Thietkenghien ctfu: md ta hoi cUu, cac xet nghiem ALT va ALP dupe truy xuat tU phan mem lUu trU dU lieu ket qua xet nghiem can lam sang tai khoa Hda sinh, thong tin trong benh an dup[r]
(1)(2)(3)(4)(5)(6)Tdm seat ton Hwang gan thuoc thong qua ket qua xet nghiem can lam sang
tqi Benh vien Huu Nghi
Tran Thj Ngoc\Tran Ngan Ha1, Nguyen Khac Dung1,
Tran Thu Thuy1, Nguyen Thj Phuong Ngoc2, Hoang Thj Minh Hien2,
PhamThj Dieu Huyen2, Nguyen Hoang Anh1
'Tn/dng Dai hoc DUpc Ha Npi 2Benh vien HCfu Nghi SUMMARY
This study revised data of inpatients at Huu Nghi hospital to determine incidence of drug-induced liver injuries (DILI) based on laboratory database of alkaline phosphatase (ALP), alanine aminotransferase (ALT) laboratory signals and the descriptions of DILI Screening was performed with the help of biochemistry database followed by detail medical record review for suspected cases and the assessment was made in accordance to the definition of DILI Of 369 patients with abnormal liver lab tests, 22 suspected drug-induced liver injuries (6.0%) cases were identified The incidence of DILI among inpatients was 22/20088 (0.11 %) Antibiotics were the leading therapeutic class implicated in DILI, in which flouroquinolones like levofloxacin, ciprofloxacin were of most common The severity of liver injuries in most of the casess were found serious and life-threathening, with short lag time of less than one week and without clear clinical symptoms DILI took about one month to be resolved Results of this study suggested the usefulness of new method to detect incidence of DILI in routine practice
TCtkhoa: ALP, ALT, ton thaong gan thuoc, DILI, tarn sodt Dot van de
Ton thoong gan thuoc (DILI) la mot van de an toan thuoc dupe quan tarn dac biet hien nay, ty le dao dpng tU - 10% cac phan Ung co hai thuoc gay ra, dong thdi la ly quan trpng nhat dan den rut so dang ky va dinh chl Idu hanh thuoc tren thj trudng [6], [9].Tren the gidi, cac nghien cdu danh gia DILI da dupe tien hanh tai Phap, Tay Ban Nha, Australia, vdi nhieu hudng tiep can khac [3], [8], [9] Tai Viet Nam, viec danh gia DILI van han che va chua cd nghien cUu nao dupe thuc hien theo hudng tiep can tarn soat cac xet nghiem can lam sang de sang Ipc cac ca ton thuong gan Hon nUa, thuc hanh lam sang, cac ca ton thuong gan thudng dupe phat hien chu yeu bdi bac si hoac dieu dudng thong qua dien bien lam sang cua benh nhan va sp tham gia cua dupe si lam sang han che Vi vay, de md rpng phuong phap phat hien DILI va tang cUdng vai trd cua dupe si lam sang, dong thPi ho trp phat hien ton thuong gan thong qua sang Ipc xet nghiem enzym gan chung tdi thpc hien nghien cUu
nay vdi muc tieu phat hien nhUng bat thudng chUc nang gan thong qua ket qua xet nghiem can lam sang va phan tich dac diem ton thuong gan nghi ngd thuoc tren nhUng benh nhan cd bat thudng chUc nang gan tai Benh vien HUu Nghj
