Article Text

Download PDFPDF
Original research
Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial
  1. Tsung-Chieh Yang1,2,3,
  2. Wen-Chi Chen2,4,5,
  3. Ming-Chih Hou1,2,3,
  4. Ping-Hsien Chen2,6,7,
  5. Pei-Chang Lee1,2,3,
  6. Chung-Yu Chang1,2,3,8,
  7. Hsiao-Sheng Lu1,2,3,
  8. Yu-Jen Chen1,2,3,
  9. Shao-Jung Hsu1,2,3,
  10. Hui-Chun Huang1,2,3,
  11. Jiing-Chyuan Luo1,2,
  12. Yi-Hsiang Huang1,2,8,9,
  13. Fa-Yauh Lee1,2,3
  1. 1 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  2. 2 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  3. 3 Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
  4. 4 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  5. 5 Department of Post-Baccalaureate Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
  6. 6 Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
  7. 7 Division of Gastroenterology and Hepatology, Department of Medicine, West Garden Hospital, Taipei, Taiwan
  8. 8 Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan
  9. 9 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  1. Correspondence to Professor Ming-Chih Hou, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; mchou{at}vghtpe.gov.tw

Abstract

Objective This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC).

Design Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3–4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression.

Results Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray’s test, p=0.009) than its counterpart, with no mortality difference (Gray’s test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL.

Conclusion EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D.

Trial registration number NCT01970748.

  • HEPATOCELLULAR CARCINOMA
  • OESOPHAGEAL VARICES
  • PORTAL HYPERTENSION

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

View Full Text

Footnotes

  • Twitter @TsungChiehYang1

  • Contributors T-CY, W-CC, M-CH and P-HC conceived and designed the study and wrote the protocol. T-CY, W-CC, M-CH, P-HC, P-CL, C-YC, H-SL and Y-JC participated in the inclusion of study participants and data acquisition. T-CY, W-CC, P-HC and P-CL were responsible for the statistical analysis plan and data analysis. All authors contributed to the data interpretation. T-CY drafted the manuscript. M-CH, S-JH, H-CH, J-CL, Y-HH and F-YL critically revised the manuscript. All authors have approved the final draft of the manuscript for submission. The guarantor of this manuscript is M-CH.

  • Funding This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST110-2314-B-075-050-MY3) and the Taipei Veterans General Hospital (V101C-016). The funding agency of the study had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.