Nghien cuu Y hpc Y Hpc TP. Ho Chi Minh * Tap 16 • Phu bdn cOa So 1 * 2012
DANH GIA GIA TRI CUA APRI VA FIB-4 TRONG DU" DOAN XO GAN Tran lhi Klidnh luimf
TOMTAT
Tong (juan va mm tim: Sinh thiii gan dmc xem li tieu chuan mng deddnh gid giai doan xa hoa jm.
APRI vii FJB i Ul nhimg jihumg tien MiSng xdm ldn de ddng CO diroc deddnh gid xo hoa gan doi v&i benh gan mm. Nghien arn nay nhim mm dich danh gii gid hi chan doan ciia APRI va FB 4 trong du dodn xo gan.
Dm tugng vd phuang phap nghiin diu: 77 henh nhan bi benh gan man duoc nghiin deu, hao gom 38 ca xa gan va39ca khong xa gan. Tai cd cac henh nhm nm/ duac Iioi benh sie clii tiel, thim Midm, thuc hien cac xet n^iem can thiel thuc hien tm BV Nhdn din US.
Kei qui: Vcti ngirong 3,37, APRI co do nhay, do diuyen, gia tn tien dodn duang va gia tri Hen doan am lan litm M 88,4%, 84,5%, 37,6% va 98,1%. V&i nguang 2,29, FIB 4 co do nhay, do chuyen, gid tii tien dodn dirang vigia tii tien dodn dm lan luat li 82,9%, 77,9%, 30,3% va 96,3%. APRI lAUC 0,86), cd gid tii du dodn xagan cao tam FIB 4 (AUC 0,84), nhung khdng co y nghia. Hang so tiiang quan Spemnan giira APRI vai Albumin, Bilimbin loan phin va INR tdn luat li -0,570, 0,540, 0,484 (p< 0,0001) va giira FIB 4 v&i Albumin, Biluubin toin phin va /NR lan luat -0,5243, 0,4973,0,4343 (p < 0,0001).
K0 luin: APRI VA FIB 4 la nhiing pliuang tlf n dm giin, re tien, khong xam lm co do nhay va do diuyen cao trang du doin xa gan. Xet nghiem niy nen thuc Men thitimg tjui cho tai ci nhiing benh nhdn co benh gan man deloai trie xa gan.
Tu^ khoa: xa gan, xa hoa gan, dii si^APRI, dii soTIB4 ABSTRACT
ASSESSING THE VALUE OF APRI AND FIB 4 FOR PREDICTION OF CIRRHOSIS Tran Thi Khanh Tuong * Y Hoc TP. Ho Chi Minh * Vol. 16 - Supplement of No 1 - 2012:12-16 Background / Objectives: Liver biopsy is the recognized gold standard Jbr liver fibrosis staging. The aspartate aminotransferase to platelet ratio index (APRI) and FIB 4 haoe been proposed as a noninvasive and readily auailable tool for tlie assessment (^ liver fibrosis in chronic hepatic disease. This study aimed to validate the diagnostic usefulness of APRI and FIB 4 fir prediction <f cirrhosis.
Patients and Methods: The study was carried out on 77 patients with chronic hepatic disease including 38 cases of cirrliosis and 39 cases of nondrrliosis Detailed clinical history, physical examination and routine and relevant investigation of all patients was done at People 115 Hospital.
Results: At ait-offl.37, APR! > had the value with sensibility, spedficity, positive predictive value, negative predictive value respectively 88.4%, 84.5%, 37,6% and 98.2%. At cut-off 2.29, FIE 4 had the value with sensibility, speafidty, positive predictive value, negative predictive value respectively 82.9%, 77.9%, 30.3% and 96.3%. For predicting arrhosis, APRI (AUC 0.86), mas nonsignificantly better than FIB 4 (AUC 0.84). The Spearman's correlation coefficient betiveen APRI and serum Albumin, total Biliruhun and INR respectively was -0S70, 0.540, 0.484 wliidi is highly significant (p < O.OOODand betiveen FIB 4 and serum Albumin, total Bilirubin and INR respectively was -0.5243, 0.4973, 0.4343 (p < 0.0001).
' Bo mon Xoi long quat - Imong Dai hoc Y Khoa Ptiam Ngoc Thach
Tlic jid lien lac. ThS. BS. Iran Thi Khanh Tuong DT: 0903364690 Emiiif: drkhanhtuongSigmail.com
Hpi nghi Khpa Hpc Ky Thual Tnrang Dai Hpc Y Pham Ngpc Thach 2012
Y Hpc TP. Hb Chi Minh * Tap 16 * Phu ban cua So 1 * 2012 Nghien cun Y hpc
CoTiclusions: APRI and FIB 4 are sunple, mexpensive, invasive and highly smsitii>e and specific }nctlwds fin- prediction of arrhosis. They should be employed routinely in the workup of all patients with dironic Iwpatic
disease to exclude the presence ofdirlwsis.
Keyword: arrhosis, APRI index, FIBi index.
D A T V A N D E
Bien chung cua xo gan la nguyen nhan tu vong chu yeu lien quan den benh gan man.
Xo hoa gan tien trieh din den xo gan la mot bieu hien chinh trong hau het cac benh gan man. Vi vay, giai doan xa hoa gan la mpt yeu to du doan tii vong lien quan den bien chung gan rat co y nglua.
Xo hoa gan la hau qua cua ton thuong man tinh o gan bieu hien boi su tich tij cac thanh phan chat dem ngoai \s bao (Extracellular matrix), xay ra cho hau het cac loai benh ly gan man bat chap nguyen nhan''^ Su tich tu cac thanh phan chat dem ngoai te bao anh hirong den cau true gan do su tao thanh nhiing seo xo hoa va sau do la thanh lap nhiing not tai tao te bao gan dua den xo gan. Xo gan lam roi loan chuc nang te bao gan va can tro dong mau trong gan gay suy te bao gan va tang ap flnh mach aia. Nguyen nhan chinh cua xo hoa gan hien nay la viem gan vi nit man, nghien ruou va viem gan nhiem mo khong do rupu'^'.
Chan doan, dieu tri va tien lupng benh gan man tinh phan lon phu thupc vao miic dp xo hoa gan. Xac dinh su hien dien xo gan ciing rat quan trpng trong dieu tri, tien lupng va tam soat cac bien chung. Sinh thiet gan dupe xem la tieu chuan vang de chan doan miic dp xo hoa gan. Tuy nhien, sinh thiet gan CO 3 han che chinh. (1) Day la mot phuong phap xam lan co bien chiing nhu dau, xuat huyet npi (khoang 0,3%*^) do do ca benh nhan va thay thuoc deu e ngai thuc hien. (2) Sai sot ve mlu mo gan nhu kich thuoc, vi tri lay mau lam anh huong den ket qua mo hpc. (3) Ket qua phu thupc nhieu vao cac nha giai phau benh'^i. Doi vol xo gan ty le chah doan sai co the len den 33%'^'. Tii nhiing han che tren, tinh chinh xac va khach quan cua sinh thiet gan v l n con tranh cai, vi the ngay cang xuat
hien nhieu cac phuong phap chan doan miic dp xo hoa gan khong xam lan, khach quan de han che sinh thiet gan.
Cac phuong tien ch&i doan miic dp xa hoa khong xam lah hien dang dupe ap dung gom do dp dan hoi gan thoang qua bang FibroScan*
(hang Echosens, Phap che tao), cac dSu ah sinh hoa huyet thanh nhu chi so ty Ie AST va tieu cau (APRI), FIB4, chi so PGA (trong gan ruou), Fibrolndex, Fibrometer, Fibrotest va Fibrosure, Hepascore, AdiTesi, Proteomics va Glycomics.
Do dp dan hoi gan la phirong phap khong xam lah dang dupe quan tam va co nhieu hiia hen.
Cac dau ah sinh hoa ke tren trong mot nghien Cliu gpp thuc hien 2011 gom cac nghien ciiu tu 2006 cho thay ket qua tuang doi chinh xac trong cham doan xo hoa, nhung doi hoi nhieu chi so sinh hoa chuyen biet, each tinh toan phiic tap ngoai tni APRI vaFIB4.
