Dominique Valla, Richard Moreau, and Didier Lebrec Journal conference 10.09.13 Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites Thomas Serste´ ,Christian Melot, Claire Francoz, Franc¸ ois Durand, Pierre-Emmanuel Rautou, Dominique Valla, Richard Moreau, and Didier Lebrec HEPATOLOGY 2010;52:1017-1022 by the Tuberculosis Network European Trials Group (TBNET) R2. 장원석

Korea National Diabetes Program Background Refractory ascites : a lack of response to high doses of diuretics the recurrence of side effects when lower doses of diuretics are given. ->The first-line treatment :repeated large-volume paracentesis. The administration of nonselective beta-blockers for the prevention of gastrointestinal hemorrhaging is frequent when esophageal varices are present. However, this treatment may have deleterious effects on patients with ascites treated by large-volume paracentesis. The aim of the present study was to evaluate the effect of the administration of nonselective beta-blockers on long-term survival in patients with cirrhosis and refractory ascites. Korea National Diabetes Program

Korea National Diabetes Program Patients and Methods Study Population. a single-center observational case-only prospective study January 2004 ~ December 2008 all consecutive patients who had cirrhosis >18 years refractory ascites * Refractory ascites : diuretic-resistant despite intensive diuretic therapy (spironolactone: 400mg/day+furosemide: 150mg/day) dietary sodium restriction (90 mmol/day). * metabolic abnormalities were diuretic induced hepatic encephalopathy hyponatremia (<serum sodium 125 mmol/L), renal impairment (>serum creatinine 1.5 mg/dL), abnormal serum potassium levels (serum potassium level 3~6 mmol/L). Korea National Diabetes Program

Study Variables demographic data etiology of cirrhosis physical examination findings, biochemical values, Child-Pugh score, Model for End-Stage Liver Disease MELD score MELD-Na score hospital course laboratory values, and outcomes (renal dysfunction development, liver transplantation, or death) hepatic venous pressure gradient (HVPG) MELD + 1.59 x (135-Na) :Na 120~135

Korea National Diabetes Program Results Korea National Diabetes Program

1. Characteristics of the Patients 총 151 명 대상이며 104명은 이뇨제로 조절되지 않는 복수를 갖고 있다. 46명(30.5%)은 renal dysfunction 이다. 58명(38.4%)은 hyponatremia 이다 모든 환자는 규칙적으로 복수천자를 통해 복수조절을 하고 있다. 77명(51%)는 GI hemorrge를 예방하기 위해 bblocker를 복용중이다. 양군의 child puch score 및 MELD /MELD na 차이는 없다.

2. Outcome and Follow-Up of the Whole Group of Patients. The median follow-up time 은 8 개월 The median survival time was 10 개월 (95% CI ¼ 8-12 months). 1 년 생존확율 41% 이며 2년 생존 확률은 28% 전체 151명중 97명 (64.2%)이 사망하였고 그중 50명은 sepsis였다.

3. Outcome According to Beta-Blocker Therapy. Bblocker 사용자 의 median survavial 은 5개월 있었으며 사용하지 않은 군은 20개월로 두군간의 유의한 차이를 보였다. 1년을 기점으로 하였을때 bblocker의 사용하지 않은 군은 64% 의 생존율을 보였으나 bblocker 를 투여한 군은 19%의 생존율을 보였으며 2년기점시 각군은 45% 와 9% 의 생존율의 차이를 보였다.

4. Factors Associated With Mortality. multivariate Cox regression model 을 통해 Motality factor 중 HR 유의한 차이를 보이는 몇가지 risk factor 가 있다. 밑줄 친 인자들은 P value가 <0.0001로 각 군의 유의한 차를 보였던 factor 들이다. 다른 figure는 높은 HR 순으로 나열 한 independent predictors 로 BB 를 사용시 HR 2.61 로 나타났으며 motality 에 중요한 인자임을 알 수 있다.

Korea National Diabetes Program Conclusion The use of beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that beta blockers should be contraindicated in these patients.. Korea National Diabetes Program