd tdi lugng vi-nit trung binh cd ty I? AntiHBe (+) cao nhat (81,8%) vd thap nhat d nhdm cd tai lugng vi- nit rdt cao (33,3%) sy khdc biet cd ^ nghTa thong ke vdi p<0,05.
T a i lieu t h a m k h a o
1. Le Thj Ngpc Lan, Pham Hodng Phift (2003) " Tim hieu moi lien quan giira HBsAg vd dinh lupng HBV-DNA", Y hoc thanh pho H6 Chi Minh, tap 7, trl34-138.
2. Ha v a n Mao (2009), " Tham do cdc chuc ndng dong mdu", Benh hpc gan mat tuy NXBYH, Hd NOi, h-.80-106
3. Dinh Dire ThSng(2009) " Tim hieu mpt so dac diem Idm sdng, cgn Idm sdng a binh nhan viem gan B mgn tinh hogt dpng co HBeAg(+) vd HBeAg(-)" Ludn van bdc sy chuyen khoa 2, Hpc vien quan y- Vien NCKH y dupe lam sang 108, Hd Npi.
4. Hodng Tiln T^iySn (2011)" Nghien cihi moi lien quan giua kieu gen, tdi lupng virus v&i cdc bieu hien lam sdng nhiem vi rut viem gan B" Luan van tien sy y hpc, Hpc vien quan y, Ha Noi
5. Alam M.M.etal (2007) "Molecular epide- mology of hepatitis B virus genotype in Pak- istan", BMC infectious diseases, 7, pp. 115 6. Chen C J . (2008), '"Viremia and long-term
outcome of liver diseases. Viral hepatitis".
New horizions in hepatology - 18th confer- ence APASL,pp. 48-54.
7. Chien J.C., Hwai L, Yang. Et al. (2006), ''''HBV - DNA (viral load) predicts risk for liver cancer", JAMA, 295, pp. 65 - 73 8. Dienstag J.L. (2008),'' Chronic viral hepati-
tis" Harrison's principles of internal medi- cine, 17* edition, pp.1955- 1971.
9. Hoeje U.H., Yang H.Y. et al. (2008), ''HBV viral load less than l<y copies/ml is associ- ated with significant risk of hepatocellular carcinomar in chronic hepatitis B patients. An update from the R.E. V.E.A.L HBV study", J.
Hepatology 2(1), p.l87
10. John M Virling. (2007), " The immunology of hepatitis B", Clin Liver Dis, pp. 727 - 759.
11. Sakugawa H., Nakasone H. et al.(2001),
"Correlation between serum transaminase activity and virus load among patient with choronic liver disease type B" Hepat research, 21,pp.l59-168
12. Yao Xie, Hui Zao, Wang-Su Dai and Dao- Zhen Xu " HBV-DNA level and concentra- tion in evaluating liver damage of patients with chronic hepatitis B" Hepatobiliary Pan- creatic disease intemational, vol 2, No 3, pp418-422.
