NGHIÊN cứu ỨNG DỤNG một số CHỈ số KHÔNG xâm lấn TRONG ĐÁNH GIÁ TÌNH TRẠNG xơ hóa GAN TRÊN BỆNH NHÂN đái THÁO ĐƯỜNG TYP 2

B GIO DC V O TO B Y T TRNG I HC Y H NI BI TH THANH THY NGHIÊN CứU ứNG DụNG MộT Số CHỉ Số KHÔNG XÂM LấN TRONG ĐáNH GIá TìNH TRạNG XƠ HóA GAN TRÊN BệNH NHÂN ĐáI THáO ĐƯờNG TYP CNG LUN VN THC S Y HC H NI 2015 B GIO DC V O TO B Y T TRNG I HC Y H NI BI TH THANH THY NGHIÊN CứU ứNG DụNG MộT Số CHỉ Số KHÔNG XÂM LấN TRONG ĐáNH GIá TìNH TRạNG XƠ HóA GAN TRÊN BệNH NHÂN ĐáI THáO ĐƯờNG TYP Chuyờn ngnh: Ni Khoa Mó s : 60720140 CNG LUN VN THC S Y HC Ngi hng dn khoa hc: PGS NGUYN KHOA DIU VN PGS NGUYN TH VN HNG H NI 2015 MC LC DANH MC BNG T VN ỏi thỏo ng (T) l tỡnh trng ri lon chuyn húa ca nhiu nguyờn nhõn, bnh c trng l tỡnh trng tng ng huyt mn tớnh phi hp ri lon chuyn húa carbohydrat, lipid v protein thiu ht ca tỡnh trng tit insulin, tỏc dng ca insulin hoc c hai [1] Theo T chc Y t th gii nm 1985 ton th gii cú 30 triu ngi mc T, c tớnh nm 2010 cú khong 240 triu ngi b T D kin nm 2030 s ny s tng thnh 400 triu ngi[1],[2] Ti Vit Nam 10 nm gn õy t l mc T khỏ cao v ang gia tng nhanh chúng iu tra nm 1991 ti mt s vựng lõn cn H Ni t l T trờn 15 tui khong 1,1% dõn sụ, nhng t l ny ó tng 2,2% vo nm 2000, c bit cú vựng lờn n 3%[1] Bnh gan nhim m khụng ru (NAFLD) c cho l nguyờn nhõn chớnh gõy nhng hot ng bt thng ca gan trờn bnh nhõn T type Giai on sm nht ca NAFLD n gin l s thoỏi húa m nhng cú th tin trin thnh bnh gan thoỏi húa m khụng ru (NASH), cui cựng dn ti x húa gan, x gan v bin chng lõu di ca bnh gan mn tớnh l ung th gan Ngi ta cho rng bnh gan nhim m khụng ru ph bin bnh nhõn T typ hn cng ng [3],[4],[5],[6] X gan l mt nguyờn nhõn quan trng gõy t vong bnh tiu ng Mt nghiờn cu khỏm nghim t thi M ó ch rng nhng bnh nhõn b bnh tiu ng cú t l gia tng x húa gan nng [7] Kho sỏt v tỡnh trng x húa gan ngi ta luụn cp ti sinh thit gan nh mt tiờu chun vng Tuy nhiờn õy l mt th thut xõm ln cú nhng tai bin nht nh v l k thut phc ũi hi ngi thc hin phi l bỏc s chuyờn khoa, nhiu kinh nghim, c bit sinh thit gan cng to nờn s khụng thoi mỏi i vi tõm lý ngi bnh nờn cú mt s lng khụng nh bnh nhõn t chi thc hin th thut ny Gn õy, nhiu xột nghim khụng hoc ớt xõm ln ó i cú th thay th mt phn cho sinh thit. Vit Nam hin cú rt ớt cụng trỡnh nghiờn cu v ny Do ú chỳng tụi tin hnh thc hin ti: Kho sỏt mt s ch s khụng xõm ln ỏnh giỏ tỡnh trng x húa gan bnh nhõn ỏi thỏo ng typ vi mc tiờu: Nhn xột tỡnh trng x húa gan bnh nhõn ỏi thỏo ng typ bng cỏc ch s: AST/ALT, APRI, FIB-4, Fibroscan Tỡm hiu yu t liờn quan ca cỏc ch s ny vi c im lõm sng v cn lõm sng ca bnh nhõn ỏi thỏo ng typ CHNG TNG QUAN 1.1 i cng v ỏi thỏo ng 1.1.1 Tỡnh hỡnh dch t ỏi thỏo ng trờn th gii v Vit Nam Vo nhng nm cui th k XX v nhng nm u th k XXI, ỏi thỏo ng l bnh khụng lõy phỏt trin nhanh nht Bnh T l mt y t mang tớnh cht ton cu quan trng nh hng n 285 triu ngi trờn ton th gii Mi nm gn triu ngi cht liờn quan trc tip n bnh T, chim 6,8 tng dõn s ton cu Bnh T l nguyờn nhõn ng hnh th t gõy t vong, v gp 80% cỏc nc