今日の臨床サポート

肝腎症候群

著者: 鍛治孝祐 奈良県立医科大学 消化器・代謝内科

著者: 吉治仁志 奈良県立医科大学 消化器・代謝内科

監修: 金子周一 金沢大学大学院

著者校正/監修レビュー済:2020/03/12
参考ガイドライン:
  1. 欧州肝臓学会(EASL):European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.(2018年)
  1. 日本消化器病学会:肝硬変診療ガイドライン2015 改訂第2版

概要・推奨   

  1. 肝硬変では、肝腎症候群だけでなく腎前性、腎性(主に急性尿細管壊死)、腎後性の全ての急性腎障害が起こり得るため、早急かつ適切な鑑別が重要である。
  1. 腹水を有する肝硬変患者に急性腎障害が生じた場合、International Club of Ascites (ICA)の急性腎障害基準および肝腎症候群診断基準に基づいて診断することが推奨される。
  1. 肝腎症候群の発症予防として、腎毒性を有する薬剤やNSAIDs、造影剤の使用は避けることが推奨される。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
鍛治孝祐 : 特に申告事項無し[2021年]
吉治仁志 : 特に申告事項無し[2021年]
監修:金子周一 : 研究費・助成金など(バイエル薬品株式会社,株式会社キュービクス,アボットジャパン合同会社,日東電工株式会社,株式会社スギ薬局,株式会社サイトパスファインダー),奨学(奨励)寄付など(小野薬品工業株式会社,エーザイ株式会社,株式会社ツムラ,アッヴィ合同会社,大日本住友製薬株式会社,ゼリア新薬工業株式会社,塩野義製薬株式会社,大塚製薬株式会社,アステラス製薬株式会社,田辺三菱製薬株式会社,マイランEPD合同会社,EAファーマ株式会社,大鵬薬品工業株式会社,中外製薬株式会社,協和キリン株式会社,持田製薬株式会社,日本ケミファ株式会社,LifeScan Japan株式会社)[2021年]

