The association between hepatic steatosis and fibrosis in chronic hepatitis B

Abstract

Chronic hepatitis B (CHB) infection affects approximately 248 million individuals worldwide and causes complications including cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease (NAFLD) is another highly prevalent chronic liver disease that leads to significant liver-related morbidity and mortality. It is estimated that 25% to 30% of CHB patients worldwide have co-existing NAFLD. However, the potential interaction between NAFLD and CHB has not been well-defined. Metabolic syndrome and body-mass index, factors closely associated with NAFLD, are known to increase risk of liver fibrosis. Yet, it is unclear whether steatosis has a similar effect on fibrosis progression. Studies regarding NAFLD and HBV virological factors are also inconclusive. Some studies have suggested steatosis to interact with HBV virological factors, while other studies propose that steatosis is independent of HBV virology.

Liver biopsy is the current standard for diagnosis of liver fibrosis and steatosis. However, liver biopsy is invasive, prone to sampling error and only allows semi-quantitative assessment. Conventional imaging methods such as ultrasound and magnetic resonance imaging are also used for steatosis assessment. However, these methods either have low sensitivity or are not readily available. Transient elastography is a non-invasive method to assess liver status through ultrasound attenuation. Liver stiffness (LS) measurements and controlled attenuation parameter (CAP) measurements through transient elastography allows the detection of liver fibrosis and steatosis respectively. Transient elastography is non-invasive, reproducible and has been well-validated in multiple patient populations.

This dissertation consists of two separate studies to investigate the association between steatosis and fibrosis in CHB. All patients from the two studies were recruited from the Liver clinics of Queen Mary Hospital, Hong Kong. Transient elastography was performed on all recruited patients.

In the first study, 601 patients with steatosis defined by CAP were matched in a 1:1 ratio with non-steatotic controls based on age, gender and CHB nucleoside analogue treatment status. The study demonstrated that HBV DNA load was an independent negative predictor of steatosis in treatment naïve CHB patients, suggesting a potential interaction between viral replication and steatosis. The study also showed that metabolic syndrome components and BMI were associated with steatosis in CHB patients, resembling NAFLD risk factors in non-HBV infected subjects.

In conclusion, the studies in this dissertation demonstrated that CHB and NAFLD are not separate disease entities. But rather, they demonstrate an intriguing relationship in both natural history and treatment response. Further studies are warranted to address the interactive effects between steatosis and fibrosis in CHB.