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
. 2020 Mar 5;3(3):CD011573.
doi: 10.1002/14651858.CD011573.pub2.

Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis

Daniela Gattini  1 , Lorena I Cifuentes  2 , Romina Torres-Robles  3 , Juan Cristóbal Gana  4
Affiliations
Meta-Analysis

Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis

Daniela Gattini et al. Cochrane Database Syst Rev. .

Abstract

Background: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Therefore, prevention is important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children.

Objectives: To assess the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Search methods: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, and two other registers in February 2019. We scrutinised the reference lists of the retrieved publications, and performed a manual search of the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstracts from January 2008 to December 2018. We searched four registries for ongoing clinical trials. There were no language or document type restrictions.

Selection criteria: We included randomised clinical trials irrespective of blinding, language, or publication status assessing sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Data collection and analysis: We used standard Cochrane methodology to perform this systematic review. We used the intention-to-treat principle to analyse outcome data, and GRADE to assess the certainty of evidence per outcome.

Main results: We found only one randomised clinical trial that fulfilled our inclusion criteria. The trial was at high risk of bias. The trial included 108 Brazilian children with median age of 4.3 years (range 11 months to 13 years). Fifty-six children were randomised to prophylactic sclerotherapy (ethanolamine oleate 2%) and 52 children to no intervention (control). Children were followed up for a median of 4.5 years. Eight children (six from the sclerotherapy group versus two from the control group) dropped out before the end of the trial. The follow-up was from 18 months to eight years. Mortality was 16% (9/56 children) in the sclerotherapy group versus 15% (8/52 children) in the control group (risk ration (RR) 1.04, 95% confidence interval (CI) 0.44 to 2.50; very low-certainty evidence). Upper gastrointestinal bleeding occurred in 21% (12/56) of the children in the sclerotherapy group versus 46% (24/52) in the control group (RR 0.46, 95% CI 0.26 to 0.83; very low-certainty evidence). There were more children with congestive hypertensive gastropathy in the sclerotherapy group than in the control group (14% (8/56) versus 6% (3/52); RR 2.48, 95% CI 0.69 to 8.84; very low-certainty evidence). The incidence of gastric varices was similar between the sclerotherapy group and the control group (11% (6/56) versus 10% (5/52); RR 1.11, 95% CI 0.36 to 3.43; very low-certainty evidence). The incidence of bleeding from gastric varices was higher in the sclerotherapy group than in the control group (4% (3/56) versus 0% (0/52); RR 6.51, 95% CI 0.34 to 123.06; very low-certainty evidence). The study did not assess health-related quality of life. Oesophageal variceal bleeding occurred in 5% (3/56) of the children in the sclerotherapy group versus 40% (21/52) of the children in the control group (RR 0.13, 95% CI 0.04 to 0.42; very low-certainty evidence). The most prevalent complications (defined as non-serious) were pain and fever after the procedure, which promptly resolved with analgesics. However, numerical data on the frequency of these adverse events and their occurrences in the two groups were lacking. No funding information was provided. We found no ongoing trials.

Authors' conclusions: The evidence, obtained from one randomised clinical trial at high risk of bias, is very uncertain on whether sclerotherapy has an influence on mortality and if it may decrease first upper gastrointestinal or oesophageal variceal bleeding in children. The evidence is very uncertain on whether sclerotherapy has an influence on congestive hypertensive gastropathy, incidence on gastric varices, and incidence of bleeding from gastric varices. Health-related quality of life was not measured. There were no serious events caused by sclerotherapy, and analysis of non-serious adverse events could not be performed due to lack of numerical data. The GRADE assessment of each outcome showed a very low-certainty evidence. The results of the trial need to be interpreted with caution. Larger randomised clinical trials, following the SPIRIT and CONSORT statements, assessing the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, failure to control bleeding, and adverse events.

PubMed Disclaimer

Conflict of interest statement

DG: none. LC: none. RTR: none. JG: none.