病態・疫学・診察

イントロダクション  
  1. 肝腎症候群は主に非代償性肝硬変に合併する進行性の腎不全であり、肝硬変の予後規定因子の一つである。
  1. 肝硬変では急性腎障害(Acute Kidney Injury: AKI)として循環血流量減少による腎前性腎不全や併用薬剤による尿細管壊死を合併することがある。また、B型肝炎の肝外病変としての膜性腎症や非アルコール性脂肪肝炎と併存する糖尿病性腎症など慢性腎障害が肝硬変に合併する症例も度々見られる。
  1. 肝腎症候群はこれらとは異なる病態であり、適切な治療を行うためには正しい鑑別が必要となる。
  1. 一方で近年AKIの分類の変遷に伴い、肝腎症候群の診療基準も改変され、新規ガイドラインでは病態分類も変更されている。また治療においても血管収縮剤が広く推奨されるようになっており、本邦においてもその保険適用化が検討されている。
定義  
  1. 肝腎症候群(Hepatorenal syndrome: HRS)の本態は、肝硬変において低アルブミン血症および門脈圧亢進に伴う相対的な有効循環血液量の減少から来る腎血管の攣縮である。腎血流低下を来した結果、腎機能の著しい低下が惹起され、この腎機能障害は、感染、エンドトキシン血症の出現でさらに進行する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver
雑誌名: J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024. Epub 2018 Apr 10.
Abstract/Text
PMID 29653741  J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.・・・
著者: Salvatore Piano, Silvia Rosi, Giulio Maresio, Silvano Fasolato, Marta Cavallin, Antonietta Romano, Filippo Morando, Elisabetta Gola, Anna Chiara Frigo, Angelo Gatta, Paolo Angeli
雑誌名: J Hepatol. 2013 Sep;59(3):482-9. doi: 10.1016/j.jhep.2013.03.039. Epub 2013 May 7.
Abstract/Text BACKGROUND & AIMS: For several years hepatologists have defined acute renal failure in patients with cirrhosis as an increase in serum creatinine (sCr) ≥ 50% to a final value of sCr>1.5mg/dl (conventional criterion). Recently, the Acute Kidney Injury Network (AKIN) defined acute renal failure as acute kidney injury (AKI) on the basis of an absolute increase in sCr of 0.3mg/dl or a percentage increase in sCr ≥ 50% providing also a staging from 1 to 3. AKIN stage 1 was defined as an increase in sCr ≥ 0.3mg/dl or increase in sCr ≥ 1.5-fold to 2-fold from baseline. AKI diagnosed with the two different criteria was evaluated for the prediction of in-hospital mortality.
METHODS: Consecutive hospitalized patients with cirrhosis and ascites were included in the study and evaluated for the development of AKI.
RESULTS: Conventional criterion was found to be more accurate than AKIN criteria in improving the prediction of in-hospital mortality in a model including age and Child-Turcotte-Pugh score. The addition of either progression of AKIN stage or a threshold value for sCr of 1.5mg/dl further improves the value of AKIN criteria in this model. More in detail, patients with AKIN stage 1 and sCr<1.5mg/dl had a lower mortality rate (p=0.03), a lower progression rate (p=0.01), and a higher improvement rate (p=0.025) than patients with AKIN stage 1 and sCr ≥ 1.5mg/dl.
CONCLUSIONS: Conventional criterion is more accurate than AKIN criteria in the prediction of in-hospital mortality in patients with cirrhosis and ascites. The addition of either the progression of AKIN stage or the cut-off of sCr ≥ 1.5mg/dl to the AKIN criteria improves their prognostic accuracy.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID 23665185  J Hepatol. 2013 Sep;59(3):482-9. doi: 10.1016/j.jhep.20・・・
著者: Ji-Tseng Fang, Ming-Hung Tsai, Ya-Chung Tian, Chang-Chyi Jenq, Chan-Yu Lin, Yung-Chang Chen, Jau-Min Lien, Pan-Chi Chen, Chih-Wei Yang
雑誌名: Nephrol Dial Transplant. 2008 Jun;23(6):1961-9. doi: 10.1093/ndt/gfm914. Epub 2008 Jan 10.
Abstract/Text BACKGROUND: End-stage liver disease is often complicated by renal function disturbances. Cirrhotic patients with acute renal failure admitted to intensive care units (ICUs) have high mortality rates. This work seeks to identify specific predictors of hospital mortality in critically ill cirrhotic patients with acute renal failure.
METHODS: A total of 111 patients with cirrhosis and acute renal failure were admitted to ICU from March 2003 to February 2005. Twenty-six demographic, clinical and laboratory variables were prospectively gathered as predictors of survival on the first day of ICU admission.
RESULTS: The overall hospital mortality rate was 81.1%. The univariate analysis identified 11 of the 32 variables as prognostically valuable. The multiple logistic regression analysis (excluding five scoring systems) indicates that the mean arterial pressure (MAP), serum bilirubin, respiratory failure and sepsis on the first day in ICU are significantly related to prognosis. The best Youden index (sensitivity + specificity - 1) yields cutoff points of 80 MAP (in mmHg) and 80 serum bilirubin (in micromol/L) (or 4.7 mg/dL) and indicates acute respiratory failure and sepsis. A simple model for mortality is developed on the basis of these four readily available parameters on Day 1 of ICU admission. The new score (MBRS score: MAP + bilirubin + respiratory failure + sepsis) displays an excellent area under the receiver operating characteristic curve (0.898 +/- 0.031, P < 0.001). The mortality rate exceeds 90% when the MBRS (MAP + bilirubin + respiratory failure + sepsis) score is 2 or higher.
CONCLUSION: The MBRS score is a straightforward, reproducible and easily adopted evaluative tool with good prognostic abilities, which generates objective data for patient families and physicians and supplements a clinical judgment of prognosis.

