Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 104 copies/ml at follow-up liver biopsy. The mean duration (± standard error of the mean) between the initial and follow-up liver biopsies was 43.9 ± 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range −2.00 to −0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02). Conclusion: Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis. (HEPATOLOGY 2007.)