Đặc điểm lâm sàng, cận lâm sàng của bệnh nhân viêm gan b mạn tính có HBeAg âm tính điều trị tại bệnh viện đa khoa trung ương thái nguyên

I HC THI NGUYấN TRNG I HC Y - DC PHNG TH TUYT NGA C IM LM SNG, CN LM SNG CA BNH NHN VIấM GAN B MN TNH Cể HBeAg M TNH IU TR TI BNH VIN A KHOA TRUNG NG THI NGUYấN LUN VN THC S Y HC THI NGUYấN - 2015 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn I HC THI NGUYấN TRNG I HC Y - DC PHNG TH TUYT NGA C IM LM SNG, CN LM SNG CA BNH NHN VIấM GAN B MN TNH Cể HBeAg M TNH IU TR TI BNH VIN A KHOA TRUNG NG THI NGUYấN Chuyờn ngnh : NI KHOA Mó s : 60.72.01.40 LUN VN THC S Y HC Hng dn khoa hc: TS NGUYN TRNG HIU THI NGUYấN - 2015 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn i LI CAM OAN Tụi xin cam oan õy l cụng trỡnh nghiờn cu ca tụi Cỏc s liu, kt qu nờu lun l trung thc v cha tng c cụng b bt k mt cụng trỡnh nghiờn cu no khỏc Thỏi Nguyờn, thỏng nm 2015 Hc viờn Phựng Th Tuyt Nga S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn ii LI CM N hon thnh lun ny tụi ó nhn c s ch o, quan tõm ging dy ca nh trng, cỏc phũng ban cựng cỏc thy cụ Tụi xin trõn cm n: - Ban Giỏm hiu, Phũng Qun lý o to sau i hc, B mụn Ni, B mụn Vi sinh Trng i hc Y - Dc Thỏi Nguyờn - Ban Giỏm c, Phũng k hoch Tng hp, Khoa Truyn nhim - Khoa Tiờu húa - Tit niu - Huyt hc lõm sng Bnh vin a khoa Trung ng Thỏi Nguyờn - Ban Giỏm hiu, Phũng T chc, B mụn Truyn nhim Trng Cao ng Y t Thỏi Nguyờn ó luụn nhit tỡnh giỳp , to iu kin thun li cho tụi quỏ trỡnh hc tp, cụng tỏc v hon thnh lun ny Vi lũng bit n chõn thnh, tụi xin gi li cm n sõu sc ti: TS Nguyn Trng Hiu - ngi Thy ó trc tip ch bo, hng dn tn tỡnh sut quỏ trỡnh hc v ch bo, sa cha giỳp tụi hon thnh lun ny Tụi cng xin by t lũng bit n chõn thnh n cỏc Thy, Cụ Hi ng khoa hc, B mụn Ni ó dnh thi gian c v úng gúp nhiu ý kin quý bỏu cho lun cng nh sut quỏ trỡnh hc ca tụi B mụn Vi sinh, c bit l TS Nguyn c Trung ó to mi iu kin giỳp tụi quỏ trỡnh hc tp, ly s liu thc hin lun Cm n cỏc ng nghip, bn bố gn, xa ó luụn giỳp , ng viờn tụi quỏ trỡnh hc v thc hin ti Vi tỡnh cm thõn thng nht, tụi xin dnh cho nhng ngi thng yờu ton th gia ỡnh, ni ó to iu kin tt nht, l im ta, ngun ng viờn tinh thn giỳp tụi thờm nim tin v ngh lc sut quỏ trỡnh hc v thc hin nghiờn cu ny Thỏi Nguyờn, thỏng nm 2015 Phựng Th Tuyt Nga S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn iii DANH MUC VIấT TT ALT : Alanine Aminotransferase AST : Aspartate Aminotransferase AntiHBc : Antibody to hepatitis B core antigen (Khỏng th i vi khỏng nguyờn lừi ca virus viờm gan B) AntiHBe : Antibody to hepatitis B e antigen (Khỏng th i vi khỏng nguyờn e ca virus viờm gan B) AntiHBs : Antibody to hepatitis B surface antigen (Khỏng th i vi khỏng nguyờn b mt cu virus viờm gan B) HBcAg : Hepatitis B core Antigen - Khang nguyờn loi virus viờm gan B HBeAg : Hepatitis B e Antigen - Khang nguyờn e virus viờm gan B : Hepatitis B surface Antigen - Khỏng nguyờn b mt virus