Summary

NASH and its complications are becoming a global epidemic. In Sri Lanka prevalence of NASH and HCC is one of the highest in the world and is further rising. In the future our health care system is going to get flooded with patients with HCC. HCC is an aggressive tumour and large majority are advanced by the time they present to the clinician, as the tumours do not clinically manifest until late.

The key to improve outcome of HCC is to detect the disease early. However, as a large proportion; close to half, is affected with NASH screening all these patients for HCC is not a cost-effective practical task. If a sub group of patients who are genetically prone to develop HCC can be identified this smaller group can be closely followed up.

Upon successful completion of this research, the method can be established to develop predictive genetic biomarkers to identify those at risk of developing NASH cirrhosis and HCC. Such early detection will help in appropriate clinical management. Development of a method to detect miRNA biomarkers in plasma will help to identify initial stages of HCC even before cancer can be detected by conventional methods. This too will facilitate institution of appropriate treatment early.

Ultimately the techniques and the methods developed during this research will benefit the health sector in Sri Lanka in facilitating institution of appropriate treatment. Tests developed will be available to state sector patients in Sri Lanka at the cost price as part of corporate social responsibility activities of the IBMBB and at a slightly higher price for the private sector. The findings of the study will also have a global interest, as this is a disease that is becoming one of the leading cancers.

Objectives

General objective

• Analysis of genetic background for NASH related HCC in a Sri Lankan population
• Specific Objectives
• To determine the association of PNPLA3, TM6SF2 and TERT genes for NASH related HCC in a cohort of Sri Lankan patients
• To determine the association of selected miRNA levels with NASH related HCC in a cohort of Sri Lankan patients
• To develop a genetic and miRNA biomarker for early diagnosis of NASH related HCC

Major Equipment Facilitated by Grant