Doi tirong va phuong phap nghien cuv
Doi twang nghien cdfu
Tat ca cac xet nghiem enzym gan alanin aminotransferase (ALT) va alkalin phosphatase (ALP) cd lam xet nghiem tU 01/01/2015 den 31/12/2015 va benh an cua nhUng benh nhan nghi ngd cd ton thuong gan thudc
Phuang phap nghien cWu
Thietkenghien ctfu: md ta hoi cUu, cac xet nghiem ALT va ALP dupe truy xuat tU phan mem lUu trU dU lieu ket qua xet nghiem can lam sang tai khoa Hda sinh, thong tin benh an dupe thu thap theo mau phieu thu thap thong tin benh nhan bao gdm: cac thong tin hanh chinh, xet nghiem enzym gan va cac gia trj xet nghiem khac, dien bien lam sang va cac thudc benh nhan sUdung thdi gian nam vien
(7)B A I N G H I E N C L T U
Khoa Hoa sinh
Khoa Dirge va Phong liru
tru h6 so'
Tat ca cac xet nghiem ALT va ALP
Xet nghiep ALT, ALP thoa man tieu chuan lira chgn
Benh nhan thoa man dinh nghTa
Dinh nghTa ton thirong gan
Benh nhan thoa man tieu chuan bo sung
Tieu chuan bo sung
Thu ttiap thong tin benh nhan ~~~^D
c Danh gia
DILI theo thang RUCAM Hinh So quy trinh tarn
Qua trinh tarn sodt ton thuong gan thuoc - Tieu chuan Ida chpn: tat ca cac xet nghiem ALT va ALP cua benh nhan nbi tru co lam xet nghiem tU 01/01/2015 den 31 /12/2015
- Dinh nghia ton thuong gan: Vdi benh nhan cd ca xet nghiem ALT va ALP: ton thuong gan la ALT > 2Ni hoac ALP > 2N2 VPi benh nhan chi cd xet nghiem ALT va khdng cd xet nghiem ALP: ton thuong gan dupe xac djnh ALT > 5Ni Trong do: Ni, N2 la gidi han tren binh thudng cua xet nghiem ALT va ALP [3], [7], [8], [9]
- Tieu chuan bo sung:
+ Tieu chuan 1: loai nhUng benh nhan khdng cd it nhat gia trj xet nghiem ALT trudc gap bat thudng < 2Ni va gia trj ALT sau gap bat thudng <2Ni
+ Tieu chuan 2: loai nhUng benh nhan tUvong khdng tiep can dupe benh an
- Quy trinh tarn soat:
Tai Khoa Hda sinh: lay thong tin xet nghiem ALT va ALP cua benh nhan tUngay 01/01/2015 den 31/12/2015, tien hanh tarn soat dua tren tieu chuan lUa chpn va dinh nghia ton thuong gan, tieu chuan bd sung
Tai Khoa Dupe: tU danh sach nhUng benh nhan cd ton thuong gan, tien hanh soat ma lUu trUtU benh an dien tU, xac djnh cac benh an cd thong tin lien quan den ton thuong gan (do mot benh nhan
sodf ton thuong gan thuoc cd the cd nhieu benh an)
Tai phdng lUu trU ho so benh an: thu thap benh an va truy xuat thong tin benh nhan
Danh gia mdi quan he nhan qua giUa thudc nghi ngd va ton thuong gan: sU dung thang RUCAM cap nhat nam 2015 de danh gia mdi quan he nhan qua giUa thudc nghi ngd va ton thuong gan xay tren benh nhan [5] Mdi thudc nghi ngd se dupe cho diem theo tieu chi: thdi gian bat dau dung thudc/ngUng thudc, dien bien ALT/ALP sau ngUng thudc, yeu to nguy co, thudc dung ddng thdi, nguyen nhan khac cd the gay ton thuong gan, thong tin ve ton thuong gan thudc dupe ghi nhan y van, dien bien cua ton thuong