Tenofovir in chronic hepatitis B


  • Potential conflict of interest: Nothing to report.

Tenofovir in Chronic Hepatitis B

To the Editor:

In their recent paper Van Bommel et al. demonstrated a greater antiviral activity of tenofovir at a dose of 300 mg/day compared to adefovir against lamivudine-resistant hepatitis B virus.1 This is the standard approved dose for HIV and HBV coinfected patients,2 but it may not be the optimal dose for HIV negative patients. Hepatitis B virus has a greater susceptibility to nucleotide analogues compared to HIV3 and is certainly less likely to develop resistant mutants. In the initial studies adefovir was used at doses up to 120 mg/day in order to achieve significant HIV inhibition, a dosage well above the approved dose for chronic hepatitis B. It is therefore feasible that tenofovir, like its parent drug adefovir could be used at a lower dosage in patients with HBV infection alone.

To test this hypothesis we treated 10 chronic hepatitis B patients (8 of them had cirrhosis) with 75 mg/day of tenofovir for a median period of 82 weeks (range 44-144). The patients had a median age of 64 years (range 40-76), were all HBeAg negative, and had no other comorbidities. All had received lamivudine for a median duration of 24 months (range 10-39) and were shifted to tenofovir immediately after stopping lamivudine. Five of them had developed YMDD resistance, the others had wild-type virus and were changed to tenofovir to prevent the emergence of lamivudine resistance. Before starting tenofovir, 4 of the 5 patients with YMDD resistance had normal levels of alanine aminotransferase, negative serum branched HBV DNA (Versant HBV DNA 3.0 Bayer, sensitivity <2000 copies/mL), but viral HBV DNA could be detected by polymerase chain reaction (PCR; Innolipa HBV DR Amplification, Innogenetics, Ghent, Belgium, sensitivity <1000 copies/mL) with the presence of YMDD-resistant mutants (Innolipa Line Probe Assay, Innogenetics). The other patient with YMDD mutants had elevated levels of alanine aminotransferase and a serum HBV DNA of 4.8 × 106 copies/mL (b-DNA). Four of the 5 patients with lamivudine resistance, including the patient with high viremia, became HBV DNA negative by PCR assay after 2-6 months of tenofovir and remained negative throughout the entire period of treatment (median 64 weeks, range 44-144) The 5 patients without YMDD mutants were shifted from lamivudine to tenofovir when their serum HBV-DNA was undetectable by PCR and remained PCR negative while receiving tenofovir (median 84 weeks, range 64-100). The drug was well tolerated and no side effects were reported. In addition, no viral breakthrough was observed, confirming the low potential of this drug to induce phenotypic resistance, even using a dose as low as 75 mg.

These excellent results have been observed in only 10 patients, all except one with very low HBV DNA levels, so they may not be generalized to all chronic hepatitis B patients, especially those with high viremia. We think, however, that a dose escalation study with a dose ranging from 75 to 300 mg/day may be warranted. The issue is clearly not safety, but cost and the fact that giving the lowest effective dose could significantly reduce the economic burden of this therapy.

P. Del Poggio*, C. Jamoletti*, M. Zaccanelli*, * Hepatology Unit, Ospedale di Treviglio (Bg), Italy