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|
|Supervisor||Sumita Verma (Supervisor), S. Mukhopadhyay (Supervisor), Manuela Mengozzi (Supervisor), Florian Kern (Supervisor) & Prof Guruprasad Aithal (Supervisor)|