gan tai sU dung thudc nghi ngd (neu cd) Can cU vao tdng diem cua tieu chi de quy ket mdi quan he nhan qua giUa thudc nghi ngd va ton thuong gan theo mUc: "chac chan la DILI" (> diem), "cd kha nang la DILI" (6 - diem), "cd the la DILI" (3 - diem), "khdng nghT den DILI" (1 - diem) hoac "loai trU DILI" (< diem) NhUng thudc ngUng trudc thdi diem bat thudng > 15 (doi vdi ton thuong te bao gan) va > 30 (doi vdi ton thuong mat hoac ton thuong hdn hop), trU amoxicilin/ clavulanat [2], [4] va nhUng thudc tiep tuc sCf dung sau enzym gan da giam se khdng dupe dua vao danh gia theo thang RUCAM cap nhat nam 2015
Chi tieu nghien c(Su:
- So lupng benh nhan dupe nhan djnh nghi ngd
(8)BAl N G H I E N C U D
co ton thuong gan thoa man djnh nghTa ton thuong gan va cac tieu chi bo sung dupe dua nghien cUu
- Danh gia mdi quan he nhan qua giUa thuoc nghi ngd va ton thuong gan tren nhUng benh nhan co ton thUOng gan theo thang RUCAM cap nhat nam 2015
- Ty le gap ton thuong gan nghi ngd thuoc (nhUng trUdng hop dupe danh gia d mUc "cd the", "cd kha nang" va "chac chan" theo thang RUCAM cap nhat nam 2015 dupe coi la ton thUOng gan nghi ngd thuoc)
- Dac diem ton thUOng gan nghi ngd thuoc theo thang RUCAM cap nhat nam 2015: Phan loai mUc nang cua ton thuong gan theo thang phan
loai cua WHO [10], thdi gian tiem tang, thdi gian hoi phuc
- Dac diem thudc gay ton thuong gan theo thang RUCAM cap nhat nam 2015: phan loai thudc theo nhdm tac dung dupe ly dua tren ma ATC cua thudc [1],[11]
Xd ly so lieu: so lieu dupe ma hda, nhap lieu va xU ly bang phan mem Microsoft Excel 2016 Ket qua dupe xU ly thong ke md ta va tinh toan theo ty le phan tram
Kef qua nghien cuv
Dgc diem benh nhan nghi ngd co ton thaong gan
Dpa tren tieu chuan lUa chpn, tU 01/01/2015 den 31/12/2015 sang Ipc dupe 36.771 xet nghiem ALT va
53 (77,9%) BN co xet nghiem ALT > 2N|
hoac ALP >2N2 va khong
co gia tri ALT tnroc hoac sau hat thuong
<2N,
3 (20.0%) BN tti vong
10 831 (97,3%) BN khong co
xet nghiem ALT > 5Ni
274 (91.0%) BN co xet nghiem ALT >
5N| va khong co gia tri ALT truoc hoac sau bat thuong
<2N,
2 (7,4%) BN h i vong
Hinh Ket qua tarn soat ton thUOng gan
(9)BAl NGHIEN CLTU
Bang Dae diem benh nhan nghi ngdeo ton thuong gan
Dac diem So lupng Ty le % (n=37)
Tuoi
Tuoi trung binh: 74,1 ±9,1
Gia tri Idn nhat: 93 Gia tri nhd nhat: 52
Giditinh
Nam 34 91,9
Nuf 8,1
Khoaphdng
Ung bifdu 21,6
Ho hap di ilng 16,2
Than tiet nieu-Loc mau 10,8
Benh nhiet ddi 8,1
Tim mach 8,1
Than kinh 8,1
Hoi sure tich cue 5,4
Truyen nhiem 5,4
Cac khoa khac 16,2
Chan dodn binh chinh
BiTdu tan sinh (C00-D48) 13 35,1 Benh he ho hap (J00-J99) 24,3 Benh nhiem trung va ky sinh trung
(A00-B99) 10,8
Benh he tuanhoan (100-199) 10,8 Benh he sinh duc-tiet nieu
(N00-N99) 5,4
Cac benh ly khac 13,5
881 xet nghiem ALP cua benh nhan npi tru tai Benh vien Hub Nghi, thong Ung vdi 11.809 benh nhan chia benh nhan nhdm: nhdm co (Jong thdi ket qua xet nghiem ALT va ALP (677 benh nhan) va nhom chi co ket qua xet nghiem ALT (11.132 benh nhan) Doi chieu vdi djnh nghia ton thuOng gan, 369 benh nhan thoa man djnh nghTa (chiem 3,1%), bao gom 68 benh nhan nhom (chiem 10,0%) va 301 benh nhan nhom (chiem 2,7%) NhUng benh nhan <JuOc tarn soat tiep theo tieu chuan bo sung thu dope 15 benh nhan nhom (22,1%) va 27 benh nhan nhom (9,0%) Tiep tuc ap dung tieu chuan bo sung 2, loai them benh nhan nhom va benh nhan nhom NhP vay, ket qua co 37 benh nhan thoa man dupe dua vao nghien cUu, co 12 benh nhan thupc nhom va 25 benh nhan thupc nhom
Trong 37 benh nhan nghi ngd co ton thuong gan, nam giPi chiem da so (91,9%), vPi tuoi trung
binh la 74,0 (± 9,1), 97,3% benh nhan tren 55 tuoi Khoa Ung budu va khoa Ho hap Dj Ung la khoa co lupng benh nhan nhieu nhat, ty le Ian lupt la 21,6% va 16,2% TUOng Ung vPi nhom benh chinh la budu tan sinh (35,1%) va benh he ho hap (24,3%) Tong cpng 423 thuoc da dupe sU dung tren 37 benh nhan nghi ngd cd ton thUOng gan thuoc Vdi so thuoc trung binh dupe sd dung la 11,4 thuoc/1 benh nhan Nhdm thuoc chiem ty le nhieu nhat la nhdm thudc dieu trj benh gan (9,7%) Moi benh nhan dUOc phat hien tang enzym gan hau het deu dupe sU dung cac thudc trj benh gan vdi hoat chat chinh la arginin (biet dupe hay dung la Euformin, Apharmincap) va I - ornithin -1 - aspartat (biet dupe hay dung la Hepaur, Qyliver) Khang sinh nhdm quinolon (6,9%), cephalosporin/carbapenem (6,4%) va cac penicillin (3,8%) la cac nhdm thuoc dupe sU dung bien d cac benh nhan ndi tren
Danh gia moi lien quan giiita thuoc nghi ngd va ton thUctng gan
Trong 423 thuoc, chung toi loai trU 315 thudc khdng thda man tieu chuan danh gia cua thang RUCAM cap nhat nam 2015 Con lai 108 thuoc (25,5%) dUOc dUa vao danh gia, cho ket qua 31 cap thudc - ton thuong gan (chiem 28,7%) tuong Ung vdi 22 benh nhan dupe danh gia la cd mdi lien quan giUa thuoc va ton thUOng gan (bang 2)
Bang Ket qua danh gia ton thuong gan thuoc
Diem Mile danh gia
So cap thuoc -ton thuong gan
Ty le (%) (n=108)
< diem Loai tru" DILI 32 29,6 - diem Khdng nghi
den DILI 45 41,7
3 - diem Co the la DILI 31 28,7 - diem Co kha nang
la DILI 0
> diem Chacchan la
DILI 0
Ty le gap ton thuong gan nghi ngd thuoc
Ty le gap ton thUOng gan nghi ngd thuoc tren tong so benh nhan cd xet nghiem chUc nang gan bat thudng la 22 benh nhan/369 benh nhan (6,0%)
Ty le gap ton thuong gan nghi ngd thudc tren tong so benh nhan npi tru cua benh vien nam 2015 la 22 benh nhan/20.088 benh nhan (0,11 %)
Ty le gap ton thuong gan nghi ngd thuoc tren tong so xet nghiem ALT va ALP cua benh nhan npi
(10)tru la 22 benh nhan/37.652 xet nghiem ALT va ALP (0,058%)
Dgc diem ton thuong gan nghi ngd thuoc
