Spontaneous HBsAg seroclearance confers excellent prognosis except in patients with cirrhosis
Authors: Yi-Cheng Chen, Yun-Fan Liaw
Journal: Hepatology (2004)

To the Editor: We read with interest the study on HBsAg seroclearance in chronic hepatitis B in the Chinese by Yuen et al.1 Their results have confirmed our recent observation in 163 patients with chronic hepatitis B virus (HBV) infection alone that the prognosis following spontaneous HBsAg seroclearance is excellent except in patients with cirrhosis.2 We particularly appreciate their original contribution in elucidating the long-term virological and histological status, including HBV-DNA in serum and peripheral blood mononuclear cells as well as intrahepatic HBV-DNA and cccDNA up to 4 years after HBsAg seroclearance. In addition, their finding that patients with genotypes B HBV infection had a higher chance of HBsAg seroclearance supports the importance of viral factors in the natural history of chronic HBV infection. Their finding that 5.4% of the 92 patients developed hepatocellular carcinoma (HCC) after HBsAg seroclearance1 is seemingly different from our finding where none of our 163 patients did.2 These two studies involved patients with the same ethnicity and our study had a longer follow-up duration after HBsAg clearance (63.4 vs 51.1 months), excluding these factors for this difference. Of note, it was not stated how many of their patients had evidence of cirrhosis at the time of HBsAg seroclearance. Our earlier study revealed that cirrhosis was one of the factors for delayed HBsAg seroclearance.3 Of the 163 patients in our most recent study, 10% had evidence of cirrhosis with a mean age of 53.8 years at the time of HBsAg seroclearance.2 The mean age of the patients in their study at the time of HBsAg seroclearance was 48.8 years, just between the mean age of our patients with cirrhosis (53.8 years) and without (43.3 years). It seems reasonable to suspect that some of their patients also had cirrhosis at the time of HBsAg seroclearance. They did indicate that 2 of their patients had had esophageal varices or ascites before HBsAg seroclearance, and 4 of the 5 patients with HCC had evidence of cirrhosis. In addition, the mean age of HBsAg seroclearance was significantly older in those who had HCC development (63.2 vs 47.9; P = .016) and 4 developed HCC only 1 to 21 months after HBsAg clearance.1 Therefore, it seems very likely that the majority of their patients with HCC had had cirrhosis at the time of HBsAg seroclearance. This is consistent with their conclusion that HCC development is still possible, particularly in patients with cirrhosis who have HBsAg seroclearance at an older age. We acknowledge that HCC may still occur in our patients upon longer follow-up after HBsAg seroclearance. In summary, the study of Yuen et al. not only has confirmed that HBsAg seroclearance confers excellent long-term prognosis, but has also provided important clinical and virological information on the natural history of chronic HBV infection. Since complications including HCC almost always occur in patients with cirrhosis in the setting of HBsAg seroclearance, the study would be even better if patients with cirrhosis were separately analyzed at the time of HBsAg seroclearance. Yi-Cheng Chen M.D.*, Yun-Fan Liaw M.D.*, * Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei, Taiwan.