We read with interest the study by C. M. Chu et al.1 Their results have overturned the traditional viewpoint that spontaneous hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B virus (HBV) infection was a rare event in high endemic areas. We particularly appreciate their original contribution in elucidating the natural history of HBV infection. Our concerns regarding this study are listed below.
In this study, the authors describe that “spontaneous HBsAg seroclearance occurred in 245 patients during 21,267 person-years of follow-up”. There were 314 patients with relapse of hepatitis, and among these patients, 24 patients underwent subsequent HBsAg seroclearance 3 to 20 (mean ± standard deviation; 9.6 ± 4.6) years after the onset of hepatitis relapse. We want to know, after the onset of hepatitis relapse, why was no antiviral therapy carried out in these patients? As we know, antiviral therapy in patients with HBV has become more and more important in the past decade. If in fact antiviral therapy had been carried out in these patients, then they should not be referred to as having undergone “spontaneous HBsAg seroclearance”.
The previous epidemiological studies on age-specific prevalence of HBsAg in the general population of Taiwan have shown that the prevalence of HBsAg decreased by 70% at age 70, by 40% at age 60, and by 60% at age 402, 3 (22.7% to 6.9%, 17.1% to 9.7%, and 15.4% to 6%, respectively). In this study, the authors grouped patients through age at entry by <30 years, 30–39 years, 40–49 years, and ≥50 years. We want to know why the group ≥50 years was not divided further into 50–59 years, 60–69 years, and ≥70 years. We think those groupings would be comparable to those obtained in previous epidemiological studies.
In this study, the authors describe that the natural history of chronic HBV infection consists of three phases: an initial immune-tolerant phase, followed by immune clearance phase, and finally the low replication phase. An up-to-date view of the natural history of HBV is that there is a fourth phase4: hepatitis B e antigen (HBeAg)-negative chronic hepatitis. In this phase, chronic hepatitis may recur in up to one-third of inactive HBV carriers without reversion of HBeAg in their serum.5 Most patients progress to this phase after a variable length of time in the inactive HBV carrier state, whereas some progress to HBeAg-negative chronic hepatitis directly from HBeAg-positive chronic hepatitis.