Dac diem ton thuong gan dPOc danh gia tren 22 benh nhan co cac cap thuoc - ton thoong gan danh gia mile "co the" Oac diem ton thUOng gan bao gdm: mbc ton thoong gan, thdi gian tiem tang va thdi gian hoi phuc cua ton thoong gan dude mo ta bang
Bang Dgc diem ton thUOng gan nghi ngd thuoc
Dac diem So lufcfng benh nhan (n=22)
Mile ton thtfdng gan theo WHO
Mtfcdol (nhe): ALT hoac ALP 1,25N - 2,5N
Mile (trung binh): ALT hoac ALP 2,6N-5N
Mufc (nang): ALT hoac 12 ALP 5,1N - ION
Mufc (de dpa tinh mang): ALT hoacALP>ION
Thdi gian tiem tang*
< 1tuan 17
1 tuan den thang 10
>1thang
Thdi gian hoi phuc**
Sau 0-1 tuan
Sau tuan -1 thang 15
Sau1thang
Khong ro***
Ghi chu: N la gidi han tren binh thudng
* Thdi gian tiem tang Id khodng thdi gian td luc bat dau sddung thuoc nghi ngd den khiphdt hien bat thudng ket qua xet nghiem chdc nang gan
**Thdi gian hoi phuc la khoang thdi gian td enzym gan dgt dinh den enzym gan trd ve binh thddng (nhd hon gidi hgn tren binh thudng)
***Khdng ro: gom trUdng hop ALT gidm xuong dudi 2NI vdng thdng nhUng sau khdng cd thong tin ve gia tri xet nghiem enzym gan
Mile ton thoong gan chu yeu mile nang va de dpa tfnh mang (20/22 benh nhan nghi ngp co DILI) Tuy nhien, da so cac trOdng hop ton thuong gan deu khong co trieu chdng lam sang dien hinh nhd man ngila, vang da, tang bach cau toan, mot so trdPng hop co sot, met moi Thdi gian tiem tang ngan, dao ddng t i l vai den tuan, trddng hop thdi gian tiem tang keo dai nhat la gemcitabin
va carboplatin (hda chat chdng ung tho) Thdi gian hoi phuc da so la sau tuan den thang (15/22 benh nhan nghi ngd cd DILI) Cd 4/22 benh nhan nghi ngd cd DILI hoi phuc sau thdi gian thang, trPdng hop hoi phuc mudn nhat la sau 102 (khoang thang)
Dgc diem thuoc gay ton thuong gan
Phan loai cac thuoc nghi ngd gay ton thdong gan theo nhdm tac dung dupe ly dupe trinh bay bang
Bang Dgc diem nhdm thudc gay ton thuong gan
m a H I v MhniYi t h n n r NIIUIII U I U U L
So cap thuoc ton thuong
gan
Ty le (%) (n=31)
J01M Khang khuan nhdm quinolon 16,1
J01D
Khang khuan nhdm betalactam khac (cephalosporin, carbapenem)
3 9,7
J01C Khang khuan betalactam, nhdm penicillin 2 6,5 J01F Khang khuan nhdm macrolid 6,5
J01X
Cacthuockhang khuan khac (fosfomycin, metronidazol)
2 6,5
N05B Thuoc giai loau 9,7
N02B Thudc giam dau, nhiet khac (paracetamol) 9,7 B01A Thudc chdng huyetkhdi 6,5 L01X
Cac hda chat chdng ungthu khac carboplatin, gemcitabin)
2 6,5
Cac nhdm khac 29,0
Khang sinh la nhdm thuoc dupe ghi nhan gay ton thuong gan nhieu nhat (14/31 cap thuoc - ton thdong gan) Thdng tin ve tilng thuoc cu the gay ton thdong gan dPOc tong hop bang Trong ciprofloxacin, diazepam, paracetamol (dang don chat hoac phoi hop) la hoat chat cd tan suat gay ton thdong gan nhieu nhat lien quan den ca ghi nhan bien cd tPOng dng vdi mdi hoat chat Ben canh do, amoxicilin/clavulanat, levofloxacin, clarithromycin cung cd tan suat gap ton thdong gan (2 ca ghi nhan bien co tuong ilng vdi mdi hoat chat) cao hon cac thudc lai {bang 5)