PMID 18187499  Nephrol Dial Transplant. 2008 Jun;23(6):1961-9. doi: 10・・・
著者: Cynthia D Tsien, Rania Rabie, Florence Wong
雑誌名: Gut. 2013 Jan;62(1):131-7. doi: 10.1136/gutjnl-2011-301255. Epub 2012 May 25.
Abstract/Text BACKGROUND: Hepatorenal syndrome in cirrhosis with ascites is a well-defined entity with significant morbidity and mortality. It is unclear whether milder degrees of acute kidney injury (AKI), defined as a serum creatinine increase of over 26.4 μmol/l (0.3 mg/dl) or by 50% from baseline, also has a negative impact on patient outcomes.
OBJECTIVES: To determine the prevalence of AKI in cirrhosis with ascites and the impact of AKI on patient outcomes.
DESIGN: Patients with cirrhosis with ascites and baseline serum creatinine less than 110 μmol/l, and no evidence of structural renal disease, prospectively underwent 4-6-weekly blood work-up for full blood count, biochemistry and liver function. Clinical assessments occurred every 4 months for the development of AKI and other complications.
RESULTS: 90 patients (mean age 55.8 ± 0.8 years) with a mean follow-up of 14.05 ± 1.07 months were enrolled. 82 episodes of AKI occurred in 49 patients, with the majority of episodes precipitated by a disturbance in systemic haemodynamics. The mean peak serum creatinine of the AKI episodes was within the laboratory's normal range. 73 episodes of AKI resolved; nine did not. There was no clear clinical predictor for the development or resolution of AKI. Despite resolution of most AKI episodes, a gradual and significant increase in serum creatinine and a gradual reduction in mean arterial pressure were observed during follow-up, associated with a significant reduction in survival compared with non-AKI patients.
CONCLUSION: Minor increases in serum creatinine are clinically relevant and can adversely affect survival. Every effort should be made to avoid precipitation of AKI in cirrhosis and ascites.

PMID 22637695  Gut. 2013 Jan;62(1):131-7. doi: 10.1136/gutjnl-2011-301・・・
著者: Florence Wong, Jacqueline G O'Leary, K Rajender Reddy, Heather Patton, Patrick S Kamath, Michael B Fallon, Guadalupe Garcia-Tsao, Ram M Subramanian, Raza Malik, Benedict Maliakkal, Leroy R Thacker, Jasmohan S Bajaj, North American Consortium for Study of End-Stage Liver Disease
雑誌名: Gastroenterology. 2013 Dec;145(6):1280-8.e1. doi: 10.1053/j.gastro.2013.08.051. Epub 2013 Aug 30.
Abstract/Text BACKGROUND & AIMS: Participants at a consensus conference proposed defining cirrhosis-associated acute kidney injury (AKI) based on a >50% increase in serum creatinine level from the stable baseline value in <6 months or an increase of ≥ 0.3 mg/dL in <48 hours. We performed a prospective study to evaluate the ability of these criteria to predict mortality within 30 days of hospitalization among patients with cirrhosis and infection.
METHODS: We followed up 337 patients with cirrhosis who were admitted to the hospital with an infection or developed an infection during hospitalization (56% men; 56 ± 10 years of age; Model for End-Stage Liver Disease [MELD] score, 20 ± 8) at 12 centers in North America. We compared data on 30-day mortality, length of stay in the hospital, and organ failure between patients with and without AKI.
RESULTS: In total, based on the consensus criteria, 166 patients (49%) developed AKI during hospitalization. Patients who developed AKI were admitted with higher Child-Pugh scores than those who did not develop AKI (11.0 ± 2.1 vs 9.6 ± 2.1; P < .0001) as well as higher MELD scores (23 ± 8 vs 17 ± 7; P < .0001) and lower mean arterial pressure (81 ± 16 vs 85 ± 15 mm Hg; P < .01). Higher percentages of patients with AKI died within 30 days of hospitalization (34% vs 7%), were transferred to the intensive care unit (46% vs 20%), required ventilation (27% vs 6%), or went into shock (31% vs 8%); patients with AKI also had longer stays in the hospital (17.8 ± 19.8 vs 13.3 ± 31.8 days) (all P < .001). Of the AKI episodes, 56% were transient, 28% were persistent, and 16% resulted in dialysis. Mortality was higher among those without renal recovery (80%) compared with partial (40%) or complete recovery (15%) or those who did not develop AKI (7%; P < .0001).
CONCLUSIONS: Among patients with cirrhosis, 30-day mortality is 10-fold higher among those with irreversible AKI than those without AKI. The consensus definition of AKI accurately predicts 30-day mortality, length of hospital stay, and organ failure.

Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 23999172  Gastroenterology. 2013 Dec;145(6):1280-8.e1. doi: 10.10・・・
著者: Claudia Fagundes, Rogelio Barreto, Mónica Guevara, Elisabet Garcia, Elsa Solà, Ezequiel Rodríguez, Isabel Graupera, Xavier Ariza, Gustavo Pereira, Ignacio Alfaro, Andrés Cárdenas, Javier Fernández, Esteban Poch, Pere Ginès
雑誌名: J Hepatol. 2013 Sep;59(3):474-81. doi: 10.1016/j.jhep.2013.04.036. Epub 2013 May 10.
Abstract/Text BACKGROUND & AIMS: The Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival.
METHODS: We performed a prospective study of 375 consecutive patients hospitalized for complications of cirrhosis. One-hundred and seventy-seven (47%) patients fulfilled the criteria of Acute Kidney Injury (AKI) during hospitalization, the causes being hypovolemia, infections, hepatorenal syndrome (HRS), nephrotoxicity, and miscellaneous (62, 54, 32, 8, and 21 cases, respectively).
RESULTS: At diagnosis, most patients had AKI stage 1 (77%). Both the occurrence of AKI and its stage were associated with 3-month survival. However, survival difference between stages 2 and 3 was not statistically significant. Moreover, if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment (1.5mg/dl), the two groups had a significantly different outcome. Combining AKIN criteria and maximum serum creatinine, 3 risk groups were identified: (A) patients with AKI stage 1 with peak creatinine ≤ 1.5mg/dl; (B) patients with stage 1 with peak creatinine >1.5mg/dl; and (C) patients with stages 2-3 (survival 84%, 68%, and 36%, respectively; p<0.001). Survival was independently related to the cause of kidney impairment, patients with HRS or infection-related having the worst prognosis.
CONCLUSIONS: A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone. The cause of impairment in kidney function is key in assessing prognosis in cirrhosis.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID 23669284  J Hepatol. 2013 Sep;59(3):474-81. doi: 10.1016/j.jhep.2・・・
著者: Javier Fernández, Miquel Navasa, Ramón Planas, Silvia Montoliu, David Monfort, German Soriano, Carmen Vila, Alberto Pardo, Enrique Quintero, Victor Vargas, Jose Such, Pere Ginès, Vicente Arroyo
雑誌名: Gastroenterology. 2007 Sep;133(3):818-24. doi: 10.1053/j.gastro.2007.06.065. Epub 2007 Jul 3.
Abstract/Text BACKGROUND & AIMS: Norfloxacin is highly effective in preventing spontaneous bacterial peritonitis recurrence in cirrhosis, but its role in the primary prevention of this complication is uncertain.
METHODS: Patients with cirrhosis and low protein ascitic levels (<15 g/L) with advanced liver failure (Child-Pugh score > or = 9 points with serum bilirubin level > or = 3 mg/dL) or impaired renal function (serum creatinine level > or = 1.2 mg/dL, blood urea nitrogen level > or = 25 mg/dL, or serum sodium level < or = 130 mEq/L) were included in a randomized controlled trial aimed at comparing norfloxacin (35 patients) vs placebo (33 patients) in the primary prophylaxis of spontaneous bacterial peritonitis. The main end points of the trial were 3-month and 1-year probability of survival. Secondary end points were 1-year probability of development of spontaneous bacterial peritonitis and hepatorenal syndrome.
RESULTS: Norfloxacin administration reduced the 1-year probability of developing spontaneous bacterial peritonitis (7% vs 61%, P < .001) and hepatorenal syndrome (28% vs 41%, P = .02), and improved the 3-month (94% vs 62%, P = .003) and the 1-year (60% vs 48%, P = .05) probability of survival compared with placebo.
CONCLUSIONS: Primary prophylaxis with norfloxacin has a great impact in the clinical course of patients with advanced cirrhosis. It reduces the incidence of spontaneous bacterial peritonitis, delays the development of hepatorenal syndrome, and improves survival.

