ABSTRACT
This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antiviral Agents , Therapeutic Uses , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Liver Cirrhosis , Drug Therapy , Allergy and Immunology , Thymidine , Therapeutic UsesABSTRACT
This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of the lysosomal enzyme acid sphingomyelinase (ASMase) in alcohol-induced hepatic fibrosis using a rat model.</p><p><b>METHODS</b>The model of liver fibrosis was induced by administration of alcohol and high fat diet using 20 rats. Six rats given no alcohol and normal diet served as the control group. Real-time PCR, western blotting, and immunohistochemistry were used to evaluate fibrosis-related changes in the mRNA and protein expressions of ASMase.</p><p><b>RESULTS</b>The fibrotic liver tissues of the model rats showed significantly higher expression levels of ASMase than the non-fibrotic liver tissues of the control rats (P less than 0.05).</p><p><b>CONCLUSION</b>Expression of ASMase is increased in the fibrotic liver tissue of an alcohol-induced hepatic fibrosis rat model, suggesting that this lysosomal enzyme may contribute to development of this disease condition.</p>
Subject(s)
Animals , Male , Rats , Liver , Liver Cirrhosis, Alcoholic , Liver Cirrhosis, Experimental , Rats, Sprague-Dawley , Sphingomyelin Phosphodiesterase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the potential therapeutic properties of the endogenous cannabinoid N-arachidonic acid aminoethanols (anandamide, AEA) in liver fibrosis by observing its affects on proliferation of and expression of phosphorylated-Erk (pErk) in primary hepatic stellate cells (HSCs) from a mouse model of schistosome-induced liver fibrosis.</p><p><b>METHODS</b>The schistosome-induced liver fibrosis model was established by attaching cercaria to the skin on the ventral side of the mouse and allowing infection to occur via direct penetration. Six weeks later, the model was confirmed by pathological analysis of liver, with Masson trichrome staining showing collagen fiber deposition around the blood vessels and hematoxylin-eosin staining showing eosinophilic granuloma formation. Primary HSCs were isolated by discontinuous density gradient centrifugation, confirmed by immunofluorescence detection of double-staining for a-smooth muscle actin and desmin (95% purity), and cultured in the presence of absence of various concentrations of AEA. Proliferative ability was evaluated by MTT assay and the expression of pErk was observed by Western blotting.</p><p><b>RESULTS</b>AEA treatment inhibited the proliferation of the primary HSCs in a concentration-dependent manner (AEA: 5 mumol/L, inhibition: 7.68%; 10 mumol/L, 11.65%; 20 mumol/L, 14.70%; 40 mumol/L, 15.07%; 60 mumol/L, 18.18%; 80 mumol/L, 20.26%; 100 mumol/L, 20.17%; 120 mumol/L, 29.24%). AEA treatment increased pERK expression in both a concentration-dependent manner (AEA: 20 mumol/L, average gray value: 39.90+/-4.61; 60 mumol/L, 43.45+/-0.91; 120 mumol/L, 52.91+/-1.97; vs. negative control, all P less than 0.05) and a time-dependent manner (time: 15 min, average gray value: 85.05+/-15.80; 30 min, 103.41+/-11.89; 1 h, 118.02+/-12.24; 3 h, 109.17+/-15.69; 6 h, 100.86+/-10.55; 12 h, 71.70+/-12.87; 24 h, 34.62+/-14.85; 48 h, 22.84+/-11.73; vs. negative control, all except 48 h had P less than 0.05).</p><p><b>CONCLUSION</b>AEA can suppress the proliferative capacity of primary HSCs from schistosome-induced fibrotic livers through activation of the Erk signaling pathway.</p>