APRI va FIB-4 la 2 phuong phap danh gia miic dp xo hoa da ap dung tii lau, day la nhiing phuang phap don gian, re tien, nhanh chong va bat ky CO so y te nao ding eo the thuc hien. Cho d&i nay, mac dii da co nhieu phuang tien hien dai han, APRI va FIB-4 van co gia tri sii dung khong nhiing a nhiing nuoc co dteu kien kinh te kho khan nhu nuoc ta ma ca nhiing nuoc tien tiSi CO dieu kien kinh te han. Tren the gioi cae nghien cuu ve gia tri eiia 2 phuong tien nay van tiep tuc ti& hanh cho den nay*^^'^'. Tai Viet Nam rat hiem nghien ciiu ve APRI va FIB-4, do do chiing toi tien hanh nghien ctiu nay de danh gia gia tri cua 2 chi so nay trong du doan xo gan.
Muc tieu nghien cihi
Xac dmh dp nhay, dp chuyen va cac gia tri tien doan duong, ben doan am APRI va FIB 4 trong du doan xo gan.
So sanh dp chinh xac aia FIB 4 voi APRI trong du doan xa gan.
Hpi nghi Khoa Hpc Ky Thuat Tnrong Dai Hpc Y Pham Ngpc Thach 2012
Nghien cmi Y hpc Y Hoc TP. Ho Chi Minh * Tap 16 * Phu ban ciia So 1 * 2012
Xac dinh su tuong quan giiia diem APRI \'a FIB 4 vod mpt so bieu hien can lam sang (INR, albumin, dp gian tinh mach thuc quan.
Bilirubin...) tren benh nhan xo gan.
DOITI/ONG -PHl/ONG PHAPNGHIEN CUtJ Doi tupng nghien cuu
Tat ca cac benh nhan dupe ehan doan benh gan man dua vao:
Ket qua xet nghiem men gan (AST, ALT) tang hoac cac dau an nhiem vi nit viem gan B, C (HBsAg hay anti HCV) duong tinh tii tren 6 thang va hoae sieu am biang 2 chieu mai thuc hien phat hien co benh ly chu mo gan man.
Thiet ke nghien cuu
Phuong phap nghien oiu cat ngang hen Cliu.
Dan so nghien cuu
Dan so dich: benh nhan tren 18 tuoi co benh gan man 6 Viet Nam
Dan so nghien ciiu: benh nhan benh nhan tren 18 tuoi co benh gan man dupe kham va dieu tri tai khoa npi Tieu hoa BV Nhan Dan 115.
Cac buoc tien hanh
Cac b?nh ttioa tieu chuan chpn benh dupe dua vao nghien ciiu.
Cac benh nhan deu dupe hoi ky ve benh sii, kham lam sang va lam cac xet nghiem theo phieu ghi nhan thong tin benh nhan (phu luc 1):
Benh nhan dupe dteu tra mot so yeu to dieh te hpc: tuoi, gioi, nghe nghiep, tien sii benh ly npi va ngoai khoa, nhiem vi nit B va C, nghien rupu, beo phi...
D^c diem lam sang: vang da, vang mat, phu, long ban tay son, sao mach, lach to, hian hoan bang he...
Dac diem can lam sang: eong thiic mau, dong mau toan bp, BUN, creatinin mau, duong mau, transaminase, bilirubin, gammaglutamyl transferase (GGT), ALP, Albumin, alphafetoprotein (AFP).
Tinh gia tri FIB4 va APRI theo 2 cong thiic
FJB 4-Tuoi. nam) X .4STiU I) Tieucau(10')x ^ALTiV! {)
AST level LLN * Platele: counts (10 •• L)
*ULN = Upper Level of Normal (gioi han tren binh thuong).
Lay ULN ciia ASTla 30 6nam va 19 aniifsi.
Cac dau an huyet tiianh oia vi nit viem gan B, C (neu chua dupe lam truoc do) nhu HBsAg and HCV, HCV RNA neu anti HCV duong.
Npi soi thue quan da day ta trang phat hien dan flnh mach thue quan-tam phinh vi. Sieu am bung 2 ehieu thong thuong khao sat cau true nhu mo gan, bo gan va kich thuac lach.
Xa gan dupe chan doan xac dinh khi thoa 2 tieu chuah sau:
Co 1 trieu chiing cua tang ap ciia (gian flnh mach thuc quan, hian hoan bang he, lach to, tieu eau giam, sieu am eo tang ap finh maeh aia) va 1 trieu chiing eiia hpi chiing suy te bao gan (vang da, sao mach, long ban tay son, nii hoa tuyen vii, phii, albumin giam, INR tang...) va sieu am hay CT scan cho thay benh ly ehii mo gan man.
