Oral Presentation Australian Society for Medical Research Annual Scientific Meeting 2016

Circulatory microRNAs for the early diagnosis of liver cirrhosis and hepatocellular carcinoma in chronic Hepatitis C (#11)

Anna Weis 1 , David Smith 2 , Leesa Wockner 2 , Isabell Hoffmann 3 , Grant A Ramm 1 , Richard Skoien 1 4
  1. Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
  2. QIMR Berghofer Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
  3. Epidemiology and Informatics, Institute of Medical Biostatistics, University Medical Centre, Johannes Gutenberg-University of Mainz, Mainz, Germany
  4. Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Qld, Australia

Despite increasingly efficacious therapies, cirrhosis due to chronic Hepatitis C (CHC) remains an enormous public health burden due to the development of complications of end-stage disease. Stratifying disease severity according to fibrosis using gold standard liver biopsy is invasive, while non-invasive tests are imperfect at distinguishing between fibrosis stages or predicting complications - such as hepatocellular carcinoma (HCC) development. Here, we show that microRNA (miRNA) have the potential to act as circulating biomarker that stratifies chronic liver disease due to CHC and identifies the presence of HCC.

 

A cohort of 60 patients with CHC were enrolled and subdivided into three groups: (i) mild to moderate fibrosis (n=20); (ii) cirrhosis (n=20); and (iii) cirrhosis complicated by HCC (n=20). The expression levels of 372 liver-related microRNAs were determined in serum samples of each patient using qRT-PCR (Liver miFinder PCR Array). Significantly-differentially expressed microRNAs (P-value<0.05) were detected using quantile normalisation and modified t-test.

 

The levels of several microRNAs were significantly differentially expressed according to the presence of cirrhosis and/or HCC. In particular miRNA-AW1* (P<0.001), miRNA-AW2* (P=0.0018) and miRNA-AW3* (P=0.0047) are differentially expressed in cirrhosis compared with mild to moderate fibrosis. Furthermore, miRNA-AW4* (P<0.0001), miRNA-AW5* (P=0.0020) and miRNA-AW6* (P=0.0023) are differentially expressed in patient with HCC compared with cirrhosis alone. MiRNA-AW4* has potential as a diagnostic biomarker with a 4.3-fold decrease seen in HCC patients.

 

This study identifies several microRNAs differentially expressed in fibrosis, cirrhosis and/or HCC. Panels of microRNAs (e.g. miRNA-AW1* + miRNA-AW2* + miRNA-AW3* in cirrhosis; miRNA-AW4* + miRNA-AW5* + miRNA-AW6* in HCC) could be developed to more accurately diagnose cirrhosis and identify HCC at an earlier stage. Furthermore, the functions of candidate miRNAs could be explored to better understand disease pathogenesis. Ongoing studies aim to confirm these preliminary findings.

 

*microRNA names have been de-identified for IP protection