(11)Bang DO lieu Hen quan 22 benh nhan nghi ngdco DILI
Tuoi Gidi Thudc nghi ngd Thdng tin tren SPC Trieu chUng lam sang Gia trj dinh
MUc dp ton thUOng gan Tuoi Gidi Thudc nghi ngd Thdng tin tren SPC Trieu chUng lam sang
ALT ALP
71 Nam Thuoc dOng y Khong rd Khdng 284 Nang
77 Nam Fosfomycin Co: khdng phd bien Khong 231 Nang
85 Nam Ciprofloxacin Cd: khdng phd' bien Khdng 236 Nang 73 Nam Clarithromycin Cd' khnnn nhn hipn L U , fXIIUMLJ U I I U U l L I f Khdng 323 Nang 73 Nam
Cpftriaxnn
U L LI IUAUI
f 6* hiem nan L.U IIIX.MI U U U
Khdng 323 Nang
80 Nam Paracetamol Co: qua lieu Met khd thd va mo I' L L , i\l I U L I I U ; VCJ I I I U
hoi (benh ly) 1490 Oedga tinh mang
58 Nam
finrnflfiY^r in V.IUI U l I U A U L I I
f h' khhnn nhn hipn
V.U l U I U I I U U I I U U l U l l BN met, the trang
gay, an kern 274 Nang
58 Nam Amoxicilin/
flaviilanat
L I U V U I U I I U L
Co: khong bien
BN met, the trang
gay, an kern 274 Nang
70 Nam f inrofloxacin L I Ul U II U A { 1 L 1
f h- khhnn nhh hipn
L U IXIIUIIli U I I U UIL-IT
Khdng 234 Nang
85 Nam Amoxifilin/ Ml 1 U A L I III/
Clavulanat Co: khong bien Khdng 210 Nang
87 Nam f pfonprazon fhL-U U I I U U l u- nhh hipn 11 Khdng 246 Nang 87 Nam
D i a P n s m
L/ICILCUQI11 fh' hihm nan L.U 111 L 1 U u U
Khdng 246 Nang
63 Nam
1 CI u L L LCI 1 Ul • Codein
fh- nna lihn U U m i l U U u I I C U paracetamol
Khdng 508 Qe dpa tinh mang
63 Nam Aspirin Khong (co mota tren trang
1 ivertoxl LI l L L U A !
Khdng 508 Qe dpa tinh mang
63 Nam
Nitrnnlvcprin M i l l U U y X-l_ II
Khhnn IU I U I I U
Khdng 508 Qe dpa tinh mang
63 Nam
Carbamazepin Co: hiem gap
Khdng 508 Qe dpa tinh mang
66 Nam Clarithromycin Cd: khdng phd' bien ^ht an
khm ri ran nhp
JUL, dll K c l l l , 11 idU pile
nann niam fhhnh lul I I C I I I U u i u i i i I U C I I I I lyj
219 Nang
84 Nam Enoxaparin Cd: bien Khdng 557 De dga tfnh mang
84 Nam
n l MlUUdlUll f h 'uu I d l pilU Ulcll rat nnh hipn
Khdng 557 De dga tfnh mang
74 Nam AciH tranpxamir
ML 1LJ L I U I I U A U I I I I l
Khhnn
l\l Ul u
Thp trann Irt mrt cnt
1 It LI til IU IU 11IU, oUL ° f nipmmarnhrft
J\J V_, l l l v l l l IIIUX 11 1U L, thieu mau
223 Nang
78 NO Levofloxacin Cd: bien Khdng 1490 De doa tinh mang
78 Nam Paracetamol/
Codein
Cd: qua lieu
paracetamol Khdng 872 80 Dedga tinh mang
64 Nam Gemcitabin Cd: rat phd bien Khdng 665 137 Dedga tinh mang 57 Nam Carboplatin Khdng (cdmdta tren trang
Livertox) Khdng 3020 De dga tinh mang
65 Nam Diazepam Cd: hiem gap Khdng 410 De dga tinh mang
85 Nam Omeprazol Cd: khdng phd bien Sot 224 Nang
79 Nam Enalapril Cd: hiem gap Khdng 124 Trung binh
72 Nam Diazepam Cd: hiem gap Khdng 309 Nang
67 Nam Levofloxacin Cd: phd' bien Sot 182 Trung binh
67 Nam
Meropenem Cd: phd' bien Sot 182 Trung binh
'Thdng tin tren tdtdm tat dgc tinh san pham ve ton thuong gan, dupe tra tren EMC [13] (neu khong cd tren EMC, tra tren FDA [12])
