Abstract
In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine whether liver disease was associated with intrahepatic or circulating markers of inflammation or burden of HIV or HBV, liver biopsies and blood were collected from HIV-HBV co-infected individuals (n = 39) living in Bangkok, Thailand and naïve to ART. Transient elastography (TE) was performed. Intrahepatic and circulating markers of inflammation and microbial translocation were quantified by ELISA and bead arrays and HIV and HBV infection quantified by PCR. Liver fibrosis (measured by both transient elastography and liver biopsy) was statistically significantly associated with intrahepatic mRNA for CXCL10 and CXCR3 using linear and logistic regression analyses adjusted for CD4 T-cell count. There was no evidence of a relationship between liver fibrosis and circulating HBV DNA, qHBsAg, plasma HIV RNA or circulating cell-associated HIV RNA or DNA. Using immunohistochemistry of liver biopsies from this cohort, intrahepatic CXCL10 was detected in hepatocytes associated with inflammatory liver infiltrates in the portal tracts. In an in vitro model, we infected an HBV-infected hepatocyte cell line with HIV, followed by interferon-γ stimulation. HBV-infected cells lines produced significantly more CXCL10 than uninfected cells lines and this significantly increased in the presence of an increasing multiplicity of HIV infection. Conclusion: Enhanced production of CXCL10 following co-infection of hepatocytes with both HIV and HBV may contribute to accelerated liver disease in the setting of HIV-HBV co-infection.
Highlights
In HIV-hepatitis B virus (HBV) co-infection, liver-related mortality is 17 times higher than HBV mono-infection [1]
Liver disease including fibrosis and cirrhosis is accelerated in those with HIV-hepatitis B coinfection, and outcomes are improved with antiviral treatment, increased morbidity and mortality are still seen for unknown reasons
We recruited people living with HIV-hepatitis B coinfection who had not been treated and assessed liver fibrosis using non-invasive means and liver biopsy
Summary
Chronic hepatitis B infection is common in people living with HIV due to shared routes of transmission. Liver disease including fibrosis and cirrhosis is accelerated in those with HIV-hepatitis B coinfection, and outcomes are improved with antiviral treatment, increased morbidity and mortality are still seen for unknown reasons. We recruited people living with HIV-hepatitis B coinfection who had not been treated and assessed liver fibrosis using non-invasive means (transient elastography or ‘Fibroscan’) and liver biopsy. We infected a hepatocyte cell line with HIV and HBV and found that production of CXCL10 was greatly increased in the presence of both viruses. We conclude that increased CXCL10 in hepatocytes, as a result of co-infection of hepatocytes with HIV and HBV, may be an important new target for treatments to reduce liver disease in people living with HIV and HBV and should be further investigated
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