TAP CHI NGHIEN CU'U Y HQC •
CA LAM SANG NHIEM VIRUS BK O BENH NHAN SAU GHEP THAN
Ha Phan Hal A n \ Nguydn Thd Cu'dng^, Nguydn Manh TlfOT^g^ Nguydn Sy Lanh^
' Tmong Dai hgc Y Ha NQI. ^Benh viin Huv nghi Viet Due Binh ly than ghep do nhiim vims BK la mpt tmng nhung nguyen nhan chinh gay mit chirc nang than ghip a binh nhan ghep than. Viic chin doin chii yeu due vao hinh anh md binh hoc thin cua tieu ban sinh thiit Tuy nhiin viic chan doan ddi khi cd thi gap kho khan do hinh anh binh hoc cOa benh thin do vims BK cd nhung dac diim ttrong tu nhu thai ghep cip gua tmng gian ti bio. Chung tdi thdng bao ca lam sang nhim minh hga them mpt lan nua nhung kho khan tmng chan doin benh than do vims BK Do cac lua chon dieu th benh than do vims BK a Viit Nam con ban che. tinh trang binh ly nay can duac phat hien kip thai de cd su diiu chinh phii hap viic sir dung thudc ire chi miin dich. Vai trd cOa su phdi kit hap chat che giira bic sy lim sang va chuyen gia mo benh hoc la diiu kiin then chdt de dam bao chin ddan va lua chon diiu tn chinh xac Mot sd khuyin cao ca ban vi chin doan va diiu tn cung duoc dd cap.
TLF khoa. Benh than do virus BK, ghep than
I. DAT
V A N D ETir ddu nhu-ng nam 90 eua thd ky XX anh hudng cua virus BK ldn chire ndng thdn ghdp b i t d i u d u p c quan tdm ddc bidt bdi ngudi ta nhdn ra rdng day la mdt trong nhung nguyen nhan chinh gdy mdt chirc ndng than ghdp [1; 2]
Virus BK la mpt trong 3 thdnh vien (BK, JC, SV40) thude ho Polyomavirus. Mae du nguyen nhan va dudng lay nhidm cdn ehua thuc s u ro rang, ngudi ta nhdn ttiiy linh trang nhidm virus BK va JC r i t pho bien tren Ihd gidi trong qudn the dan c u va xay ra h i u het a dp tuoi tre em, tuy nhien Ihudng khdng gay hau qua gi d ngudi cd dap irng midn dieh binh thudng Ddi vdi ngudl d u a c ghep than phai dimg thudc ire ehd midn dich. n h i l m virus BK ed the la nguyen nhan gay ton thuang than ghep, d i n ddn m i t chirc ndng thgn ghdp khdng hdi phue. Benh ly than ghdp do virus BK cd the
Dia chi ben he Hi Phan Hai An. bd mon Noi tong hup Tnrong Bai hoc Y Ha Noi
Email- haphanhaian@yahoo com Ngay nhan-12/01/2015 Ngay a-joc chap Ihuin 18/5/2015
gdp d khoang ttr 2 ddn 10% ngudi nhan than va ed tdi 40 - 90% s6 benh nhan nay bi m i t chuc ndng than ghep vinh vidn [3] do duac chan doan mudn.
Mac di) virus da d u p c phan lap lir nudc lieu eua nhirng t)dnh nhan ghep than vd txi ehit hep nieu quan vdo ndm 1971, anh hudng cua nd ddi vdi chirc ndng than ghdp chi dupc quan tam thuc s u tir cuoi nhu-ng nam 1990.
do ed hang loat ca benh d u p c thdng bao Dieu ndy eung trCjng hap vdi thdi ky x u i t hidn nhidu loai thude ire ehe midn dich manh. Cho ddn nay, tren thd gidi da dua ra cac lieu chuan dd sang Ipe, phdt hidn vd chan doan tinh Irang nhidm virus BK trdn qudn the benh nhan ghep lang, dde bidt la ghep than d giai doan sdm n h i m han chd anh hudng tieu cue cua virus len chire ndng thdn ghdp ddi han [4; 5]. Tuy nhidn, d Vidl Nam vide chan dean benh than ghdp do virus BK vdn cdn Id thdch thirc ddi vdi cac nha lam sdng hoat ddng trong Hnh vue ghep than/lang Bdn eanh dd, cac lua chpn didu tri trong nude cdn r i t han ehe do cac thudc khang virus dac hieu chua sdn ed
TCNCYH 93 (1) - 2015
• TiBiP CHi NGHIEN COU Y HQC
II. GIOI THIEU CA BENH
ChiJng tdi ihdng bdo mdt tnj-dng hpp bdnh nhdn nam, 44 tuoi, suy than giai dogn cu6i do viem than Lupus, d u a c ghdp thdn thdng 01 ndm 2013 tir n g u d i cho song eung nhdm mdu;
HLA khdng t u p n g dong 6/6 khdng nguyen.