ang phỏt trin [8] - iu ỏng lo ngi l T tng nhanh cỏc nc ang phỏt trin, s ny a s l T typ 2, thng thỡ c 10 ngi mc bnh T thỡ cú ti ngi l T typ S bựng n T typ v nhng bin chng ca bnh ang l thỏch thc ln vi cng ng Theo thng kờ ca T chc Y t th gii (WHO) bnh T typ chim khong 85% - 95% tng s ngi mc T [9] - Theo thụng bỏo ca Hip hi T Quc t(IDF:) Nm 1994 c th giúi cú 110 ngi mc bnh T Nm 1995 c th cú 135 triu ngi mc Tchim t l 4,0% dõn s ton cu Nm 2000 cú 151 triu ngi mc bnh T Nm 2010 cú ti 285 triu ngi mc bnh T Theo WHO c tớnh s ny s tng cú khong 438 triu ngi vo nm 2030 [8] - Ti M theo thụng bỏo ca trung tõm kim soỏt bnh tt v phũng bnh CDC, bnh T tng 14% hai nm, t 18,3 triu ngi mc bnh T nm 2003 n 20,8 triu ngi nm 2005 - Ti Vit Nam, nm 2001 ln u tiờn iu tra dch t ỏi thỏo ng c tin hnh theo cỏc quy chun quc t Vi s giỳp ca cỏc chuyờn gia hng u ca WHO, iu tra c tin hnh thnh ph ln H Ni, Hi Phũng, Nng v thnh ph H Chớ Minh i tng iu tra l la tui t 30 n 64 T l T l 4,0 %; t l ri lon dung np glucose l 5,1%; t l cỏc yu t nguy c dn n T l 38,5% nhng iu c bit lm ngi ta phi quan tõm l cú ti trờn 60% (64,9%) s ngi mc bnh T khụng c phỏt hin v khụng c hng dn iu tr Nm 2002, bỏo cỏo kt qu ca mt nghiờn cu c tin hnh t nhng nm 1990 cng gõy c s chỳ ý Nghiờn cu c tin hnh H Ni, i tng la tui t 20 n 74 tui, cựng mt phng phỏp v a bn nh nghiờn cu nm 1990; kt qu cho thy t l bnh T ó tng gp ụi (2,16%) so vi 10 nm trc[10] Nm 2002 2003 iu tra quc gia v tỡnh hỡnh bnh T v yu t nguy c c tin hnh trờn c nc Ton b lónh th Vit Nam c chia thnh vựng sinh thỏi T l mc T ton quc l 2,7%, n l 3,7%, nam l 3,3% Vựng nỳi cao l 2,1%, vựng trung du l 2,2%, vựng ng bng v ven bin l 2,7%, vựng ụ th v cụng nghip l 4,4% c bit t l mc bnh T nhúm i tng cú yu t nguy c , tui t 30 n 64 tui, chim t l cao 10,5% T l ri lon dung np glucose l 13,8% T l mc T tng t l thun theo tui (p11,1mmol/l (200mg/dl) v cú cỏc triu chng ca - tng ng huyt: khỏt nhiu, tiu nhiu, n nhiu, gy sỳt ng huyt tng lỳc (nhn n > 8-14 gi) >7,0 mmol/l (126mg/dl ) - bui sỏng khỏc ng huyt tng gi sau ung 75g glucose > 11,1mmol/l (200mg/dl) - (Nghim phỏp tng ng huyt) HbA1c (nh lng bng phng phỏp sc ký lng) 6,5% 1.1.4 C ch bnh sinh ỏi thỏo ng typ [1][9][11][13][14][15] Bnh cn ca T nhiu yu t gõy nờn, cú mi liờn quan gia yu t gen v yu t mụi trng Trong ú ni cm c ch bnh sinh l mi liờn quan mt thit vi ca yu t rilon tit insulin v s khỏng insulin 1.1.4.1 Sinh tng hp insulin ngi, gen iu hũa bi tit insulin nm trờn cỏnh tay ngn ca nhim sc th th 11 Quỏ trỡnh sinh tng hp insulin cú th túm tt qua cỏc bc sau: - u tiờn ribosom tng hp cht preproinsulin, mt polypeptide cú on gm 23 acid amin u N tn, cú trng lng phõn t khong 11500, c - phiờn mó t preproinsulin mARN li ni bo tng ca cỏc t bo Cht preproinsulin c chuyn n li ni nguyờn sinh v chuyn thnh - proinsulin gm 86 acid amin cú trng lng phõn t khong 9000 Tip ú, phn ln cht proinsulin c chuyn n b Golgi ú xy quỏ trỡnh ct chui peptid ni gm 33 acid amin tc C-peptid S to thnh insulin t proinsulin tip tc nang bi tit Di tỏc dng