HBsAg viờm gan B CccDNA : Covalently closed cicular DNA) HBV : Hepatitis B Virus - Virus viờm gan B HCC : Hepatocelluler carcinoma - Ung th t bo gan nguyờn phỏt HCV : Hepatitis C Virus - Virus viờm gan C HDV : Hepatitis D Virus - Virus viờm gan D HEV : Hepatitis E Virus - Virus viờm gan E HGV : Hepatitis G Virus - Virus viờm gan G HTV : Hepatitis T Virus - Virus viờm gan T VGBMT : Viờm gan B mn tớnh VGB : Viờm gan B KN, KT : Khỏng nguyờn, khỏng th HBV- DNA : Desoxyribonucleic acid of Hepatitis B Virus PC, CP : Pre - core , Core promoter BCP : Basic Core - promoter UTTBBMG : Ung th t bo biu mụ gan TMTQ : Tnh mch thc qun S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn iv MC LC Li cam oan i Li cm n ii Danh mc ch vit tt iii Mc lc iv Danh mc bng vi Danh mc hỡnh vii Danh mc biu viii T VN i CHNG 1: TNG QUAN 1.1 Tỡnh hỡnh nhim HBV trờn Th gii v Vit Nam 1.1.1 Tỡnh hỡnh nhim HBV trờn Th gii 1.1.2 Tỡnh hỡnh nhim HBV Vit Nam 1.2 Mt s c im v virus viờm gan B (HBV) 1.2.1 Hỡnh th v cu trỳc ca HBV 1.2.2 Kiu gen ca HBV 1.2.3 S nhõn lờn ca virus HBV 1.2.4 Cỏc th t bin ca HBV 1.2.5 ỏp ng dch viờm gan B v cỏc du n huyt 10 1.3 Triu chng ca VGBMT 17 1.3.1 Triu chng lõm sng 17 1.3.2 Triu chng cn lõm sng 18 1.4 Din bin t nhiờn nhim virus VGB 19 1.4.1 Viờm gan virus cp 20 1.4.2 Viờm gan virus mn 20 1.5 iu tr 23 1.6 Cỏc nghiờn cu v VGBMT trờn Th gii v Vit Nam 24 1.6.1 Nghiờn cu trờn th gii v viờm gan B mn tớnh HBeAg (-) 24 1.6.2 Nghiờn cu ti Vit Nam v viờm gan B mn tớnh HBeAg (-) 26 CHNG 2: I TNG V PHNG PHP NGHIấN CU 27 2.1 i tng nghiờn cu 27 2.1.1 Tiờu chun chn bnh nhõn 27 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn v 2.1.2 Tiờu chun loi tr bnh nhõn 27 2.2 a im v thi gian nghiờn cu 28 2.3 Phng phỏp nghiờn cu 28 2.3.1 Thit k nghiờn cu 28 2.3.2 Phng phỏp chn mu 28 2.3.3 Ch tiờu nghiờn cu 29 2.3.4 Phng phỏp thu thp s liu 30 2.4 Vt liu nghiờn cu 35 2.5 X lý s liu 36 2.6 Vn o c nghiờn cu 36 CHNG 3: KT QU NGHIấN CU 38 3.1 c iờ m lõm sng, cn lõm sng bnh nhõn VGBMT ca hai nhúm nghiờn cu 38 3.1.1 c iờ m chung ca hai nhúm nghiờn cu 38 3.1.2 Triu chng lõm sng ca hai nhúm nghiờn cu 41 3.1.3 c im cn lõm sng ca hai nhúm nghiờn cu 42 3.2 Mi liờn quan gia nng HBV - DNA vi mt s ch s sinh húa, huyt hc ca bnh nhõn viờm gan B mn tớnh 49 CHNG 4: BN LUN 52 4.1 c iờ m lõm sng, cn lõm sng bnh nhõn VGBMT ca hai nhúm nghiờn cu 52 4.1.1 c iờ m chung ca hai nhúm nghiờn cu 52 4.1.2 Triu chng lõm sng 53 4.1.3 c im cn lõm sng 56 4.2 Mi liờn quan gia nng HBV - DNA vi mt s ch s sinh húa, huyt hc ca bnh nhõn viờm gan B mn tớnh 62 KT LUN 67 KHUYN NGH 68 DANH MC CC CễNG TRèNH NGHIấN CU CA TC GI CễNG B Cể LIấN QUAN N LUN VN THC S 69 TI LIU THAM KHO BNH N NGHIấN CU S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn vi DANH MC BNG Bng 1.2 í ngha cỏc Markers ca HBV trờn lõm sng 17 Bng 3.1 Phõn b bnh nhõn theo tui ca hai nhúm 38 Bng 3.2 Phõn b bnh nhõn theo gii ca hai nhúm 39 Bng 3.3 Thi gian