(12)Ban luqn
Ket qua dang chu y nghien cufu la khao sat dupe ty le gap ton thUPng gan nghi ngd thuoc va ghi nhan cac thuoc co the gay ton thuang gan cung nhu mo ta dupe dac diem ton thUPng gan nghi ngd thuoc gay Ty le gap ton thuong gan thuoc tren tong so benh nhan cd bat thudng chile nang gan nghien cilu cua chung tdi la 6,0%, tuong tu ket qua da cong bo trudc tai Phap nam 2000 [3], Tay Ban Nha nam 2010 [8] va Australia nam 2013 [9] vdi ty le tUOng ling la 6,8%, 6,8% va 6,4% Nguyen nhan cua sil khac tUdng doi nhd gida cac nghien cilu cd the khac biet ve quy md va djnh nghia ton thuong gan Chung tdi sil dung djnh nghia ton thuong gan cd mile gidi han cao hdn cac nghien cilu khac (> 5Ni) nen cd the bo qua nhilng trudng hop ton thuong gan ma enzym gan tang dUdi 5Ni dan den ty le gap ton thuong gan thuoc tren tong so benh nhan cd bat thudng chile nang gan cd the thap hon Ngoai ra, viec ap dung thang RUCAM cap nhat nam 2015 de danh gia ton thuong gan thuoc nghien cilu han che thieu dU lieu xet nghiem dan den ket qua cd the thap hon cac nghien cilu khac
Ty le gap ton thuong gan thuoc tren tong so benh nhan npi tru cua benh vien nam 2015 la 22 benh nhan/20088 benh nhan (0,11%) cao hon so vOi ty le nghien cilu cua Sistanizad va cpng sU nam 2013 tai Australia la 30 benh nhan/100.000 benh nhan (0,03%) [9] Nguyen nhan chinh cua sU khac biet la dac thu benh nhan cua moi benh vien la khac nhau, tai Benh vien HOu Nghj benh nhan phan Idn la ngUdi cao tuoi, do, tai benh vien d Australia benh nhan thupc nhieu nhdm doi tupng khac (ngUdi trUdng thanh, ngudi cao tuoi ) Nhdm doi tupng ngudi cao tuoi la nhdm doi tupng nhay cam hon vdi cac phan ilng cd hai cua thuoc, dong thdi tinh trang benh ly philc tap hon, sil dung dong thdi nhieu thuoc han do ty le gap ton thuong gan thuoc tinh tren toan the benh nhan npi tru cua Benh vien HUu Nghj se cao hon
Khang sinh la nhdm thuoc dupe ghi nhan gay ton thuong gan nhieu nhat (14/31 cap thuoc - ton
thuong gan), thupc ve nhom penicilin, betalactam khac, quinolon, macrolid va nhdm khang khuan khac Quinolon la nhom khang sinh chiem ty le cao nhat la 5/14 cap thuoc - ton thuong gan (35,7%) tong so cac khang sinh gay DILI Ramirez va cpng sU (2010) tien hanh nghien cilu tren CP sd dU lieu tai Tay Ban Nha cho thay ty le DILI khang sinh la 19,5% Con theo nghien cilu cua Sistanizad va cpng sUtai Australia (2013), ty le len tdi 65% Khang sinh dupe ghi nhan gay DILI nhieu nhat cac nghien cilu deu la amoxicilin/ clavulanatI8], [9]