Fibroscan dio ket qua F4 Xu ly va phan tich so lieu
Tinh dp nhay, dp chuyen, gia trj hen doan duong va am theo tung gia tri diem cat (cut-off) aia APRI va FIB4 chon ra gia tri diem cat tot nhat.
Xac dinh dp chinh xac ciia APRI va EFB 4 trong du doan xa gan b5ng phan tieh duang cong ROC (Receiver Operating Characteristic) gom dien tich duoi duong cong (AUC; Area Under de ROC Curve), khoang tin cay (KTC.
Hpi nghi Khoa Hpc Ky Thuat Truong Dai Hpc Y Pham Ngpc Thach 2012
Y Hoc TP. Hb Chi Minh * Tap 16 * Phu ban cua So 1 * 2012 Nghien c u u Y hpc
Danh gia moi tuong quan giira cac 2 bien so bang tuong quan thii bae Spearman (Spearman's rank correlation), tinh he so tuong quan r va p.
r = l-6Edi=/(n(n2-l))
d: la su khac biet ve thii bac thong ke giiia cac bien so tuong iing.
Ket qua co y nghia khi p < 0,05.
KETQUA
Trong thai gian tix thang 2/ 2010- 2/2011, chung toi thu thap dupe 77 ca dii tieu chuan ehan doan.
Bdng 1: Dgc diem dan so nghien cun
€)acdi4m Tuoi Gidi (nam/nO)
AST (lU/L) Gian TMTQ 6t> 1
II III Tilu cau (lO'/L)
Albumin g/dl Biiiiubin toan phan
(mg/dl) INR
Khong xo gan (n=39) 44.3 ± 12.2
21/18 54,6 ± 16.2
0 0 0 234±98 39 ±15 0.9 ±0.5 0.9 ±0.45
Xo-gan (n-33) 55.3 ±11.5
23/15 36.4 ±9.8
13 8 2 127±65 29±13 2.18*1.32 1.89 ±1.02
P
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
Bdng
APRi n B 4
2: APRI va f IB-4 troii^ du dodn xo gan f}|4m
cat (cut- off) 1.37 2.29
AUC
0.86 0.84
95%
Cl 0.79- 0.93 0.77- 0 91
P
<0.00 1
<0.00 1
0 9 nhjy
88.4 829
0 6 chuyen
84.5 77.9
PPV
37.6 30.1
NPV
98.2 96.3 Bang 3; Moi tirang quan giUa APRI, FIB 4 voi mdt so'bieu hien can lam sang tren BN xa gan
Albumin g/dl
Bilirubin TP (mg/dl)
INR r FIB4 D.5243 14971
1.4343 APRI
0570
0.540
0.4843 95%CI FIB4 (-0.6732)- (-0.4436) 0.3707- 0.5446 03164- 0 4025
APRI (-0.6726)
(-0.4483) 0.4118- 0.6473 03466- 05016
P
=0.00C 1
<0.000 1
=0.000 1
BANLUAN
Dac dirai dan so nghien ctiu
Ty le benh nhan nam trong nhom nghien Cliu la 58,6%, ty le nay eao hon khong dang ke trong nhom bi xo gan 60,5%. AST himg binh ciia ca 2 nhom xo gan va khong xa gan deu tang nhe, trong do AST cua nhom khong xo gan cao hon CO y nghia thong ke so vai nhom xa gan.
Dae diem nay phu hpp voi y van. Men gan thuong tang nhe duoi 300UI/1 doi voi berth gan man. Tieu cau, albumin mau giam trong nhom xa gan va khac biet co y nghia so voi nhom khong xa gan. Nguoe lai. Bilirubin toan phan va INR tang trong nhom xo gan.
Gia tri cua APRI voi FIB-4
Sinh thiet gan van la mot tieu chuan vang tiong chain doan xo gan. Tuy nhien, nhat la 6 nuac ta, sinh thiet gan van chua dupe lam trong hau het eae benh vien. Ben canh do, viec phan tich ket qua sinh thiet gan van con nhieu van de.
Vi the, ngay ea a eae nuoe phat trieh, nhieu tac gia van trien khai nhieu nghien eiiu nham tim ra bien phap chah doan tinh tiang xo gan khong xam lah nhu APRI va FIB 4.