Benh nhdn dup'c chay thgn nhdn tgp 2 ndm trudc khi ghdp thdn vd bi nhiem virus viem gan C (HCV) Irong thdi gian ndy, dd d u p e diiu trj de dua tai lupng HCV ve d u d i ngudng phdt hidn tm-dc khi ghdp. Sau ghep thdn heat ddng ngay, creatinin khi ra vien {ngdy t h u 12 sau mo) 109 pmol/L. Thudc ire ehd midn djch duy tri sau khi ra vien gdm: Tacrolimus (Prograf), Myccphenplale mpfetil (Cellcept) va Prednisolon
Benh nhan dup-c theo ddi dinh ky hdng thdng tgi bdnh vldn huu nghj Viet D i r e Ndng dd Tacrolimus ndm trong khoang 8 - lOng/ml.
Trong 3 thang dau sau ghep, tinh trang ldm
sdng cua bgnh nhdn eai thidn rd ret, creatinine mdu duy tri d mirc 130 - 140 pmol/L, protein ni$u ludn dm llnh, huyet ap on dinh, sidu am thdn ghdp khdng phdl hien bat thudng. Sau ghdp 8 thdng {thdng 9/2013) creatinine mdu ldng rd r$t, den 156 ^jmol/L trong khi tinh trang ldm sdng vdn on djnh vd ede xdt nghidm nudc lieu, chi>e ndng gan, sidu dm thdn ghdp ddu cho ket qua Irong gidi hgn binh thudng. Tai lupng HCV Irpng mdu vdn d u d i ngudng phdt hidn Ben eanh cdc xdl nghidm thudng quy de tim nguyen nhdn gdy giam chuc ndng than ghdp, benh nhan d u p c chi dinh Idm xel nghiem djnh luang virus BK trpng mau vd nudc tieu va sinh thiet thdn ghdp.
Ket qua sinh Ihiet than ghep chp t h i y cd hinh anh Ion thuang ong than vd md ke. thdm nhdp td bap dan nhdn md ke. Khdng thay ed d i u hieu tap trung te bdo viem d mao mach quanh dng than vd p dng than, nhudm hda md midn dich vdi C4d dm tinh.
TAP CHl NGHIEN CCPU Y HOC •
Hinh 1 . Hinh anh s i n h thidt than g h e p
A Qng thdn vd md ke - nhudm H&E; B. Ong thdn vd md ke - nhudm Trichrome, C. Cau than - nhudm H&E; D. Cau than - nhudm Trichrome; E. Nhudm hda md midn dich anti - C4d
K^t qua xet nghidm tim virus BK bdng ky thudt real-time PCR thang 9 ndm 2013 cho thiy virus BK nudc lieu: 8,27x10^°eopies/ml, virus B K m d u : 1,7 x 10"* copies/ml.
Didn bien Idm sang vd tinh trang chuc ndng thdn cho den thdi diem sinh thiet d u p c trinh bdy tren bieu do 1.
-•-Creatinin mau
» ^ -•-Ndng i56tacrolimus
£t(h$n
^ ^ ^ .
' J^ J^ -
Bieu d d 1. Chii-c nang than va n d n g do t h u o c thai g h e p den thdn d i d m s i n h t h i e t than Dua tren cac ket qua thu duac, benh nhdn dupe c h i n dpan BKVAN. Li^u thuoc ire chd midn dieh (tacrolimus, myccphenplale mofettil) d u p c giam dan, tuy nhidn chuc ndng than khdng cai thidn, creatinin t i i p tyc tang (bieu dd 1). Sau 1 thdng di^u tn, lai lupng virus trpng mdu va nudc lieu tang ldn (virus B K m d u 1,27x10^ cppies/mL; virus BKnidu 1,64x10" copies/mL).
Chung ldi quyet dinh thay dpi thuoc ire ch4 midn dieh, chuyen sang sir dung Cyclosporin A lieu t h i p phoi hpp vdi Everolimus. Didn bi4n creatinine mdu va nong dd cac thuoc u c chd midn dich dupe Irinh bay d bieu dd 2.
TCNCYH 93 (1) - 2015
• T<LP CHl N G H * N CI>U Y HQC
-' V,
••-Creatinin mau
\ .
