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. 2020 Jan 16;1(1):CD013123.
doi: 10.1002/14651858.CD013123.pub2.

Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis

Amine Benmassaoud  1 , Suzanne C Freeman  2 , Davide Roccarina  1 , Maria Corina Plaz Torres  3 , Alex J Sutton  2 , Nicola J Cooper  2 , Laura Iogna Prat  1 , Maxine Cowlin  4 , Elisabeth Jane Milne  5 , Neil Hawkins  6 , Brian R Davidson  7 , Chavdar S Pavlov  8   9 , Douglas Thorburn  1 , Emmanuel Tsochatzis  1 , Kurinchi Selvan Gurusamy  7   9
Affiliations

Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis

Amine Benmassaoud et al. Cochrane Database Syst Rev. .

Abstract

Background: Approximately 20% of people with cirrhosis develop ascites. Several different treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative efficacy.

Objectives: To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy.

Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites.

Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.

Data collection and analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.

Main results: We included a total of 49 randomised clinical trials (3521 participants) in the review. Forty-two trials (2870 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, without other features of decompensation, having mainly grade 3 (severe), recurrent, or refractory ascites. The follow-up in the trials ranged from 0.1 to 84 months. All the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Approximately 36.8% of participants who received paracentesis plus fluid replacement (reference group, the current standard treatment) died within 11 months. There was no evidence of differences in mortality, adverse events, or liver transplantation in people receiving different interventions compared to paracentesis plus fluid replacement (very low-certainty evidence). Resolution of ascites at maximal follow-up was higher with transjugular intrahepatic portosystemic shunt (HR 9.44; 95% CrI 1.93 to 62.68) and adding aldosterone antagonists to paracentesis plus fluid replacement (HR 30.63; 95% CrI 5.06 to 692.98) compared to paracentesis plus fluid replacement (very low-certainty evidence). Aldosterone antagonists plus loop diuretics had a higher rate of other decompensation events such as hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding compared to paracentesis plus fluid replacement (rate ratio 2.04; 95% CrI 1.37 to 3.10) (very low-certainty evidence). None of the trials using paracentesis plus fluid replacement reported health-related quality of life or symptomatic recovery from ascites.

Funding: the source of funding for four trials were industries which would benefit from the results of the study; 24 trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 21 trials was unclear.

Authors' conclusions: Based on very low-certainty evidence, there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality, adverse events, or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites. Based on very low-certainty evidence, transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement. Based on very low-certainty evidence, aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement.

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Conflict of interest statement

None known for any of the authors

Figures

1
1
A high resolution version of this image can be found at: https://doi.org/10.5281/zenodo.3604788.. The network plots showing the outcomes for which network meta‐analysis was performed. The size of the node (circle) provides a measure of the number of trials in which the particular Intervention was included as one of the intervention groups. The thickness of the line provides a measure of the number of direct comparisons between two nodes (Interventions). A higher resolution image of this picture is available at: http://doi.org/10.5281/zenodo.3531818. Abbreviations Alb = Albumin
 AldoAnt = Aldosterone antagonists
 Fluid = Fluid replacement
 LoopD = Loop diuretics
 No active treatment = No active treatment
 OsmoD = Osmotic diuretics
 Paracen = Paracentesis
 PVShunt = Peritoneovenous shunt
 Reinf = Reinfusion
 Vasocons = Systemic vasoconstrictors
 Vasodil = Systemic vasodilator
 ThiazD = Thiazide diuretics
 TIPS = Transjugular intrahepatic portosystemic shunt
2
2
Study flow diagram.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
Inconsistency factor plots showing the inconsistency factors for the outcomes with direct and indirect evidence available for one or more comparisons. There was no evidence of inconsistency except for hospital stay. A higher resolution image of this picture is available at: http://doi.org/10.5281/zenodo.3531818. Abbreviations: Alb = Albumin
 AldoAnt = Aldosterone antagonists
 Fluid = Fluid replacement
 LoopD = Loop diuretics
 No active treatment = No active treatment
 OsmoD = Osmotic diuretics
 Paracen = Paracentesis
 PVShunt = Peritoneovenous shunt
 Reinf = Reinfusion
 Vasocons = Systemic vasoconstrictors
 Vasodil = Systemic vasodilator
 ThiazD = Thiazide diuretics
 TIPS = Transjugular intrahepatic portosystemic shunt
6
6
Forest plots showing the outcomes for which the random‐effects model were different from the fixed‐effect model. The more conservative random‐effects model was used. In this figure, mortality at maximal follow‐up, any adverse events (number of people), and resolution of ascites are shown. Figure 7 shows the remaining outcomes (other decompensation events and length of hospital stay), the other outcomes in which the fixed‐effect and random‐effects model were different. A higher resolution image of this picture is available at: http://doi.org/10.5281/zenodo.3531818. Abbreviations: Alb = Albumin
 AldoAnt = Aldosterone antagonists
 Fluid = Fluid replacement
 LoopD = Loop diuretics
 No active treatment = No active treatment
 OsmoD = Osmotic diuretics
 Paracen = Paracentesis
 PVShunt = Peritoneovenous shunt
 Reinf = Reinfusion
 Vasocons = Systemic vasoconstrictors
 Vasodil = Systemic vasodilator
 ThiazD = Thiazide diuretics
 TIPS = Transjugular intrahepatic portosystemic shunt
7
7
Forest plots showing the outcomes for which the random‐effects model were different from the fixed‐effect model. The more conservative random‐effects model was used. In this figure, other decompensation events and length of hospital stay are shown. Figure 6 shows the remaining outcomes (mortality at maximal follow‐up, any adverse events (number of people), and resolution of ascites), the other outcomes in which the fixed‐effect and random‐effects model were different. A higher resolution image of this picture is available at: http://doi.org/10.5281/zenodo.3531818. Abbreviations: Alb = Albumin
 AldoAnt = Aldosterone antagonists
 Fluid = Fluid replacement
 LoopD = Loop diuretics
 No active treatment = No active treatment
 OsmoD = Osmotic diuretics
 Paracen = Paracentesis
 PVShunt = Peritoneovenous shunt
 Reinf = Reinfusion
 Vasocons = Systemic vasoconstrictors
 Vasodil = Systemic vasodilator
 ThiazD = Thiazide diuretics
 TIPS = Transjugular intrahepatic portosystemic shunt
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References

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Strauss 1991 {published data only}
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    1. Strauss E, Moreira E, Caly WR, Honain NZ, Mfgde S. Paracentesis during diuretic treatment of ascites due to hepatic cirrhosis: results of randomized clinical assay. Gastroenterologia Endoscopia Digestiva 1991;10(2):53‐8.
Tuttolomondo 2016 {published data only}
    1. Tuttolomondo A, Raimondo D, Bellia C, Clemente G, Pecoraro R, Maida C, et al. Immune‐inflammatory and metabolic effects of high dose furosemide plus hypertonic saline solution (HSS) treatment in cirrhotic subjects with refractory ascites. PlOS One 2016;11(12):e0165443. - PMC - PubMed

