DANH GIA KET QUA DIEU TRj BENH NHAN VIEM GAN VI RUT C MAN TI'NH BANG PHAC DO PEG - INTERFERON a - 2 b
KET HOP RIBAVIRIN (07/2013 - 04/2015)
Ng6 Anh The', Nguyen Ngoc Phuc^
Trinh Thi Ngoc^ Biii Vu Huv\ Nguyin Van Kinh^
Ddt vdn di: Thu6c khang vi nit dac hieu c6 Xhh giup loai bo vi nit ra khoi ca the nguoi nhilm viem gan vi nit C man tinh va gop phan cai thien cuoc song nguoi benh va han che cac bien chumg. Muc tieu: Danh gia kdt qua di^u tri viem gan vi nit C man tinh bang phac d6 peg - IFN alfa - 2b/Ribavirin. Ddi tuang vd phuang phdp: 31 b?nh nhan viem gan vi nit C man tinh, dieu tri tai Benh vien Benh nhiet doi Trung uong (BVENSTU), trong giai doan 7/2013 - 4/2015 da duac chpn vao nghien curu. Kit qud vd kit lugn: 67,7% so benh nhan hgp co dap iing dieu tri nhanh (RVR), 25,8% benh nhan dat dugc dap vmg som (EVR), 6,5% benh nhan co dap iing vi nit c h ^ , 100% so benh nhan dat dugc tai lugng vi nit duoi nguong phat hien 6 tuan 48. Cac tac dung phu chii yeu bao gom hpi chiing gia ciim (67,7%), gay sut can (54,8%), phan iing tai diem tiem (45,2%) va thay doi huyet hpc. Phac do peg - interferon alfa - 2b phoi hgp ribavirin CO hieu qua cao trong dieu tri cho cac benh nhan viem gan vi nit C man tinh tai Viet Nam.
Tir khoa: HCV, xa hoa gan, Peg - Interferon alfa - 2b, SVR.
DAT VAN DE
Viem gan vi rut C man tinh (VGVRCMT) dang la mpt trong nhiJng van de su'c khoe cua cong dong. Theo eac thong bao, tren toan the gidi hien cd khoang 135 - 180 trieu ngudi nhiem vl rut viem gan C (HCV) va neu khong dieu trj, hau het cac tru'dng hdp nhiem HCV tien trien thanh viem gan man tinh, xd gan va ung thu te bao gan'^.
Cac ket qua nghiSn ciiu trong nhOYig nam gan day cting eho thay, do HCV cd 6 typ khang nguyen khac nhau, vi vay ket qua dap uHg dieu tri khae nhau va thdi gian dieu tri eung khac nhau'''. Hien nay. To chu'c Y te The gidi (TCYTTG), cung nhU eae Hiep hpi gan mat tren toan eau dang tiep tyc di sau, tim hieu cac giai phap dieu trj nham cai thien cuoc cong eho ngutfi nhiem HCVt^i.
"'Bfnh vifn Hihi nghi S^ift - Tifp. Hdi Phong. <2)Benh vifn Bfnh nhift dm Trung uang. '"Khoa Truyen nhiem Bfnh vifn Bach Mai.
Vcaj nh^n bai: 04/6/2015 Nga> phan b i f n xong: IS'd 2015 N g i ) duyft dSng: 25/6/2015
Ngirtri chju trach nhi|m n$i dung khoa h^c Ngo Anh The. Bfnh vifn Huu nghl Vift - Tif p. Hai Phong
Difn thoifv 0902210218. E-mail: [email protected]
Tai Viet Nam, theo cae ket qua dieu tra, ty le nhiem HCV thay doi d tijlig nhdm doi tu'dng, khoang 2% d nhom dan eu' chung, 6% d benh nhan lpc than ehu ky, 40% d ngu'di sir dung ma tuy tinh maeh™. Nam 2013 Bp Yte Viet Nam da ban hanh phac do dieu trj HCV^]. Oieu tri dutfc coi la thanh eong khi benh nhan dat du'dc dap liTig vi nit ben viJng (SVR)[=3'[^]. De danh gia hieu qua eiia phac do tren chung toi tien hanh nghien culi nham mue tieu; (1) Danh gia ket qua dieu tri benh nhan HCV man tinh bang phac do Peg - IFNo - 2b + ribavirin va mot so yeu to lien quan den hieu qua dieu tn. (2) Nghien ciili mot so tac dung phu khong mong muon eiia thuoe.
OOI JiigUG VA PHUONG PHAP
Ooi tu'dng nghien cuTu: gom 31 benh nhan VGVRCMT dii tieu chuan dieu tri bang lieu trinh Peg - IFN alfa - 2b + ribavirin theo hu'dng dan cua Bg Y te Viet Nam.
Oia diem, Thdi gian: Nghien cu\j dUde thi/c hien tai Benh vien Benh nhiet ddi Trung Udng, trong giai doan 7/2013 - 4/2015.
PhUdng phap: Nghien culi mo ta tien ciilj.
14 - T R U Y ^ N H i 6 M V l $ T N A M * s o DAC BIET N G A Y VIEM GAN THE GlOl - 2015
Cach chpn mau: Chpn mau co ehu dich.
Tieu chuan lu^ chon: Benh nhan cd du tieu chuan chan doan xac djnh VGVRCNTT: gom co anti - HCV (+) va ARN - HCV (+) ton tai tren 6 thang^^]. Oil tieu chuan dieu tri bang Peg - IFN alfa - 2b + ribavirint^i. Benh nhan dong y tham gia nghien cirlj.
Tieu chuan loai triT: Benh nhan dang nghien rUdu nang hoae dang tiem chfch ma tuy. Benh nhan dang mac hoac CO tien sii bj benh tam than hoac tram cam nang. Co thai hoac sir dung bien phap b-anh thai khong hieu qua. Dpng kinh khong kiem soat. Benh ly tim mach cd trieu chuYig.
Viem tuyen giap tU mien hoac roi loan tu" mien khac dang tien trien. Suy than nang.
Phu'dng phap tien hanh: Benh nhan co dii tieu chuan nghien cirtj du'pc nhan vao khoa Viem gan, BVBNOTl/ va du'dc tien hanh eae bu'dc sau: Tu'van ve benh VGVRCMT dien bien benh, xet nghiem can chi djnh trong theo doi diilu tn, quy trinh dieu tri bang thuoe khang vi nit va lay phieu dong thuan tham gia nghien cufU.
Cach danh gia trong nghien cihi: Oanh gia eae bieu hien lam sang, eong thiTc mau va xet nghiem danh gia chiTc nang gan (ALT, AST, bilirubin); tai cae thdi diem 4 tuan, 12 tuan, 24 tuan va 48 tuan eiia dieu tri. Oinh typ HCV: tru'dc dieu tri. Oanh gia nong dp RNA - HCV: tai eae thdi diem 4 tuan, 12 tuan, 24 tuan va 48 tuan eiia dieu tri.
Phat hien cae tae dung khong mong mudn eiia thuoe dieu trPl
Cac xet nghiem: Oinh lu'dng RNA - HCV, dinh type HCV, huyet hpe, sinh hoa mau 6Mc thu'c hien tai khoa Xet nghiem - BVBNOTLT, do Ddn vi nghien eirtj lam sang Dai hpc Oxford ho trd xay dyng va dat chuan ISO 9001: 2008.
Oieu trj: Tat ea cae benh nhan nghien ciTu dUpc dieu tri bang phac do Peg-IFN alfa-2b + R theo hudng dan dieu tri cua Bp Y t e Viet Nam!=].
Thu thap va xuf ly so lieu: Theo mpt m i u benh an thong nhat. Quan !y va phan tieh so lieu bang phan mem SPSS 16.0. Cae thuat toan sir dung trong de tai; tinh ty le phan tram, gia tri trung binh, so sanh eae ty le bang test x2.
KET QUA
Ket qua theo doi dieu trj eiia 31 benh nhan VGVRCMT da dUde lua chpn vao nghien ciTU nhU sau:
Bang 1 : Phan bo Genotype - HCV va tai lu'dng vi nit tru'dc diieu trj d 3 1 benh nhan VGVRCMT
Genotype la lb 2 6 ea
6e 6h
n S 3 1 1 15 2 1 RNA • HCV tnjng binh (Ul/ml)
%
25,8 9,7 3,2 3,2 48,5 6,4 3,2 2,99 X 10' ± 13,5 X 10'
Nhan xet: Co 11/31 (35,5%) benh nhan co kieu gen 1,19/31 (61,3%) benli nlian co kieu gen 6, chi co 1 benh nhan (3,2%) co kieu gen 2. Nong do I^NA - HCV trung binh tru'dc dieu trj la 2,99 x 10' ± 13,5 x 10' Ul/ml.
Bl^u da 1: S i c diem 13m s^ng tn/drc v i sau dieu t i i
Hi
Nhan xet: Trieu chirtig lam sang chu yeu ciia benh nhan mac VGVRCMT la met moi (60%) va chan an (40%).