Figures

1
1
Study flow diagram. RCT: randomised clinical trial.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.
1.1
1.1. Analysis
Comparison 1: Sclerotherapy versus no intervention, Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Sclerotherapy versus no intervention, Outcome 2: Upper gastrointestinal bleeding
1.3
1.3. Analysis
Comparison 1: Sclerotherapy versus no intervention, Outcome 3: Liver‐related morbidity
1.4
1.4. Analysis
Comparison 1: Sclerotherapy versus no intervention, Outcome 4: Oesophageal variceal bleeding
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011573

References

References to studies included in this review

Gonçalves 2000 {published data only}
    1. Gonçalves ME, Cardoso SR, Maksoud JG. Prophylactic sclerotherapy in children with esophageal varices: long-term results of a controlled prospective randomized trial. Journal of Pediatric Surgery 2000;35(3):401-5. - PubMed

References to studies excluded from this review

Ogusu 2003 {published data only}
    1. Ogusu T, Iwakiri R, Sakata H, Matsunaga K, Shimoda R, Oda K, et al. Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients without hepatocellular carcinoma: a comparison of long term survival between prophylactic therapy and emergency therapy. Journal of Gastroenterology 2003;38(4):361-4. [PMID: ] - PubMed
Rivet 2009 {published data only}
    1. Rivet C, Robles-Medranda C, Dumortier J, Le Gall C, Ponchon T, Lachaux A. Endoscopic treatment of gastroesophageal varices in young infants with cyanoacrylate glue: a pilot study. Gastrointestinal Endoscopy 2009;69(6):1034-8. [PMID: ] - PubMed
Sauerbruch 1988 {published data only}
    1. Sauerbruch T, Wotzka R, Kopcke W, Harlin M, Heldwein W, Bayerdorffer E, et al. Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. New England Journal of Medicine 1988;319(1):8-15. [PMID: ] - PubMed
Svoboda 1999 {published data only}
    1. Svoboda P, Kantorova I, Ochmann J, Kozumplik L, Marsova J. Preventive sclerotherapy of esophageal varices with a high risk of hemorrhage: a prospective randomized controlled study [Preventivni skleroterapie jicnovych varixu s vysokym rizikem krvaceni: prospektivni randomizovana kontrolovana studie.]. Rozhledy V Chirurgii 1999;78(7):337-42. [PMID: ] - PubMed

