ABSTRACT
BACKGROUND/AIMS: The aim of this study was to elucidate the antiviral efficacy of lamivudine (LMV)-adefovir (ADV) combination therapy in chronic hepatitis B patients who showed resistance to LMV and ADV consecutively. METHODS: A retrospective review was performed in eighteen patients with chronic hepatitis B who developed virologic breakthroughs during LMV-ADV sequential mono-therapy and treated with LMV-ADV combination therapy. RESULTS: The median duration of follow up was 17 months (range, 6-27) after the start of LMV-ADV combination therapy. Mean HBV DNA level in log10 IU/mL was 6.08+/-0.95, 4.05+/-1.66, 3.17+/-1.58, 3.18+/-2.16, and 2.35+/-1.52 at 0, 3, 6, 12, and 24 months, respectively. Sixteen patients (88.9%) showed HBV DNA reduction below detection limit (<20,000 IU/mL). HBeAg seroconversion was observed in one patient (7.1%) after 8 months of combination therapy. Virologic breakthrough occurred in only one patient after 21 months of combination therapy. Viral rebound occurred in two patients at 12 months and 14 months of combination therapy. Normalization of serum ALT was achieved in twelve patients (66.7%). Primary non-response was observed in two cases (11.1%). CONCLUSIONS: LMV-ADV combination treatment was effective in 88.9% of patients with resistance to LMV and ADV in a short-term follow up. It may be applied as a bridge therapy until another effective antiviral regimen becomes available.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Adenine/analogs & derivatives , Antiviral Agents/therapeutic use , DNA, Viral/analysis , Drug Resistance, Viral , Drug Therapy, Combination , Genotype , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Phosphorous Acids/therapeutic use , Time FactorsABSTRACT
Objective To investigate the role of TLR4 in the pathogenesis of chronic hepatitis B(CHB) by study the expression of TLR4 in liver tissues in patients with CHB, and the relationship among TLR4 and serum HBV DNA level, clinical severity degrees and histo-logical grades and stages. Methods Expression of TLR4 in liver tissues was semi-quantitatively determined by immunohistochemistry and e-valuated by a scoring system in 75 patients with CHB and 10 health controls. Results The positive staining of TLR4 mainly located in the cytoplasm and some on cell membrane of bepatocytes. Expression of TLR4 in the liver tissues of patients with CHB was stronger than that of health controls. The scores of TLR4 expression in patients with mild, moderate and severe CHB were 1.0±0.5,2.3±0.5 and 2.9±0.4. The scores increased gradually and significantly along with the increase of clinical severity degrees( F = 104.8, P<0.01). The scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with the clinical severity degrees (r=0.838, P<0.01) and histological grades (r=0.579, P<0.05), but not correlated with Lg (serum HBV DNA) or histological stages. Conclusion TLR4 was up-regulated in the hepatocytes of patients with CHB. There may be a role of TLR4 in the pathogenesis of CHB.