9$,75Ñ&ê$7(5/,35(66,17521* ,Ä875Î+Ü,&+ì1**$1...
Transcript of 9$,75Ñ&ê$7(5/,35(66,17521* ,Ä875Î+Ü,&+ì1**$1...
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VAI TRÒ C A TERLIPRESSIN TRONG ĐI U TR H I CH NG GAN-TH N
PGS.TS.BS BÙI H U HOÀNG
Trưởng Khoa Tiêu hóa B nh vi n Đ i Học Y Dược TpHCM
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Hộià hứ gàga -thậ àl àgì?à
Suy th n ch c năng và có kh năng hồi ph c
ở b nh nhân b suy gan nặng (c p hoặc m n tinh) và tăng áp
tĩnh m ch cửa
Không có nguyên nhân
gây suy th n được phát hi n
CH N ĐOỄN LO I TR Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310-1318
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BỆNHàSINHàCỦáàHRS
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Clinical Journal of the American Society of Nephrology (VD: vasodilators; VC: vasoconstrictors, SNS: sympathetic nervous system)
Stimulation of
Vasoconstrictor system
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BỆNHàSINHàCỦáàHRS
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Vasoactive Factors Involed in the Regulation of Renal
Perfusion in Cirrhosis and the Pathogenesis of Hepatorenal
Syndrome
Vasodilators
Prostacyclin Prostaglandin E2 Nitric oxide Atrial natriuretic peptide Kallikrein-kinin system Vasoconstrictors
Angiotensin II Norepinephrine Neuropeptide Y Endothelin-I Adenosine Thromboxane A2 Cysteinyl leukotrienes F2-isoprostanes
BỆNHàSINHàCỦáàHRS
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Source: Am J Kidney Dis 2012; The National Kidney Foundation
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Bằ gà hứ gà hoàthấ àThậ àvẫ à àhứ à ă gà ì hàthườ g
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Tiêu huẩ hẩ đo chính ủa HRS
1- Cị B NH GAN (c p hay m n ) ti n tri n suy gan nặng và tăng áp l c tĩnh m ch cửa
2- Cị SUY TH N: GFR th p bi u th bằng creatinine clearance < 40 mL/min hoặc creatinine máu >1,5mg/dL (>133mmol/L)
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Tiêu huẩ hẩ đo chính ủa HRS
3- KHÔNG Cị B NH TH N trước đó
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Tiêu huẩ hẩ đo chính ủa HRS
4- KHÔNG Cị NGUYÊN NHÂN TR C TH N
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Tiêu huẩ hẩ đo chính ủa HRS
4- KHÔNG Cị NGUYÊN NHÂN TR C TH N
After at least 2 days
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Tiêu huẩ hẩ đo chính ủa HRS
4- KHÔNG Cị NGUYÊN NHÂN SAU TH N
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Lưuàý:àCreati i eàkh gàphảiàl àth gàsốàđ gàti à ậ àđểàđ hàgi à hứ à ă gàthậ àtro gàHRS
• Tăng bilirubin máu nặng có th nh hưởng làm gi m k t qu creatinine
• Suy th n v n có th hi n di n mặc dù k t qu creatinine còn bình thường (BN suy dinh dưỡng, gi m khối cơ)
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Phân loại HRS
• Típ 1: cấp (vd. viêm gan c p do rượu) ậ Creatinine máu tăng g p đôi > 2,5mg/dL (220 mmol/L) hoặc creatinine clearance 24 giờ gi m < 20ml/min < 2 tu n
ậ Thường có y u tố khởi phát (vd nhi m trùng) ậ Thời gian sống trung bình khi không đi u tr : 2 tu n
• TỦp 2: mạn ậ Di n ti n t t , creatinine máu # 1,5-2,5 mg/dL
ậ Thường gặp trong cổ trướng kháng tr
ậ Thời gian sống trung bình: 4-6 tháng
International Ascites Club
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XHTH
Thuốc đ c
th n
Vàng da
tắc m t
VPM
nhi m khuẩn
nguyên phát
Chọc tháo
d ch báng
l ng nhi u
Dùng nhi u
l i tiểu
↓ Thể tích máu ĐM hi u quả
(EABV)
Yếuàtốàthuậ àlợià? Đốiàtượ gà gu à ơà?