PMID 17854593  Gastroenterology. 2007 Sep;133(3):818-24. doi: 10.1053/・・・
著者: Pere Ginès, Robert W Schrier
雑誌名: N Engl J Med. 2009 Sep 24;361(13):1279-90. doi: 10.1056/NEJMra0809139.
Abstract/Text
PMID 19776409  N Engl J Med. 2009 Sep 24;361(13):1279-90. doi: 10.1056・・・
著者: Faisal Kamal, Muhammad Ali Khan, Zubair Khan, George Cholankeril, Tariq A Hammad, Wade M Lee, Aijaz Ahmed, Bradford Waters, Colin W Howden, Satheesh Nair, Sanjaya K Satapathy
雑誌名: Eur J Gastroenterol Hepatol. 2017 Oct;29(10):1109-1117. doi: 10.1097/MEG.0000000000000940.
Abstract/Text Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

PMID 28763340  Eur J Gastroenterol Hepatol. 2017 Oct;29(10):1109-1117.・・・
著者: Thomas D Boyer, Arun J Sanyal, Florence Wong, R Todd Frederick, John R Lake, Jacqueline G O'Leary, Daniel Ganger, Khurram Jamil, Stephen Chris Pappas, REVERSE Study Investigators
雑誌名: Gastroenterology. 2016 Jun;150(7):1579-1589.e2. doi: 10.1053/j.gastro.2016.02.026. Epub 2016 Feb 16.
Abstract/Text BACKGROUND & AIMS: Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1.
METHODS: Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n = 97) or placebo (n = 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February 2013.
RESULTS: Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P = .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P = .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2) = .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P = .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events.
CONCLUSIONS: Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 26896734  Gastroenterology. 2016 Jun;150(7):1579-1589.e2. doi: 10・・・
著者: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander Krag
雑誌名: Cochrane Database Syst Rev. 2012 Sep 12;(9):CD005162. doi: 10.1002/14651858.CD005162.pub3. Epub 2012 Sep 12.
Abstract/Text BACKGROUND: Clinical trials suggest that terlipressin improves renal function in hepatorenal syndrome, but the evidence concerning mortality is equivocal.
OBJECTIVES: To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for hepatorenal syndrome.
SEARCH METHODS: Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012.
SELECTION CRITERIA: Randomised clinical trials involving patients with type 1 or type 2 hepatorenal syndrome were included irrespective of publication status or language.
DATA COLLECTION AND ANALYSIS: The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of hepatorenal syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I(2) statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed.
MAIN RESULTS: We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 hepatorenal syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of hepatorenal syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms.
AUTHORS' CONCLUSIONS: Terlipressin may reduce mortality and improve renal function in patients with type 1 hepatorenal syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.

PMID 22972083  Cochrane Database Syst Rev. 2012 Sep 12;(9):CD005162. d・・・
著者: Antonio Paulo Nassar Junior, Alberto Queiroz Farias, Luiz Augusto Carneiro D' Albuquerque, Flair José Carrilho, Luiz Marcelo Sá Malbouisson
雑誌名: PLoS One. 2014;9(9):e107466. doi: 10.1371/journal.pone.0107466. Epub 2014 Sep 9.
Abstract/Text BACKGROUND: Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS.
METHODS: We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events.
RESULTS: Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83).
CONCLUSIONS: Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

PMID 25203311  PLoS One. 2014;9(9):e107466. doi: 10.1371/journal.pone.・・・
著者: Richard Ruiz, Yousri M Barri, Linda W Jennings, Srinath Chinnakotla, Robert M Goldstein, Marlon F Levy, Greg J McKenna, Henry B Randall, Edmund Q Sanchez, Goran B Klintmalm
雑誌名: Liver Transpl. 2007 Jun;13(6):838-43. doi: 10.1002/lt.21149.
Abstract/Text Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long-term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10-yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non-HRS patients undergoing LT over the same study period (P = 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non-HRS population (P < 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients.

PMID 17539003  Liver Transpl. 2007 Jun;13(6):838-43. doi: 10.1002/lt.2・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから