Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection

Abstract

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.

Keywords:

• Fibrosis
• HBV
• metabolic syndrome
• IL-13
• CCL11

Acknowledgements

The authors are grateful to all the participants, clinical, paraclinical, and laboratory staff of the University of Malaya Medical Centre for assistance with patient recruitment, specimen collection, and cooperation.

Author contributions

RM, YKY, EMS conceived and designed the experiments; RM, SWW, YWT established cohort and collected the clinical data for patients; JBC, YYK and HYT collected clinical specimens and carried out experiments; SWW, YWT, YKY, VV and HYT carried out data analysis and documented the findings; SWW, YWT, YKY, EMS wrote the manuscript; MB, JBC, KKT and RM contributed the reagents and analysis tools; EMS, VV, ML and RM provided critical inputs to the manuscripts; all authors proofread the manuscript; SWW, YWT and YKY contributed equally to the experimental work and writing of the manuscript; EMS and RM contributed equally to the supervision of the project and writing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Additional information

Funding

This work was supported by a Frontier Research Grant (FRG), [FG019-17AFR] to Mohamed Rosmawati, and Xiamen University Malaysia Research Funding (XMUMRF), [XMUMRF/2018-C2/ILAB/0001] to Yean Kong Yong. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linköping University Hospital Research Fund, ALF Grants Region Östergötland, FORSS. Esaki M Shankar is supported by the Department of Science and Technology-Science and Engineering Research Board, Government of India (Grant number CRG/2019/006096).