• N6ng do Everolimus
Bteu d d 2. Creatinin mdu va n d n g d o t h u d c thai ghep s a u khi ehuydn phac d d t h u d c iyc ehd midn d j c h
Sau khi chuyen doi phdc do dieu tn ire eh^ m i i n dich, lai luang virus BK trong mdu ed xu hudng giam dan, ddn thang 2 ndm 2014 tai lupng virus BK mdu 5,52x10^ cppies/mL, cdn trong nude lieu la 5,86x10^ copies/mL. Tuy nhien, khd Idu sau dd linh trang chire nang thdn cua bdnh nhdn mdi cd d i u hidu on djnh t r d lai vd khdng the hoi phuc trd ve tinh trang ban dau d thdi di^m ngay sau ghep.
III. BAN LUAN
Ddy Id ea bdnh nhdn ghep thdn d i u tien d Viel nam d u p c chan dodn xdc dinh bi bdnh Ihdn do nhidm virus BK. Vide chan dodn ban dau gap nhieu khd khan do bieu hidn ldm sdng khdng dde hidu, nghdo tridu chO-ng Neu bdc sy ldm sdng khdng ed cdeh tiep edn c h i n dodn loan didn se il khi nghT ldi tinh trgng bpnh ly ndy. T r u d c ddy, khi trong n u d c chua cd p h u a n g tidn de dmh lupng virus BK vd ehua cd kinh nghidm ldm sang de nhdn dinh ton thuang than trdn tidu ban sinh thiet, c h i n dodn ndy thudng bi bd sdt
TCr khi v i n de nay d u p c ghi nh^n vd chii y, cde nhdm nghidn ciru tren the gidi nhdn thay tinh trang nhidm virus BK g i n lien vdi s u xuat
hien cdc thucc ire che midn djch the he mdi, vd! tde dyng ire c h i m i i n dich mgnh han cdc thucc t h l he cu. Bdn canh dd, s u xuat hidn ten thuang than lidn quan d i n virus BK rat thudng xay ra sau cdc d p i dieu tn thai ghdp cap [4; 5], D i l u ndy k h i l n cde nhd lam sdng e nggi r i n g hidn nay cd the cdc bdnh nhdn thudng bj ire ehe midn dich qua muc, dc m6i IP ngai bj thai ghdp v i n ludn dm anh ea bdnh nhan vd nhan vidn y l l , k h i l n ddi khi ngudi ta qudn m i t mdt s6 nguy c a khdc.
B$nh nhdn cd dau hidu rci b a n chirc ndng thdn ghdp xuat hidn sau m^t dpt npng do Ihuoc u-c c h l m i i n dieh trong mau dao ddng d mirc cap hpn thdng 10. Tuy nhidn, do chua ed phuang tidn d l sdng loc vd theo ddi hd thong,
TAP CHi NGHIEN COU Y HQC • phai den khi creatinine mdu tdng ddng k l benh nhdn mdi d u a c sinh I h i l t thdn. Ngay ca khi da sinh Ihilt, vide chan doan phan bidl giu-a benh than do virus BK hay thai ghep t l bdo c i p ddi khi eOng khd khdn, do linh chat ton thupng mp ke than khd gidng nhau. Cdc nhdm nghien ciru cdn nhdn thdy r i n g cd mdi moi lien quan nhat dinh giu-a vide nhidm virus BK va tinh trang thai ghdp cap. Vi vdy, mdt so benh nhan cd dap irng mdt phdn vdi didu tri thai ghdp edp, luy nhien la dap irng khdng b i n vu'ng va chirc ndng than cd the xdu di sau dot d i l u In dd.
Khi ede thuang ton d than ghep dd xudt hien, kha nang hoi phyc chirc ndng than vd eimg khd khan. Do linh chal nghiem trpng eua tinh trang bdnh ly ndy, each l i l p can xu- tri d l i vdi benh nhan ghep than da cd nhung thay doi dang k l . Ngudi ta xdc djnh nhdm bdnh nhdn ed nguy ca cao va chu ddng thep ddi de kjp thdi phdt hidn virus BK trudc khi ed ddu hieu rdi Ipgn chuc nang thdn tren lam sdng, dae bidt Id trong nam ddu tidn sau ghdp than.
