The efficacy of adefovir in lamivudine-resistant hepatitis B virus infections
Adefovira dipivoxil is also effective in the treatment of chronic hepatitis B, regardless of the genotype of resistance to lamivudine.
Liver transplantation remains the only method of treating patients with advanced chronic hepatitis B. However, reinfection by transplant can lead to the rapid development of liver failure. To avoid this, lamivudine and a hepatitis B specific immunoglobulin (HBIg) are used after surgery. Treatment with HBIg is limited by the high cost of the drug. The effectiveness of lamivudine decreases over time due to the development of resistance. 27% of patients after liver transplantation developed resistance to lamivudine within one year of treatment.
Adefovir (the oral form of adefovir dipivoxil) belongs to a new class of antiviral drugs - nucleotide analogs. The drug is approved in the United States and the European Union for the treatment of chronic hepatitis B.
During the work presented, an evaluation was made of the correlation between the clinical signs of ineffectiveness of lamivudine and the presence of mutations in the hepatitis B virus (HBV) which offer drug resistance, as well as a evaluation of the effectiveness of the 48-week course of adipovir dipivoxil in patients infected with HBV resistant to lamivudine and undergoing liver transplantation.
A multicenter study included 131 patients with chronic hepatitis B after liver transplantation in whom treatment with lamivudine was ineffective. Patients received adefovir dipivoxil 10 mg once daily.
In the HBV strains studied, 4 genotypes of resistance to lamivudine dominated: rtL180M + rtM240V, rtV173L + rtL180M + rtM240V, rtM240I and rtL180M + rtM240I. Under the influence of a 48-week treatment with adefovir, an average decrease in the serum HBV DNA concentration of 4.1 log10 copies / ml was noted (compared to the initial level, the differences were statistically significant, p less than 0.001); while the decrease in serum viral load under the influence of adefovir was not dependent on the genotype of lamivudine resistance.
There was no statistically significant difference in the level of decreased alanine aminotransferase (ALT), changes in serum albumin and prothrombin time under the influence of treatment with adefovir depending on the genotype of resistance to HBV.
Since the identification of mutations responsible for lamivudine resistance is not readily available, in practice when determining the need for a drug change, clinical indicators should be used lamivudine ineffective, as an indirect sign of the presence of such mutations in HBV. Signs of ineffectiveness of lamivudine included detection of serum HBV DNA using a hybridization reaction or a serum HBV DNA concentration of more than 1x106 copies / ml, determined by PCR, treatment with lamivudine for more than 24 weeks, ALT more than 1.2 upper limit of normal. The presence of these clinical signs was significantly correlated with the presence of HBV mutations responsible for drug resistance.
Thus, based on clinical data, it is highly likely to suspect the presence of hepatitis B virus mutations that provide resistance to lamivudine. Adefovira dipivoxil is equally effective regardless of the genotype of lamivudine resistance.