Skip to main content
Log in

Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease

  • IM - ORIGINAL
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Fatty liver and splenomegaly are typical features of genetic lysosomal acid lipase (LAL) deficiency. No data in adult patients with non-genetic reduction of LAL activity are available. We investigate the association between spleen dimensions and LAL activity in non-alcoholic fatty liver disease (NAFLD) patients, in whom a reduced LAL activity has been reported. We include 425 consecutive patients who underwent abdominal ultrasound to evaluate hepatic steatosis and spleen dimensions. LAL activity was measured with dried blood spot method (Lalistat2). NAFLD was present in 74.1% of screened patients. Higher median spleen longitudinal diameter (10.6 vs. 9.9 cm; p < 0.001) and spleen area (SA) (32.7 vs. 27.7 cm2; p < 0.001), together with a higher and proportion of splenomegaly (17.8 vs. 5.5%, p = 0.001), are present in patients with NAFLD compared to those without. In NAFLD patients, median LAL activity is 0.9 nmol/spot/h. LAL activity is lower in 56 patients with splenomegaly, as compared to those without (p = 0.009). At multivariable logistic regression analysis, age (above median, OR 0.344; p = 0.003), LAL activity (below median, OR 2.206, p = 0.028), and platelets (OR 0.101, p = 0.002) are significantly associated with splenomegaly. NAFLD patients disclose a relatively high prevalence of spleen enlargement and splenomegaly, which are significantly associated with a reduced LAL activity, suggesting that LAL may contribute to spleen enlargement in this setting.

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.

Similar content being viewed by others

References

  1. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40(6):1387–1395. doi:10.1002/hep.20466

    Article  PubMed  Google Scholar 

  2. Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34(3):274–285. doi:10.1111/j.1365-2036.2011.04724.x

    Article  CAS  PubMed  Google Scholar 

  3. Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR (2009) Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 29(1):113–119. doi:10.1111/j.1478-3231.2008.01718.x

    Article  CAS  PubMed  Google Scholar 

  4. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C (2000) Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132(2):112–117

    Article  CAS  PubMed  Google Scholar 

  5. Bernstein DL, Hulkova H, Bialer MG, Desnick RJ (2013) Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol 58(6):1230–1243. doi:10.1016/j.jhep.2013.02.014

    Article  CAS  PubMed  Google Scholar 

  6. Baratta F, Pastori D, Polimeni L, Tozzi G, Violi F, Angelico F, Del Ben M (2015) Does lysosomal acid lipase reduction play a role in adult non-alcoholic fatty liver disease? Int J Mol Sci 16(12):28014–28021. doi:10.3390/ijms161226085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hoffman EP, Barr ML, Giovanni MA, Murray MF (1993) Lysosomal acid lipase deficiency. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews(R). University of Washington, Seattle (WA)

  8. Reiner Z, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, Jones S, Coric M, Calandra S, Hamilton J, Eagleton T, Ros E (2014) Lysosomal acid lipase deficiency—an under-recognized cause of dyslipidemia and liver dysfunction. Atherosclerosis 235(1):21–30. doi:10.1016/j.atherosclerosis.2014.04.003

    Article  CAS  PubMed  Google Scholar 

  9. Baratta F, Pastori D, Del Ben M, Polimeni L, Labbadia G, Di Santo S, Piemonte F, Tozzi G, Violi F, Angelico F (2015) Reduced lysosomal acid lipase activity in adult patients with non-alcoholic fatty liver disease. EBioMedicine 2(7):750–754. doi:10.1016/j.ebiom.2015.05.018

    Article  PubMed  PubMed Central  Google Scholar 

  10. Angelico F, Ginanni Corradini S, Pastori D, Fargion S, Fracanzani AL, Angelico M, Bolondi L, Tozzi G, Pujatti PL, Labbadia G, Corazza GR, Averna M, Perticone F, Croce G, Persico M, Bucci T, Baratta F, Polimeni L, Del Ben M, Violi F, Group LA-CCR (2017) Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study. Atherosclerosis. doi:10.1016/j.atherosclerosis.2017.03.038

    Google Scholar 

  11. Kim MY, Jeong WK, Baik SK (2014) Invasive and non-invasive diagnosis of cirrhosis and portal hypertension. World J Gastroenterol 20(15):4300–4315. doi:10.3748/wjg.v20.i15.4300

    Article  PubMed  PubMed Central  Google Scholar 

  12. Goyal N, Jain N, Rachapalli V, Cochlin DL, Robinson M (2009) Non-invasive evaluation of liver cirrhosis using ultrasound. Clin Radiol 64(11):1056–1066. doi:10.1016/j.crad.2009.05.010

    Article  CAS  PubMed  Google Scholar 

  13. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F, American Heart A, National Heart L, Blood I (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112(17):2735–2752. doi:10.1161/CIRCULATIONAHA.105.169404

    Article  PubMed  Google Scholar 

  14. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Task Force M (2013) 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 31(7):1281–1357. doi:10.1097/01.hjh.0000431740.32696.cc

    Article  CAS  PubMed  Google Scholar 

  15. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (2014) 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311(5):507–520. doi:10.1001/jama.2013.284427

    Article  CAS  PubMed  Google Scholar 

  16. Taskforce M, Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL, Guidelines ESCCfP, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document R, De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Schachinger V, Scheen A, Schirmer H, Stromberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, Xuereb RG (2013) ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 34(39):3035–3087. doi:10.1093/eurheartj/eht108

    Article  Google Scholar 

  17. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C (2006) The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 6:33. doi:10.1186/1471-230X-6-33

    Article  PubMed  PubMed Central  Google Scholar 

  18. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, Sanchez-Avila F, Vargas-Vorackova F (2008) AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol 7(4):350–357

    CAS  PubMed  Google Scholar 

  19. Saverymuttu SH, Joseph AE, Maxwell JD (1986) Ultrasound scanning in the detection of hepatic fibrosis and steatosis. BMJ 292(6512):13–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hamaguchi M, Kojima T, Itoh Y, Harano Y, Fujii K, Nakajima T, Kato T, Takeda N, Okuda J, Ida K, Kawahito Y, Yoshikawa T, Okanoue T (2007) The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. American J Gastroenterol 102(12):2708–2715. doi:10.1111/j.1572-0241.2007.01526.x

    Article  Google Scholar 

  21. Berzigotti A, Ashkenazi E, Reverter E, Abraldes JG, Bosch J (2011) Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension. Dis Markers 31(3):129–138. doi:10.3233/DMA-2011-0835

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hamilton J, Jones I, Srivastava R, Galloway P (2012) A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta Int J Clin Chem 413(15–16):1207–1210. doi:10.1016/j.cca.2012.03.019

    Article  CAS  Google Scholar 

  23. Tsushima Y, Endo K (2000) Spleen enlargement in patients with nonalcoholic fatty liver: correlation between degree of fatty infiltration in liver and size of spleen. Dig Dis Sci 45(1):196–200

    Article  CAS  PubMed  Google Scholar 

  24. Burton BK, Balwani M, Feillet F, Baric I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sanchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG (2015) A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med 373(11):1010–1020. doi:10.1056/NEJMoa1501365

    Article  CAS  PubMed  Google Scholar 

  25. Loftus WK, Chow LT, Metreweli C (1999) Sonographic measurement of splenic length: correlation with measurement at autopsy. J Clin Ultrasound 27(2):71–74

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank nurses Daniela Salzano and Monica Brancorsini for their skilful cooperation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniele Pastori.

Ethics declarations

Conflict of interest

The authors have not disclosed any potential conflict of interest.

Statement of human and animal rights

The study was conducted according to the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. The study did not involved animals.

Informed consent

Each patient provided written informed consent at baseline.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Polimeni, L., Pastori, D., Baratta, F. et al. Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease. Intern Emerg Med 12, 1159–1165 (2017). https://doi.org/10.1007/s11739-017-1746-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-017-1746-1

Keywords

Navigation