Additional references

Angelico 2019
    1. Angelico R, Pietrobattista A, Candusso M, Tomarchio S, Pellicciaro M, Liccardo D, et al. Primary prophylaxis for gastrointestinal bleeding in children with biliary atresia and portal hypertension candidates for liver transplant: a single-center experience. Transplantation Proceedings 2019;51(1):171-8. [PMID: ] - PubMed
Brok 2008
    1. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. Journal of Clinical Epidemiology 2008;61:763-9. - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive – trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. International Journal of Epidemiology 2009;38(1):287-98. - PubMed
Carneiro 2018
    1. Carneiro de Moura M, Chen S, Kamath BM, Ng VL, Ling SC. Acute variceal bleeding causes significant morbidity. Journal of Pediatric Gastroenterology and Nutrition 2018;67(3):371-6. [PMID: ] - PubMed
Chan 2013
    1. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ (Clinical Research Ed.) 2013;346:e7586. [PMID: ] - PMC - PubMed
Chapin 2018
    1. Chapin CA, Bass LM. Cirrhosis and portal hypertension in the pediatric population. Clinics in Liver Disease 2018;22(4):735-52. [PMID: ] - PubMed
Cifuentes 2021a
    1. Cifuentes LI, Gattini D, Torres-Robles R, Gana JC. Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Cochrane Database of Systematic Reviews 2021, Issue 1. Art. No: CD011973. [DOI: 10.1002/14651858.CD011973.pub2] - DOI - PMC - PubMed
Cifuentes 2021b
    1. Cifuentes LI, Gattini D, Torres-Robles R, Gana JC. Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. Cochrane Database of Systematic Reviews 2021, Issue 1. Art. No: CD011561. [DOI: 10.1002/14651858.CD011561.pub2] - DOI - PMC - PubMed
Di Giorgio 2019
    1. Di Giorgio A, De Angelis P, Cheli M, Vajro P, Iorio R, Cananzi M, et al. Etiology, presenting features and outcome of children with non-cirrhotic portal vein thrombosis: a multicentre national study. Digestive and Liver Disease 2019;51(8):1179-84. [PMID: ] - PubMed
Duche 2008
    1. Duche M, Habes D, Roulleau P, Haas V, Jacquemin E, Bernard O. Prophylactic endoscopic sclerotherapy of large esophagogastric varices in infants with biliary atresia. Gastrointestinal Endoscopy 2008;67(4):732-7. [PMID: ] - PubMed
Duche 2010
    1. Duche M, Ducot B, Tournay E, Fabre M, Cohen J, Jacquemin E, et al. Prognostic value of endoscopy in children with biliary atresia at risk for early development of varices and bleeding. Gastroenterology 2010;139(6):1952-60. [PMID: ] - PubMed
Duche 2013
    1. Duche M, Ducot B, Ackermann O, Baujard C, Chevret L, Frank-Soltysiak M, et al. Experience with endoscopic management of high-risk gastroesophageal varices, with and without bleeding, in children with biliary atresia. Gastroenterology 2013;145(4):801-7. [PMID: ] - PubMed
Ebel 2019
    1. Ebel NH, Carlin K, Shaffer ML, Shivaram G, Hawkins M, Lane ER, et al. Hepatic venous pressure gradient measurements in children: correlation with hepatic histology and clinical indicators of portal hypertension. Journal of Pediatric Gastroenterology and Nutrition 2019;68(6):788-92. [PMID: ] - PMC - PubMed
El‐Karaksy 2015
    1. El-Karaksy HM, El-Koofy N, Mohsen N, Helmy H, Nabil N, El-Shabrawi M. Extrahepatic portal vein obstruction in Egyptian children. Journal of Pediatric Gastroenterology and Nutrition 2015;60(1):105-9. [PMID: ] - PubMed
Eroglu 2004
    1. Eroglu Y, Emerick KM, Whitingon PF, Alonso EM. Octreotide therapy for control of acute gastrointestinal bleeding in children. Journal of Pediatric Gastroenterology and Nutrition 2004;38(1):41-7. [PMID: ] - PubMed
Gana 2011a
    1. Gana JC, Turner D, Mieli-Vergani G, Davenport M, Miloh T, Avitzur Y, et al. A clinical prediction rule and platelet count predict esophageal varices in children. Gastroenterology 2011;141(6):2009-16. [PMID: ] - PubMed
Gana 2011b
    1. Gana JC, Valentino PL, Morinville V, O'Connor C, Ling SC. Variation in care for children with esophageal varices: a study of physicians', patients', and families' approaches and attitudes. Journal of Pediatric Gastroenterology and Nutrition 2011;52(6):751-5. [PMID: ] - PubMed
Gana 2019
    1. Gana JC, Cifuentes LI, Gattini D, Villarroel Del Pino LA, Pena A, Torres-Robles R. Band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No: CD010546. [DOI: 10.1002/14651858.CD010546.pub2] - DOI - PMC - PubMed
Gana 2020
