Serum miR-33a is associated with steatosis and inflammation in patients with non-alcoholic fatty liver disease after liver transplantation


Autoři: Denisa Erhartova aff001;  Monika Cahova aff003;  Helena Dankova aff003;  Marie Heczkova aff003;  Irena Mikova aff001;  Eva Sticova aff004;  Julius Spicak aff001;  Ondrej Seda aff005;  Pavel Trunecka aff001
Působiště autorů: Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic aff001;  Charles University, First Faculty of Medicine, Institute of Physiology, Prague, Czech Republic aff002;  Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic aff003;  Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic aff004;  Charles University and General University Hospital in Prague, First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224820

Souhrn

Background & aims

MiR-33a has emerged as a critical regulator of lipid homeostasis in the liver. Genetic deficiency of miR-33a aggravates liver steatosis in a preclinical model of non-alcoholic fatty liver disease (NAFLD), and relative expression of miR-33a is increased in the livers of patients with non-alcoholic steatohepatitis (NASH). It was unknown whether miR-33a is detectable in the serum of patients with NAFLD. We sought to determine whether circulating miR-33a is associated with histological hepatic steatosis, inflammation, ballooning or fibrosis, and whether it could be used as a serum marker in patients with NAFLD/NASH.

Methods

We analysed circulating miR-33a using quantitative PCR in 116 liver transplant recipients who underwent post-transplant protocol liver biopsy. Regression analysis was used to determine association of serum miR-33a with hepatic steatosis, inflammation, ballooning and fibrosis in liver biopsy.

Results

Liver graft steatosis and inflammation, but not ballooning or fibrosis, were significantly associated with serum miR-33a, dyslipidemia and insulin resistance markers on univariate analysis. Multivariate analysis showed that steatosis was independently associated with serum miR-33a, ALT, glycaemia and waist circumference, whereas inflammation was independently associated with miR-33a, HbA1 and serum triglyceride levels. Receiver operating characteristic analysis showed that exclusion of serum miR-33a from multivariate analysis resulted in non-significant reduction of prediction model accuracy of liver steatosis or inflammation.

Conclusions

Our data indicate that circulating miR-33a is an independent predictor of liver steatosis and inflammation in patients after liver transplantation. Although statistically significant, its contribution to the accuracy of prediction model employing readily available clinical and biochemical variables was limited in our cohort.

Klíčová slova:

Biopsy – Fatty liver – Fibrosis – Inflammation – Lipid metabolism – Liver transplantation – MicroRNAs – Steatosis


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Článek vyšel v časopise

PLOS One


2019 Číslo 11