HBsAg loss was observed in four patients

(3%) after 9, 17, 23, and 25 months of TDF treatment, respectively; all of them were HBV genotype A. ALT levels normalized in 64 of 96 patients (65%) who had elevated ALT levels at the start of the observation period. At the end of observation ALT levels were within normal ranges in 84% of all patients. TDF treatment was well tolerated and no clinically significant side effects were reported. No significant increase in creatinine was observed (mean creatinine levels were 72 μmol/L [range, 27–105] at baseline and 74 μmol/L [range, 28–97] at the end of the observation period) apart from a mild elevation of creatinine level from 91 μmol/L to 112 μmol/L which was observed in one patient at month

12. However, for this patient creatinine levels subsequently decreased to within the normal range without modification of TDF treatment. No ALT flares (>5 × upper limit of normal) were observed ABT-263 cell line PARP inhibitor during TDF treatment. This long-term (up to 5 years) retrospective study represents the first large-scale, retrospective analysis of the efficacy of TDF monotherapy in treatment-experienced patients who were switched to TDF monotherapy because they had failed on previous NA regimens due to either incomplete response or genotypic resistance. In order to reduce selection bias, all patients from the participating 16 hepatology centers in Germany selleck and the Netherlands who met the

inclusion/exclusion criteria were selected for this retrospective TDF treatment study. TDF administered as monotherapy suppressed HBV DNA to below 400 copies/mL in the majority of patients. This effect was especially obvious in the large group of patients with LAM-associated variants and in wildtype-infected patients because both patient groups achieved undetectable HBV DNA within 20 months. These observations further confirm in vitro studies in which HBV strains bearing mutations associated with LAM resistance (e.g., rtM204V/I) remained fully sensitive to TDF.18, 19 This is of special interest because LAM is still the most prescribed first-line drug in many countries and resistance to LAM will remain a considerable concern for the future. However, there was a marked difference in TDF response in patients with incomplete response to ADV without genotypic resistance compared to patients with genotypic ADV resistance and viral breakthrough. Whereas all ADV incomplete responders reached undetectable HBV DNA levels during the observation period, the response to TDF was less pronounced in ADV-resistant patients (HBV DNA undetectable in only 52%). The previously described in vitro cross-resistance of ADV and TDF may have affected the response to TDF.13, 14 Conversely, another study found no difference in response to TDF monotherapy between patients with and those without genotypic ADV resistance after failure to ADV therapy.