Year 2024 / Volume 116 / Number 10
Original
Low phospholipid-associated cholelithiasis syndrome, a not uncommon cause of biliary problems and hospital admissions

532-538

DOI: 10.17235/reed.2024.10425/2024

Isabel María Spigarelli, Beatriz Pillado, David Vincent, Joaquín Poza Cordón, Marta Abadía, Gloria Ruiz-Fernández, Eva Marín, Pilar Castillo Grau, Benjamín Polo, Antonio Olveira Martín,

Abstract
Background and aims: biliary diseases are a major cause of morbidity and mortality for patients and a burden for the healthcare system. The genetic syndrome of low phospholipid-associated cholelithiasis (LPAC) is a little known and rare entity whose treatment with bile salts avoids symptoms, admissions and the need for surgery. The aim of this study was to determine its incidence and characteristics in our center. Methods: prospective study performed between February 2021 and September 2022. LPAC was diagnosed if at least two of the following were present: onset of biliary problems < 40 years of age, recurrence of symptoms after cholecystectomy, ultrasound image of hepatolithiasis (multiple echoic foci, comet-tail images, hepatolithiasis with acoustic shadow). Demographic, clinical, genetic (analysis of MDR3 gene mutations) and ultrasound characteristics and their incidence were analyzed in hospital admissions for biliary causes. Results: thirty-six patients with LPAC were identified. Of these, six were among 237 admissions due to biliary causes in the previous nine months, with an incidence of 2.5 % (95 % CI: 1.17-5.41). By age subgroup, the incidence was 16.7 % in those admitted < 40 years of age and 9.1 % in those < 50. Considering females only, the incidence was 21 % in those admitted < 40 years and 15.8 % in those < 50 years. All patients remained asymptomatic after treatment with ursodeoxycholic acid and there were no new admissions. Conclusions: LPAC syndrome is not as uncommon as it may appear, especially in women < 50 years of age admitted with biliary problems. Its correct diagnosis based on simple criteria could avoid a significant number of hospital admissions and unnecessary cholecystectomies.
Lay Summary
A prospective study was conducted to determine the incidence and characteristics of LPAC syndrome, a little known genetic disorder that causes the formation of hepatolithiasis and biliary problems, especially in young patients. A total of 36 patients with LPAC were identified according to established clinical and diagnostic criteria. These included the onset of biliary problems before the age of 40 years, the recurrence of symptoms after cholecystectomy, and the presence of hepatolithiasis on ultrasound. The incidence of LPAC syndrome among admissions for biliary causes was 2.5%. This was found to be more prevalent among young patients and women. Specifically, LPAC syndrome was the cause of 16.7% of admissions in patients under 40 years of age and 21% in women under 40 years of age. The administration of ursodeoxycholic acid proved to be an efficacious treatment, effectively preventing recurrences and new hospitalizations. Therefore, LPAC is not as uncommon as it might appear, particularly among young women with biliary problems. It is essential to consider this diagnosis, as a correct diagnosis based on simple criteria could avoid numerous hospitalizations and unnecessary surgeries.
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References
1. Subdirección General de Información Sanitaria M de S. Registro de Actividad Sanitaria Especializada (RAE-CMBD): Actividad y resultados de la hospitalización en el Sistema Nacional de Salud Año 2018. 2018.
2. Observatorio de resultados - Portal de Salud de la Comunidad de Madrid. Sanidadmadrid.org. Índice de colecistectomía laparoscópica. Sanidadmadrid.org [Internet, citado a 22 de febrero de 2023]
3. Lammert F, Matern S. The Genetic Background of Cholesterol Gallstone Formation: An Inventory of Human Lithogenic Genes. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Jun 1;5(2):163–70.
4. European Reference Networks. ERN Hepatological Diseases - RARE-LIVER. [Internet, citado a 22 de febrero de 2023]
5. Dong C, Condat B, Picon-Coste M, et al. Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities. JHEP Reports. 2021 Apr;3(2):100201.