    1. Gana JC, Cifuentes LI, Gattini D, Torres-Robles R. Band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No: CD011803. [DOI: 10.1002/14651858.CD011803.pub2] - DOI - PMC - PubMed
Garcia‐Tsao 2007
    1. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey WD. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. American Journal of Gastroenterology 2007;102(9):2086-102. [PMID: ] - PubMed
Garcia‐Tsao 2008
    1. Garcia-Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding – unresolved issues. Summary of an American Association for the Study of Liver Diseases and European Association for the Study of the Liver single-topic conference. Hepatology (Baltimore, Md.) 2008;47(5):1764-72. [PMID: ] - PubMed
Garcia‐Tsao 2017
    1. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology (Baltimore, Md.) 2017;65(1):310-35. [PMID: ] - PubMed
Gattini 2020
    1. Gattini D, Cifuentes LI, Torres-Robles R, Gana JC. Sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. Cochrane Database of Systematic Reviews 2020, Issue 1. Art. No: CD011659. [DOI: 10.1002/14651858.CD011659.pub2] - DOI - PMC - PubMed
Gluud 2012
    1. Gluud LL, Krag A. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No: CD004544. [DOI: 10.1002/14651858.CD004544.pub2] - DOI - PMC - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 4 December 2019. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015. Available at gradepro.org.
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clinical Research Ed.) 2003;327(7414):557-60. [PMID: ] - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice CFR & ICH Guidelines. Vol. 1. Philadelphia (PA): Barnett International/PAREXEL, 1997.
Jeanniard‐Malet 2017
    1. Jeanniard-Malet O, Duche M, Fabre A. Survey on clinical practice of primary prophylaxis in portal hypertension in children. Journal of Pediatric Gastroenterology and Nutrition 2017;64(4):524-7. [PMID: ] - PubMed
Kamath 2001
    1. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology (Baltimore, Md.) 2001;33(2):464-70. [PMID: ] - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Annals of Internal Medicine 2001;135(11):982-9. - PubMed
Lampela 2012
    1. Lampela H, Kosola S, Koivusalo A, Lauronen J, Jalanko H, Rintala R, et al. Endoscopic surveillance and primary prophylaxis sclerotherapy of esophageal varices in biliary atresia. Journal of Pediatric Gastroenterology and Nutrition 2012;55(5):574-9. [PMID: ] - PubMed
Lee 2017
    1. Lee WS, Ong SY, Foo HW, Wong SY, Kong CX, Seah RB, et al. Chronic liver disease is universal in children with biliary atresia living with native liver. World Journal of Gastroenterology 2017;23(43):7776-84. [PMID: ] - PMC - PubMed
Ling 2011
    1. Ling SC, Walters T, McKiernan PJ, Schwarz KB, Garcia-Tsao G, Shneider BL. Primary prophylaxis of variceal hemorrhage in children with portal hypertension: a framework for future research. Journal of Pediatric Gastroenterology and Nutrition 2011;52(3):254-61. [PMID: ] - PMC - PubMed
Lundh 2017
    1. Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2017, Issue 2. Art. No: MR000033. [DOI: 10.1002/14651858.MR000033.pub3] - DOI - PMC - PubMed
Lykavieris 2000
    1. Lykavieris P, Gauthier F, Hadchouel P, Duche M, Bernard O. Risk of gastrointestinal bleeding during adolescence and early adulthood in children with portal vein obstruction. Journal of Pediatrics 2000;136(6):805-8. [PMID: ] - PubMed
McDiarmid 2002
    1. McDiarmid SV, Anand R, Lindblad AS. Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation. Transplantation 2002;74(2):173-81. [PMID: ] - PubMed
Miga 2001
    1. Miga D, Sokol RJ, Mackenzie T, Narkewicz MR, Smith D, Karrer FM. Survival after first esophageal variceal hemorrhage in patients with biliary atresia. Journal of Pediatrics 2001;139(2):291-6. [PMID: ] - PubMed
Mileti 2011
    1. Mileti E, Rosenthal P. Management of portal hypertension in children. Current Gastroenterology Reports 2011;13(1):10-6. [PMID: ] - PMC - PubMed
Moher 1998
    1. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 1998;352(9128):609-13. - PubMed
PCORI 2012
    1. Basch E, Aronson N, Berg A, Flum D, Gabriel S, Goodman SN, et al. Methodological standards and patient-centeredness in comparative effectiveness research: the PCORI perspective. JAMA 2012;307(15):1636-40. [PMID: ] - PubMed
Pugh 1973
    1. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. British Journal of Surgery 1973;60(8):646-9. [PMID: ] - PubMed