ca ion Ca++, cỏc nang bi tit c chuyn n sỏt mng t bo, nhng nang ny s gii phúng insulin v C-peptid bi hin tng ngoi thc bo Nh vy preproinsulin v proinsulin khụng hot ng v l nhng tin thõn ca insulin hot ng Cú 32 3.2 Nhn xột cỏc ch s: t l AST/ALT, APRI, FIB4, Fibroscan vi tỡnh trng x húa gan 3.2.1 Giỏ tr ca t l AST/ALT (AAR), APRI, FIB-4, Fibroscan nhúm i tng nghiờn cu Bng 3.4 Giỏ tr ngng chn oỏn ca cỏc ch s nhúm i tng nghiờn cu Ngng chn oỏn AAR APRI FIB-4 Cutoff AUROC p Se Sp PPV NPV 3.2.2 Giỏ tr ngng chn oỏn ca t l AST/ALT (AAR), APRI, FIB-4 nhúm bnh nhõn cú gan nhim m Bng 3.5 Giỏ tr ngng chn oỏn ca cỏc ch s nhúm bnh nhõn cú gan nhim m Ngng chn oỏn AAR APRI FIB-4 Cutoff AUROC p Se Sp PPV NPV 33 3.3 Mi liờn quan gia cỏc ch s AAR, APRI, FIB-4 vi mt s c im lõm sng v cn lõm sng 3.3.1 S thay i gia cỏc ch s AAR, APRI, FIB-4 vi thi gian b bnh Bng 3.6 S phõn b ch s AAR vi thi gian b bnh Ch s Thi gian b bnh AAR ( TB SD ) p 10 nm Bng 3.7 S phõn b ch s APRI vi thi gian b bnh Ch s Thi gian b bnh 10 nm APRI ( TB SD ) p Bng 3.8 S phõn b ch s FIB-4 vi thi gian b bnh Ch s Thi gian b bnh FIB-4 ( TB SD ) p 10 nm 3.3.2 S thay i gia cỏc ch s AAR, APRI, FIB-4 vi phng phỏp iu tr Bng 3.9 S phõn b ch s AAR vi phng phỏp iu tr Ch s Phng phỏp iu tr Thuc ung n c AAR ( TB SD ) p 34 Insulin thuc ung Bng 3.10 S phõn b ch s APRI vi phng phỏp iu tr Ch s APRI ( TB SD ) Phng phỏp iu tr p Thuc ung n c Insulin thuc ung Bng 3.11 S phõn b ch s FIB-4 vi phng phỏp iu tr Ch s Phng phỏp iu tr Thuc ung n c Insulin thuc ung FIB-4 ( TB SD ) p 35 3.3.3 S thay i cỏc ch s AAR, APRI, FIB-4 vi cỏc bin chng mn tớnh ca bnh ỏi thỏo ng typ Bng 3.12 S phõn b ch s AAR vi bin chng mn tớnh Ch s Bin chng AAR ( TB SD ) p Cú Khụng Bng 3.13 S phõn b ch s APRI vi bin chng mn tớnh Ch s Bin chng APRI (TB SD) p Cú Khụng Bng 3.14 S phõn b ch s FIB-4 vi bin chng mn tớnh Ch s Bin chng FIB-4 (TB SD) p Cú Khụng 3.3.4 S thay i cỏc ch s AAR, APRI, FIB-4 vi ri lon chuyn húa lipid Bng 3.15 S phõn b ch s AAR vi RLCH lipid 36 Ch s RLCH lipid AAR ( TB SD ) p Cú Khụng Bng 3.16 S phõn b ch s APRI vi RLCH lipid Ch s APRI ( TB SD ) RLCH lipid p Cú Khụng Bng 3.17 S phõn b ch s FIB-4 vi RLCH lipid Ch s RLCH lipid FIB-4 ( TB SD ) Cú Khụng p 37 3.3.5 S thay i cỏc ch s AAR, APRI, FIB-4 vi gan nhim m Bng 3.18 S phõn b ch s AAR vi gan nhim m Ch s Gan nhim m AAR (TB SD) p Cú Khụng Bng 3.19 S phõn b ch s APRI vi gan nhim m Ch s Gan nhim m APRI (TB SD) p Cú Khụng Bng 3.20 S phõn b ch s FIB-4 vi gan nhim m Ch s Gan nhim m FIB-4 (TB SD) p Cú Khụng 3.3.6 S thay i cỏc ch s AAR, APRI, FIB-4 vi nng glucose mỏu Bng 3.21 Mi liờn quan gia cỏc ch s nghiờn cu v nng glucose mỏu Nng glucose Ch s AAR H s tng quan r Phng trỡnh tuyn tớnh p 38 APRI FIB-4 39 CHNG D KIN BN LUN Da vo kt qu nghiờn cu 40 D KIN BN LUN TI LIU THAM KHO Nguyn Khoa Diu Võn (2012),ỏi Thỏo ng, Bi ging bnh hc ni khoa, NXB Y Hc, Tr 322- 339, Trn c Th (2009), ỏi Thỏo ng, Bnh hc ni khoa sau i hc, NXB Y hc, Tr 218 - 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