89 Resistance is much less common than with lamivudine: 0% at one year and 29% at 5 years.90 This makes adefovir an option as add-on therapy in patients who have developed lamivudine resistance.91 Adefovir has not been well examined in patients with renal failure. A French study used adefovir in a composite series of 12 patients with CKD,92 all of whom had lamivudine-resistant HBV. There was a significant fall in HBV DNA levels after a median of 15 months of therapy. Only one of these patients was actually receiving dialysis during the study. A case report described successful treatment of HBV infection in
a dialysis-dependent liver transplant recipient who had lamivudine-resistant infection and cirrhosis of the allograft.93 Entecavir is a promising drug in the management GSK458 of HBV infection. In patients with normal renal function, entecavir has been shown to be superior to lamivudine94 and adefovir95 in reducing HBV DNA levels. Although there are not the long-term data that exist for lamivudine, resistance
rates appear to be low. Entecavir has not been studied in dialysis patients, although the dose should be reduced in renal failure.79 Tenofovir, a nucleotide reverse transcriptase inhibitor, is recommended as a buy MLN0128 first-line oral antiviral in HBV patients with normal renal function.96 Although larger series have not found tenofovir to be culpable in HIV patients with Erastin mouse renal failure,97 there have been a number of case reports of tubular toxicity and acute kidney injury98–100 with tenofovir use. This raises concern regarding the potential for nephrotoxicity in dialysis patients with residual renal function. A case report showed that tenofovir was effective in a single HBV-infected HD patient. This paper also assessed tenofovir pharmacokinetics,101 and recommended
a dose of 300 mg once a week to prevent accumulation. This was endorsed by the manufacturers in a study of nine HD patients.102 In summary, lamivudine has the most solid body of experience to support its use. Tenofovir and entecavir are likely to be more effective, and tenofovir has been shown to be safe in HD patients, but neither drug has any significant evidence base from this patient group. Determining which dialysis patients with chronic HBV infection to treat is a matter of controversy. In the case of patients with normal renal function, treatment is recommended for those with active HBV replication (HBeAg positive and/or HBV DNA positive) and raised alanine transaminase (ALT) levels.103 It is clear that patients with ESRD exhibit a different clinical and biochemical picture in chronic HBV infection.104 HD patients with HBV infection are less likely to have a symptomatic acute illness, and are more likely to develop chronic carrier status.