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Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis

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Abstract

Background and aims

Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients.

Methods

In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child–Pugh score and class.

Results

The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child–Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups.

Conclusion

Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications.

Clinical trial number

NCT02190357

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Abbreviations

SBP:

Spontaneous bacterial peritonitis

EGVB:

Oesophageal and gastric variceal bleeding

HE:

Hepatic encephalopathy

HRS:

Hepatorenal syndrome

HCC:

Hepatocellular carcinoma

GI:

Gastrointestinal

AKI:

Acute kidney injury

HBV:

Hepatitis B virus

AIH:

Autoimmune hepatitis

PBC:

Primary biliary cholangitis

MELD:

Model For End-Stage Liver Disease

PT:

Prothrombin time

INR:

International normalized ratio

ITT:

Intention-to-treat

PHC:

Primary hepatic cancer

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

γ-GT:

γ-Glutamyl transferase

ALP:

Alkaline phosphatase

HVPG:

Hepatic venous pressure gradient

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Acknowledgements

The authors would like to thank the patients and their families for their contribution to this study.

Funding

The study was supported by an Emerging advanced technology joint research project from Shanghai Hospital Development Center (NO SHDC12016103), a Top-Level Clinical Discipline Project from Shanghai Pudong Health Committee (NO PWYgf2018-04), a Key Projects from Shanghai Science and Technology Committee (NO 17411950800) and two grants from the National Natural Science Foundation Committee of China (NO 81530019, 81770600).

Author information

Author notes

  1. Xin Zeng, Xia Sheng and Pei-Qin Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Xin Zeng, Xia Sheng, Pei-Qin Wang, Yong Lin, Pei-Mei Shi, Zong-Li Yuan & Wei-Fen Xie

  2. Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China

    Xin Zeng

  3. Department of Infectious Disease, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Hai-Guang Xin

  4. Department of Health Statistics, Second Military Medical University, Shanghai, 200433, China

    Yi-Bin Guo

  5. Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, China

    Jia-Wei Zhong, Xuan Zhu & Nong-Hua Lv

  6. Division of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China

    Cheng-Zhi He & Chang-Qing Yang

  7. Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Jie Yin, Tao-Tao Liu & Xi-Zhong Shen

  8. Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Wei-Juan Ma & Jian-Ming Xu

  9. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and HepatologyState Key Laboratory for Oncogenes and Related GenesSchool of Medicine, Ministry of HealthRenji HospitalShanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, 200001, China

    Xiao Xiao & Xiong Ma

  10. Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ling Yang

Authors
  1. Xin Zeng
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Contributions

XZ and W-FX designed the research and drafted the manuscript. XZ, LY, XM, J-MX, X-ZS, C-QY, XZ and N-HL presided over the enrolment and exclusion of the patients. XS, H-GX, YL, J-WZ, C-ZH, JY, T-TL, W-JM and XX followed up the patients and collected the data. P-MS and Z-LY check the data. P-QW and Y-BG established the database and analysed the data statistically.

Corresponding author

Correspondence to Wei-Fen Xie.

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Conflict of interest

Xin Zeng, Xia Sheng, Pei-Qin Wang, Hai-Guang Xin, Yi-Bin Guo,Yong Lin, Jia-Wei Zhong, Cheng-Zhi He, Jie Yin, Tao-Tao Liu, Wei-Juan Ma, Xiao Xiao, Pei-Mei Shi, Zong-Li Yuan, Ling Yang, Xiong Ma, Jian-Ming Xu, Xi-Zhong Shen, Chang-Qing Yang, Xuan Zhu, Nong-Hua Lv and Wei-Fen Xie declares that they have no conflict of interesting.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the institutional review board or ethics committee at each centre.

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Written informed consent was obtained from all patients.

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Zeng, X., Sheng, X., Wang, PQ. et al. Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis. Hepatol Int 15, 155–165 (2021). https://doi.org/10.1007/s12072-020-10117-y

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