The Fatty Liver, Cirrhosis & Liver cancer study-TENDENCY: Case control study (Preprint)

BACKGROUND Hepatocellular cancer (HCC) is associated with high mortality and early diagnosis leads to better survival. Patients with cirrhosis especially due to Non-Alcoholic Fatty Liver disease (NAFLD) and viral hepatitis are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6 monthly screening with serum Alpha Fetoprotein and Ultrasound liver) have low sensitivity and hence there is a need for better screening markers for HCC. OBJECTIVE Our study, TENDENCY, aims to validate the novel screening markers (Methylated SEPTIN9, Urinary Volatile Organic Compounds and Urinary peptides) for HCC diagnosis and study these non-invasive biomarkers in liver disease. METHODS This is a multicentre nested case-control study which involves comparing the plasma levels of methylated Septin9 between confirmed HCC cases and Cirrhotic patients (control group). It also includes the comparison of urine samples for the detection of HCC specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at UHCW, we have estimated our sample size to be 308 (88 HCC and 220 cirrhotic patients). Urine and plasma samples will be collected from all the participants and will be frozen at -80°C till the end of recruitment. Gas Chromatography-mass spectrometry (GC-MS) will be used for urinary volatile organic compounds detection and Capillary electrophoresis-mass spectrometry (CE-MS) will be utilised for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated Septin9(mSEPT9). The study will be monitored by the Research and Development department at UHCW. RESULTS NA(ongoing study) CONCLUSIONS NA (ongoing study) CLINICALTRIAL TENDENCY has been approved by Northeast-York Ethics Committee. The IRAS number for the study is 260179 and the NIHR portfolio ID is 42438.