Development of Steatohepatitis and Fibrosis in Chronic HBV Infection Is Linked to Inflammatory Responses Mediated by IL-13 and CCL11

Background: In view of the importance of chronic HBV (CHB) infection and the global burden of non-alcoholic fatty liver disease (NAFLD), it is imperative to understand the potential interplay between the two diseases. Methods: Here, we retrospectively investigated the association between NAFLD and CHB infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between year 2013 and 2016, we studied 449 subjects in the current investigation. Findings: CAP and LSM scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the 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. Interpretations: Together, we found that there was a high concurrence of NAFLD among patients with CHB. The presence of metabolic syndrome and chronic inflammation in CHB patients were two independent factors that led to progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components. Plasma markers of liver steatosis and fibrosis progression are key to development of cell-targeted therapies exploiting specific molecular pathways. Funding Statement: This work was supported by a grant from the Frontier Research Grant (FRG), FG019-17AFR to Mohamed Rosmawati and Xiamen University Malaysia Research Funding (XMUMRF), XMUMRF/2018-C2/ILAB/0001. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linkoping University Hospital Research Fund, ALF Grants Region Ostergotland, FORSS. Declaration of Interests: The authors declare no conflicts interest. Ethics Approval Statement: The medical records of patients were extracted from the hospital database using patients’ unique hospital registration number. This study was approved by the Medical Ethics Committee of the University Malaya Medical Centre (MEC-938.42).