Fibrosis evolution in chronic hepatitis B e antigen‐negative patients across a 10‐year interval

Abstract

Summary The degree of liver fibrosis in chronic hepatitis B (CHB) infection influences outcome and management. Existing data describing the long‐term dynamic changes of liver fibrosis are limited. This study aimed to evaluate the evolution of liver fibrosis in CHB across a 10‐year period. CHB patients with liver stiffness measurement (LSM) by transient elastography 10 years ago were recruited for follow‐up LSM. Fibrosis stages were classified according to EASL‐ALEH guidelines. Fibrosis progression/regression was arbitrarily defined as ≥1 fibrosis stage change from baseline. A total of 459 hepatitis B e antigen (HBeAg)‐negative patients (224 untreated, 235 treated with nucleos(t)ide analogues [NAs]) were recruited. The mean age at baseline LSM was 41.7 ± 9.0 years (56.2% male). Over 10 years, the proportion of patients with advanced fibrosis/cirrhosis significantly reduced from 16.3% to 5.7% (P < 0.001). Fibrosis progression and regression were observed in 8.7% and 37.5%, respectively. No treatment with NAs (OR 2.259, 95% confidence interval [CI]: 1.032‐4.945), metabolic syndrome (OR 4.379, 95% CI: 1.128‐16.999) and hepatic steatosis (OR 7.799, 95% CI: 2.271‐26.776) was associated with fibrosis progression. Liver stiffness decline demonstrated positive correlation with the time after HBsAg seroclearance (r = −0.50, P < 0.001). Median liver stiffness was higher both at baseline (14.0 vs 6 kPa, P < 0.001) and 10 years (9.1 vs 4.9 kPa, P < 0.001) in patients with cirrhosis‐related complications/hepatocellular carcinoma compared with those without. In conclusion, CHB‐related liver fibrosis changed dynamically across 10 years. Metabolic syndrome and hepatic steatosis were associated with fibrosis progression, while antiviral therapy was associated with fibrosis regression. Patients with HBsAg seroclearance demonstrated time‐dependent decline in liver stiffness.

East Asia expert opinion on treatment initiation for chronic hepatitis B

“…In a parallel study of 361 patients with HBeAg‐negative CHB, 3% had ≥30% increase in LSM and 8% required anti‐viral therapy at a mean follow‐up of 44 months 43 . In a longer term study of 459 patients with HBeAg‐negative CHB, 9% had ≥1 stage of fibrosis progression as estimated by LSM and 51% required anti‐viral therapy in 10 years 44 . Therefore, performing fibrosis assessment in untreated patients at an interval of 3 years or more is reasonable.…”

“…required anti-viral therapy in 10 years. 44 24,[43][44][45][46] Therefore, the practical role of HCC risk scores is limited in identifying patients who may benefit from but are not indicated for treatment by current practice guidelines (Figure 1). practice guidelines and reimbursement policies recommend using HCC risk scores in deciding treatment initiation in patients with CHB.…”

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

“…Recently, a cohort study evaluated the evolution of liver fibrosis using liver stiffness measurement, along with hepatic steatosis by controlled attenuation parameter, in 459 HBeAgnegative patients across a 10-year interval. 112 They found that hepatic steatosis was associated with fibrosis progression in CHB patients (OR = 7.799). 112 Following similar measurement methods, their prior cross-sectional study also showed a positive association between severe steatosis and severe fibrosis in both treatment-naïve patients (OR = 3.60) and patients receiving NAs treatment for at least three years (OR = 1.95).…”

“…112 They found that hepatic steatosis was associated with fibrosis progression in CHB patients (OR = 7.799). 112 Following similar measurement methods, their prior cross-sectional study also showed a positive association between severe steatosis and severe fibrosis in both treatment-naïve patients (OR = 3.60) and patients receiving NAs treatment for at least three years (OR = 1.95). 113 According to another study, among 1202 patients with CHB, the proportion of individuals with severe fibrosis was significantly higher among those with severe steatosis than those with mild or moderate steatosis (23.2% vs 12.6%).…”

“…Liver fibrosis has been found to be aggravated in CHB concomitant with both hepatic steatosis and NASH, inevitably increasing the risk of developing cirrhosis. Recently, a cohort study evaluated the evolution of liver fibrosis using liver stiffness measurement, along with hepatic steatosis by controlled attenuation parameter, in 459 HBeAg‐negative patients across a 10‐year interval . They found that hepatic steatosis was associated with fibrosis progression in CHB patients (OR = 7.799) .…”