References to studies excluded from this review

Abdel‐Khalek 2010b {published data only}
    1. Abdel‐Khalek EE, Arif S. Randomized trial comparing human albumin and hydroxyethyl starch 6% as plasma expanders for treatment of patients with liver cirrhosis and tense ascites after large‐volume paracentesis. Journal of Hepatology 2010;52:S327.
    1. Abdel‐Khalek EE, Arif SE. Randomized trial comparing human albumin and hydroxyethyl starch 6% as plasma expanders for treatment of patients with liver cirrhosis and tense ascites following large volume paracentesis. Arab Journal of Gastroenterology 2010;11(1):24‐9.
Altman 1998 {published data only}
    1. Altman C, Bernard B, Roulot D, Vitte RL, Ink O. Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis. European Journal of Gastroenterology and Hepatology 1998;10(1):5‐10. - PubMed
Angeli 1994 {published data only}
    1. Angeli P, Dalla Pria M, Bei E, Albino G, Caregaro L, Merkel C, et al. Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites. Hepatology (Baltimore, Md) 1994;19(1):72‐9. - PubMed
Antillon 1993 {published data only}
    1. Antillon MR, Runyon BA. Extracorporeal ultrafiltration and intravenous reinfusion of ascitic fluid vs. large‐volume paracentesis: a randomized controlled trial. Hepatology (Baltimore, Md) 1993;17(3):520‐2. - PubMed
Applefeld 1994 {published data only}
    1. Applefeld JJ, Kasmer RJ, Hak LJ, Dukes GE, Wermeling DP, McClain CJ. A dose‐response study of orally administered torsemide in patients with ascites due to cirrhosis. Alimentary Pharmacology & Therapeutics 1994;8(4):397‐402. - PubMed
Arrigoni 1988 {published data only}
    1. Arrigoni A, Andriulli A, Gindro T, Verme G. The use of diuretics in preventing ascites recurrence. British Journal of Clinical Practice 1988;42(3):116‐20. - PubMed
Bories 1986 {published data only}
    1. Bories P, Garcia Compean D, Michel H, Bourel M, Capron JP, Gauthier A, et al. The treatment of refractory ascites by the Leveen shunt. A multi‐centre controlled trial (57 patients). Journal of Hepatology 1986;3(2):212‐8. - PubMed
Bostan 2019 {published data only}
    1. Bostan F, Cekin AH. Long‐term albumin administration in decompensated cirrhosis. Turkish Journal of Gastroenterology 2019;30(4):385‐6. - PMC - PubMed
Boyer 1983 {published data only}
    1. Boyer TD, Warnock DG. Use of diuretics in the treatment of cirrhotic ascites. Gastroenterology 1983;84(5 pt 1):1051‐5. - PubMed
Brater 2001 {published data only}
    1. Brater DC, Chalasani N, Gorski JC, Horlander JC Sr, Craven R, Hoen H, et al. Effect of albumin‐furosemide mixtures on response to furosemide in cirrhotic patients with ascites. Transactions of the American Clinical and Climatological Association 2001;112:108‐15; discussion 16. - PMC - PubMed
Bureau 2017a {published data only}
    1. Adebayo D, Bureau C, Rieu MC, Valla D, Elkrief L, Peck‐Radosavljevic M, et al. Alfapump system versus large volume paracentesis in the treatment of refractory ascites; results from a multicenter randomised controlled study (RCT). Journal of Hepatology 2016;64(2 Suppl):S185.
    1. Adebayo D, Bureau C, Valla D, Peck‐Radosavljevic M, McCune A, Vargas V, et al. Alfapump system versus large volume paracentesis in the treatment of refractory ascites. A multicenter randomised controlled study. Journal of Hepatology 2015;62:S849‐S50. - PubMed
    1. Adebayo D, Mohammed A, Arora S, Chiara F, Trepte C, Whitaker S, et al. A randomized controlled trial comparing the alfapumpa© with paracentesis in patients with refractory ascites: clinical and pathophysiological effects on cardiac, haemodynamic, inflammatory, renal and nutritional parameters. Journal of Hepatology 2015;62:S374.
    1. Bureau C, Adebayo D, Chalret de Rieu M, Elkrief L, Valla D, Peck‐Radosavljevic M, et al. Alfapump system vs. large volume paracentesis for refractory ascites: a multicenter randomized controlled study. Journal of Hepatology 2017;67(5):940‐9. - PubMed