Bang 2: Ket qua mot so xet nghiem huyet hoc va sinh hoa cua 3 1 benh nhan tru'dc va sau dfeu tri TenXN
HCC/L) B C ^ L ) T C m ) HBG(9/L) ALT (U/L) AST (U/L) BilirubinTP (pmoi/L) BilimbinTT (Umol/L)
Tuan 4 4,3 ± 1,2 5,2 ± 1,5 211,1 ± 81,3 121,4 ± 16,6 135,6 ± 134,6 119,7 ± 110,6
23,8 ± 1,3
10,0 ± 0,54 Tuan 12 3,5 ± 1,17 3,6 ±2,07 152,7 ± 56,9 101,4 ± 14,9 97,2 ± 22,7 58,3 ± 19,8
17,2 ± 1,7
7,4 ± 0,45 T u i n 24 3,1 ± 1,06
3,5 ± 1,2 94,2 ± 36,8 97,8 ± 12,0 65,6 ± 11,3 45,4 ± 10,2
17,0 ± 0,9
5,2 ± 0,31 TuSn 4 8 3,3 ± 0,97 3,4 ± 0,89 86,8 ± 17,5 98,3 ±19,5 38,4 ± 23,6 37,5 ± 7,9
16,4 ± 1,5
5,3 ± 0,7
Nhan xet: Co SLT eai thien ro ret gia tri trung binh ciia
TRUY^NHlilUI V i r r N A M * S 6 D A C BIET NGAY VIEM GAN THE Gl6l - 2015 - 15
AST va ALT trudc va sau dieu tri. C6 hien tUdng giam 3 dong te bao mau ed the lien quan den cac tac dung khong mong muon eua thuoe (bang 2).
Bang 3: Dap ufng vi rut cua 3 1 benh nhan VGVRCMT
Dap ulig virus Ket qua TLVR trong qua trinh dfeu t r i : - TLVR dulS ngu9ng phat hien vao tuan
t h i r l (RVR)
- TLVR dul3i nguBng phat hien vao tuan thir 12 (EVR)
• TLVR dLfdi nguQng phat hien vao tuanthu'24(ReVR) K€t qua danh gia sau dieu tri - Dap iJng virus ben viJng (SVR)
n
21
8
2
31
%
67,7
25,8
6,5
100
Nhan xet: Tai thdi diem 4 tuan sau dieu trj, ket qua dap nhanh la 67,7%, dap img sdm la 25,8% va cd 6,5%
benh nhan eo dap iTng vi riit cham. Tat ea 31 benh nhan (100%) deu dat dUde tai lu'dng vi njt dudi ngudng phat hien d tuan 48.
Bang 4: Mot so yeu to lien quan tdi dap ufng diieu trj Cac y^u ts
Tuoi Gicli
TiicJi gian nliiem HCV Genotype - HCV RNA-HCVtrulicdieutn Miit do xi3 hoa gan
P (RVR) 0,626' 0,624"
0,507"
0,3' 0,024' 0,026'
p(EVR) 0,252- 0,405' 0,169' 0,471' 0,769' 0,795' 'Knjskal Walhs test: / ; "Pearson test
Nhan xet: Nhieu yeu to khae nhau ed the ed lien quan den dap utig dieu trj tuy nhien ehi nong dp RNA - HCV va mirc dp xd hda gan trUdc dieu tri co lien quan chat che tdi dap img vi rut nhanh vdi p < 0,05.
Bang 5: Cac tac dung phu khong mong muon Tri^u chulig
HOI Chung gia cijm Viem da tai diem tiem Run tay Gay Slit can
n 21 14 10 17
%
67,7 45,2 32,3 54,8
Trifu Chiang Rung toe Buon non Kho mieng Dau bung Lao phoi Viem vong mac
n 11
5 4 3 2 1
%
35,5 16,1 12,9 9,6 6,5 3,2
Nhan xet: Cac tac dung khong mong muon hay gap nhat la hpi ehuTig gia cum (67,7%), viem da tai Mm tiem (32,3%), gay siit can (54,5%), rung toe (35,5%).
Bang 6: Bien doi huyet hoc sau dieu tri Trieu ChuTng
BC < 1,5 «/L
BC da nhan trung tinh < 0,75 7L.
HGB: 10 - 110 9/dL HGB: 8,5 - lOg/dL HGB < 8,5g/dL Tieu cau < 50g/dL
n 2
%
6,4 3,2 22,6 22,6 3,2 3,2
Nhan xet: Cac tac dung phu khong mong muon eiia thuoe trong bien doi thanh phan huyet hpe bao gom thieu mau, giam tieu cau va giam bach cau (bang 6).
