ABSTRACT
In Egypt, treatment of chronic HBV is not extensively studied and there were no comparative studies between different treatments all together. Also, worldwide, few such studies were performed with little or no significant differences in achieving both end of treatment and sustained virological responses when comparing lamuvidine to the combination of interferon and lamuvidine. The aim of this work is to compare the three arms of treatment; pegylated interferon, lamuvidine and combination of both agents; of chronic HBV infection who are HBe Ag positive in our Egyptian patients. This study included 71 Egyptian patients with chronic HBe Ag positive HBV infection divided into three arms: Group I including 23 patients treated with lamuvidine 100mg once daily for one and half year, group II including 23 patients treated with pegylated interferon alfa 2b 1.5micro g/kg/week for one and half year and group III including 25 patients treated with both agents for one and half years also. All patients were subjected to clinical, biochemical, histological and virological evaluation before, during and for about one and half years after treatment. History of schistosomiasis, antischistosomal treatment, in addition to ultrasonographic features of thickened portal tracts and antischistosomal antibody positivity were taken as evidences of presence of associated schistosomiasis. Serum ferritin level was estimated before and after treatment. Hepatitis serologies including HBsAg, HBsAb, HBeAg, HBeAb, anti HBdgG, and anti HCV and anti-HDV were determined by an enzyme immunoassay. Serum HBV DNA quantification was determined by a real time polymerase chain reaction [PCR], with serum samples obtained at baseline, at the end of therapy and one and half year later. The YMDD [tyrosine, methionine, aspartate, and aspartate] motif was tested on the serum samples at the end of first year of therapy or after by line probe assay. In lamivudine group, 30.4% showed complete biochemical and virological response to therapy with the mean ALT level of 35.29 +/- 5.06u/dL and AST level of 30.00 +/- 2.52u/dE in responding patients in comparison to 121.81 +/- 28.23u/dL and AST level of 107.25 +/- 39.48u/dL in non-responding patients after treatment. After 24 months, YMDD mutants were found in five patients in this group [21.7%]. In pegylated IFN group, 47.8% showed complete biochemical and virological response to therapy with the mean ALT level of 29.82 +/- 5.72u/dl and AST level of 22.6413.53u/dl in responding patients in comparison to 122.65 +/- 40.50u/dL and AST level of 112.33 +/- 23.02u/dl in non-responding patients after treatment. No YMDD mutants were detected during or after treatment. In combination therapy group, 32% showed complete biochemical and virological response to therapy with the mean ALT level of 30.00 +/- 3.12u/dl and AST level of 23.75 +/- 2.55u/dl in responding patients in comparison to 110.33 +/- 22.74u/dL and AST level of 144.71 +/- 44.18u/dL in non-responding patients after treatment. YMDD mutants were detected in 3 patients after the end of treatment [12%]. HBsAg and HBeAg seroconversion were detected more in patients treated by pegylated interferon and combination therapy but not statistically significant. Serum ferritin showed significant elevation [p<0.01] in all patients before treatment, and after treatment there were significant reduction in its levels in all groups [p<0.01] when compared to normal, this reduction was significantly obvious in responding than non responding patients in all groups. The change in histological activity index [HAI score] is significantly prognostic for interferon than lamuvidine therapy [p=0.014]. Changes in [HAI score] in combination therapy group was obvious than lamuvidine group but didn't reach statistical significance. In this study, no significant differences in biochemical and virological response between the three arms of treatment. Thus, from the virological point of view, three types of therapy are similar and still far from the hope of treatment of HBV. However, the development of YMDD resistance with the use of lamuvidine is a major concern and if a new nucleoside analogue can be added to or replace this drug to delay the development of resistance, such medications would be the best for their safety, route of administration and cost. The more HBsAg and HBeAg seroconversion in patients treated by combination therapy and pegylated interferon than lamuvidine, in addition to the rare development of YMDD mutants and the significantly better histological response; puts pegylated interferon in front of lamuvidine in the treatment of this disease. However, still the seroconversion and viral response is far beyond the goal and the door is widely open for more trials and different combinations to get the best effect adding new drugs recently approved for such infection such as adefovir, enticavir and others. Also, the dynamic observation of serum ferritin levels in patients with chronic viral hepatitis B during treatment might be helpful for monitoring and predicting patients' responses to the therapy