I read with interest the article by Gordon et al. regarding the efficacy of tenofovir disoproxil fumarate (TDF) in patients with hepatitis B virus (HBV) infection. The investigators demonstrated that chronic HBV patients with high viral load (HVL) could achieve 98.3% HBV DNA negatively with long-term TDF treatment, as compared with 99.2% of non-HVL. A remarkable finding was that up to 19.3% hepatitis B e antigen (HBeAg)+ with HVL patients had hepatitis B surface antigen (HBsAg) loss and 13.6% became anti-HBsAb+, significantly higher than the figure of only 4.3% in non-HVL with HBsAg loss and seroconversion.
The clearance of HBsAg with seroconversion is an ideal ultimate endpoint of antiviral therapy for HBV patients. Previous studies showed that it is very difficult to achieve this endpoint by therapy with either nucleoside or nucleotide analog. Low HBsAg titer, low viral load, HBeAg negative, old age, and cirrhosis have been shown to be important determinants of spontaneous HBsAg clearance.[3-5] The results of 3-year TDF treatment for HBV disclosed that 8% of HBeAg+ lost HBsAg.6 Race and genotype A may partly explain the remarkably high rate of seroconversion.6 However, contrary to available evidence, baseline HBV DNA, HBsAg titer, and HBeAg+ were significantly higher among those who cleared HBsAg than those with HBsAg+ persistently. Is this good outcome related to simply TDF effect, previous treatment with adefovir, duration of HBV infection, or inexplicable coincidence? The investigators should explain in more detail on this important issue.
Gin-Ho Lo, M.D.
Department of Medical Research