t phỏt hin bnh ca hai nhúm 40 Bng 3.4 Lý vo vin ca hai nhúm 41 Bang 3.5 Cỏc triu chng c nng, ton thõn ca hai nhúm 41 Bang 3.6 Cỏc triu chng thc th ca hai nhúm 42 Bng 3.7 S lng mỏu ngoi vi ca hai nhúm 42 Bang 3.8 Giỏ tr AST, ALT huyt ca hai nhúm 44 Bng 3.9 Giỏ tr Albumin huyt tng, Protein huyt ca bnh nhõn VGBMT 45 Bng 3.10 Giỏ tr Bilirubin huyt ton phn ca hai nhúm 46 Bng 3.11 Giỏ tr Prothrombin huyt ca hai nhúm 46 Bng 3.12 Nng trung bỡnh HBV- DNA ca hai nhúm 47 Bng 3.13 c im ni soi thc qun ca hai nhúm 48 Bng 3.14 c im siờu õm gan, lỏch ca hai nhúm 48 Bng 3.15 Tng quan gia HBV- DNA vi mt s ch s sinh húa mỏu ca hai nhúm 49 Bng 3.16 Tng quan gia HBV- DNA vi mt s ch s huyt hc, ụng mỏu ca hai nhúm 50 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn vii DANH MC HèNH Hỡnh 1.1 Phõn b HBV mn tớnh trờn th gii Hỡnh 1.2 Hỡnh th virus viờm gan B Hỡnh 1.3 S nhõn ụi ca HBV Hỡnh 1.4 Cỏc giai on ca viờm gan B mn tớnh 21 Hỡnh 1.5 T l din tin bnh gan hng nm ca nhim HBV mn 23 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn viii DANH MC BIU Biu 1.1 T l nhim HBV cỏc nghiờn cu cng ng v trờn cỏc i tng khe mnh Biu 1.2 Quỏ trỡnh tin trin HBV mn tớnh 19 Biu 3.1 Phõn b bnh theo nhúm ca bnh VGBMT 38 Biu 3.2 Phõn b bnh nhõn theo nhúm tui ca bnh VGBMT .39 Biu 3.3 Phõn b bnh theo ni c trỳ ca hai nhúm 40 Biu 3.4 S lng t bo mỏu ngoi vi ca hai nhúm 43 Biu 3.5 Giỏ tr AST, ALT huyt ca hai nhúm 44 Biu 3.6 Giỏ tr Albumin huyt tng, Protein huyt ca hai nhúm 45 Biu 3.7 Phõn loi theo Child Pugh ca hai nhúm 47 Biu 3.8 Mi tng quan gia HBV- DNA v ALT nhúm HBeAg (-) 49 Biu 3.9 Mi tng quan gia HBV-DNA v AST nhúm HBeAg õm tớnh 50 Biu 3.10 Mi tng quan gia HBV- DNA v tiu cu nhúm HBeAg (-) .51 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn 69 DANH MC CC CễNG TRèNH NGHIấN CU CA TC GI CễNG B Cể LIấN QUAN N LUN VN THC S Phựng Th Tuyt Nga, Nụng Th Tuyn, Nguyn Trng Hiu (2015) c im lõm sng, cn lõm sng ca bnh nhõn viờm gan B mn tớnh cú HBeAg õm tớnh iu tr ti Bnh vin a khoa trung ng Thỏi Nguyờn, Tp y hc thc hnh s thỏng S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn TI LIU THAM KHO Ting Vit ụng Th Hoi An (2011), "Phõn b cỏc kiu gen vius viờm gan B cỏc bnh cnh lõm sng v cỏc bin chng ca viờm gan B", Lun tin s y hc, Trng i hc y dc thnh ph H Chớ Minh Trn Ngc nh (2010)," Vai trũ ca tiu cu , t l AST, ALT, APRI ỏnh giỏ tỡnh trng x húa gan " nghiờn cu y hc, 64, trang 41, 45 Nguyn Th Võn Anh (2009), "Nghiờn cu gen Pres, gen X ca virut viờm gan B mụ, huyt v mt s du n huyt bnh nhõn ung th biu mụ t bo gan", Lun ỏn tin s y hc, Trng i hc y H Ni Nguyn Th Kim Chớnh (2009), "c im lõm sng v xột nghim bnh nhõn viờm gan virut B mn cú HBeAg õm tớnh v HBeAg dng tớnh" Tp nghiờn cu y hc, 64 (5), trang 41-45 V Cụng Danh (2011), "Nghiờn cu nụng HBsAg, HBV-DNA bnh nhõn viờm gan B mn tớnh", Lun thc s, Trng i hc y H Ni Nguyn Vn Dng, Bựi Th Lan Anh, Nguyn Thựy Linh (2013), "Nghiờn cu t bin vựng gen precore/core