Mile dp ton thUOng gan theo WHO d mile nang va de dpa tinh mang la 20/22 benh nhan nghi ngd cd DILI, dinh gia trj ALT cao nhat la 3020 Ul/ml (gap 75,5 Ian gidi han tren binh thudng) Trong do, da so cac benh nhan khong cd trieu chilng lam sang cua ton thuong gan nhu sot, vang da, ngila, met mdi, tang bach cau Ua acid NhUng trUdng hop neu khdng dupe can thiep kjp thdi se cd nguy co dan den suy gan va t i l vong VI vay, thuc hanh lam sang, can bp y te can lUu y han den xet nghiem enzym gan va kiem tra, danh gia chat che nhUng trUdng hop cd tang enzym gan de cd bien phap xil trf phu hop Viec xac djnh thuoc nghi ngd gay ton thUOng gan sau rat quan trpng de dU phdng khdng tai xuat hien phan ilng cd the benh nhan vd tinh dung lai thuoc
Lan dau tien nghien cilu tarn soat ton thuong gan thuoc thdng qua ket qua xet nghiem can lam sang dupe thile hien tai Viet Nam, do khdng tranh khdi mot so han che ve hinh thile trien khai (hoi cilu, khdng can thiep) va chat lupng dU lieu (cu the chua day du, benh nhan cd nhieu benh mac kern va sil dung dong thdi nhieu thuoc) Tuy nhien, ket qua thu dupe da tao co sd cho cac phan tich giam sat tien cilu day du hon thdng qua hoat dpng dupe lam sang ve ton thuong gan thuoc ndi rieng va phat hien phan ilng cd hai cua thuoc ndi chung thong qua tarn soat cd chu dich cac ket qua xet nghiem can lam sang qua trinh dieu trj cua ngUdi benh
Ket luqn
Ty le gap ton thuong gan cd the thuoc tren tong so benh nhan cd bat thudng chile nang gan la 6,0%, tuong ilng vdi 0,11 % benh nhan dieu trj npi tru
(13)trong Benh vien HOu Nghj Khang sinh la thuoc thudng dupe ghi nhan gay ton thuong gan, hay gap nhat la quinolon Mile dp ton thuong gan chu yeu la mile dp nang va de dpa tinh mang xuat hien vdi thdi gian tiem tang ngan (vai den tuan), da so hoi phuc sau tuan den thang
Ket qua bo sung dCf lieu ve ty suat benh, dac diem ton thuong gan nghi ngd thuoc thong qua giam sat phan ilng cd hai cua thuoc, gdp phan tang cUdng sil dung thuoc an toan, hop ly benh vien
TAI LIEU THAM KHAO
1 Bp Y te (2015), Dupe thuQuoc gia Viet Nam, NXB Y hoc Ha Npi
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8 Ramirez E., Carcas A.J., Borobia A.M., Lei S.H., Pihana E., Fudio S., Frias J (2010), "A pharmacovigilance program from laboratory signals for the detection and reporting of serious adverse drug reactions in hospitalized patients", Clinical Pharmacology and Therapeutics, 87(1), pp 74-86
9 Sistanizad M., Peterson G.M (2013), "Drug-induced liver injury in the Australian setting", Journal of Clinical Pharmacy and Therapeutics, 38(2), pp 115-120
10 WHO (2003), "WHO Toxicity Grading Scale for Determining The Severity of Adverse Events" 11 Worth Health Organization (2016), "http://www.whocc.no/atc ddd index/"
12 "http://www.accessdata.fda.gov/scripts/cder/ drugsatfda/index.cfm" (Ngay truy cap cuoi cung 05/05/2016)
13 "https://www.medicines.orq.uk/emc/" (Ngay truy cap cuoi cung 05/05/2016)
(Ngay gdi dang: 16/8/2016 - Ngay duyet dang: 10/10/2016)
"http://www.whocc.no/atc dd "http://www.accessdata.fda.gov/scripts/cder/ drugsatfda/index.cfm "https://www.medicines.orq.uk/emc/"