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H i ch ng gan-th n (HRS) Các y u tố tiên đoán v di n ti n
• Phát tri n sau khởi phát cổ trướng t i thời đi m:
ậ 2 năm 32%
ậ 5 năm 41%
• Nguyên nhân thường gặp nh t c a HRS típ 1 là
viêm phúc m c nguyên phát (SBP)
• 30% b nh nhân b SBP s phát tri n thành HRS.
• HRS là y u tố tiên đoán quan trọng nh t v tỷ l
tử vong t i b nh vi n ở b nh nhân b SBP
Gines, 1993
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DI N TI N T NHIểN C A H I CH NG GAN-TH N
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TIÊN L NG TÙY THU C TệP C A HRS
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NGUYÊNàTẮCààĐIỀUàTRỊ Dựa trên Sinh lý ệ h
HEPATO-RENAL
SYNDROME
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NGUYÊNàTẮCààĐIỀUàTRỊ Dựa trên Sinh lý ệ h
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NGUYÊNàTẮCààĐIỀUàTRỊ
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NGUYÊNàTẮCààĐIỀUàTRỊ
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NGUYÊNàTẮCààĐIỀUàTRỊ
Terlipressin, IV 1mg q4-6h to start, increase dose if SCr does not fall at least 25% after 3 days. For partial response (SCr does not fall < 133 umol/L) or non-responders, treatment be stopped within 14 days
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Terlipressi à ảiàthiệ àGFRàtro gàHRS
J. Uriz et al J. Hepatol. 2000
0
1
2
3
4
5
Baseline TreatedS
er.
Cre
at
(mg
/dl)
0
30
60
90
Baseline Treated
Me
an
Art
. P
res
su
re (
mm
Hg
) *
*
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Terlipressi àứ à hếà ate hola i esàv ààhoạtàh aàRááS
0
500
1000
1500
2000
Baseline Treated
Pl. N
ore
pin
ep
hrin
e (
pg
/ml)
0
10
20
30
40
Baseline Treated
PR
A (
ng
/ml/h
)
**
J. Uriz et al J. Hepatol. 2000
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HRS-1 hồi ph c khi đi u tr bằng Terlipressin + albumin
Sanyal AJ et al. 2008. Gastroenterology;134:1360-1368.
Prospective randomized double blind placebo-controlled study
Type 1 HRS Terlipressin 1mg Q6H + albumin (n=56)
Placebo + albumin (n=56)
Rev
ersa
l: ≤1
.5 m
g/dL
34%
13%
P=0.008
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C i thi n nồng đ Creatin máu trong HRS-1 khi đi u tr bằng Terlipressin
Sanyal AJ et al. 2008. Gastroenterology;134:1360-1368.
Mean change from baseline in SCr (mg/dL) to end of treatment
P=0.009
Overall survival at 6 months: 43% (terlipressin) vs 38% (placebo), p=0.839
(mg/dL)
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Terlipressin + Albumin so với Albumin đơn thu n trong đi u tr HRS
Martin-Llahi M et al. 2008. Gastroenterology;134:1352-1359.
HRS Type 1&2 (N=46)
Terlipressin 1-2mg/Q4H + albumin (n=23)
Albumin (n=23)
Complete response Cr <133 umol/L Partial response ≥50% decrease in SCr
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Phân tích g p v các Thử nghi m ng u nhiên c a các thuốc co m ch
trong đi u tr HRS
Gluud LI et al. 2010. Hepatology;51:576-584.
Terlipressin + albumin may prolong short term survival of type 1 HRS RR 95% CI
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Tỷ l sống còn chưa c n ghép gan khi đi u tr HRS bằng Terlipressin
Sagi SV et al. 2010. J Gastro Hepatol;25:880-885.
