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Pro-fibrogenic role of alarmin HMGB1 in HIV-HBV co-infection

Singh, Kasha P; Pallett, Laura J; Singh, Harsimran; Chen, Antony; Otano, Itziar; Duriez, Marion; Rombouts, Krista; ... Maini, Mala K; + view all (2023) Pro-fibrogenic role of alarmin HMGB1 in HIV-HBV co-infection. AIDS , 37 (3) pp. 401-411. 10.1097/QAD.0000000000003435. Green open access

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Abstract

OBJECTIVE: Liver disease is accelerated in people living with HIV (PLWH) with hepatitis B (HBV) coinfection. We hypothesised that liver fibrosis in HIV-HBV is triggered by increased hepatocyte apoptosis, microbial translocation and/or HIV/HBV viral products. DESIGN: Sera from PLWH with HBV coinfection versus from those with HBV only or putative mediators were used to examine the pathogenesis of liver disease in HIV-HBV. METHODS: We applied sera from PLWH and HBV coinfection versus HBV alone, or putative mediators (including HMGB1), to primary human hepatic stellate cells (hHSC) and examined pro-fibrogenic changes at the single cell level using flow cytometry. HMGB1 levels in the applied sera were assessed according to donor fibrosis stage. RESULTS: Quantitative flow cytometric assessment of pro-fibrogenic and inflammatory changes at the single cell level revealed an enhanced capacity for sera from PLWH with HBV coinfection to activate hHSC. This effect was recapitulated by LPS, HIV-gp120, hepatocyte conditioned-media and the alarmin HMGB1. Induction of hepatocyte cell death increased their pro-fibrogenic potential, an effect blocked by HMGB1 antagonist glycyrrhizic acid. Consistent with a role for this alarmin, HMGB1 levels were elevated in sera from PLWH and hepatitis B coinfection compared to HBV alone and higher in those with HIV-HBV with liver fibrosis compared to those without. CONCLUSIONS: Sera from PLWH and HBV coinfection have an enhanced capacity to activate primary hHSC. We identified an increase in circulating HMGB1 which, in addition to HIV-gp120 and translocated microbial products, drove pro-fibrogenic changes in hHSC, as mechanisms contributing to accelerated liver disease in HIV-HBV.

Type: Article
Title: Pro-fibrogenic role of alarmin HMGB1 in HIV-HBV co-infection
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAD.0000000000003435
Publisher version: https://doi.org/10.1097/QAD.0000000000003435
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: liver; HBV; HIV; fibrosis; hepatic stellate cells; pro-fibrogenic; HIV-HBV
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10160317
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