Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

Abstract

Background/aims: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection.

Methods: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels.

Results: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥ 5.1 × 10(7) IU/mL and ALT ≥ 5 × ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure.

Conclusions: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.

Keywords: Hepatitis B virus, chronic hepatitis B; acute exacerbation of hepatitis B, HBV genotype.

Figure 1

Biochemical or symptomatic deterioration in patients with HBeAg-positive CHB according to serum HBV DNA and ALT levels. The patients were categorized into the following four groups: group 1 (n=24), low HBV DNA (<5.1×10⁷ IU/mL) and low ALT (<5×ULN); group 2 (n=15), low HBV DNA and high ALT (≥5×ULN); group 3 (n=36), high HBV DNA (≥5.1×107 IU/mL) and low ALT; and group 4 (n=15), high HBV DNA and high ALT.

Figure 2

Clinical course of a 62-year-old female patient with HBeAg-positive CHB who received liver transplantation because of acute-on-chronic liver failure. This patient was followed at weekly intervals over a 6-month period without any antiviral therapy before week 0, at which point her serum ALT, bilirubin, and HBV DNA levels were 55 IU/mL, 0.6 mg/dL, and 3.1×10⁸ IU/mL, respectively; at 12 weeks these levels had increased to 282 IU/mL, 0.8 mg/dL, and 2.8×10⁹ IU/mL. It was requested that the patient be followed without antiviral therapy even though her ALT levels were elevated to more than twice the ULN. At 14 weeks her serum ALT and bilirubin levels were 314 IU/mL and 0.7 mg/dL, respectively. At 16 weeks, the patient visited the emergency room because of severe anorexia and nausea. Her serum ALT, bilirubin, and HBV DNA levels at that point were 2,039 IU/mL, 19 mg/dL, and 3.85×10⁸ IU/mL, respectively. Entecavir was introduced immediately. However, at 18 weeks her serum bilirubin level had increased to 35.3 mg/dL and she had developed hepatic encephalopathy. The patient made a complete recovery following emergent liver transplantation.