    1. Engelmann C, Brosteanu O, Tenckhoff H, Babatz J, Lammert F, Manns M, et al. Alfapump system versus transjugular intrahepatic portosystemic shunt and paracentesis in the treatment of ascites. A multicentre randomised controlled study (Agua‐trial). Journal of Hepatology 2015;62:S846‐S7.
Cadranel 1992a {published data only}
    1. Cadranel JF, Gargot D, Grippon P, Lunel F, Bernard B, Valla D, et al. Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate versus large paracentesis in cirrhotic patients with intractable ascites: a randomized study. International Journal of Artificial Organs 1992;15(7):432‐5. - PubMed
Cadranel 1992b {published data only}
    1. Cadranel JF, Grippon P, Gargot D, Lunel F, Bernard B, Valla D, et al. Simultaneous dialytic ultrafiltration and intraperitoneal reinfusion in cirrhotic patients with intractable ascites. Preliminary results of a comparative study versus large paracentesis. Journal of Hepatology 1992;15(1‐2):271‐2. - PubMed
Castagnolo 1977 {published data only}
    1. Castagnolo B, Colibus V, Napolitano L, Aliperta A, Caldarelli G, Abignente F. Clinical evaluation of the use of diuretics in the ascitic phase of hepatic cirrhosis. Clinica Terapeutica 1977;83(6):625‐9. - PubMed
Chang 1998 {published data only}
    1. Chang R, Chang YW, Lee JI, Kim BH, Kim HJ, Dong SH. The efficacy of hydroxyethyl starch as plasma expander in cirrhotic patients with tense ascites treated with large volume paracentesis. Korean Journal of Gastroenterology 1998;31(5):651‐60.
Eknoyan 1970 {published data only}
    1. Eknoyan G, Martinez‐Maldonado M, Yium JJ, Suki WN. Combined ascitic‐fluid and furosemide infusion in the management of ascites. New England Journal of Medicine 1970;282(13):713‐7. - PubMed
Fassio 1992 {published data only}
    1. Fassio E, Terg R, Landeira G, Abecasis R, Salemne M, Podesta A, et al. Paracentesis with dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites. Results of a randomized study. Journal of Hepatology 1992;14(2‐3):310‐6. - PubMed
Fuller 1977 {published data only}
    1. Fuller RK, Khambatta PB, Gobezie GC. An optimal diuretic regimen for cirrhotic ascites. A controlled trial evaluating safety and efficacy of spironolactone and furosemide. JAMA 1977;237(10):972‐5. - PubMed
Gadano 1997 {published data only}
    1. Gadano A, Moreau R, Vachiery F, Soupison T, Yang S, Cailmail S, et al. Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites. Journal of Hepatology 1997;26(6):1229‐34. - PubMed
Garcia‐Compean 1993 {published data only}
    1. Garcia‐Compean D, Villarreal JZ, Cuevas HB, Cantu DAG, Estrella M, Tamez EG, et al. Total therapeutic paracentesis (TTP) with and without intravenous albumin in the treatment of cirrhotic tense ascites: a randomized controlled trial. Liver 1993;13(5):233‐8. - PubMed
Garcia‐Compean 2002 {published data only}
    1. Garcia‐Compean D, Blanc P, Larrey D, Daures JP, Hirtz J, Mendoza E, et al. Treatment of cirrhotic tense ascites with dextran‐40 versus albumin associated with large volume paracentesis: a randomized controlled trial. Annals of Hepatology 2002;1(1):29‐35. - PubMed
Gentilini 1989b {published data only}
    1. Gentilini P, Meacci E, Laffi G, Buzzelli GP, Marra F, Cotrozzi G. Comparison of torasemide (T), a new loop diuretic, and furosemide (F) in the treatment of cirrhotic patients with ascites. Italian Journal of Gastroenterology 1989;21(2):31.
Gerbes 1990a {published data only}
    1. Gerbes AL, Berthau U, Falkner CH, Paumgartner G. Effects of torasemide, a new loop diuretic vs furosemide in patients with cirrhosis and ascites: a randomized double‐blind cross‐over study. Hepatology (Baltimore, Md) 1990;12(4 pt 2):991.
    1. Gerbes AL, Bertheau U, Falkner C, Jüngst D, Paumgartner G. Advantages of torasemide vs. furosemide in patients with liver cirrhosis and ascites. A randomized double‐blind cross‐over study. Gastroenterology 1991;100(5 pt 2):A746.
