Non-alcoholic fatty liver disease in obese children and co-existing liver diseases

Year 2019, Volume: 13 Issue: 4, 258 - 262, 30.07.2019

Ceyda Tuna Kırsaçlıoğlu , Aslıhan Sanrı , Gülin Hizal , Esra Karakuş

https://doi.org/10.12956/tchd.544048

Abstract

Objective:

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children increased parallel to the increment of childhood obesity. Also, NAFLD may be the presenting feature of different liver diseases in non-obese children. We aimed to determine whether there were co-existing liver diseases in overweight and obese children with NAFLD.

Material and Methods:

Pediatric gastroenterology outpatient clinic records of obese and overweight patients, aged between 5-18 years, were retrospectively reviewed. Seventy patients who had liver steatosis on ultrasonography, and alanine aminotransferase (ALT) levels were higher than 1.5 times the upper limit of normal were recruited to the study. The demographic findings, laboratory tests for infectious, metabolic, and autoimmune causes, abdominal ultrasonography and liver biopsy findings of patients were recorded.

Results: At presentation, 94.2% of the patients (n: 66) had mild transaminase elevation. All patients were negative for viral hepatitis, anti-tissue transglutaminase immunoglobulin (Ig) A, anti-liver-kidney-microsome type 1 and anti-smooth muscle antibody. They had normal erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ceruloplasmin, and total IgG levels. Only one patient with low alpha-1 antitrypsin levels had heterozygotes of the PiMZ phenotype. Three (4.3%) patients had antinuclear antibody (ANA) positivity. 44.7% of patients were given ursodeoxycholic acid treatment. On follow-up, normalization of ALT was achieved in 31 (44.2%) patients at mean 6.1±4.6 (2-19) months, but no relation was found between normalization and ursodeoxycholic acid treatment. A patient with ANA positivity had increased ALT, ESR, CRP, IgG levels and ANA titers on follow-up, and she was diagnosed with autoimmune hepatitis with the support of liver biopsy. Under prednisolone and azathioprine treatment, ESR and IgG levels were normalized, ALT and ANA titers decreased.

Conclusion: Other causes of chronic hepatitis should be screened in obesity-related non-alcoholic fatty liver disease and the development of autoimmune hepatitis should be kept in mind in the presence of ANA.

Keywords

Child, non-alcoholic fatty liver disease, autoimmunity, obesity

Obez çocuklarda alkolik olmayan yağlı karaciğer hastalığı ve eşlik eden diğer karaciğer hastalıkları

Abstract

Giriş: Çocuklarda obezitede
artışa parallel olarak alkolik olmayan yağlı karaciğer hastalığı (AOYKH) da
giderek artmaktadır. Ancak obez olmayan çocuklarda, farklı karaciğer hastalıklarında
da karaciğer yağlanması görülebilir. Bu çalışmada
aşırı kilolu ve obez çocuklarda, AOYKH’ye eşlik edebilecek diğer karaciğer hastalıklarının
belirlenmesi amaçlandı.

Gereç ve yöntemler: Polikliniğimizde aşırı kilo ya da obezite ile izlenen, 5-18 yaş
aralığındaki hastaların dosyaları geriye dönük tarandı. Ultrasonografide
karaciğerde yağlanma ve normalin üst sınırından en az 1.5 kat kadar alanin transaminaz
(ALT) yüksekliği olan 70 hasta çalışmaya alındı. Hastaların demografik
verileri, enfeksiyöz, metabolik ve otoimmun nedenler için yapılan laboratuvar
testleri, abdominal ultrasonografi ve karaciğer biyopsi bulguları kaydedildi.

Bulgular: Tanıda
olguların %94,2’ünde (66 olgu) hafif transaminaz yüksekliği vardı. Tanıda
viral hepatit tarama, anti-doku transglutaminaz immunglobulin (Ig) A, anti-liver-kidney-mikrozomal-1
ve anti-düz kas antikor negatifdi.  Eritrosit
sedimentasyon hızı (ESH), C-reaktif protein (CRP), total Ig G, seruloplazmin 
düzeyleri normaldi. Bir olguda  alfa-1 antitripsin düzeyi düşüktü ve PiMZ fenotipi saptandı. Üç (%4,3)
olguda antinükleer antikor  (ANA) pozitifliği saptandı. Olguların %44,7’sine
ursodeoksikolik asit verildi. İzlemde 31 (%44,2) olguda ortalama 6,1± 4,6 (2-19) ayda ALT normalleşme görüldü
ancak ursodeoksikolik asit tedavisi ile ilişkisi saptanmadı. Tanıda ANA pozitif
olan bir olguya izlemde ALT ve ANA titre düzeyi artması, eşlik eden IgG, ESH ve
CRP yükselmesi nedeni ile karaciğer biyopsisi yapılarak otoimmun hepatit (OİH)
tanısı konuldu, prednizolon ve azatiopürin tedavisi ile ALT düzeyinde ve ANA
titresinde gerileme, ESR ve IgG’de normalleşme saptandı. 

