Hepatitis B and non-alcoholic fatty liver disease: A bidirectional population-based cohort study
Authors: Zhou Yiran , Aiken Gulijiayina , Ju Keke , Wang Yue , Abudurezhake Yakupu , Zhang Yuhang , Lu YaoQin 
Published: April 2023

Abstract
Background Both hepatitis B and NAFLD are associated with chronic liver injury and its malignant progression, and the bidirectional relationship between the two has attracted increasing attention, but the findings are still controversial.
Methods Based on a natural population cohort in Xinjiang province, a multicenter longitudinal cohort was established using pooled data from the project from January 2016 to December 2021 for the Longitudinal Surveillance Cohort for Factors Affecting NAFLD and the Longitudinal Surveillance Cohort for Factors Affecting Hepatitis B, respectively. Valid variables collected were selected using Lasso regression, and Cox multifactor regression was used to assess the association between hepatitis B and the risk of NAFLD onset or NAFLD and the risk of hepatitis B. Sensitivity analyses were performed by excluding onset data within 6 months of the start of follow-up and mortality data, respectively.
Results During a median follow-up period of 5 years, we recorded 15,046 cases of NAFLD and 219,126 cases of hepatitis B in the two cohorts, respectively. First, in the longitudinal surveillance cohort of factors influencing NAFLD: those who were overweight (HR=2.71, 95% CI=2.68–2.74), those who were obese (HR=6.56, 95%CI=6.49–6.63), hypertensive (HR=1.18, 95%CI=1.16–1.19), those with a family history of hypertension (HR=1.08, 95%CI=1.07–1.09), diabetic (HR=1.38, 95%CI=1.36–1.40), those with a family history of diabetes (HR= 1.13, 95%CI=1.11–1.16), patients with LDL (HR=1.04, 95%CI=1.03–1.05), patients with hypercholesterolemia (HR=1.05, 95%CI=1.04–1.07), patients with hypertriglyceridemia (HR=1.15, 95%CI=1.14–1.17), patients with mixed hyperlipidemia (HR=1.24, 95%CI=1.21–1.27), lipid metabolism disorders (HR=1.04, 95%CI=1.03–1.05), and metabolic syndrome (HR=1.35, 95%CI=1.33–1.36; HR=1.05, 95%CI=1.04–1.06) all had a higher risk of NAFLD; those with impaired fasting glucose (HR=0.97, 95% CI=0.96–0.99), myopia (HR=0.99, 95% CI=0.98–1.00), dental caries (HR=0.93, 95% CI=0.92–0.94), hepatitis B (HR=0.94, 95% CI=0.89–0.98) had a lower risk of NAFLD. Secondly, in the hepatitis B influencing factor surveillance cohort: hypertensive patients (HR=1.10, 95%CI=1.07–1.13) had a higher risk of hepatitis B, overweight people (HR=0.97, 95% CI=0.95–0.99), patients with hypertriglyceridemia (HR=0.93, 95% CI=0.90–0.97), patients with mixed hyperlipidemia (HR=0.87, 95% CI=0.80–0.95), patients with metabolic syndrome (HR=0.97, 95% CI=0.95–1.00; HR=0.96, 95% CI=0.94–0.99), those with impaired fasting glucose (HR=0.88, 95%CI=0.84–0.91), those with a family history of hypertension (HR=0.81, 95%CI=0.78–0.83), those with dental caries (HR=0.85, 95%CI=0.82–0.87), those with NAFLD (HR=0.93, 95% CI=0.89–0.96) all had a lower risk of hepatitis B. Finally, the risk of NAFLD was reduced in those with hepatitis B compared to those without hepatitis B, HR=0.94 (95% CI=0.89–0.98), P=0.006, and the risk of hepatitis B was reduced in those with NAFLD compared to those without NAFLD, HR=0.93 (95% CI=0.89–0.96), P＜0.001.
Conclusion In the general population, firstly, overweight, obese, hypertension, family history of hypertension, diabetes mellitus, family history of diabetes mellitus, low-density lipoproteinemia, hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, disorders of lipid metabolism, metabolic syndrome may be risk factors for NAFLD, impaired fasting glucose, myopia, dental caries, hepatitis B may be protective factors for NAFLD; secondly, hypertension may be risk factors for hepatitis B, overweight, hypertriglyceridemia, mixed hyperlipidemia, metabolic syndrome, impaired fasting glucose, family history of hypertension, dental caries, NAFLD may be protective factors for hepatitis B; finally, hepatitis B and NAFLD may be protective factors for each other.