    1. Gerbes AL, Bertheau U, Falkner C, Jüngst D, Paumgartner G. Pharmacodynamic advantages of torasemide, a new loop diuretic, against furosemide in patients with cirrhosis of the liver and ascites. Results of a randomised, double‐blind study with cross‐over design. Zeitschrift für Gastroenterologie 1990;28(12):693‐4.
Ginès 1988 {published data only}
    1. Ginès P, Titó L, Arroyo V, Planas R, Panés J, Viver J, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988;94(6):1493‐502. - PubMed
Gines 1996 {published data only}
    1. Gines A, Fernandez‐Esparrach G, Monescillo A, Vila C, Domenech E, Abecasis R, et al. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology 1996;111(4):1002‐10. - PubMed
Giostra 2000 {published data only}
    1. Giostra E, Spahr L, Nadereh AP, Martin PY, Ferraille E, Hadengue A. Effects of the vasoconstrictor terlipressin on renal function in patients with cirrhosis and ascites: a double‐blind randomized controlled trial. Hepatology (Baltimore, Md) 2000;32(4 pt 2):523a.
He 2012 {published data only}
    1. He HR, Li M, Wei DP, Zhu JJ, Yang JB, Feng XH, et al. Therapeutic schemes for refractory ascites of advanced schistosomiasis: a clinical control study. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2012;24(5):570‐2. - PubMed
Heinrich 1983 {published data only}
    1. Heinrich F, Loew D, Dycka J. Repeated‐dose, double‐blind comparative trial of muzolimine‐spironolactone, furosemide‐spironolactone, and placebo‐spironolactone. Clinical Nephrology 1983;19(Suppl 1):S69‐75.
Hernandez 1995 {published data only}
    1. Hernandez Perez RE, Aguilar Ramirez JR, Hernandez Lopez JM, Gomez Maganda y Silva TG. Massive paracentesis and administration of dextran 70 vs albumin in cirrhotic patients with tense ascites. Revista de Gastroenterología de México 1995;60(1):22‐6. - PubMed
Inoue 1969 {published data only}
    1. Inoue J, Mori Y, Kawamura T. Refractory hepatic cirrhosis and the ineffectiveness of diuretics in ascites and edema. Naika Internal Medicine 1969;24(5):834‐9. - PubMed
Kalambokis 2007 {published data only}
    1. Kalambokis G, Fotopoulos A, Economou M, Pappas K, Tsianos EV. Effects of a 7‐day treatment with midodrine in non‐azotemic cirrhotic patients with and without ascites. Journal of Hepatology 2007;46(2):213‐21. - PubMed
Kalambokis 2008 {published data only}
    1. Kalambokis GN, Tsianos EV. Vasoconstrictor therapy for patients with cirrhosis with ascites but without hepatorenal syndrome. Hepatology (Baltimore, Md) 2008;48(2):686. - PubMed
Knauf 1994 {published data only}
    1. Knauf H, Mutschler E. Liver cirrhosis with ascites: pathogenesis of resistance to diuretics and long‐term efficacy and safety of torasemide. Cardiology 1994;84(Suppl 2):87‐98. - PubMed
    1. Knauf H, Wenk E, Scholmerich J, Goerg KJ, Gerok W, Leser HG, et al. Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion. Klinische Wochenschrift 1990;68(11):545‐51. - PubMed
Krag 2007b {published data only}
    1. Krag A, Møller S, Henriksen JH, Holstein‐Rathlou N, Larsen FS, Bendtsen F. Terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology (Baltimore, Md) 2007;46(4 Suppl 1):566a. - PubMed
    1. Krag A, Møller S, Henriksen JH, Holstein‐Rathlou NH, Larsen FS, Bendtsen F. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology (Baltimore, Md) 2007;46(6):1863‐71. - PubMed
Krag 2008 {published data only}
    1. Krag A, Bendtsen F, Pedersen EB, Holstein‐Rathlou NH, Møller S. Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects. American Journal of Physiology ‐ Renal Physiology 2008;295(5):f1295‐300. - PubMed
    1. Krag A, Møller S, Henriksen JH, Bendtsen F. Effects of a single dose of terlipressin on transcutaneous oxygen pressures. Scandinavian Journal of Gastroenterology 2010;45(7‐8):953‐8. - PubMed
Kurt 2011 {published data only}
