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

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.