The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis

Arturo Solano-Urrusquieta; Nelson Eduardo Alvarez-Licona; Jose Antonio Morales-Gonzalez; Raul Fierros-Oceguera; Javier Bastida-Alquicira; Alicia Sarahi Ojeda-Yuren; Eira Cerda-Reyes

doi:doi:10.11648/j.ajim.20210903.16

The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis

Arturo Solano-Urrusquieta, Nelson Eduardo Alvarez-Licona, Jose Antonio Morales-Gonzalez, Raul Fierros-Oceguera, Javier Bastida-Alquicira, Alicia Sarahi Ojeda-Yuren, Eira Cerda-Reyes

Published in American Journal of Internal Medicine (Volume 9, Issue 3)

Received: 24 March 2021 Accepted: 21 April 2021 Published: 4 June 2021

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Abstract

Lysosomal acid lipase is an enzyme that intervenes in the last steps of lipid metabolism to hydrolyze cholesteryl esters. Patients with cryptogenic cirrhosis present a clear deficiency of lysosomal acid lipase with an unknown mechanism. Design: The present study has an analytical and retrospective design, of a sample of 55 patients with cryptogenic cirrhosis. The degree of association of lysosomal acid lipase was determined with the results of the enzymes alanine aminotransferase and alkaline phosphatase, as well as with the clinical manifestations of portal hypertension and splenic volume. The sensitivity and specificity of the test were determined for the diagnosis of the manifestations of portal hypertension. Results: The most frequent complication of portal hypertension was variceal hemorrhage with 40%, followed by ascites with 32.7%, and last, by hepatic encephalopathy, with 18.2%. Association by the x² test was without statistical significance with values of 0.177, 0.299, and 0.184 for encephalopathy, variceal hemorrhage, and ascites, respectively. The association of lysosomal acid lipase and splenic volume utilizing the Student t-test had a low degree of association and p >0.05. Through ROC curves, we obtained AUROC results close to 0.5. Conclusion: It is established that there is no correlation of the levels of activity of lysosomal acid lipase with the values of alanine aminotransferase and alkaline phosphatase, as well as with the presence or absence of clinical manifestations and by ultrasound of portal hypertension. Lysosomal acid lipase is not a good test for the diagnosis of the clinical manifestations of portal hypertension.

Published in	American Journal of Internal Medicine (Volume 9, Issue 3)
DOI	10.11648/j.ajim.20210903.16
Page(s)	142-147
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Lysosomal Acid Lipase, Cryptogenic Cirrhosis, Portal Hypertension, Liver Cirrhosis, Liver Cirrhosis