    1. Kurt M. Deleterious effects of beta‐blockers on survival in patients with cirrhosis and refractory ascites. Hepatology (Baltimore, Md) 2011;53(4):1411‐2. - PubMed
Laffi 1992 {published data only}
    1. Laffi G, Marra F, Carloni V, Azzena G, Feo ML, Pinzani M, et al. Thromboxane‐receptor blockade increases water diuresis in cirrhotic patients with ascites. Gastroenterology 1992;103(3):1017‐21. - PubMed
Laffi 2003 {published data only}
    1. Laffi G, Gentilini P, Romanelli RG, Villa G. Is the use of albumin of value in the treatment of ascites in cirrhosis? The case in favour. Digestive and Liver Disease 2003;35(9):660‐3. - PubMed
Lai 1991 {published data only}
    1. Lai KN, Li P, Law E, Swaminathan R, Nicholls MG. Large‐volume paracentesis versus dialytic ultrafiltration in the treatment of cirrhotic ascites. Quarterly Journal of Medicine 1991;78(285):33‐41. - PubMed
Leodolter 1972 {published data only}
    1. Leodolter I, Wenzl M. Operative treatment of ascites in liver cirrhosis, resistant to internal medical treatment. Munchener Medizinische Wochenschrift 1972;114(17):797‐800. - PubMed
Lieberman 1965 {published data only}
    1. Lieberman FL, Reynolds TB. The use of ethacrynic acid in patients with cirrhosis and ascites. Gastroenterology 1965;49(5):531‐8. - PubMed
Lowenthal 1973 {published data only}
    1. Lowenthal DT, Shear L. Use of a new diuretic agent (metolazone) in patients with edema and ascites. Archives of Internal Medicine 1973;132(1):38‐41. - PubMed
Luca 1995 {published data only}
    1. Luca A, Garciapagan JC, Bosch J, Feu F, Jimenez W, Ginés A, et al. Beneficial‐effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. Hepatology (Baltimore, Md) 1995;22(3):753‐8. - PubMed
Marra 1979 {published data only}
    1. Marra N, Micheli E, Spagnolo G. Controlled clinical study of the effect of combined administration of ethacrynic acid and spironolactone in ascitic liver cirrhosis. Clinica Terapeutica 1979;90(2):143‐63. - PubMed
Merino 1967 {published data only}
    1. Merino I, Bardi A, Generini G, Rendic Y, Plaza de los Reyes M. The effects of the drug M.K. 870 on the diuresis, salidiuresis and plasma electrolyte concentration in liver cirrhosis patients with ascites. Revista Medica de Chile 1967;95(6):295‐9. - PubMed
Misra 2010 {published data only}
    1. Misra VL, Vuppalanchi R, Jones D, Hamman M, Kwo PY, Kahi C, et al. The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites. Alimentary Pharmacology & Therapeutics 2010;32(8):1044‐50. - PMC - PubMed
Moreau 2006 {published data only}
    1. Moreau R, Valla DC, Durand‐Zaleski I, Bronowicki JP, Durand F, Chaput JC, et al. Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: a randomised controlled pilot trial. Liver International 2006;26(1):46‐54. - PubMed
    1. Moreau R, Valla DC, Durand‐Zaleski I, Golly D, Tellier Z. Multicenter, randomized, controlled, double‐blind trial comparing albumin with polygeline for intravascular fluid loading in patients with cirrhosis and ascites. Hepatology (Baltimore, Md) 2003;38(4 Suppl 1):420a‐1a.
    1. Moreau R, Valla DC, Golly D, Tellier Z. Multicenter, randomized, double‐blind trial comparing albumin and polygeline for intravascular fluid loading in patients with cirrhosis and tense ascites treated with paracentesis. Liver International 2004;24(Suppl 4):7.
Nakamura 2014 {published data only}
    1. Nakamura T, Sata M, Suzuki K, Moriwaki H, Fukui H, Fujiyama S, et al. Open‐labeled randomized controlled trial to compare diuretic therapy with recombinant human serum albumin and diuretic therapy for therapeutic treatment of ascites in patients with advanced liver cirrhosis: an exploratory trial. Hepatology Research 2014;44(5):502‐14. - PubMed
Narahara 2009 {published data only}
    1. Narahara Y, Kanazawa H, Taki Y, Kimura Y, Atsukawa M, Katakura T, et al. Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis. Journal of Gastroenterology and Hepatology 2009;24(11):1791‐7. - PubMed
