Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance.

The process of liver fibrosis is reversible and involves a recovery phase. In the present study, the potential side effects of combination leflunomide and methotrexate (LEF+MTX), a conventional rheumatoid arthritis therapy used in the resolution of liver fibrosis, was investigated. In a carbon tetrachloride­induced liver fibrosis model, the results of hepatic pathology demonstrated that the LEF+MTX combination delayed the recovery of fibrosis, although the activation of hepatic stellate cells in vitro was inhibited. A total of four liver fibrosis­associated indicators, hyaluronic acid, laminin, procollagen type III and collagen IV, maintained high levels in the serum of LEF+MTX­treated mice, while detection of bone marrow­driven monocytes in the blood by flow cytometry indicated that they were significantly decreased. Notably, the results of immunofluorescence staining of hepatic myeloid cells and detection of vascular growth factor A (VEGF­A) in blood and liver suggested that the reduced degeneration of collagen in liver sinusoids was associated with decreased myeloid cell adhesion and the downregulation of VEGF­A in the liver. The present results suggested that in certain cases, treatment with LEF+MTX may impede the recovery of hepatic fibrosis­associated diseases in mice.

[Changes in HBsAg titer and HBV DNA load and their correlation in patients with chronic hepatitis B and HBV-related liver cirrhosis].

OBJECTIVE: To explore the changes in HBsAg titer and HBV DNA load and their correlation in patients with chronic hepatitis B (CHB) and HBV-related liver cirrhosis (HBV-LC). METHODS: Forty-six patients with mild to moderate CHB (CHB-LM), 24 patients with severe CHB (CHB-S), and 28 patients with HBV-LC at admission, and 51 patients with HBV-LC at 4.08 ± 3.06 months during antiviral treatment were tested for serum HBsAg titer and HBV DNA load using Abbott chemiluminescence and fluorescence quantitative PCR, respectively. RESULTS: The serum HBsAg titer and HBV DNA load gradually decreased with increased disease severity (from CHB-LM, CHB-S to HBV-LC; χ(2)=12.537 and 8.381, respectively, P<0.05). HBsAg titer and HBV DNA load were significantly higher in CHB-LM and CHB-S groups than in HBV-LC group (P<0.05), but comparable between CHB-LM and CHB-S groups (Z=-0.649 and 0.032, respectively, P>0.05). Among HBeAg-positive patients, HBsAg titer and HBV DNA load tended to decrease with increased disease severity (from CHB-LM, CHB-S to HBV-LC; χ(2)=6.146, P=0.046 and χ(2)=1.017, P>0.05; respectively), and CHB-LM group had significantly higher HBsAg titer than HBV-LC group (Z=-2.247, P=0.025). Among the HBeAg-negative patients, serum HBsAg and HBV DNA load gradually declined with the disease severity (χ(2)=8.660 and 13.581, respectively, P<0.05), and were obviously higher in CHB-LM and CHB-S groups than in HBV-LC group (P<0.05). Positive correlations were found between serum HBsAg and HBV DNA levels in CHB-LM (r=0.389, P=0.009) and HBV-LC groups (r=0.431, P=0.022), but not in CHB-S group (r=0.348, P=0.104). After antiviral therapy, the serum HBsAg titer was slightly decreased (Z=-1.050, P=0.294) while HBV DNA load markedly reduced (Z=-5.415, P<0.001), showing no correlation between them (r=0.241, P=0.111) or between the measurements before and after treatment (r=0.257, P=0.085). CONCLUSION: Serum HBsAg titer and HBV DNA load decreases progressively from CHB-LM to CHB-S and HBV-LC in both HBeAg- positive and -negative patients. The serum HBsAg titer is positively correlated with HBV DNA load, but their levels are not consistently parallel.