Distinct bile acid profiles in chronic hepatitis B are influenced by HBV DNA levels and presence of concomitant steatosis

Abstract

Background: Bile acids (BAs) are known mediators of hepatic inflammation, with their altered metabolism and signaling implicated in both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB). The BA profiles of patients with both chronic liver diseases and their relationship with clinical and virological parameters remain poorly characterized. Methods: We prospectively recruited both treatment-naïve and on-treatment CHB patients, with liver steatosis and stiffness assessed by vibration-controlled transient elastography (VCTE) (Fibroscan, Echosens, Paris). Steatosis and severe steatosis were defined as controlled attenuation parameter (CAP) ≥248 dB/m & ≥280 dB/m respectively, while advanced fibrosis was defined as ≥ 9 kPa in patients with normal alanine aminotransferase. HBV DNA was measured by Cobas 4800 system (Roche Diagnostics, USA) with the lower limit of detection of 10 IU/mL. Fasting plasma 7α-hydroxy-4-cholesten-3-one (C4) and 28 different BAs were quantified by liquid chromatography-tandem mass spectrometry analysis carried on an Acquity I-Class ultra-high-performance liquid chromatographic system by Waters (Milford, MA, USA) and a QTRAP®6500+ from AB Sciex (Framingham, MA, USA). Results: Among 109 patients (73.4% male, median age 61.0 years), 76 (69.7%) were treated with nucleoside analogue therapy for a median duration of 81 (51-104) months. Undetectable serum HBV DNA was present in 50 (45.9%) patients, of which 39 (78%) were on-treatment. 61 (56%) and 52 (47.7%) had steatosis and advanced fibrosis respectively. Steatotic patients, when compared to non-steatotic patients, had significantly higher median plasma C4 levels (52.68 [41.68-76.17] ng/mL vs 42.99 [35.38-57.91] ng/mL, p=0.013), lower total hyocholic acid (HCA) levels (2.32 [1.20-5.23] ng/mL vs 3.72 [2.36-8.46] ng/mL, p=0.015) and lower total muricholic acid (MCA) levels (1.04 [0.36-3.15] ng/mL vs 3.00 [0.94-7.04] ng/mL, p=0.0067). No significant differences in total BA, total conjugated and total primary BA were noted between the two groups. When stratifying patients based on HBV DNA levels, among patients with undetectable HBV DNA, steatotic patients, when compared to non-steatotic patients, they displayed similarly pronounced differences in BA profiles (Table 1, all p<0.05). This difference was no longer present when comparing steatotic and non-steatotic paients with detectable viremia (Table 1, all p>0.05). No significant differences in C4, total HCA and total MCA levels were noted when comparing patients with and without advanced fibrosis (p>0.05). Conclusion: CHB patients with hepatic steatosis demonstrated distinct BA profiles, especially in patients with undetectable viremia. BA metabolism could be a potential target of future study in understanding the interaction between the two chronic liver diseases.