Eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, prevents dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C.

AIM: We conducted a trial to evaluate whether eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, would decrease the rate of the patients who required dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C. METHODS: Sixty patients given weekly subcutaneous administration of pegylated interferon alpha-2a at a dose of 180 mug for 48 weeks were allocated into the meloxicam group (n = 22) and the control group (n = 38) before interferon treatment. Meloxicam was given orally at a dose of 10 mg once a day for eight weeks from the start of interferon treatment. RESULTS: The cumulative rate of dose-reduction-free patients was significantly higher in the meloxicam group (P < 0.05). Until week eight, 44.7% of the control group and 9.1% of the meloxicam group required dose reduction. Dose was modified by neutropenia in 31.6% and 18.2% of the control and meloxicam groups, respectively. Meloxicam relieved a declineof neutrophil count within the first eight weeks from 54.2% to 44.2% (P < 0.05). Multivariate analysis revealed that greater pretreatment neutrophil count and the use of meloxicam were independent factors associated with avoiding dose reduction. Sustained virological response was obtained in 52.6% of the patients. The multivariate logistic analysis revealed that viral serotype and viral load were the only independent factors associated with sustained virological response. CONCLUSION: Eight-week administration of meloxicam prevented dose reduction of pegylated interferon by relieving a decline of neutrophil count in the treatment of chronic hepatitis C.

Predictive factors for the response to lamivudine in HBV-infected patients with chronic hepatitis and cirrhosis.

OBJECTIVE: To determine predictors for virological response to lamivudine, a retrospective-cohort study was designed. METHODS: Seventy HBV positive patients who received lamivudine were classified according to virological response into responders and non-responders. Background conditions and normalization and flare-up of hepatitis were compared using student-t test and chi-square test. Logistic regression analysis was performed to determine the effect of explanatory variables, age, sex, ALT, HBV-DNA, hepatic fibrosisi, presence of absence of HBeAg, former IF non-response on the response to lamivudine. RESULTS: There were no difference in gender, age, observed period, ALT level, liver fibrosis, former response to Interferon in background but viral titer and rate of HBeAg (+) was higher in non-responders. Hepatitis normalization rates were not different but flare-up rates were significantly higher in non-responders. Multivariate analysis showed HBeAg is the relevant factor for the response to lamivudine. CONCLUSIONS: The presence of HBeAg was a risk for non-response to lamivudine therapy.

Ribozyme mediated suppression of vascular endothelial growth factor gene expression enhances matrix metalloproteinase 1 expression in a human hepatocellular carcinoma cell line.

The levels of expression of various genes were altered in cellular transformants with manipulation of expression of single genes. Vascular endothelial growth factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear how VEGF-A expression regulates various genes. Multiple gene expression levels were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of other members of MMP family or tissue inhibitors of MMPs did not show any alteration. These results suggested that intracellular suppression of VEGF-A gene was specifically linked to up-regulation of MMP1 in human hepatocellular carcinoma cells.