Srivastava, Ankur; (2022) The Use Of Non-Invasive Fibrosis Markers In Stratification Care Pathways For The Management Of Chronic Liver Disease. Doctoral thesis (Ph.D), UCL (University College London).

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Text Ankur Srivastava 14103661 FINAL PhD thesis 12.01.2022.pdf - Accepted Version Download (10MB) | Preview

Abstract

The health, societal and economic consequences of chronic liver disease (CLD) are substantial and increasing exponentially. Cirrhosis is typically detected in the latter stages when prognosis is poor. Timely diagnosis is hindered by reliance on non-discriminatory tests for fibrosis. I explored the role of non-invasive tests (NITs) of liver fibrosis in primary care to promote earlier disease detection. In this thesis, a systematic review revealed a paucity of published studies evaluating NIT in the community setting. A national survey demonstrated that UK specialists consider current fibrosis assessment methods to be sub-optimal, and NIT are important in improving disease stratification in primary care. To benchmark standard care, a one-year retrospective study of GP referrals for non-alcoholic fatty liver disease (NAFLD) established 93% of referrals to have non-significant fibrosis (Brunt ≤ F2) as assessed by liver specialists. Over two-thirds had a low-risk FIB-4 (<1.30) and could have avoided referral, although a quarter of patients with indeterminate FIB-4 (1.30 – 3.25) had significant liver fibrosis suggesting patients in this subgroup warrant further evaluation. As part of the Camden and Islington liver working group, I developed and evaluated a NAFLD pathway that employs FIB-4 and ELF to identify patients with advanced fibrosis or cirrhosis (Brunt ≥ F3 fibrosis). The pathway processed nearly 1500 patients over two years, resulting in a reduction in the proportion of total patients referred and an 81% decrease in referral of patients with non-significant fibrosis. The pathway achieved a 5-fold increase in the referral of patients with advanced fibrosis and 3-fold increase in the detection of liver cirrhosis. To further extrapolate these findings, I developed a probabilistic decision analytical model which tested FIB-4, ELF and fibroscan, either alone or in combination in primary care pathways. Cost consequence analyses revealed all strategies to be clinically effective and cost-saving compared to standard care.

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