Quy Irinh chan dodn d u p e n h i l u trung tam hien nay thuc hien bao gom xet nghiem nudc tieu de tim "te bdo bay" (decoy cell) hoac dinh lupng virus BK trong n u d c lieu va trong mdu bdng k? thudt PCR. Tuy nhidn, de c h i n doan chinh xac ton thuang than do BK virus, vai trd q u y l t dinh thupc v l md benh hpc. Tren tidu ban sinh thiel than, ngudi ta quan sat thay cac t h l vui cua virus trong nhdn l l bdo bieu md dng than va c i u thdn, va d i u hidu xdm nhidm t l bdc viem d md ke Ihudng di kem Hinh anh xdm n h i l m t l bap viem d md ke thdn ehinh la d i u hidu eung cd the quan sal t h i y d bdnh nhdn cd thai ghep te bao cap vd gdy nhdm l i n Cdn cd ehuydn gia md benh hpc duae ddo tao tot, ed kinh nghidm d l cd t h l nhan didn ra cdc ton thuang than dc BK virus gdy ra tren h i l n vi quang hoc. Ngodi
ra, ky thudt hda md m i l n djch/miln djch huynh quang vdi anti - SV40 hay h i l n vi ^ d n t u cd I h l giup k h i n g djnh chan doan [4; 5; 6J. Vdi xu hudng lim k i l m thdm cdc ky thudt khdng xam lan d l c h i n dcdn s d m va chinh xac thupng t i n , phan bidt cac nguydn nhdn gay thuang ten ma vdn dam bap an tPdn eho ngudi bdnh, mdt so ddu i n sinh hpc trpng n u d c t i l u dang d u p c nghien ciru. Thdng qua vide irng dung cdng nghe sinh hoc phan t u de phdn tich hd protein trong n u d c l i l u , cac nhdm nghidn edu da phat hien d u a c cac hinh anh dae hidu d l chan doan phan bidl ton thuang than do virus BK va thai ghep c i p [7], tuy nhien ky thudi nay chua t h l ap dyng rdng rai trong thuc hdnh ldm sang.
C h i l n l u p c dieu In n i n tang ddi vdi benh than do vims BK hidn nay id giam l i l u thudc O'C c h l m i l n dich [3; 6]. V d khia eanh ldm sang, d i l u ndy ludn ddt bdnh nhdn trudc nguy ca bi thai ghep. Nhdm nghidn eiru eua Weiss AS nhan t h i y , de bao ton ehue ndng than ghep, viec ngCrng mpl Ipgi thuoc ire c h l miln dieh (phdc do 2 thudc) cd ve cd lai hpn so vdi vide giam lieu vd duy tri phac dd 3 thuoc [3].
Han nOa, viec s u dung Tacrolimus dudng nhu thudng di kem vdi tinh trang bdnh than do virus BK han so vdi s u dyng Cyelcsponn hay ire ehe mTOR [8, 9]. D l bao Ion ehue ndng than ghep, can dieu chmh l i l u thuoc uc che midn dich de iam giam tai luang virus vd trdnh s u x u i t hien cac ton thuang seo hda P thdn, tuy nhien d i l u ndy cd the chf dat d u p c d khpang 20% SP bdnh nhdn [6].
Viec S U dung cac thudc didt vinjs ddc hieu v i n cdn cd k i t qua chua ihue su- on ^ n h va kdm theo nhieu tde dung khdng mong mudn.
Leflunomide cd lac dyng chdng vidm vd ii'C c h l s u nhdn ban virus nhung cd linh ddc cho gan va cd the gay giam 3 ddng mdu. Cidofovir Id thudc cd tdc dung diet virus mgnh in vitro.
146 TCNCYH 93 (1) - 2015
• TAP CHi NGHIEN CU'U Y HQC nhung cd tinh ddc d l i vdi thdn cao. Can theo
ddi sat tinh trang chirc ndng thdn khi sir dung Cidofovir vd cd the phai giam l i l u t h u l c mijt cdeh dang k l . Immunoglobulin tTnh mgch (IVIG) cd t h l giup trung hda khdng nguydn virus nhung cd t h l ed tdc dyng d i l u bien m i l n djch n h i l u han, IVIG cdn cd t h l gdy ra phan irng ngng, chi phi d i l u trj eung r i t cao. Bdn canh nhung ldc dyng khdng mong m u l n eua ede thude didt virus, b i n g chCrng v l hidu qua dieu tri eung ehua day du, m d i ehi cd mpt s6 lupng han c h l cac Irudng hpp cd k i t qua dieu In kha quan va vdn c i n them cdc nghidn ciru quy mc Idn, Iren mdt c d mau ldn hpn
Bdnh nhan dup'c giam l i l u ire c h l m i l n djch va khdng d u p e s i j dung thuoc diet virus dp thupc khdng s i n ed d thj trudng Vidt Nam.