Review Manager 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591-603. - PubMed
Savović 2012a
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine 2012;157(6):429-38. - PubMed
Savović 2012b
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Health Technology Assessment 2012;16(35):1-82. - PubMed
Savović 2018
    1. Savović J, Turner RM, Mawdsley D, Jones HE, Beynon R, Higgins JPT, et al. Association between risk-of-bias assessments and results of randomized trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study. American Journal of Epidemiology 2018;187(5):1113-22. [PMID: ] - PMC - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12. - PubMed
Shneider 2004
    1. Shneider BL. Approaches to the management of pediatric portal hypertension: results of an informal survey. In: Groszmann RJ, Bosch J, editors(s). Portal Hypertension in the 21st Century. Dordrecht (The Netherlands): Kluwer Academic Publishers, 2004:167-74.
Shneider 2012a
    1. Shneider BL, Abel B, Haber B, Karpen SJ, Magee JC, Romero R, et al. Portal hypertension in children and young adults with biliary atresia. Journal of Pediatric Gastroenterology and Nutrition 2012;55(5):567-73. [PMID: ] - PMC - PubMed
Shneider 2012b
    1. Shneider BL, Bosch J, Franchis R, Emre SH, Groszmann RJ, Ling SC, et al. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. Pediatric Transplantation 2012;16(5):426-37. [PMID: ] - PubMed
Shneider 2016
    1. Shneider BL, Ville de Goyet J, Leung DH, Srivastava A, Ling SC, Duche M, et al. Primary prophylaxis of variceal bleeding in children and the role of MesoRex Bypass: summary of the Baveno VI Pediatric Satellite Symposium. Hepatology (Baltimore, Md.) 2016;63(4):1368-80. [PMID: ] - PubMed
Stringer 1989
    1. Stringer MD, Howard ER, Mowat AP. Endoscopic sclerotherapy in the management of esophageal varices in 61 children with biliary atresia. Journal of Pediatric Surgery 1989;24(5):438-42. [PMID: ] - PubMed
Thorlund 2009
    1. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses. International Journal of Epidemiology 2009;38(1):276-86. - PubMed
Thorlund 2010
    1. Thorlund K, Anema A, Mills E. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals. Clinical Epidemiology 2010;2:57-66. - PMC - PubMed
Thorlund 2017
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/wp-content/uploads/2020/12/tsa_manual_ENG.pdf 2017 (accessed 28 January 2021).
TSA 2017 [Computer program]
    1. Copenhagen Trial Unit TSA - Trial Sequential Analysis. Version 0.9.5.10 Beta. Copenhagen: Copenhagen Trial Unit, 2017. ctu.dk/tsa/downloads/.
van Buuren 2003
    1. Buuren HR, Rasch MC, Batenburg PL, Bolwerk CJ, Nicolai JJ, Werf SD, et al. Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899]. BMC Gastroenterology 2003;3:22. [PMID: ] - PMC - PubMed
van Heurn 2004
    1. Heurn LW, Saing H, Tam PK. Portoenterostomy for biliary atresia: long-term survival and prognosis after esophageal variceal bleeding. Journal of Pediatric Surgery 2004;39(1):6-9. [PMID: ] - PubMed
van Wessel 2018
    1. Wessel DB, Witt M, Bax N, Verkade HJ, Scheenstra R, Kleine RH, et al. Variceal bleeds in patients with biliary atresia. Zeitschrift fur Kinderchirurgie [Surgery in Infancy and Childhood] 2018;28(5):439-44. [PMID: ] - PubMed
Verdaguer 2016
    1. Verdaguer DS, Gana A JC. Management of pediatric patients with esophageal varices [Enfrentamiento de pacientes pediatricos con varices esofagicas]. Revista Medica de Chile 2016;144(7):879-85. [PMID: ] - PubMed
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. Journal of Clinical Epidemiology 2008;61(1):64-75. - PubMed
Wetterslev 2009
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in a random-effects meta-analysis. BMC Medical Research Methodology 2009;9:86. - PMC - PubMed
Wetterslev 2017
    1. Wetterslev J, Jakobsen JC, Gluud C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Medical Research Methodology 2017;17(1):39. - PMC - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman GD, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ (Clinical Research Ed.) 2008;336:601-5. - PMC - PubMed

References to other published versions of this review

Gana 2015
    1. Gana JC, Cifuentes LI, Cerda J, Villarroel del Pino LA, Peña A, Rivera-Cornejo M. Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children. Cochrane Database of Systematic Reviews 2015, Issue 3. Art. No: CD011573. [DOI: 10.1002/14651858.CD011573] - DOI - PMC - PubMed

MeSH terms