BAN LUAN
Trong so 31 benh nhan tnang nghien eulJ nay dUde dieu tri bang phac do Peg - IFN alfa - 2b + ribavirin, c6 tdi 67,7% cae trUdng hdp cd dap Ung dieu tn nhanh, 25,8%
benh nhan dat dUde dap utig sdm, chi 6,5% benh nhan ed dap iTng vi riit cham tuy nhien eo 100% so benh nhan dat dUde tai IUdng vi njt dudi nguQng phat hien d tuan 48.
Ket qua nay co sU khac biet vdi mpt so nghien ciTU tren the gidi nhU trong nghien eUu eiia Me Hutchison va cpng sU, t / le benh nhan dat SVR neu co dap litig nhanh va sdm ehi khoang 78,6 - 86,2%'^]. Mot nghien eUu khac eiia Lam K.D va cpng sU thUc hien tren benh nhan nhiem HCV genotype 6 eho thay co tdi hdn 90% eac trUdng hdp dat dap iTng vi rut sdm tuy nhien ehi khoang tren 70% eac trudng hdp dat dap irtig vi mt ben vijtigt'l
Mot sd yeu to eo the anh hUdng den dap iTng dieu tri bao gom tuoi, ehung tpc, kieu gen HCV, nong dp RNA - HCV va mUe dp xd hoa gan tnjng do kieu gen HCV dong vai tro quan trpng nhat, quyet djnh ty le dap irtig vl nit
1 6 • T R U Y ^ N H l 6 M V i | T N A M * s 6 D A C BIET NGAY VIEM GAN THE GlOl - 2015
ben vutig. Trong nghien cirtj nay, nong dp RNA - HCV va mufc dp xd hda gan trUde dieu tri co anh hudng chat che tdi dap iiffig vi mt nhanh vdi p < 0,05.
O^c diem lam sang ciia eac benh nhan VGVRCMT thudng khong dien hinh khi trieu diirtig lam sang ehii yeu la met moi (60%) va ehan an (40%). Mpt so trieu chutig khac nhu dau ha sUdn phai va vang da cung khong dac hieu cho VGVRCMT. Ket qua nay phii hdp vdi eac bao cao trUde do, benh nhan VGVRCMT co bieu hien chii yeu la met moi. Cae bieu hien khae khong dien hinh bao gom dau khdp, dau cd, buon non, non, chan an, dau bung.
Trong so 31 benh nhan thupe nghien cirtj nay, cae kieu gen chiem uU the la kieu gen 6 (61,3%) va kieu gen 1 (35,5%). Ket qua eiia ehung toi cung phu hdp vdi ket qua ciia Pham A.D khi co 47,1% cac trUdng hdp nhilm kieu gen 6[^i.
Hpi chutig gia ciim (sdt, dau ngUdI, dau ed...) la tac dung khdng mong muon hay gap nhat trong qua trinh dieu tri. Tac dung phu nay hay gap d nhutig tuan dau cua qua trinh dieu trj. Ket qua eiia ehiing toi cung phii hdp vdi nghien culi ciia Mc Hutchison, theo dd hpi chirtng gia cum la tac dyng phy hay g§p nhat khi dieu trj bang PeglFNa - 2b[^]. Tuy nhien tac dung phy nay thUdng d mdc dp trung binh hoac nhe va co t h i xu' tri bang thudc ha sot thong thudng. Cae tac dung Wiong mong muon khac bao gom gay sut can (54,8%), viem da tai diem tiem (45,2%), aing tde (35,5%), buon non (16,1%). Cd 2 trUdng hdp (6,4%) xuat hien benh lao phoi trong qua trinh dieu tn. Cac benh nhan nay dUdc dieu trj bang eac thuoe khang lao va tiep tue dieu trj thuoe khang vi nit.
Mpt trUdng hdp (3,2%) xuat hien viem vong mac d
tuan thU 45. Tae dung phu tren vong mac cung thUdng hay gap d benh nhan VGVRCMT dieu trj bang Peg - IFNa 2b - ribavirin'^'. Khi xuat hien tinh trang benh ly vong mac a n phai dutig dieu trj bang cae thuoe khang vi nJt ngay lap tiTc.