Tinh trgng chu-c nang than ghdp cua bpnh nhdn khdng dup'c cai thidn rc rpl, khdng hoi phue v l lgi mCrc ban dauma chl giu- d u p c d mirc tuang ddi an djnh trong thdi gian su- dung phdc do t h u l c mdi. Do vay, P thdi d i l m hidn lai c h i n dodn s d m vdn la y l u to q u y l t djnh Ihanh cdng trong viec bao ton chirc ndng thdn ghep.
IV. K^T LUAN
Chan dodn bdnh thdn do virus BK vdn edn khd khdn trong didu kipn Viet Nam hien nay vi thilu cdc phuang tipn c h i n dodn, ddc bidt Id khdng the ddc hidu d l phat hien virus Irong md Ihdn vd chuyen gia md benh hpc d cac c a s d ghep thdn. Do ehu yeu d y a vdo dau hidu Idm sang, bdnh nhdn t h u d n g duo-c phat hidn mudn, khi cdn rdt il C P hdi bao ton d u p c ehue ndng thdn ghdp, dac bi$l khi thuoc d i l u tri dde hi^u chua sdn cd P Vi$t Nam, Can xdy dung quy trinh sang lpc va c h i n dcdn bdnh s d m d l cd c h i l n i u d c sir dung t h u l c dc c h l midn djch phil ^o'p n h i m cai thidn chire ndng thdn ghdp ddi
Lo'i cam c n
Nhdm nghidn ciru trdn Irpng cam an khoa Thdn - Lpc mdu vd khea Giai p h i u bdnh dd giiip d d Chung tdi Irpng vide phdl hidn vd c h i n dodn ca bdnh ndy
TAI LIEU THAM KHAO
1 . Phuong-Thu Pham, Joanna Schaen- man., Phuong-Chi Pham (2012). BK Virus Screening and Management Fpllpwing Kidney Transplantation: A n Update. J Transplant Technol Res. 2, 3,
2. S Hariharan (2006) BK virus nephritis after renal transplantation. Kidney Intema- tional. 69, 655 - 662
3. Andrew S. Weiss, Jane Gralla, Larry Chan et al (2008). Aggressive immunosup- pression minimization reduces graft loss fol- lowing diagnosis of BK virus-associated neph- ropathy: a comparison of two reduction strate- gies CJASN. 3, 1 8 1 3 - 1 8 1 9 .
4. Denise A. Boyum, RN.BSN, CCTC (2004). BK virus in kidney transplantation: a case study. Progress in Transplantation, 14, 1 7 6 - 1 8 0 .
5. Hirsch HH, Brennan DC, Drachenberg CB et al (2005). Polyomavirus-associaled nephropathy in renal transplantation: interdis- ciplinary analyses and recommendations.
Transplantation, 79, 1277 - 1 2 8 6
6. Nasimul Ahsan (2006). Polyomaviruses and Human Diseases, edited by Eurekah com, 1 6 , 2 1 3 - 2 2 7 .
7. Tlmo Jahnukainen, David Malehorn, Mai Sun et al (2006). Proleomic Analysis of Urine in Kidney Transplant Patients with BK Virus Nephropathy J Am Soc Nephrol. 17, 3248 - 3256.
TAP CHi NGHIEN CLPU Y H p C •
8. Acott PD, O'Regan PA, Lee SH, Crocker JF (2008), In vitro effect of cyc- losponneA on primary and chrome BK polyo- mavitrus infection in Vero E6 cells, Transpllnfect Dis. 10, 385 - 390.
9. Hardinger KL., Koch MJ., Bohl DJ et al (2011). Polyomavirus BK (BKV) replication in renal tubular epithelial cells is inhibited by mTOR inhibitors but activated by tacrolimus in a pathway involving the FKBP12, Am J Transplant. 497
Summary
BK VIRUS - ASSOCIATED NEPHROPATHY IN KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT
BK virus-assoeiated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney recipients. The diagnosis is principally based on renal allograft biopsy However tiie diagnosis can sometimes be difficult because of some similarities in pathological features of BKVAN and cell-mediated acute rejection We reported a case of BKVAN lo illustrate again some difficulties in making diagnosis of BKVAN Due to the cun-ent limitation of available therapeutic options for BKVAN in Vietnam, the condition must be timely identified in order to appropriately adjust the immunosuppressant prescription. The close collaboration between clinician and pathologist is crucial for ensunng accurate diagnosis and appropriate therapeutic approach.
Recent diagnostic and therapeutic recommendations have also been discussed Ket w o r d s : BK virus-associated nephropathy, kidney t r a n s p l a n t a t i o n
TCNCYH 93(1)-2015