Serum markers in diagnostics of steatohepatitis
Barbora Nováková 1,2; Radan Brůha 1
IV. interní klinika – klinika hepatologie a gastroenterologie 1. LF UK a VFN v Praze
1; Centrální výzkumné laboratoře ÚLBLD 1. LF UK a VFN v Praze
Vnitř Lék 2019; 65(9): 577-582
Along with the increasing incidence and prevalence of obesity and the metabolic syndrome, the number of patients with its hepatic manifestation – NAFL, characterized by triglyceride storage in liver, is rising. NAFL (non-alcoholic fatty liver) is now, with the prevalence of 40 %, the most common liver disease in Western countries. Despite that NAFL has usually no symptoms and in most patients, it is diagnosed as an incidental finding by abdominal ultrasound, every third of these patients develops NASH (non-alcoholic steatohepatitis), resulting in an individual progression of the sequence of fibrosis – cirrhosis – hepatocellular carcinoma. Due to the fact, that NASH is, along with the cardiovascular causes, involved in liver-related mortality of patients with the metabolic syndrome, from clinical view, it is fundamental to distinguish between benign NAFL and potentially progressive NASH. This appears even more serious realizing that patients with NASH are being often underdiagnosed because of limited indications of liver biopsy, a common diagnostically gold standard. This work emphasizes the relationship between metabolic syndrome and liver disease and presents the main diagnostic possibilities of NAFL/NASH, the most dealing with serum markers. It is based on a research, using the PubMed database and putting the key words as search terms. Considering the huge number of patients diagnosed with fatty liver, a non-invasive, widely approachable method should be established, to make the diagnostic and staging of progression of NASH broadly possible. A new method using LCMS (Liquid Chromatography-Mass Spectrometry) analysis of serum lipids now fulfils these criteria, having high enough specificity and sensitivity, and have also been validated by comparing with a large cohort of patients diagnosed with liver biopsy.
LCMS analysis of serum lipidome – Liquid Chromatography-Mass Spectrometry (LCMS) – NAFL – NASH – serum markers
- Adams LA, Lymp JF, St Sauver J et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129(1): 113–121. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2005.04.014
- Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of non alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55(6): 2005–2023. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.25762>.
- de Barros F, Setúbal S, Martinho JM et al. The correlation between obesity-related diseases and non-alcoholic fatty liver disease in women in the pre-operative evaluation for bariatric surgery assessed by transient hepatic elastography. Obes Surg 2016; 26(9): 2089–2097. Dostupné z DOI: <http://dx.doi.org/10.1007/s11695–016–2054-y>.
- Mayo R, Crespo J, Martínez-Arranz I et al. Metabolomic based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts. Hepatol Commun 2018; 2(7): 807–820. Dostupné z DOI: <http://dx.doi.org/10.1002/hep4.1188>.
- Sung KC, Wild SH, Kwag HJ et al. Fatty liver, insulin resistance, and features of metabolic syndrome: relationships with coronary artery calcium in 10,153 people. Diabetes Care 2012; 35(11): 2359–2364. Dostupné z DOI: <http://doi: 10.2337/dc12–0515>.
- Petäjä EM, Zhou Y, Havana M et al. Phosphorylated IGFBP-1 as a non-invasive predictor of liver fat in NAFLD. Sci Rep 2016; 6: 24740. Dostupné z DOI: <http://dx.doi.org/10.1038/srep24740>.
- Caldwell S, Carolin L. Perspectives on NASH Histology: Cellular Ballooning. Ann Hepatol 2017; 16(2): 182–184. Dostupné z DOI: <http://dx.doi.org/10.5604/16652681.1231550>.
- Lombardi R, Giuseppina P, Silvia F. Role of serum uric acid and ferritin in the development and progression of NAFLD. Int J Mol Sci 2016; 17(4): 548. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms17040548>.
- Miyake T, Kumagi T, Hirooka M et al. Body mass index is the most useful predictive factor for the onset of nonalcoholic fatty liver disease: a community-based retrospective longitudinal cohort study. J Gastroenterol 2013; 48(3): 413–422. Dostupné z DOI: <http://dx.doi.org/10.1007/s00535–012–0650–8>.
- Naveau S, Lamouri K, Pourcher G et al. The diagnostic accuracy of transient elastography for the diagnosis of liver fibrosis in bariatric surgery candidates with suspected NAFLD. Obes Surg 2014; 24(10): 1693–1701. Dostupné z DOI: <http://dx.doi.org/10.1007/s11695–014–1235–9>.
- Dixon JB, Prithi SB, O‘brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121(1): 91–100. Dostupné z DOI: <http://dx.doi.org/10.1053/gast.2001.25540>.
- Kalra S, Vithalani M, Gulati G et al. Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT). J Assoc Physicians India 2013; 61(7): 448–453.
- Romeo S, Kozlitina J, Xing C et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40(12): 1461. Dostupné z DOI: <http://dx.doi.org/10.1038/ng.257>.
- Zain SM Zahurin M, Rosmawati M. A common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: A meta analysis. J Gastroenterol Hepatol 2015; 30(1): 21–27. Dostupné z DOI: <http://dx.doi.org/10.1111/jgh.12714>.
- Li MR, Zhang SH, Chao K et al. Apolipoprotein C3 (-455T> C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population. World f Gastroenterol 2014; 20(38): 14010. Dostupné z DOI: <http://dx.doi.org/10.3748/wjg.v20.i38.14010>.
- Kiziltas S, Ata P, Colak Y et al. TLR4 gene polymorphism in patients with nonalcoholic fatty liver disease in comparison to healthy controls. Metab Syndr Relat Disord 2014; 12(3): 165–170. Dostupné z DOI: <http://dx.doi.org/10.1089/met.2013.0120>.
- Willebrords J, Pereira IV, Maes M et al. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research. Prog Lipid Res 2015; 59: 106–125. Dostupné z DOI: <http://dx.doi.org/10.1016/j.plipres.2015.05.002>.
- Pirola CJ, Gianotti TF, Burgueño AL et al. Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. Gut. 2013 Sep;62(9):1356–63. Dostupné z DOI: <http://dx.doi.org/10.1136/gutjnl-2012–302962>.
- Jun HJ, Kim J, Hoang MH et al. Hepatic lipid accumulation alters global histone h3 lysine 9 and 4 trimethylation in the peroxisome proliferator-activated receptor alpha network. PLoS One 2012; 7(9): e44345. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0044345>.
- Sookoian S, Rosselli MS, Gemma C et al. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator–activated receptor γ coactivator 1α promoter. Hepatology 2010; 52(6): 1992–2000. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.23927>.
- Arab JP, Hernández-Rocha C, Morales C et al. Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the Chilean population. Gastroenterol Hepatol 2017; 40(6): 388–394. Dostupné z DOI: <http://dx.doi.org/10.1016/j.gastrohep.2017.02.009>.
- Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol 2016; 65(5): 1006–1016. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2016.06.005>.
- Park CC, Nguyen P, Hernandez C et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology 2017; 152(3): 598–607. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2016.10.026>.