Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Dec 17:13:1-11.
doi: 10.2147/DDDT.S172324. eCollection 2019.

Combination of rifaximin and lactulose improves clinical efficacy and mortality in patients with hepatic encephalopathy

Zhida Wang  1 , Pei Chu  2 , Wenjin Wang  2
Affiliations
Meta-Analysis

Combination of rifaximin and lactulose improves clinical efficacy and mortality in patients with hepatic encephalopathy

Zhida Wang et al. Drug Des Devel Ther. .

Abstract

Background: Rifaximin and lactulose are common effective agents for hepatic encephalopathy (HE). Whether a combination of rifaximin and lactulose improves the efficacy and mortality in patients with HE compared with lactulose alone needs to be analyzed.

Methods: A systematic search was performed in electronic databases and other sources for possible studies focusing on combination therapy of rifaximin and lactulose for HE between January 2000 and February 2018. A meta-analysis was performed by the method recommended by the Cochrane Collaboration, and estimated effect size was presented as risk difference (RD), 95% CI, and the number needed to treat (NNT). Subgroup analysis, sensitivity analysis, and Trial Sequence Analysis were comprehensively performed to indicate the source of heterogeneity and risk of bias.

Results: Five randomized and five observational studies involving 2,276 patients were included. Combination therapy had a significant advantage in both clinical efficacy increase (RD 0.26, 95% CI 0.19-0.32, NNT 5) and mortality decrease (RD -0.16, 95% CI -0.20-0.11, NNT 9) in overall analysis. In the pooled analysis of randomized studies, combination therapy showed similar results in clinical efficacy (RD 0.25, 95% CI 0.16-0.35, NNT 4) and mortality (RD -0.22, 95% CI -0.33-0.12, NNT 5). Compared with lactulose, hospital stay was also reduced in combination therapy, and there was no significant difference in treatment-related adverse events between the two groups.

Conclusion: Combination of rifaximin and lactulose has beneficial effects on HE. Compared with lactulose alone, additional rifaximin increases clinical efficacy and decreases mortality. However, its effects on different types of HE are still uncertain.

Keywords: HE; combination therapy; lactulose; meta-analysis; rifaximin.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Process of including studies evaluating combination therapy for hepatic encephalopathy.
Figure 2
Figure 2
Meta-analysis result of clinical efficacy in overall analysis between combination therapy and lactulose alone. Abbreviation: M–H, Mantel–Haenszel test.
Figure 3
Figure 3
Meta-analysis result of clinical efficacy in randomized controlled trials between combination therapy and lactulose alone. Abbreviation: RCT, randomized controlled trial.
Figure 4
Figure 4
Trial sequence analysis result of clinical efficacy.
Figure 5
Figure 5
Inverted funnel plot of clinical efficacy. Abbreviations: RD, risk difference; SE, standard error.
Figure 6
Figure 6
Meta-analysis result of mortality in overall analysis between combination therapy and lactulose alone.
Figure 7
Figure 7
Meta-analysis result of mortality in randomized controlled trial between combination therapy and lactulose alone.
Figure 8
Figure 8
Trial sequence analysis result of mortality.
Figure 9
Figure 9
Inverted funnel plot of mortality. Abbreviation: RD, risk difference.
Figure 10
Figure 10
Meta-analysis result of adverse event in overall analysis between combination therapy and lactulose alone.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–735. - PubMed
    1. Riggio O, Ridola L, Pasquale C, et al. Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2011;9(2):181–183. - PubMed
    1. Pereira K, Carrion AF, Salsamendi J, Doshi M, Baker R, Kably I. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm. Cardiovasc Intervent Radiol. 2016;39(2):170–182. - PubMed
    1. Stepanova M, Mishra A, Venkatesan C, Younossi ZM. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol. 2012;10(9):1034.e1–1041.e1. - PubMed
    1. Amodio P, Del Piccolo F, Pettenò E, et al. Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. J Hepatol. 2001;35(1):37–45. - PubMed