References

[1]	G. Eason, B. Noble, and I. N. Sneddon, “On certain integrals of Lips Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A et al. The Epidemiology of Cirrhosis in the United States. Journal of Clinical Gastroenterology. 2015; 49 (8): 690-696.
[2]	Setiawan V, Stram D, Porcel J, Lu S, Le Marchand L, Noureddin M. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort. Hepatology. 2016; 64 (6): 1969-1977.
[3]	Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int 2018; 38 (Suppl 1): 2–6. https://doi.org/10.1111/liv.13682.
[4]	Gao E, Hercun J, Heller T, Vilarinho S. Undiagnosed liver diseases. Transl Gastroenterol Hepatol [Internet]. 2021 Apr 1 [cited 2021 Apr 16]; 6 (28): 1–14. Available from: /pmc/articles/PMC7829073/.
[5]	Kim D, Li AA, Gadiparthi C, Khan MA, Cholankeril G, Glenn JS, et al. Changing trends in etiology-based annual mortality from chronic liver disease, from 2007 through 2016. Gastroenterology 2018. https://doi.org/10.1053/j.gastro.2018.07.008.
[6]	Cholankeril G, Wong RJ, Hu M, Perumpail RB, Yoo ER, Puri P, Younossi ZM, Harrison SA, Ahmed A. Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes. Dig Dis Sci 2017; 62: 29152922 [PMID: 28744836 DOI: 10.1007/s106200174684x].
[7]	Mendez-Sánchez N, et al. Etiology of Liver Cirrhosis in Mexico. 2004; Annals of Hepatology January (3): 30-33.
[8]	Méndez-Sánchez N, Zamarripa-Dorsey F, Panduro A, Purón-González E, Coronado-Alejandro EU, Cortez-Hernández CA, et al. Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions. World J Clin Cases [Internet]. 2018 Dec 1 [cited 2021 Apr 17]; 6 (15): 922–30. Available from: https://pubmed.ncbi.nlm.nih.gov/30568947/.
[9]	Camarena C, Aldamiz-Echevarria L, Polo B, Barba Romero M, García I, Cebolla J et al. Update on lysosomal acid lipase deficiency: diagnosis, treatment and follow-up of patients. Clinical Medicine. 2017; 148 (9: 429. e1-429. e10.
[10]	Ponziani F, Pecere S, Gasbarrini A, Ojetti V. Physiology and pathophysiology of liver lipid metabolism. Expert Review of Gastroenterology & Hepatology. 2015; 9 (8): 1055-1067.
[11]	Angelico F, Corradini S, Pastori D, Fargion S, Fracanzani A, Angelico M et al. Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicenter cohort study. Atherosclerosis. 2017; 262: 179-184.
[12]	Vespasiani-Gentilucci U, Gallo P, Piemonte F, Riva E, Porcari A, Vorini F et al. Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known Etiology. PLOS ONE. 2016; 11 (5): e0156113.
[13]	Bernstein DL, Lobritto S, Iuga A, Remotti H, Schiano T, Fiel MI, et al. Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients. Mol Genet Metab [Internet]. 2018; 124 (1): 11–9. Available from: https://doi.org/10.1016/j.ymgme.2018.03.010.
[14]	Baratta F, Pastori D, Del Ben M, Polimeni L, Labbadia G, Di Santo S et al. Reduced Lysosomal Acid Lipase Activity in Adult Patients with Non- alcoholic Fatty Liver Disease. EBioMedicine. 2015; 2 (7): 750-754.
[15]	Polimeni L, Pastori D, Baratta F, Tozzi G, Novo M, Vicinanza R et al. Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease. Internal and Emergency Medicine. 2017; 12 (8): 1159-1165.
[16]	Vázquez-Frias R, García-Ortiz J, Valencia-Mayoral P, Castro-Narro G, Medina-Bravo P, Santillán-Hernández Y et al. Mexican consensus on the diagnosis of lysosomal acid lipase deficiency. Journal of Gastroenterology of Mexico. 2018; 83 (1): 51-61.
[17]	Baratta F, Pastori D, Polimeni L, Tozzi G, Violi F, Angelico F et al. Does Lysosomal Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease? International Journal of Molecular Sciences. 2015; 16 (12): 28014-28021.
[18]	Bernstein D, Hulkova H, Bialer M, Desnick R. Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease. Journal of Hepatology. 2013; 58 (6): 1230-1243.
[19]	Tovoli F, Napoli L, Negrini G, D’Addato S, Tozzi G, D’Amico J, et al. A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease. Int J Mol Sci [Internet]. 2017 Jun 1 [cited 2021 Apr 15]; 18 (6): 1–15. Available from: /pmc/articles/PMC5485958/.
[20]	Shteyer E, Villenchik R, Mahamid M, Nator N, Safadi R. Low Serum Lysosomal Acid Lipase Activity Correlates with Advanced Liver Disease. International Journal of Molecular Sciences. 2016; 17 (3): 312.
[21]	Strebinger G, Müller E, Feldman A, Aigner E. Lysosomal acid lipase deficiency – early diagnosis is the key . Hepatic Med Evid Res [Internet]. 2019 May [cited 2021 Apr 19]; Volume 11: 79–88. Available from: /pmc/articles/PMC6536894/.
[22]	Pastores GM, Hughes DA. Lysosomal acid lipase deficiency: Therapeutic options [Internet]. Vol. 14, Drug Design, Development and Therapy. Dove Medical Press Ltd.; 2020 [cited 2021 Apr 19]. p. 591–601. Available from: /pmc/articles/PMC7023879/.
[23]	Schulz P, Ferreira F, Nascimento M, Vieira A, Ribeiro M, David A et al. Association of nonalcoholic fatty liver disease and liver cancer. World Journal of Gastroenterology. 2015; 21 (3): 913.
[24]	Pericleous M, Kelly C, Wang T, Livingstone C, Ala A. Wolman’s disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency. Lancet Gastroenterol Hepatol [Internet]. 2017; 2 (9): 670–9. Available from: http://dx.doi.org/10.1016/S2468-1253(17)30052-3.
[25]	Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease [Internet]. Vol. 23, World Journal of Gastroenterology. Baishideng Publishing Group Co; 2017 [cited 2021 Apr 19]. p. 8263–76. Available from: /pmc/articles/PMC5743497/.
[26]	Liu Z, Alsaggaf R, Mcglynn KA, Anderson LA, Tsai HT, Zhu B, et al. Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink. Gut [Internet]. 2019 Aug 1 [cited 2021 Apr 18]; 68 (8): 1458–64. Available from: /pmc/articles/PMC6525087/.
[27]	Smith A, Baumgartner K, Bositis C. Cirrhosis: Diagnosis and Management. Am Fam Physician. 2019; 100 (12): 759–70.
[28]	Rinaldi L, Nascimbeni F, Giordano M, Masetti C, Guerrera B, Amelia A et al. Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis. World Journal of Gastroenterology. 2017; 23 (8): 1458.
[29]	Vespasiani-Gentilucci U, D'Amico J, De Vincentis A, Tozzi G, Vorini F, Gallo P et al. Platelet count may impact on lysosomal acid lipase activity determination in dried blood spot. Clinical Biochemistry. 2017; 50 (12): 726-728.

