Non-invasive assessment of chronic liver disease in vulnerable and homeless adults in the community

Abstract

People who are homeless (PWAH), are at high risk of developing chronic liver disease (CLD) due to the high prevalence of alcohol use disorder (AUD) and injecting drug use (IDU). Nonetheless, their access to healthcare and overall engagement with liver services remain suboptimal. Moreover, this group represents a hard-to-reach population when it comes to the implementation of hepatitis C (HCV) elimination plans. Various models have been proposed to develop community liver screening services for PWAH employing passive and active case finding strategies. Our systematic review of these models suggests that community-based FibroScan is the most common method for liver fibrosis assessment; the prevalence of clinically significant hepatic fibrosis (CSHF)/>F2 fibrosis (liver stiffness measurement >8kPa) being 37%. Additionally, quality of evidence assessing the effectiveness of interventions in PWAH remains poor, but where good quality evidence exists it highlights that communitybased interventions for PWAH can improve their linkage to care and HCV treatment outcomes. In Brighton, the Vulnerable Adults LIver Disease (VALID) study was modelled on our previous successful ITTREAT model based at Addiction centres. In VALID Study, we focused primarily on homeless adults and established a hostel-based liver screening service offering alcohol (AUDIT) questionnaire and substance misuse assessment, blood-borne viruses (BBVs) testing, mobile transient elastography (TE) and dedicated treatment for CLD. Our primary outcome was the prevalence of CSHF. Secondary outcomes included service uptake (BBV screening, FibroScan, HCV treatment), prevalence of HCV, IDU, alcohol dependence, and cirrhosis and HCV treatment outcomes. We also assessed correlation between LSM and peripheral cytokines (Th17 panel, IL-6, TNF and IFN-γ), hepatocyte senescence markers [Matrix metalloproteinase-2 (MMP-2), cytokeratin -18 (CK-18)] and Enhanced Liver Fibrosis (ELF) score [Hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen III amino-terminal peptide (PIIINP)] in a community setting. Of 131 individuals approached, service uptake was 97% (n=127). At baseline 96 (76%) were homeless, half (n=63) were alcohol dependent (AUDIT questionnaire) with 49 (39%) being HCV PCR positive. Using TE, CSHF and cirrhosis were detected in 33 (26%) and 21 (17%), respectively, with AUD being an independent predictor of both. There was moderate agreement between LSM and ELF score for CSHF (Kappa value 0.536, p<0.001). In comparison to ELF, APRI had a lower degree of agreement with LSM for CSHF (Kappa value 0.452, p<0.001). Serum concentrations of TNF, IFN-γ, IL-6, IL-10 hepatic senescence biomarkers and ELF biomarkers were significantly elevated in those with CSHF. Of the 29 who received DAA-based HCV treatment, sustained virological response rates were 83% with 93% successfully completing treatment. In conclusion, this work demonstrates the significant burden of CLD in PWAH; the two main aetiological factors being AUD and HCV, leading to a high prevalence of CSHF (as assessed by LSM). This work is also amongst the first to assess additional non-invasive markers of hepatic fibrosis (ELF, APRI), as well as cytokines and hepatic senescence biomarkers in PWAH and their correlation with LSM. Despite the vulnerable nature of the cohort, service uptake and HCV treatment outcomes were excellent. Our work endorses the need for a national model evaluating community-based interventions to address CLD amongst PWAH to improve overall liver health.

Date of Award	2021
Original language	English
Awarding Institution	University of Brighton
Supervisor	Sumita Verma (Supervisor), S. Mukhopadhyay (Supervisor), Manuela Mengozzi (Supervisor), Florian Kern (Supervisor) & Prof Guruprasad Aithal (Supervisor)