HBV suppresses hepatic innate immune response
medwireNews: The host hepatic innate immune response is downregulated in untreated patients with chronic hepatitis B virus (HBV) infection, shows a gene expression analysis.
Of note, the degree of suppression is affected by serum levels of hepatitis B surface antigen (HBsAg), but not intrahepatic HBV markers, say the researchers.
They analyzed the expression of 23 genes involved in innate immunity pathways in liver biopsy samples from 105 chronic HBV patients – of whom four had received antiviral therapy 4–10 years before the biopsy, while the remainder were treatment-naïve – and nine control patients who were undergoing abdominal or gall bladder surgery. A further 44 genes were assessed in a subset of 91 HBV patients, owing to limited specimen quantity, and in the controls.
The majority of evaluated genes, which included genes involved in the Toll-like and pattern recognition receptor pathways as well as antiviral effector and interferon-stimulated genes, were downregulated in samples from chronic HBV patients relative to controls.
Indeed, just five genes had a higher level of intrahepatic expression in HBV patients than controls, report Fabien Zoulim (INSERM U1052-Cancer Research Center of Lyon, France) and co-workers.
Interestingly, they found no or weak correlations between intrahepatic gene expression and serum or intrahepatic viral markers, such as HBV DNA levels, and alanine aminotransferase levels.
However, among the 71 hepatitis B e antigen (HBeAg)-negative patients, interferon-stimulated genes and genes involved in the type I interferon response, innate immunity, and liver disease were suppressed to a greater degree among patients with serum HBsAg levels above versus below the median of 5.7 x 103 IU/mL.
No such association was observed among the 34 HBeAg-positive participants when the HBsAg median of 2.9 x 104 IU/mL was used, but certain genes were downregulated to a greater level in patients with HBsAg levels above versus below the first quartile (8.1 x 103 IU/mL).
The study authors write in the Journal of Hepatology that “[a]dditional studies including longitudinal samples from patients in all phases of the disease and, eventually, a broader genome wide approach to analyse the intrahepatic transcriptome are warranted in the future.”
But they believe that their findings “support the use of immune-modulators and/or HBsAg targeting agents as strategies to restore immune responsiveness with the aim of achieving a functional cure of HBV infection,” with serum HBsAg levels serving as a marker to identify patients most likely to benefit.
Editorialists Thomas Vanwolleghem and Andre Boonstra (both from University Medical Center Rotterdam, the Netherlands) consider the study “an important contribution to the field since the host-virus interaction during infection with HBV has been a controversial issue for many years, with conflicting data reported from cell-culture systems and animal models.”
They continue: “Unraveling the complex virus-host interactions is crucial for the rational design of antivirals and immunotherapeutics to achieve functional cure of a chronic HBV infection: this study leads us a step closer in the long road to understanding HBV.”
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