Voi gia tri diem eit eiia APRI la 1,37 eo dp nhay va dp chuyen tiong chan doan xo gan deu ti^n 80% (88,4 % va 84,5%). Trong khi do FIB 4 vtii gia tri diem cat 2,29 cho dp nhay va dp chuyen Ian luot la 82,9% va 77,9 %. AUC ciia APRI lon han eiia FIB 4 eho thay APRI eo gia tri du doan xo gan tot hon FIB4, tuy nhien su khac biet khong co y nghia thong ke (p>0,05). Nghien ctiu ciia Roxana 5irli'^^i thye hien 2010 tien 150 benh nhan viem gan C man cho thay voi diein APRI= 1,38 CO dp nhay dp chuyen tiong chah doan xo gan IMI lupt la 99,3% va 83%; voi diem FIB 4 = 2,3122 eo dp nhay, dp chuyen Ian lupt la 80% va 77,8%. Gia tii du doan xo gan eiia APRI (AUC = 0,909) tot hon so voi FIB 4 (AUC=0,842).
Mpt nghien aiu gom 2007*'"' cho thay vdi gia tri diem cit la 1, APRI eho dp nhay, dp ehuyen tiong d\i doan xo gan la 76% va 71%. Do tieu chuah chem doan xo gan khac nhau, dac diem dan so nghien ctiu khac nhau, nen viee so sanh
Hpi nghi Khoa Hpc Ky Thuat Truong Dai Hpc Y Pham Ngpc Th^ch 2012 15
Nghien cuu Y hpc Y Hpc TP. Hb Chi Minh * Tap 16 * Phu ban ciia So 1 * 2012
ket qua giua cac nghien ciiu la khap khenh. Tuy vay, ket qua nghien ciiu ciia chiing toi ciing tuong duong so voi ket qua eiia cae nghien a i u nuoc ngoai va eho thay APRI va FIB 4 thue su CO gia tri trong du doan xa gan, co the ap dung tiong tiiue hanh lam sang, dae biet co gia hi tot trong chan doan loai trii xo gan do co gia tri tien doan am cao deu tien 95%.
Moi tuong quan gjiia mpt so dau hieu can Iam sang voi APRI va FIB4
Ket qua nghien eiiu aia chiing toi cho fhay APRI va FIB 4 co moi tuong quan nghich vai Albumin mau (r = - 0,570 va - 0,5243), co moi tuong quan thuan voi Bilirubin toan phan (r = 0,540 va 0,4971) va voi INR (r = 0,4843 va 0,4343).
Albumin, INR va Bilirubin toan phan la cac chi so giup danh gia miie dp suy gan trong bang diem Child-Pugh Ket qua tren cho fhay diem APRI hay FIB 4 cang cao Albumin cang tiiap tiong khi do Bilirubin toan phan va DMR cang cao, CO nghia la suy gan cang nang.
KET LUAN
Cac chi so APRI, FIB4 co gia hi kha tot tiong du doan xo gan, dac biet giiip loai tru xa gan.
Do eae thong so nay tinh toan kha don gian, khong xam lari, re tien nen chung ta eo the ap dung rpng rai trong thuc hanh lam sang nhat la
6 nhung nai khong eo dieu kien lam sinh thiet hay do dp dan hoi gan.
TAILIEUTHAMKHAG
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115(2): 209-218,
2 Bourliere M. Fenararvja G. Rgxni C (2006) Vafidabon and CDu^jan-scBi of indexes for fibroas and drrhoas prediction in chroiiic hepatitis C patients: pre^wsal for a pragmatic s^)proad) dasafieatKHi withoul liver bwpaes. I Viral Hepal 2006 Octl3(10)65»-70.
3 Fnedman SL. (2003) Liver fibrosis - from bendi to bedside. ], HepaloL38(SuppL 1)538-553
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5 Mona H.l and Pmzari! M (20091 Reversal of liver Fibroas. Saudi 1
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8. Prati D, et aL (2002) Updated Linuts for EWemuning Nonnal ALT, A m bitem Med,137:l-10,
9 Regev A, et aL (2002) Samphng error and intr»<)bseiver variation m liver biopsy in patients witti dironic HCV infectioR Am. J Gastroentero]„-972614-2618
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Hpi nghi Khoa Hpc Ky Thuat Tnrong Dai Hpc Y Pham Ngpc Thach 2012
