KEY WORDS: hepatorenal syndrome, liver cirrhosis, albumin, terlipressin

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1 2009; 15: mg/dl 142 International Ascites Club Child-Pugh score mg/dl 3.22 mg/dl terlipressin Terlipressin KEY WORDS: hepatorenal syndrome, liver cirrhosis, albumin, terlipressin Narahara Y 1, Kanazawa H 1, Fukuda T 1, Harimoto H 1, Matsushita Y 1, Kidokoro H 1, Katakura T 1, Atsukawa M 1, Nakatsuka K 1, Sakamoto C 1 : Incidence, clinical characteristics, treatment and prognosis of type 1 hepatorenal syndrome: A single institution experience. JJPH 2009; 15: I , 2 1 spontaneous bacterial peritonitis: SBP 3, 4 1 transjugular intrahepatic portosystemic shunt: TIPS 3, , International Ascites Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan Club IAC 3, 7 1 IAC 1 IAC 1 retrospective II creatinine: Cre 1.5 mg/dl Cre mg/dl Cre 1.5 mg/dl Cre ; 15:

2 1 1.5 L g 1 L plasma volume expansion Cre creatinine clearance: Ccr Cre Ccr IAC 7 Major criteria 5 2 Cre 2.5 mg/dl Ccr ml/min IAC 1 5 terlipressin pilot study terlipressin terlipressin IAC 1 mean S.D., Wilcoxon p 0.05 Kaplan-Meier III β Ca International Ascites Club Major criteria 1 2 Creatinine 1.5 mg/dl creatinine clearance 40 ml/min L plasma volume expansion mg/day Additional criteria ml/day 4 RBC 50/HPF 2 Na 10 meq/l 5 Na 130 meq/l ; 15:

3 1 2 (n = 27) median (range) (n =16) median (range) Age (year) (45 82) (51 82) Sex (male/female) 18/9 10/6 Etiology (HCV/HBV/ALC/Others) 11/3/10/3 6/2/6/2 Ascites (moderate/severe) 11/16 9/7 Hepatic encephalopathy (yes/no) 7/20 6/10 Hepatocellular carcinoma (yes/no) 8/19 6/10 Child grade (B/C) 1/26 0/16 Child-Pugh score (9 13) (10 13) MELD score ( ) ( ) Serum total bilirubin (mg/dl) ( ) ( ) Serum albumin (g/dl) ( ) ( ) Prothrombin time ( ) ( ) ( ) Serum creatinine (mg/dl) ( ) ( ) Creatinine clearance (ml/min) ( ) ( ) Mean arterial pressure (mmhg) (57 97) (57 91) Heart rate (beats/min) (60 104) (60 104) Urine volume (ml/day) (0 1726) (0 763) Urinary sodium excretion (meq/day) ( ) ( ) Serum sodium (meq/l) ( ) ( ) Plasma renin activity (ng/ml/hr) ( ) Aldosterone (pg/ml) ( ) Norepinephrine (pg/ml) ( ) Antidiuretic hormone (pg/ml) ( ) Atrial natriuretic peptide (pg/ml) ( ) HCV: hepatitis C virus, HBV: hepatitis B virus, ALC: alcoholic, MELD: model for end stage liver disease SBP L 2009; 15:

4 Child-Pugh score mg/dl g/dl Cre mg/dl Ccr ml/min Na hemodiafiltration: HDF Cre 2 Cre mg/dl mg/dl p = Cre 1.5 mg/dl Cre 1.5 mg/dl Cre g/ Cre 2.74 mg/dl 1.22 mg/dl HDF g/ μg/kg/ Cre 4.72 mg/dl 1.39 mg/dl 11 HDF g/ 5 24 Cre 4.01 mg/dl 3.05 mg/dl μg/kg/ 12.5g/ Cre 3 Cre mg/dl 1 DOA 3 μg/kg/ (135) 11 2 Alb 12.5 g 7 + DOA 3 μg/kg/ (123) (250) (0) 2 5 Alb 12.5 g 1 + DOA 3 μg/kg/ (30) (59) 6 7 Alb 20g (-24) 15 8 Alb 12.5 g 3 + DOA 3 μg/kg/ (0) 3 9 Alb 12.5 g 3 + DOA 3 μg/kg/ (56) 6 10 DOA 3 μg/kg/ (80) 7 11 Alb 12.5 g 1 + DOA 3 μg/kg/ (148) Alb 20 g (-56) HDF 11 +Alb 12.5 g 9 + DOA 3 6 μg/kg/ (-71) 25 HDF 14 Alb 12.5 g 1 + DOA 3 μg/kg/ (58) 3 15 DOA 3 μg/kg/ (85) 7 16 NE μg/kg/ 14 + Alb 12.5 g (-24) 19 Cre: creatinine, DOA: dopamine, NE: norepinephrine, Alb: albumin, HDF: hemodiafiltration ; 15:

5 Creatinine (mg/dl) P= n = Probability of survival Days 3 1 n = mg/dl 1.53 mg/dl IV. IAC 1 IAC IAC 1 1, ; 15:

6 5, 12 Cre 1.5 mg/dl ml/min 13 IAC 3, TIPS 1 SBP , vasopressin ornipressin terlipressin α 1 terlipressin terlipressin , 14 16, 1 5 terlipressin pilot study HDF 1 1 8, 17, , 17, 18 terlipressin 1 terlipressin 2 4 terlipressin 19, 20 21, 22 TIPS TIPS 25 TIPS 2 4, 14, terlipressin V SBP 12 1 Gines A, Escorsell A, Gines P, et al: Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology 1993; 105: Gines P, Guevara M, Arroyo V, et al: Hepatorenal syndrome. Lancet 2003; 362: Salerno F, Gerbes A, Gines P, et al: Diagnosis, prevention and treatment of hepatorenal syndrome. Gut 2007; 56: Arroyo V, Terra C, Gines P, et al: Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol 2007; 46: Garcia-Tsao G, Parikh CR, Viola A: Acute kidney injury in cirrhosis. Hepatology 2008; 48: Moreau R, Lebrec D: Acute kidney injury: new concepts. Hepatorenal syndrome: the role of vasopressors. Nephron Physiol 2008; 109: Arroyo V, Gines P, Gerbes AL, et al: Definition and ; 15:

7 diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996; 23: Peron JM, Bureau C, Gonzalez L, et al: Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study. Am J Gastroenterol 2005; 100: Moreau R, Lebrec D: Diagnosis and treatment of acute renal failure in patients with cirrhosis. Best Pract Res Clin Gastroenterol 2007; 21: Fang JT, Tsai MH, Tian YC, et al: Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure. Nephrol Dial Transplant 2008; 23: : terlipressin 2006; 12: Moreau R, Lebrec D: Acute renal failure in patients with cirrhosis: perspectives in the age of MELD. Hepatology 2003; 37: Bataller R, Gines P, Guevara M, et al: Hepatorenal syndrome. Semin Liver Dis 1997; 17: Arroyo V, Bataller R, Guevara M: Treatment of hepatorenal syndrome in cirrhosis. in Ascites and renal dysfunction in liver disease: pathogenesis, diagnosis, and treatment, ed by Arroyo V, Gines P, Rodes J, Schrier RW, 1st Ed, Blackwell Science, Malden, 1999: Arroyo V, Terra C, Gines P: New treatments of hepatorenal syndrome. Semin Liver Dis 2006; 26: Moreau R, Lebrec D: The use of vasoconstrictors in patients with cirrhosis: type 1 HRS and beyond. Hepatology 2006; 43: Martin-Llahi M, Pepin M, Guevara M, et al: Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008; 134: Sanyal AJ, Boyer T, Garcia-Tsao G, et al: A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008; 134: Alessandria C, Ottobrelli A, Debernardi-Venon W, et al: Noradrenaline vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol 2007; 47: Sharma P, Kumar A, Shrama BC, et al: An open label, pilot randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol 2008; 103: Angeli P, Volpin R, Gerunda G, et al: Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999; 29: Wong F, Pantea L, Sniderman K: Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology 2004; 40: Brensing KA, Textor J, Perz J, et al: Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study. Gut 2000; 47: Guevara M, Gines P, Bandi JC, et al: Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems. Hepatology 1998; 28: : TIPS ; 106: Moreau R, Durand F, Poynard T, et al: Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology 2008; 134: Incidence, clinical characteristics, treatment and prognosis of type 1 hepatorenal syndrome: A single institution experience Yoshiyuki Narahara 1, Hidenori Kanazawa 1, Takeshi Fukuda 1, Hirotomo Harimoto 1, Yoko Matsushita 1, Hideko Kidokoro 1, Tamaki Katakura 1, Masanori Atsukawa 1, Katsuhisa Nakatsuka 1, Choitsu Sakamoto 1 1 Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School A total of 929 patients with liver cirrhosis were admitted to our department between 2004 and Of these, 142 patients were complicated by kidney injury, with creatinine of 1.5 mg/dl or higher at or after admission. One hundred six out of 142 patients developed acute kidney injury, and including 27 with type 1 hepatorenal syndrome. We retrospectively investigated the background, treatment and prognosis of type 1 hepatorenal syndrome in 27 patients. The 27 patients were selected according to the diagnostic criteria for hepatorenal syndrome proposed by International Ascites Club. Average Child-Pugh score was 12.4, total bilirubin 15.1 mg/dl, and creatinine 3.22 mg/dl in the 27 patients. Precipitating factors were infection (n=16), paracentesis (n=5) and other causes (n=6). These 27 patients were treated with albumin (n=21), terlipressin (n=11), dopamine (n=11), noradrenaline (n=1), hemodiafiltration (n=1). Of 16 patients treated with conventional therapies other than terlipressin, 15 died. Their mean survival time was 12 days. Type 1 hepatorenal syndrome occurred in 25 of the cirrhotic patients with acute kidney injury. This syndrome developed as a consequence of severe hepatic failure and the prognosis following conventional therapy was quite poor. 2009; 15: