European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver.
EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.
J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024. Epub 2018 Apr 10.
Abstract/Text
Piano S, Rosi S, Maresio G, Fasolato S, Cavallin M, Romano A, Morando F, Gola E, Frigo AC, Gatta A, Angeli P.
Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites.
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.
Fang JT, Tsai MH, Tian YC, Jenq CC, Lin CY, Chen YC, Lien JM, Chen PC, Yang CW.
Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure.
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.
Tsien CD, Rabie R, Wong F.
Acute kidney injury in decompensated cirrhosis.
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.
Wong F, O'Leary JG, Reddy KR, Patton H, Kamath PS, Fallon MB, Garcia-Tsao G, Subramanian RM, Malik R, Maliakkal B, Thacker LR, Bajaj JS; North American Consortium for Study of End-Stage Liver Disease.
New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection.
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.
Fagundes C, Barreto R, Guevara M, Garcia E, Solà E, Rodríguez E, Graupera I, Ariza X, Pereira G, Alfaro I, Cárdenas A, Fernández J, Poch E, Ginès P.
A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis.
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.
Fernández J, Navasa M, Planas R, Montoliu S, Monfort D, Soriano G, Vila C, Pardo A, Quintero E, Vargas V, Such J, Ginès P, Arroyo V.
Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis.
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.
Ginès P, Schrier RW.
Renal failure in cirrhosis.
N Engl J Med. 2009 Sep 24;361(13):1279-90. doi: 10.1056/NEJMra0809139.
Abstract/Text
Kamal F, Khan MA, Khan Z, Cholankeril G, Hammad TA, Lee WM, Ahmed A, Waters B, Howden CW, Nair S, Satapathy SK.
Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis.
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.
Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, Ganger D, Jamil K, Pappas SC; REVERSE Study Investigators.
Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1.
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.
Gluud LL, Christensen K, Christensen E, Krag A.
Terlipressin for hepatorenal syndrome.
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.
Wong F, Pappas SC, Curry MP, Reddy KR, Rubin RA, Porayko MK, Gonzalez SA, Mumtaz K, Lim N, Simonetto DA, Sharma P, Sanyal AJ, Mayo MJ, Frederick RT, Escalante S, Jamil K; CONFIRM Study Investigators.
Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.
N Engl J Med. 2021 Mar 4;384(9):818-828. doi: 10.1056/NEJMoa2008290.
Abstract/Text
BACKGROUND: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe.
METHODS: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons.
RESULTS: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group.
CONCLUSIONS: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.).
Copyright © 2021 Massachusetts Medical Society.
Nassar Junior AP, Farias AQ, D' Albuquerque LA, Carrilho FJ, Malbouisson LM.
Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis.
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.
Wan YM, Huang SQ, Wu HM, Li YH, Yin HJ, Xu Y.
Terlipressin versus placebo or noradrenalin in the treatment of hepatorenal syndrome: a systematic review and meta-analysis.
Front Pharmacol. 2024;15:1418826. doi: 10.3389/fphar.2024.1418826. Epub 2024 Sep 4.
Abstract/Text
BACKGROUND: Hepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs).
METHODS: PubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: "hepatorenal syndrome", "terlipressin", "noradrenaline", and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events.
RESULTS: 15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5).
CONCLUSION: Terlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.
Copyright © 2024 Wan, Huang, Wu, Li, Yin and Xu.
Ruiz R, Barri YM, Jennings LW, Chinnakotla S, Goldstein RM, Levy MF, McKenna GJ, Randall HB, Sanchez EQ, Klintmalm GB.
Hepatorenal syndrome: a proposal for kidney after liver transplantation (KALT).
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.
