Metabolic Syndrome is Associated with Lack of Fibrosis Regression During Chronic Hepatitis B Treatment: a 3-Year Longitudinal Study with Paired Transient Elastographies

Abstract

Background: Fibrosis regression during long-term nucleoside analogue for chronic hepatitis B virus (HBV) infection is not universally guaranteed . Metabolic factors may play a role in HBV-related fibrogenesis, but their impact on fibrosis regression during HBV treatment has not been prospectively evaluated . Methods: Nucleoside analoguetreated patients with a baseline transient elastography (TE) (Fibroscan, Echosens), anthropometry and virological assessment between January 2015 to April 2016 and at least severe liver fibrosis noted on TE were invited for a second assessment after 3 years. Severe liver fibrosis (F3) was defined as liver stiffness >9.0kPa with normal alanine aminotransferase (ALT) level, or >12.0kPa with ALT one to five times above the upper limit of normal (ULN). Cirrhosis (F4) was defined as liver stiffness >12kPa with normal ALT, or >13.4kPa in patients with ALT 1-5 above ULN. Remaining measurements are categorized as F≤2. Fibrosis regression was defined as a down-staging of liver fibrosis from F4 to F≤3 or F3 to F≤2. Liver steatosis was quantified via controlled attenuation parameter measurements . Metabolic syndrome was defined following the International Diabetes Federation consensus . Results: 160 patients (mean age 59 .2±9 .3 years, 73 .1% male) with a median nucleoside analogue treatment duration of 6.1 (IQR 3.3-8.5) years were recruited. Median liver stiffness significantly decreased from 12.4 (IQR 10.6- 19.6) kPa at baseline to 11.9 (IQR 8.4-17.3) kPa at year 3 (p=0.004). 60 patients (37.5%) developed fibrosis regression, with 12 (20%) and 48 (80%) down-staged to F3 and F≤2 at year 3 respectively . By multivariate analysis, the presence of metabolic syndrome was independently associated with the lack of fibrosis regression (p=0.005, OR 3.1, 95% CI 1.4-6.7). Median reduction in liver stiffness in patients with (n=76) and without metabolic syndrome (n=84) were 1 .2 kPa and 3 .3 kPa respectively (p=0 .003) . Low platelet count was also associated with lack of fibrosis regression (p=0.018, OR 1.009, 95% 1 .001-1 .016) . Other clinical, virological and metabolic factors demonstrated no associations . Conclusion: Metabolic syndrome negates the beneficial effect of chronic hepatitis B treatment with reduced rates of fibrosis regression. Control of metabolic factors may be needed to achieve better long-term outcomes in chronic HBV infection. [https://doi.org/10.1002/hep.30941]