Elsevier

The American Journal of Medicine

Volume 119, Issue 1, January 2006, Pages 71.e9-71.e16
The American Journal of Medicine

Clinical research study
AJM Online
Long-Term Outcome after Hepatitis B Surface Antigen Seroclearance in Patients with Chronic Hepatitis B

https://doi.org/10.1016/j.amjmed.2005.02.033Get rights and content

Abstract

Purpose

The aim of this study was to elucidate the long-term outcome after hepatitis B surface antigen (HBsAg) seroclearance in a large number of Japanese patients.

Methods

We studied the biochemical, virologic, histologic, and prolonged prognoses of 231 Japanese patients with HBsAg seroclearance (median follow-up, 6.5 years). Serum alanine aminotransferase, serum hepatitis B virus (HBV) markers, liver histology, and clinical aspects were monitored. HBV-DNA levels were measured with the qualitative polymerase chain reaction assay. The mean age of patients with HBsAg seroclearance was 52 years.

Results

After HBsAg seroclearance, 203 patients (87.9%) had normal alanine aminotransferase levels 1 year after HBsAg seroclearance. HBV-DNA showed positive results in 4 patients (1.7%) 1 year after HBsAg seroclearance. Thirteen patients were examined for histologic changes of the liver after HBsAg seroclearance. All patients showed marked improvement of necroinflammation of the liver, but only 2 of the 13 patients showed no liver fibrosis. Liver cirrhosis and hepatocellular carcinoma did not develop in any of the 164 patients without evidence of liver cirrhosis at the time of HBsAg seroclearance. Hepatocellular carcinoma developed in 2 of the 67 patients with liver cirrhosis at the time of HBsAg seroclearance. During the observation period, 15 patients died. However, the cause of death of these 15 patients was not related to liver disease, such as hepatocellular carcinoma, decompensated liver cirrhosis, and rupture of esophageal varices.

Conclusion

Our results suggest that HBsAg seroclearance confers favorable long-term outcomes in patients without hepatocellular carcinoma or decompensated liver cirrhosis at the time of HBsAg seroclearance

Section snippets

Patients

From 1972 to 2002, a total of 5055 chronic HBsAg carriers, who were known to be seropositive for HBsAg for at least 6 months, were studied at Toranomon Hospital in Tokyo, Japan. After a mean follow-up period of 4 years (range 0.5-30 years), 231 patients were noted to have delayed HBsAg seroclearance, which is defined as persistent absence of HBsAg antigenemia by radioimmunoassay for at least 1 year and until the last examination. We excluded from the study all patients with: concurrent

Changes of Liver Biochemistry After HBsAg Seroclearance

Table 1 shows the characteristics of the 231 patients who had seroclearance of HBsAg. These patients were classified into a liver cirrhosis group or a non-liver cirrhosis group by ultrasonographic findings. A total of 67 patients showed a finding of liver cirrhosis. Histologic evidence of liver cirrhosis before HBsAg seroclearance was seen in 47 patients.

The alanine aminotransferase test showed that 203 of 231 patients (87.9%) had normal alanine aminotransferase levels 1 year after

Discussion

The results of this study indicate that patients with HBsAg clearance have a good prognosis. None of the patients with liver cirrhosis who had lost serum HBsAg progressed to decompensated liver cirrhosis. Moreover, no patients without liver cirrhosis with HBsAg clearance progressed to liver cirrhosis and/or hepatocellular carcinoma. Our findings agree with the published data by Chen et al16 (Table 4). However, 2 of 67 patients with liver cirrhosis at the time of HBsAg clearance had

Conclusion

The prognosis after HBsAg clearance was excellent except in patients with liver cirrhosis. However, patients with liver cirrhosis should be closely monitored for predictable complications.

Acknowledgment

The authors acknowledge the editorial assistance of Thomas Hughes.

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    The present work was supported in part by grants-in-aid from Okinaka Memorial Institute for Medical Research and Japanese Ministry of Health, Labor, and Welfare.

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