Skip to main content
Log in

A pilot study using lactulose in management of minimal hepatic encephalopathy in children with extrahepatic portal vein obstruction

  • Original article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

Minimal hepatic encephalopathy (MHE) is not associated with overt neuropsychiatric symptoms but rather with subtle changes in psychometric and/or neurophysiologic tests. We aimed to diagnose MHE in children with extrahepatic portal vein obstruction (EHPVO) and to evaluate the effect of lactulose on MHE.

Methods

A prospective study was carried out on 30 patients with EHPVO (21 males; mean age 10±2.5 years). The study was carried out in the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Cairo, Egypt, between 2011 and 2013. All patients were subjected to clinical and laboratory assessment, neuropsychmetric testing using the arabic version of Wechsler intelligence tests, neurophysiological testing by visual electroencephalogram and P300 event related potentials (ERP).

Results

The prevalence of MHE among children with EHPVO was 20% (6/30). After randomization to treatment and no-treatment groups using lactulose, all tests were repeated after three months. Among four patients with MHE who received lactulose, three (75%) improved. On the other hand, one of the patients in the no-treatment group developed MHE. Only one patient in the treatment arm had to discontinue lactulose because of severe diarrhea.

Conclusions

This pilot study revealed that the prevalence of MHE was 20%. Improvement on psychometic tests was seen in 75% of our patients (3/4) after treatment with lactulose. Lactulose treatment was well tolerated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sarin SK, Agrawal SR. Extrahepatic portal vein obstruction. Sem Liv Dis 2002;22:43–58.

    Article  Google Scholar 

  2. Yachha SK, Khandur A, Sharma BC, Kumar M. Gastrointestinal bleeding in children. J Gastroenterol Hepatol 1996;11:903–907.

    Article  PubMed  CAS  Google Scholar 

  3. Arora NK, Lohda R, Gulati S, Gupta AK, Mathur P, Joshi MS, et al. Portal hypertension in north Indian children. Indian J Pediatr 1998;65:585–591.

    Article  PubMed  CAS  Google Scholar 

  4. Abd El-Hamid N, Taylor RM, Marinello D, Mufti GJ, Patel R, Mieli-Vergani G, et al. Aetiology and management of extrahepatic portal vein obstruction in children: King’s College Hospital experience. J Pediatr Gastroenterol Nutr 2008;47:630–634.

    Article  PubMed  Google Scholar 

  5. Gehrke I, John P, Blundell J, Pearson L, Williams A, de Ville de Goyet J. Meso-portal bypass in children with portal vein thrombosis: rapid increase of the intrahepatic portal venous flow after direct portal hepatic reperfusion. J Pediatr Surg 2003;38:1137–1140.

    Article  PubMed  CAS  Google Scholar 

  6. Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology 2006;43:121–131.

    Article  CAS  Google Scholar 

  7. Bosch J. Vascular deterioration in cirrhosis. J Clin Gastroenterol 2007;41:247–253.

    Article  Google Scholar 

  8. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, 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;60:715–735.

    Article  PubMed  Google Scholar 

  9. American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol 2014;61:642–659.

    Article  Google Scholar 

  10. Guerit JM, Amantini A, Fischer C, Kaplan PW, Mecarelli O, Schnitzler A, et al; members of the ISHEN commission on Neurophysiological Investigations. Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009;29:789–796.

    Article  PubMed  Google Scholar 

  11. Randolph C, Hilsabeck R, Kato A, Kharbanda P, Li YY, Mapelli D, et al; International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN). Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009;29:629–635.

    Article  PubMed  Google Scholar 

  12. Sarin SK, Sollano JD, Chawla YK, Amarapurkar D, Hamid S, Hashizume M, et al; Members of the APASL Working Party on Portal Hypertension. Consensus on extra-hepatic portal vein obstruction. Liver Int 2006;26:512–519.

    Article  PubMed  Google Scholar 

  13. Kaufman AS. Tests of Intelligence. In: Sternberg RJ. Handbook of Intelligence. United States, New York, Cambridge University Press, 2000: 445–476.

    Chapter  Google Scholar 

  14. Das A, Dhiman RK, Saraswat VA, Verma M, Naik SR. Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J Gastroenterol Hepatol 2001;16: 531–535.

    Article  PubMed  CAS  Google Scholar 

  15. Wall G, Davidson A, Dalebout D. Determining latency and amplitude for multiple peaked P300 waveform. J Am Acad Audiol 1991;2:189–194.

    PubMed  CAS  Google Scholar 

  16. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 2002;35:716–721.

    Article  PubMed  Google Scholar 

  17. Montagnese S, Amodio P, Morgan MY. Methods for diagnosing hepatic encephalopathy in patients with cirrhosis: a multidimensional approach. Metab Brain Dis 2004;19:281–312.

    Article  PubMed  Google Scholar 

  18. Bajaj JS. The modern management of hepatic encephalopathy. Aliment Pharmacol Ther 2010;31:537–547.

    Article  PubMed  CAS  Google Scholar 

  19. El-Karaksy HM, El-Koofy N, Mohsen N, Helmy H, Nabil N, El-Shabrawi M. Extrahepatic portal vein obstruction in egyptian children. J Pediatr Gastroenterol Nutr 2015;60:105–109.

    Article  PubMed  Google Scholar 

  20. Rangari M, Gupta R, Jain M, Malhotra V, Sarin S K. Hepatic dysfunction in patients with extrahepatic portal venous obstruction. Liver Int 2003;23:434–439.

    Article  PubMed  CAS  Google Scholar 

  21. Mínguez B, García-Pagán JC, Bosch J, Turnes J, Alonso J, Rovira A, et al. Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy. Hepatology 2006;43:707–714.

    Article  PubMed  Google Scholar 

  22. Sharma P, Sharma BC, Puri V, Sarin SK. Minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Am J Gastroenterol 2008;103:1406–1412.

    Article  PubMed  Google Scholar 

  23. Sharma P, Sharma BC. Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Saudi J Gastroentrol 2012;18:168–172.

    Article  Google Scholar 

  24. Quero JC, Hartmann IJ, Meulstee J, Hop WC, Schalm SW. The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis. Hepatology 1996;24:556–560.

    Article  PubMed  CAS  Google Scholar 

  25. Amodio P, Del Piccolo F, Pettenò E, Mapelli D, Angeli P, Iemmolo R, et al. Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. J Hepatol 2001;35:37–45.

    Article  PubMed  CAS  Google Scholar 

  26. Saxena N, Bhatia M, Joshi YK, Garg PK, Tandon RK. Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study. J Gastroenterol Hepatol 2001;16:322–327.

    Article  PubMed  CAS  Google Scholar 

  27. Watanabe A, Sakai T, Sato S, Imai F, Ohto M, Arakawa Y, et al. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997;26:1410–1414.

    Article  PubMed  CAS  Google Scholar 

  28. Dhiman RK, Sawhney MS, Chawla YK, Das G, Ram S, Dilawari JB. Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci 2000;45:1549–1552.

    Article  PubMed  CAS  Google Scholar 

  29. Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 2004;39:1441–1449.

    Article  PubMed  Google Scholar 

  30. Prasad S, Dhiman RK, Duseja A, Chawla Y, Sharma A, Agarwal R. Lactulose improves cognitive functions and healthrelated quality of life in cirrhotic patients with minimal hepatic encephalopathy. Hepatology 2007;45:549–559.

    Article  PubMed  Google Scholar 

  31. Bajaj JS, Saeian K, Christensen KM, Hafeezullah M, Varma RR, Franco J. Probiotic yogurt for treatment of minimal hepatic encephalopathy. Am J Gastroenterol 2008;103:1707–1715.

    Article  PubMed  Google Scholar 

  32. Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomized trials. BMJ 2004;328:1046.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003;114:188–193.

    Article  PubMed  CAS  Google Scholar 

  34. Sundaram V, Shaikh OS. Hepatic encephalopathy: pathophysiology and emerging therapies. Med Clin North Am 2009;3:819–836.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study has been partially funded by Cairo University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hanaa Mostafa El-Karaksy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Karaksy, H.M., Afifi, O., Bakry, A. et al. A pilot study using lactulose in management of minimal hepatic encephalopathy in children with extrahepatic portal vein obstruction. World J Pediatr 13, 70–75 (2017). https://doi.org/10.1007/s12519-016-0066-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-016-0066-2

Key words

Navigation