Tartışma: Obezite ile ilişkili alkolik olmayan yağlı karaciğer
hastalığında diğer kronik hepatit nedenleri taranmalı, ANA pozitifliğinde OİH
gelişebileceği akılda tutulmalıdır.

Keywords

Çocukluk çağı, obezite, yağlı karaciğer hastalığı, otoimmun hepatit

References

• 1. Berardis S, Sokal E. Pediatric non-alcoholic fatty liver disease: an increasing public health issue. Eur J Pediatr 2014; 173: 131-9.
• 2. Middleton JP, Wiener RC, Barnes BH, Gurka MJ, DeBoer MD. Clinical features of pediatric nonalcoholic fatty liver disease: a need for increased awareness and a consensus for screening. Clin Pediatr (Phila) 2014; 53: 1318-25.
• 3. Sharma A, Freese DK, Chandan V, Zarroug AE, Swain JM, Kumar S. Hepatic cirrhosis secondary to nonalcoholic fatty liver disease in a 12-year-old girl with morbid obesity. Clin Pediatr (Phila) 2014; 53: 86-8.
• 4. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the expert committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017; 64: 319-34.
• 5. Mann JP, Valenti L, Scorletti E, Byrne CD, Nobili V. Nonalcoholic fatty liver disease in children. Semin Liver Dis 2018;38:1-13.
• 6. Pittschieler K. Liver involvement in alpha1-antitrypsin-deficient phenotypes PiSZ and PiMZ. Acta Pædiatr 2002; 91: 239–40.
• 7. Gorska K, Korczynski P, Struniawski R, Krenke R, Oldakowska-Jedynak U, Grabczak EM et al. Heterozygous alpha-1 antitrypsin deficiency in liver transplant candidates. Pol Arch Med Wewn 2013; 123: 14-20.
• 8. Loria P, Lonardo A, Leonardi F, Fontana C, Carulli L, Verrone AM et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci 2003; 48: 2173-81.
• 9. Niwa H, Sasaki M, Haratake J, Kasai T, Katayanagi K, Kurumaya H, Masuda S et al. Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis. Hepatol Res 2007; 37: 923-31.
• 10. Vuppalanchi R, Gould RJ, Wilson LA, Unalp-Arida A, Cummings OW, Chalasani N et al. Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int 2012; 6: 379-85.
• 11. Adams LA, Lindor KD, Angulo P. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2004; 99: 1316-20.
• 12. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 2004;38:801-4.
• 13. Ravi S, Shoreibah M, Raff E, Bloomer J, Kakati D, Rasheed K et al. Autoimmune Markers Do Not Impact Clinical Presentation or Natural History of Steatohepatitis-Related Liver Disease. Dig Dis Sci 2015; 60: 3788-93.
• 14. Yatsuji S, Hashimoto E, Kaneda H, Taniai M, Tokushige K, Shiratori K. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol 2005; 40: 1130-8.
• 15. Tsuneyama K, Baba H, Kikuchi K, Nishida T, Nomoto K, Hayashi S et al. Autoimmune features in metabolic liver disease: a single-center experience and review of the literature. Clin Rev Allergy Immunol 2013; 45: 143-8.
• 16. Weiler-Normann C, Lohse A.W. Nonalcoholic fatty liver disease in patients with autoimmune hepatitis: further reason for teeth GNASHing? Dig Dis Sci 2016; 61; 2462-4.
• 17. Komura T, Ohta H, Seike T, Shimizu Y, Nakai R, Omura H, et al. The efficacy of corticosteroid therapy in a patient with non-alcoholic steatohepatitis overlapping autoimmune hepatitis. Intern Med 2018;57:807-12.
• 18. Fukuda S, Komori A, Itoh M, Mihara Y, Hashimoto S, Bae SK, et al. Histological remission during corticosteroid therapy of overlapping nonalcoholic steatohepatitis and autoimmune hepatitis: Case report and literature review. Case Rep Gastroenterol 2011;5:553-7.