Perez 1983 {published data only}
    1. Perez Ayuso RM, Arroya V, Planas R, Gaya J, Bory F, Rimola A. Randomized comparative study of the efficacy of furosemide in relation to spironolactone in non‐azotemic cirrhosis with ascites relationship between the diuretic response and the activity of the renin‐aldosterone system. Folha Medica 1984;88(4):205‐11. - PubMed
    1. Perez Ayuso RM, Arroyo V, Planas R. Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin‐aldosterone system. Gastroenterology 1983;84(5 i):961‐8. - PubMed
    1. Perez Ayuso RM, Bory F, Planas R, Gaya J, Arroyo V, Rivera F, et al. Controlled study on the efficacy of furosemide versus spironolactone in non‐azotemic cirrhosis with ascites, relationship between the diuretic response and the degree of activation on the renin‐aldosterone system. Liver 1982;2(3 pt 2):303. - PubMed
Perkins 2006 {published data only}
    1. Perkins JD. Distal splenorenal shunt vs. TIPS: a rare randomized trial of a common therapy. Liver Transplantation 2006;12(11):1717‐8.
Planas 1990 {published data only}
    1. Planas R, Ginès P, Arroyo V, Llach J, Panés J, Vargas V, et al. Dextran‐70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Results of a randomized study. Gastroenterology 1990;99(6):1736‐44. - PubMed
Ring‐Larsen 1988 {published data only}
    1. Ring‐Larsen H, Siemssen O, Krintel JJ, Stadager C, Henriksen JH. Denver shunt in the treatment of refractory ascites in cirrhosis a randomized controlled trial. Journal of Hepatology 1989;9(Suppl 1):S77.
    1. Ring‐Larsen H, Siemssen O, Krintel JJ, Stadager C, Henriksen JH. Diuretic resistant ascites in cirrhosis treated with peritoneo‐venous shunt a randomized controlled trial. Hepatology (Baltimore, Md) 1988;8(5):1353.
Roseau 2000 {published data only}
    1. Roseau E. Cirrhotic ascites: puncture versus transjugular intrahepatic portocaval shunt. Presse Medicale 2000;29(33):1820.
Runyon 1989 {published data only}
    1. Runyon BA, Antillon MR, Montano AA. Effect of diuresis versus therapeutic paracentesis on ascitic fluid opsonic activity and serum complement. Gastroenterology 1989;97(1):158‐62. - PubMed
Sadikali 1973 {published data only}
    1. Sadikali F. Spironolactone and frusemide in cirrhosis with ascites. British Journal of Clinical Practice 1973;27(6):222‐4. - PubMed
Salerno 1991 {published data only}
    1. Salerno F, Badalamenti S, Lorenzano E, Moser P, Incerti P. Randomized comparative study of hemaccel vs. albumin infusion after total paracentesis in cirrhotic patients with refractory ascites. Hepatology (Baltimore, Md) 1991;13(4):707‐13. - PubMed
Salerno 1997 {published data only}
    1. Salerno F, Lorenzano E, Boscani PF. Efficacy and safety of torasemide in nonazotemic cirrhotic patients with ascites: an open multicenter study. Advances in Therapy 1997;14(6):323‐37.
Santos 2003 {published data only}
    1. Santos J, Planas R, Pardo A, Durandez R, Cabre E, Morillas RM, et al. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. Journal of Hepatology 2003;39(2):187‐92. - PubMed
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Sarin 1988 {published data only}
    1. Sarin SK, Sachdev G, Mishra SP, Sundaram KR, Shrivastwa A, Talukdar V, et al. Bumetanide, spironolactone and a combination of the two, in the treatment of ascites due to liver disease. A prospective, controlled, randomized trial. Digestion 1988;41(2):101‐7. - PubMed
Sarti 1984 {published data only}
    1. Sarti F, Milandri GL, Piemontese A, Macchia S, Simoni S, Dal Monte PR. Use of canrenoate potassium given orally in ascitogenic cirrhosis. Minerva Dietologica e Gastroenterologica 1984;30(3):273‐80. - PubMed
Schmukler 1968 {published data only}
    1. Schmukler B, Bisio S, Iovine E, Cervini BA. New diuretic with anti‐kaliuretic effect in the treatment of cirrhotic ascitis: Mk 870(amyloid hydrochlorate). Clinico‐humoral study. Prensa Medica Argentina 1968;55(30):1442‐6. - PubMed