6. Goubault P, Brunel T, Rode A, et al. Low-Phospholipid Associated Cholelithiasis (LPAC) syndrome: A synthetic review. J Visc Surg. 2019 Sep;156(4):319–28.
7. Rosmorduc O, Poupon R, Hermelin B. MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis. Gastroenterology. 2001 May;120(6):1459–67.
8. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine. 2015 May;17(5):405–24.
9. Poupon R, Rosmorduc O, Boëlle PY, et al. Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: A study of 156 consecutive patients. Hepatology. 2013 Sep;58(3):1105–10.
10. Su S, Trinh A, Metz AJ, et al. Targeted liver ultrasound performed by an expert is the pivotal imaging examination for low phospholipid-associated cholelithiasis. Eur J Gastroenterol Hepatol. 2023 Mar 8;35(3):327–32.
11. Gille N, Karila-Cohen P, Goujon G, et al. Low phospholipid-associated cholelithiasis syndrome: A rare cause of acute pancreatitis that should not be neglected. World J Hepatol. 2020 Jun 27;12(6):312-322.
12. Nayagam JS, Williamson C, Joshi D, et al. Review article: liver disease in adults with variants in the cholestasis‐related genes ABCB11, ABCB4 and ATP8B1. Aliment Pharmacol Ther. 2020 Dec 18;52(11–12):1628–39.
13. Maurer KR, Everhart JE, Knowler WC, et al. Risk factors for gallstone disease in the hispanic populations of the United States. Am J Epidemiol. 1990 May;131(5):836–44.
14. Everhart JE. Gallstones and ethnicity in the Americas. J Assoc Acad Minor Phys. 2001 Jul;12(3):137-43.
15. Krawczyk M, Miquel JF, Stokes CS, et al. Genetics of biliary lithiasis from an ethnic perspective. Clin Res Hepatol Gastroenterol. 2013 Apr;37(2):119–25.
16. Condat B, Zanditenas D, Barbu V, et al. Prevalence of low phospholipid-associated cholelithiasis in young female patients. Digestive and Liver Disease. 2013 Nov;45(11):915–9.
17. Avena A, Puggelli S, Morris M, et al. ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed. Dig Liver Dis. 2021 Mar;53(3):329-344.
18. Schatz SB, Jüngst C, Keitel-Anselmo V, et al. Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset. Hepatol Commun. 2018 Mar 22;2(5):504-514.
19. Nakken KE, Labori KJ, Rødningen OK, et al. ABCB4 sequence variations in young adults with cholesterol gallstone disease. Liver Int. 2009 May;29(5):743-7
20. Fein F, Hermelin B, Becker MC, et al. Acute recurrent biliary pancreatitis associated with the ABCB4 gene mutation. Gastroenterol Clin Biol. 2007 Jan;31(1):106-9.
21. Poupon R, Barbu V, Chamouard P, et al. Combined features of low phospholipid-associated cholelithiasis and progressive familial intrahepatic cholestasis 3. Liver Int. 2010 Feb;30(2):327-3.
22. Gouveia C, Flor de Lima M, Pereira F, et al. Should patients with symptomatic cholelithiasis before 30 years of age be tested for ABCB4 gene mutations? Scand J Gastroenterol. 2020 Aug;55(8):958-962.
23. Kubitz R, Bode J, Erhardt A, et al. Cholestatic liver diseases from child to adult: the diversity of MDR3 disease. Z Gastroenterol. 2011 Jun;49(6):728-36.
24. Medhioub M, Ayedi H, Hamzaoui ML, et al. LPAC syndrome: An uncommon etiology of intrahepatic cholelithiasis. Presse Med. 2019 Jan;48(1 Pt 1):72-74.
25. Biyoukar M, Corpechot C, El Mouhadi S, et al. ABCB4 variant is associated with hepatobiliary MR abnormalities in people with low-phospholipid-associated cholelithiasis syndrome. JHEP Reports. 2022 Nov;4(11):100590.
26. Wendum D, Barbu V, Rosmorduc O, et al. Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations. Virchows Archiv. 2012 Mar 14;460(3):291–8.
27. Condat B, Le syndrome LPAC (Low Phospholipid- Associated Cholelithiasis): mythe ou réalité? PostU FMC-HGE. 2016, p. 1-8
28. Castro I, Martínez M. Transportadores de lípidos biliares: una revisión actualizada. Gen [Internet]. 2013 Mar [citado en 2024 Abr 22] ; 67( 1 ): 49-57
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Spigarelli I, Pillado B, Vincent D, Poza Cordón J, Abadía M, Ruiz-Fernández G, et all. Low phospholipid-associated cholelithiasis syndrome, a not uncommon cause of biliary problems and hospital admissions. 10425/2024


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Publication history

Received: 24/03/2024

Accepted: 04/05/2024

Online First: 14/06/2024

Published: 09/10/2024

Article revision time: 31 days

Article Online First time: 82 days

Article editing time: 199 days


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