Virologic Response at 12 Months of Treatment Predicts Sustained Antiviral Efficacy in Patients with Adefovir-Treated Lamivudine-Resistant Chronic Hepatitis B

Abstract

Background/Aims: The aim of our study was to define the potential role of virologic response at 12 months of treatment (VR12) in predicting subsequent virologic and clinical outcomes in adefovir (ADV)-treated lamivudine-resistant chronic hepatitis B. Methods: Two hundred and four patients with lamivudine-resistant chronic hepatitis B virus (HBV) treated with ADV monotherapy were included. Serum HBV DNA was quantified by real-time polymerase chain reactions. VR12 was defined as a HBV DNA level of less than 4 log10 copies/mL after 12 months of ADV treatment. Results: VR12 was observed in 110 of the 204 patients (54%). The mean HBV DNA reductions from baseline after 12 months of ADV treatment were 3.8 and 1.9 log10 copies/mL in patients with and without VR12, respectively (p＜0.001). The hepatitis B "e" antigen (HBeAg) seroconversion rates in patients with and without VR12 were 32% and 14% at 12 months treatment, respectively (p=0.018), and 40% and 27% at 24 months of treatment (p=0.032). The genotypic mutation rates to ADV in patients with and without VR12 were 0% and 6% at 12 months of treatment, respectively (p=0.033), and 21% and 42% at 24 months (p= 0.012). The rates of viral breakthrough in patients with and without VR12 were 0% and 7% at 12 months of treatment, respectively (p=0.072), and 9% and 25% at 24 months (p=0.006). Conclusions: Patients without VR12 may need to switch to or add on other potent antiviral drugs in their medical regimens. (Gut Liver 2010;4:212-218)

Variables determining the virologic response to adefovir treatment in patients with chronic HBV infection previously treated with lamivudine

“…Gender was not reported to seemingly affect the response to adefovir treatment except one study which shows that the virologic response to adefovir was better in female patients (Kin et al, 2011;Jung et al, 2010;Aizawa et al, 2011;Reijnders et al, 2009;Ong et al, 2011;Wang et al, 2011;Buti et al, 2007). There was no effect of gender in response to the adefovir treatment in our study.…”

“…It has been observed that the probability of virologic response to adefovir treatment was decreased in HBeAgpositive patients (Jung et al, 2010;Reijnders et al, 2009;Wang et al, 2011;Buti et al, 2007). Furthermore, in our study, virologic response to adefovir treatment was better in patients with HBeAg-negativity than patients with HBeAg positivity.…”

“…We explain this inconsistency with that pretreatment serum HBV DNA levels in some patients which were measured with hybrid capture 2 (a method with a low level of sensitivity) in our study and so, numbers of the patient with lower serum HBV DNA levels were small. We observed that the pretreatment serum ALT level was not a variable determining the response to adefovir treatment which is in contrast to literature (Jung et al, 2010;Aizawa et al, 2011;Reijnders et al, 2009). We think that this might be explained with the fluctuation of serum ALT levels in patients with chronic HBV infection, and also we used only one measurement of those levels instead of the mean of the at least three separate measurements.…”

The Feasibility of Discontinuing Lamivudine in Lamivudine-Resistant Chronic Hepatitis B Patients on Lamivudine and Adefovir Combination Therapy

“…So, according to their economic conditions, these patients had only the option of self-paid LAM and insurance-covered ADV for the LAM + ADV combination therapy or a discontinuation of LAM with insurance-paid ADV monotherapy [23,25]. Therefore, after achieving VR, many were willing to discontinue the self-paid LAM.…”

Virologic response is not durable after adefovir discontinuation in lamivudine-resistant chronic hepatitis B patients

“…Genotypic resistance was analyzed in some patients with suspected LMV-R CHB and performed using the restriction fragment mass polymorphism method (Green Cross Reference Lab., Yongin, Korea) as previously described. 11 …”