4 different trials: total 223 patients Type 1 HRS with ≥3 days terlipressin + albumin
The RR for reversal of Type 1 HRS with terlipressin was 3.66 (95% CI, 2.15ậ6.23; p<0.0001)
Terlipressin treatment 1.85x more likely to be alive at 90-days without transplantation
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Phân tích g p: Terlipressin trong đi u tr HRS
Gluud LL et al. 2012. Cochrane Database Syst Rev;Sep 12;9.
Randomized trials in Type 1 or 2 HRS with terlipressin +/- albumin vs placebo +/- albumin 5 randomized clinical trials with 249 patients
Outcome: Mortality
Terlipressin reduced mortality compared with no intervention, placebo, or albumin
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TIPS có th c i thi n ch c năng th n ở m t số BN nhưng chưa đ d li u cho vi c sử d ng trong HRS-1
Transjugular Intrahepatic Portosystemic
Stent-Shunt (TIPS)
EASL Guidelines. 2010. J Hepatol;53:397-417
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ĐIỀUàTRỊàLỌCàTHẬN
Lọc th n được ch đ nh ngắn h n đ bắc c u chờ đợi ghép gan
Không có bằng ch ng cho th y Lọc th n s làm tăng tỷ l sống lâu dài khi không ghép gan
Lọc th n có th giúp gi i quy t m t số bi n ch ng c a HRS: toan máu, tăng urê máu,
tăng kali máu
EASL Guidelines. 2010. J Hepatol;53:397-417
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C n đi u tr HRS trước khi ghép gan: - Nh ng BN có đáp ng với đi u tr HRS c n được ghép gan đơn
thu n - Nh ng BN không đáp ng với đi u tr HRS và c n ph i lọc th n
cũng thường được ghéop gan đơn thu n - Nh ng BN c n ph i lọc th n kéo dài (> 12 tu n) c n xem xét k t
hợp ghép gan và th n
CỄCH ĐI U TR DUY NH T Cị HI U QU CHO
C HRS-1 VÀ HRS-2
GHÉP GAN
EASL Guidelines. 2010. J Hepatol;53:397-417 EASL Guidelines. 2010. J Hepatol;53:397-417
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Ph gà gừaà hưàthếà o?
(NSAID, Aminosides, Contrast)
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Th n trọng khi s d ng l i tiểu
Thăm dò li u lợi ti u th p nh t đ t hi u qu cho t ng b nh nhân
Suy th n liên quan dùng lợi ti u: - 20% b nh nhân xơ gan nh p vi n vì cổ trướng - thường không nặng - hồi ph c nhanh chóng sau khi ngưng lợi ti u
BảoàvệàThậ àởà ệ hà h à ơàga
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Bảoàvệàthậ àởà ệ hà h à ơàga
Phòng ngừa nhi m trùng: ậ Xu t huy t tiêu hóa do vỡ giãn TM th c qu n
* 35-66% có nhi m trùng * 7-15% b SBP
* XHTH kèm cổ trướng: 30-50% b SBP ậ Viêm phúc m c nhi m khu n nguyên phát
Gia tăng th tích huy t tương trong tình tr ng nhi m trùng
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30% SBP
Suy th n
Gines, 1997
Bảoàvệàthậ àởà ệ hà h à ơàga
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Tiêu chuẩn chọn bệnh
• Tuổi 18–80
• Protein dịch báng < 15 g/L
• Suy chức năng thận (Cr 1.2 mg/dL, BUN 25 mg/dL hoặc Na 130 mEq/L)
hoặc Điểm số Child–Pugh 9 points với bilirubin 3 mg/dL.
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Khả năng ti n triển sang HRS ở b nh nhân đ c dự phòng bằng norfloxacin so v i placebo
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Khả năng sống 1 năm ở nh ng b nh nhân đ c dự phòng bằng norfloxacin so v i placebo
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Hãy chăm sóc lá gan của bạn