Trong so cae trUdng hdp co tac dung phu tren huyet hpc, mpt trudng hdp (3,2%) eo so IUdng bach cau giam dudi 1,5°/L va bach cau da nhan tmng tanh giam dudi 0,7G/L dUdc giam lieu peg - interferon alfa - 2b va dieu tri bang thuoe kich thieh sinh bach cau (leucokine 300mg/ngay, 3 lan/tuan). Cac trUdng hdp co hemoglobin giam dUdi lOg/dl dUdc giam lieu ribavirin va b6 sung ery- thropoietin. Mpt trUdng hdp cd hemoglobin giam dUdi 8,5g/dl phai ngimg dieu trj tuy nhien benh nhan nay van dat dUdc dap irtig vi rut ben vijtig khi ket thiie dieu tri.
KET LUAN
Qua nghien ciili chiing toi rut ra mot so ket luan sau:
dieu trj bSng phac do Peg - IFN alia - 2b + Ribavirin cho thay:
- 67,7% cae trUdng hdp ed dap utig dieu tri nhanh, 25,8% benh nhan dat dUde dap utig sdm, 6,5% benh nhan co dap utig vi rut cham, 100% so benh nhan dat dUdc tai IUdng vi rut dUdi ngu8ng phat hien d tuan 48.
- Cae yeu to ed lien quan den dap Ung dieu tri la nong dp RNA - HCV va mUe dp xd hoa gan trUde dieu tri.
- Cae tac dyng khong mong muon chii yeu bao giSm hpi chutig gia cum (67,7%), gay sut can (54,8%), phan Ung tai diem tiem (45,2%), thay doi huyet hpe. Hau het eac tae dung phu nay deu d mUc dp trung binh hoae nhe.
Chi cd 1 trUdng hdp giam hemoglobin dUdi 8,5g/dl phai ngutig dieu tri.
T H U Y ^ N H f e w i V l l T N A M * SO D A C BIET NGAY VIEM GAN THE G l 6 i - 2 0 1 5 - 17
TAI UEU THAM KHAO 1. Lavanctiy D. (2011). Evolving epidemiology of hep-
atitis C virus, ain Microbiol Infect, 17(2), 107-15.
2. McHutchison ].G, Lawitz E.J, Shiffman M.L et ai (2009). Peginterferon Alfa-2b or Alfa-2a with lybavinn for Treatment of Hepatitis C Infection. New England Joumai of Medicine, 361(6), 580 - 593.
3. W.H.O (2014) Hepatitis C fact sheet. Updated April 2014. Available at: http://www.who.int/mediacentre/fact- Sheets/f5l64/en. Accessed Mach 31, 2015.
4. Dunford L, Carr M.], Dean J et al (2012). Hepatitis C virus in Vietnam: high prevalence of Infection in dialysis and muiti-transfijsed patients involving diverse and novel virus variants. PLoS One, 7(8), e41266.
5. Bg Y te Viet Nam (2013). Hu'dng dan chan doan va dieu trj viem gan vi njt C. 11.
6. AASLD and IDSA (2014). Recommendations for testing, managing, and treating hepatitis C. Available at http://hcvguidelines.org/full-report-view. Accessed My 16, 2011.
7. Lam K.D, Trinh H.N, Do S.T et al (2010). Random- ized controlled trial of pegylated interferon - alfa 2a and ribavirin in treatment - naive chronic hepatitis C genotype 6. Hepatology, 52(5), 1573 - 80.
8. Pham D.A, Leuangwufwong P, Jittmittraphap A et al (2009). High prevalence of Hepatitis C virus genotype 6 in Vietnam. Asian l^c J Allergy Immunol, 27(2 - 3), 153 - 60.
RESULTS OF TREATMENT FOR CHRONIC HEPATITIS C PAHENTS BY PEG - INTERFER0Na-2b COMBINED RIBAVIRIN ( 0 7 / 2 0 1 3 - 0 4 / 2 0 1 5 )
Summary Treatment using antivirus leads to reduced mortality, morbidity, improved liver fibrosis thus limiting progress to cirrhosis, liver failure and hepatocellular carcinoma. Aims:
Evaluated the results of treatment by peg - IFN alfa - 2b association with ribavirin for chronic hepatitis C patients.
Subjects and Methods: 31 patients eligible included in to the study during period from 7/2013 to 4/2015. Results and condussions: 67.7% patients achieved RVR at weelt
Key words: HCV, fibrosis, peg - interferon alfa - 2b, SVR.
4, 25.8% patients achieved EVR, only 6.5% have viral load undetectable, 100% of patients achieved a viral load Is undetectable at week 48. The main side effects include influenzafte syndrome (67.7%), weight loss (54.8%), re- actions at the Injection point (45.2%). The combination of peg - interferon alfa 2b - ribavirin has a high efficiency for the treatment of chronic hepatitis C in Vietnam.
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