virus HBV trờn bnh nhõn viờm gan B mn tớnh ti bnh vin Bch Mai" Tp y hc d phũng,s (143), trang 19 Lờ Thu H (2002), "p dng k thut PCR phỏt hin HBV-DNA huyt bnh nhõn viờm gan B mn tớnh hot ng v ngi mang HBsAg khụng triu chng", Lun thc s y hc, Nguyn Trn Hin (2008), "Tiờm phũng vacxin viờm gan virus B chng trỡnh tiờm chng m rng Vit Nam Nhng thnh tu v thỏch thc" Tp gan mt, s S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn Phm Th L Hoa, Phan Vnh Th (2008), "c im viờm gan siờu vi B mn tớnh HBeAg (-) trờn bnh nhõn ni trỳ ti bnh vin nhit i " Tp y hc TP H Chớ Minh,tp 12 (ph bn s 1), trang 1-8 10 Bựi Hu Hong (2004), "c im ca du n huyt v kiu gen ca virus viờm gan B trờn bnh nhõn x gan v ung th biu mụ t bo gan", Lun ỏn tin s y hc, Trng i hc y dc thnh ph H Chớ Minh 11 ng c Hong (2012), "ỏnh giỏ kt qu d phũng chy mỏu tỏi phỏt sm bng tht bỳi gión phi hp Propranolol bnh nhõn cú v tnh mch thc qun ti bnh vin a khoa Thỏi Nguyờn ", Lun tt nghip bỏc s ni trỳ, Trng i hc y dc Thỏi Nguyờn 12 on Th Thỳy Hng (2008), "Nghiờn cu mi tng quan gia nng HBV DNA ,du n HBeAg vi lõm sng v mt s ch s sinh hc mỏu bnh nhõn x gan viờm gan B mn tớnh" 13 Hong V Hựng (2001), "Din bin lõm sng, sinh húa, du n HBV, t bo TCD3, TCD4, TCD8 v nh hng ca plasma giu anti-HBs trờn bnh nhõn viờm gan virut cp", Lun ỏn tin s, Hc vin quõn y 14 Nguyn Cụng Long (2012), "ỏnh giỏ ỏp ng iu tr viờm gan virus B mn tớnh cú HBeAg (+) v 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(2014), "Hepatitis B surface antigen levels during natural history of chronic hepatitis B: a Chinese perspective study" World J Gastroenterol,vol 20 (27), pp 9178-9184 S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn BNH N NGHIấN CU Hnh chớnh 1.1 Mó lu tr: 1.2 H v tờn: 1.3 Tui: 1.4 Gii : Nam N 1.5 Ngh nghip: 1.6 a ch Thnh th Nụng thụn 1.7 Ngh nghip Lm rung Hu trớ Cụng nhõn Trớ thc Khỏc 1.8 Ngy vo vin: 1.9 Lý vo vin Tng ALT Mt mi n kộm Vng da, vng mt Khỏm nh k au h sn phi Tin s ó tng phỏt hin viờm gan B cỏch (thỏng/nm): thỏng - nm >1- nm > nm c im lõm sng 3.1 Lõm sng 3.1.1 Cỏc triu chng S húa bi Trung tõm Hc liu HTN http://www.lrc.tnu.edu.vn Vo vin Triu chng Cú Khụng Mt mi St t Vng da vng mt Phự chõn Gan to Lỏch to C trng Xut huyt Tun hon bng h Sao mch au h sn phi Bn tay son Ri lon tiờu húa Bun nụn Chỏn n s m Ng kộm ỏi ớt, nc tiu sm mu 3.2 Cn lõm sng 3.2.1 Sinh húa mỏu Ngy Ch s Bilirubin TP (àmol/l) Protein TP (g/l) Albumin (g/l) AST (U/l) ALT (U/l) S húa bi Trung tõm Hc liu HTN 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HỌC THÁI NGUYÊN TRƯỜNG ĐẠI HỌC Y - DƯỢC PHÙNG THỊ TUYẾT NGA ĐẶC ĐIỂM LÂM SÀNG, CẬN LÂM SÀNG CỦA B NH NHÂN VIÊM GAN B MẠN TÍNH CÓ HBeAg ÂM TÍNH ĐIỀU TRỊ TẠI B NH VIỆN ĐA KHOA TRUNG ƯƠNG THÁI NGUYÊN... HBV- DNA cải thiện nhiều nguy gây biến chứng cho người b nh Để hiểu rõ diễn biến b nh viêm gan B mạn tính có HBeAg âm tính Thái Nguyên tiến hành nghiên cứu đề tài: Đặc điểm lâm sàng, cận lâm