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APA Style

Arturo Solano-Urrusquieta, Nelson Eduardo Alvarez-Licona, Jose Antonio Morales-Gonzalez, Raul Fierros-Oceguera, Javier Bastida-Alquicira, et al. (2021). The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. American Journal of Internal Medicine, 9(3), 142-147. https://doi.org/10.11648/j.ajim.20210903.16

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ACS Style

Arturo Solano-Urrusquieta; Nelson Eduardo Alvarez-Licona; Jose Antonio Morales-Gonzalez; Raul Fierros-Oceguera; Javier Bastida-Alquicira, et al. The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. Am. J. Intern. Med. 2021, 9(3), 142-147. doi: 10.11648/j.ajim.20210903.16

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AMA Style

Arturo Solano-Urrusquieta, Nelson Eduardo Alvarez-Licona, Jose Antonio Morales-Gonzalez, Raul Fierros-Oceguera, Javier Bastida-Alquicira, et al. The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. Am J Intern Med. 2021;9(3):142-147. doi: 10.11648/j.ajim.20210903.16

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@article{10.11648/j.ajim.20210903.16,
  author = {Arturo Solano-Urrusquieta and Nelson Eduardo Alvarez-Licona and Jose Antonio Morales-Gonzalez and Raul Fierros-Oceguera and Javier Bastida-Alquicira and Alicia Sarahi Ojeda-Yuren and Eira Cerda-Reyes},
  title = {The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis},
  journal = {American Journal of Internal Medicine},
  volume = {9},
  number = {3},
  pages = {142-147},
  doi = {10.11648/j.ajim.20210903.16},
  url = {https://doi.org/10.11648/j.ajim.20210903.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20210903.16},
  abstract = {Lysosomal acid lipase is an enzyme that intervenes in the last steps of lipid metabolism to hydrolyze cholesteryl esters. Patients with cryptogenic cirrhosis present a clear deficiency of lysosomal acid lipase with an unknown mechanism. Design: The present study has an analytical and retrospective design, of a sample of 55 patients with cryptogenic cirrhosis. The degree of association of lysosomal acid lipase was determined with the results of the enzymes alanine aminotransferase and alkaline phosphatase, as well as with the clinical manifestations of portal hypertension and splenic volume. The sensitivity and specificity of the test were determined for the diagnosis of the manifestations of portal hypertension. Results: The most frequent complication of portal hypertension was variceal hemorrhage with 40%, followed by ascites with 32.7%, and last, by hepatic encephalopathy, with 18.2%. Association by the x² test was without statistical significance with values of 0.177, 0.299, and 0.184 for encephalopathy, variceal hemorrhage, and ascites, respectively. The association of lysosomal acid lipase and splenic volume utilizing the Student t-test had a low degree of association and p >0.05. Through ROC curves, we obtained AUROC results close to 0.5. Conclusion: It is established that there is no correlation of the levels of activity of lysosomal acid lipase with the values of alanine aminotransferase and alkaline phosphatase, as well as with the presence or absence of clinical manifestations and by ultrasound of portal hypertension. Lysosomal acid lipase is not a good test for the diagnosis of the clinical manifestations of portal hypertension.},
 year = {2021}
}

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TY  - JOUR
T1  - The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis
AU  - Arturo Solano-Urrusquieta
AU  - Nelson Eduardo Alvarez-Licona
AU  - Jose Antonio Morales-Gonzalez
AU  - Raul Fierros-Oceguera
AU  - Javier Bastida-Alquicira
AU  - Alicia Sarahi Ojeda-Yuren
AU  - Eira Cerda-Reyes
Y1  - 2021/06/04
PY  - 2021
N1  - https://doi.org/10.11648/j.ajim.20210903.16
DO  - 10.11648/j.ajim.20210903.16
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 142
EP  - 147
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20210903.16
AB  - Lysosomal acid lipase is an enzyme that intervenes in the last steps of lipid metabolism to hydrolyze cholesteryl esters. Patients with cryptogenic cirrhosis present a clear deficiency of lysosomal acid lipase with an unknown mechanism. Design: The present study has an analytical and retrospective design, of a sample of 55 patients with cryptogenic cirrhosis. The degree of association of lysosomal acid lipase was determined with the results of the enzymes alanine aminotransferase and alkaline phosphatase, as well as with the clinical manifestations of portal hypertension and splenic volume. The sensitivity and specificity of the test were determined for the diagnosis of the manifestations of portal hypertension. Results: The most frequent complication of portal hypertension was variceal hemorrhage with 40%, followed by ascites with 32.7%, and last, by hepatic encephalopathy, with 18.2%. Association by the x² test was without statistical significance with values of 0.177, 0.299, and 0.184 for encephalopathy, variceal hemorrhage, and ascites, respectively. The association of lysosomal acid lipase and splenic volume utilizing the Student t-test had a low degree of association and p >0.05. Through ROC curves, we obtained AUROC results close to 0.5. Conclusion: It is established that there is no correlation of the levels of activity of lysosomal acid lipase with the values of alanine aminotransferase and alkaline phosphatase, as well as with the presence or absence of clinical manifestations and by ultrasound of portal hypertension. Lysosomal acid lipase is not a good test for the diagnosis of the clinical manifestations of portal hypertension.
VL  - 9
IS  - 3
ER  -

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Author Information

Arturo Solano-Urrusquieta

Internal Assistance Department, Secretary of National Defense, Mexico City, Mexico
Nelson Eduardo Alvarez-Licona

Post-graduate Department, Higher School of Medicine, National Polytechnic Institute, Mexico City, Mexico
Jose Antonio Morales-Gonzalez

Laboratory of Conservation Medicine, Higher School of Medicine National Polytechnic Institute, México City, Mexico
Raul Fierros-Oceguera

Department of Palliative Care, “El Buen Samaritano” Hospital, Mexico City, Mexico
Javier Bastida-Alquicira

Radiology Department, Ultrasonography and non-Invasive Images Section, Central Military Hospital, City of Mexico, Mexico
Alicia Sarahi Ojeda-Yuren

Faculty of Bioethics, Anahuac University Mexico, Mexico City, Mexico
Eira Cerda-Reyes

Gastroenterology Section, Central Military Hospital, Mexico City, Mexico

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Arturo Solano-Urrusquieta, Nelson Eduardo Alvarez-Licona, Jose Antonio Morales-Gonzalez, Raul Fierros-Oceguera, Javier Bastida-Alquicira, et al. (2021). The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. American Journal of Internal Medicine, 9(3), 142-147. https://doi.org/10.11648/j.ajim.20210903.16

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ACS Style

Arturo Solano-Urrusquieta; Nelson Eduardo Alvarez-Licona; Jose Antonio Morales-Gonzalez; Raul Fierros-Oceguera; Javier Bastida-Alquicira, et al. The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. Am. J. Intern. Med. 2021, 9(3), 142-147. doi: 10.11648/j.ajim.20210903.16

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AMA Style

Arturo Solano-Urrusquieta, Nelson Eduardo Alvarez-Licona, Jose Antonio Morales-Gonzalez, Raul Fierros-Oceguera, Javier Bastida-Alquicira, et al. The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis. Am J Intern Med. 2021;9(3):142-147. doi: 10.11648/j.ajim.20210903.16

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@article{10.11648/j.ajim.20210903.16,
  author = {Arturo Solano-Urrusquieta and Nelson Eduardo Alvarez-Licona and Jose Antonio Morales-Gonzalez and Raul Fierros-Oceguera and Javier Bastida-Alquicira and Alicia Sarahi Ojeda-Yuren and Eira Cerda-Reyes},
  title = {The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis},
  journal = {American Journal of Internal Medicine},
  volume = {9},
  number = {3},
  pages = {142-147},
  doi = {10.11648/j.ajim.20210903.16},
  url = {https://doi.org/10.11648/j.ajim.20210903.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20210903.16},
  abstract = {Lysosomal acid lipase is an enzyme that intervenes in the last steps of lipid metabolism to hydrolyze cholesteryl esters. Patients with cryptogenic cirrhosis present a clear deficiency of lysosomal acid lipase with an unknown mechanism. Design: The present study has an analytical and retrospective design, of a sample of 55 patients with cryptogenic cirrhosis. The degree of association of lysosomal acid lipase was determined with the results of the enzymes alanine aminotransferase and alkaline phosphatase, as well as with the clinical manifestations of portal hypertension and splenic volume. The sensitivity and specificity of the test were determined for the diagnosis of the manifestations of portal hypertension. Results: The most frequent complication of portal hypertension was variceal hemorrhage with 40%, followed by ascites with 32.7%, and last, by hepatic encephalopathy, with 18.2%. Association by the x² test was without statistical significance with values of 0.177, 0.299, and 0.184 for encephalopathy, variceal hemorrhage, and ascites, respectively. The association of lysosomal acid lipase and splenic volume utilizing the Student t-test had a low degree of association and p >0.05. Through ROC curves, we obtained AUROC results close to 0.5. Conclusion: It is established that there is no correlation of the levels of activity of lysosomal acid lipase with the values of alanine aminotransferase and alkaline phosphatase, as well as with the presence or absence of clinical manifestations and by ultrasound of portal hypertension. Lysosomal acid lipase is not a good test for the diagnosis of the clinical manifestations of portal hypertension.},
 year = {2021}
}

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TY  - JOUR
T1  - The Severity of the Clinical Expression of Lysosomal Acid Lipase in Patients with Cryptogenic Cirrhosis
AU  - Arturo Solano-Urrusquieta
AU  - Nelson Eduardo Alvarez-Licona
AU  - Jose Antonio Morales-Gonzalez
AU  - Raul Fierros-Oceguera
AU  - Javier Bastida-Alquicira
AU  - Alicia Sarahi Ojeda-Yuren
AU  - Eira Cerda-Reyes
Y1  - 2021/06/04
PY  - 2021
N1  - https://doi.org/10.11648/j.ajim.20210903.16
DO  - 10.11648/j.ajim.20210903.16
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 142
EP  - 147
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20210903.16
AB  - Lysosomal acid lipase is an enzyme that intervenes in the last steps of lipid metabolism to hydrolyze cholesteryl esters. Patients with cryptogenic cirrhosis present a clear deficiency of lysosomal acid lipase with an unknown mechanism. Design: The present study has an analytical and retrospective design, of a sample of 55 patients with cryptogenic cirrhosis. The degree of association of lysosomal acid lipase was determined with the results of the enzymes alanine aminotransferase and alkaline phosphatase, as well as with the clinical manifestations of portal hypertension and splenic volume. The sensitivity and specificity of the test were determined for the diagnosis of the manifestations of portal hypertension. Results: The most frequent complication of portal hypertension was variceal hemorrhage with 40%, followed by ascites with 32.7%, and last, by hepatic encephalopathy, with 18.2%. Association by the x² test was without statistical significance with values of 0.177, 0.299, and 0.184 for encephalopathy, variceal hemorrhage, and ascites, respectively. The association of lysosomal acid lipase and splenic volume utilizing the Student t-test had a low degree of association and p >0.05. Through ROC curves, we obtained AUROC results close to 0.5. Conclusion: It is established that there is no correlation of the levels of activity of lysosomal acid lipase with the values of alanine aminotransferase and alkaline phosphatase, as well as with the presence or absence of clinical manifestations and by ultrasound of portal hypertension. Lysosomal acid lipase is not a good test for the diagnosis of the clinical manifestations of portal hypertension.
VL  - 9
IS  - 3
ER  -

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