Shafei 1967 {published data only}
    1. Shafei AZ, Habib YA, El‐Khangry HA, Abou‐Khair SA, Abaza HH, Nibal AH. Studies on furosemide: an effective oral saludiuretic for bilharzial ascites. Journal of Tropical Medicine and Hygiene 1967;70(12):286‐92. - PubMed
Sohn 2017 {published data only}
    1. Sohn JH, Cho YK, Kim JH, Jung YK, Um SH, Ahn SB, et al. A prospective, randomized, multicenter and phase 3b study to evaluate the efficacy of terlipressin and albumin in cirrhotic patients with ascites and acute kidney injury in the range of serum creatinine between 1.5 mg and 2.5 mg/dl: interim analysis. Journal of Hepatology 2017;66(1 Suppl 1):S11.
Sola‐Vera 2003 {published data only}
    1. Sola‐Vera J, Minana J, Ricart E, Kolle L, Gómez C, Murugó M, et al. Albumin versus saline infusion in cirrhotic patients with tense ascites treated with total paracentesis. A randomized study. Hepatology (Baltimore, Md) 1997;26(4 pt 2):285a.
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Stanley 1989a {published data only}
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Steigmann 1966 {published data only}
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Tempini 1984 {published data only}
    1. Tempini S, Bellati G, Ideo G. Spironolactone and k‐canrenoate effect in decompensated liver cirrhosis: double blind study. Minerva Dietologica e Gastroenterologica 1984;30(3):255‐61. - PubMed
Thompson 1977 {published data only}
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Tsai 1996 {published data only}
    1. Tsai YT, Lin HC, Lee FY, Hou MC, Wang SS, Lee SD. Effects of captopril on renal functions, renal and portal hemodynamics in patients with cirrhosis. Proceedings of the National Science Council, Republic of China ‐ Part B, Life Sciences 1996;20(2):44‐50. - PubMed
Vizzutti 2001 {published data only}
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Wapnick 1979 {published data only}
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Yakar 2016 {published data only}
    1. Yakar T, Demir M, Dogan O, Parlakgumus A, Ozer B, Serin E. High dose oral furosemide with salt ingestion in the treatment of refractory ascites of liver cirrhosis. Clinical and Investigative Medicine 2016;39(6):S52‐60. - PubMed
Yamada 1970 {published data only}
    1. Yamada S, Reynolds TB. Amiloride (mk‐870), a new antikaluretic diuretic. Comparison to other antikaluretic diuretics in patients with liver disease and ascites. Gastroenterology 1970;59(6):833‐41. - PubMed
Yosry 2019 {published data only}
    1. Yosry A, Soliman ZA, Eletreby R, Hamza I, Ismail A, Elkady MA. Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large‐volume paracentesis: results of a pilot study. European Journal of Gastroenterology and Hepatology 2019;31(3):345‐51. - PubMed
Zaak 2001 {published data only}
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Zhang 2013 {published data only}
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Zhao 2000 {published data only}
    1. Zhao J, Yuan C, Wang D, Li X. Mannitolum infusion on cirrhotic patients with tense ascites treated by paracentesis. Chinese Medical Journal 2000;113(1):27‐30. - PubMed

References to ongoing studies

EUCTR 2018 {published data only}
    1. EUCTR ES. Long‐term albumin administration in cirrhotic patients with ascites. www.clinicaltrialsregister.eu/ctr‐search/search?query=eudract_number: 2016‐001789‐28 (first received 25 April 2018).
    1. NCT03506893. Medical‐economic evaluation of the care of refractory ascites by implantation of alfapump® device in cirrhotic patients. clinicaltrialsgov/show/nct03506893 (first received 24 April 2018).
Macken 2018 {published data only}
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References to other published versions of this review

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