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The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P

The purpose of the present study was to compare the size and configuration of the ablation zones created by SuperSlim and CoAccess electrodes, using various ablation algorithms in ex vivo bovine liver and in clinical cases. In the experimental study, we ablated explanted bovine liver using 2 types of electrodes and 4 ablation algorithms (combinations of incremental power supply, stepwise expansion and additional low-power ablation) and evaluated the ablation area and time. In the clinical study, we compared the ablation volume and the shape of the ablation zone between both electrodes in 23 hepatocellular carcinoma (HCC) cases with the best algorithm (incremental power supply, stepwise expansion and additional low-power ablation) as derived from the experimental study. In the experimental study, the ablation area and time by the CoAccess electrode were significantly greater compared to those by the SuperSlim electrode for the single-step (algorithm 1, p=0.0209 and 0.0325, respectively) and stepwise expansion algorithms (algorithm 2, p=0.0002 and

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a metabolic syndrome characterized by accumulation of hepatic fat, inflammation and varying degrees of fibrosis. Angiotensin (AT)-II has been reported to play a role in the establishment of NASH. This study examined the effects of an AT-II receptor blocker, irbesartan, on NASH using fatty liver Shionogi (FLS)-ob/ob male mice as the closest animal model of human metabolic syndrome-related NASH. Irbesartan (30 mg/kg/day) was orally administered to FLS-ob/ob mice for 12 weeks (irbesartan group). The effects of irbesartan on steatohepatitis were examined using factors including steatosis, fibrosis, inflammation and oxidative stress. The areas of hepatic fibrosis and hepatic hydroxyproline content were significantly lower in the irbesartan group compared to controls. The areas of α-smooth muscle actin-positivity and F4/80-positive cells were significantly decreased in the irbesartan group. The percentage of 8-hydroxy-2-deoxyguanosine (8-OHdG)-positive cells and 8-OHdG DNA content were significantly decreased in the irbesartan group compared to controls. Levels of RNA expression for procollagen I, transforming growth factor β1, tumor necrosis factor-α, sterol regulatory element-binding protein 1c and fatty acid synthase were significantly lower in the irbesartan group compared to controls. In contrast, the gene expression of peroxisome proliferator activated receptor-α was significantly higher in the irbesartan group compared to controls. Irbesartan administration improved hepatic steatosis and attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Kupffer cells and reducing oxidative stress.

The aim of this study was to examine the preventative and therapeutic effects of an angiotensin-converting enzyme inhibitor, perindopril, on cholestasis-induced liver fibrosis. Perindopril was administered orally for 21 days immediately after bile duct ligation at a dose of 2 mg/kg in order to evaluate the preventative effects, and for 21 days starting 3 weeks after bile duct ligation at doses of 2 and 8 mg/kg in order to evaluate the therapeutic effects. With regard to the preventative effects, perindopril reduced the hepatic hydroxyproline content by 33%, collagen-I mRNA by 38%, α-smooth muscle actin (α-SMA)-positive cells by 46%, α-SMA mRNA by 40%, transforming growth factor-β1 (TGF-β1) mRNA by 21% and connective tissue growth factor (CTGF) mRNA by 27%. With regard to the therapeutic effects, at 2 mg/kg perindopril had no inhibitory effects on the progression of liver fibrosis, but at 8 mg/kg, it reduced hepatic hydroxyproline contents by 63%, collagen-I mRNA by 94%, TGF-β1 mRNA by 79%, CTGF mRNA by 97% and tissue inhibitor of metalloproteinase-1 mRNA by 87%. Significant decreases in the oxidative stress markers hepatic 4-hydroxy-2-nonenal and 8-hydroxy-2-deoxyguanosine were noted for perindopril administration at 8 mg/kg, but not at 2 mg/kg. In conclusion, perindopril had preventative and therapeutic effects on cholestasis-induced liver fibrosis through the inhibition of oxidative stress and/or the activation of hepatic stellate cells, thus suggesting the possible application of perindopril as an antifibrotic drug.

Bile duct-ligated rats have been widely used as a model of cholestatic liver fibrosis. The aim of this study was to analyze the sequential expression of extracellular matrix (ECM) metabolism-related genes in these rats. We analyzed the intrahepatic messenger RNA (mRNA) expression of several ECM metabolism-related genes: transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), procollagen-α1 (collagen-I), matrix metalloproteinase (MMP)-2, MMP-13 and tissue inhibitor of metalloproteinases (TIMP)-1 on days 10, 21 and 42 after bile duct ligation (BDL). A DNA microarray was used to evaluate the expression of genes related to early fibrogenesis on day 10 following BDL; the grade of hepatic fibrosis was found to gradually progress from day 10 to 42. Collagen-I mRNA expression significantly increased from day 10 to day 42, as did TGF-β1 and CTGF mRNA. On the other hand, MMP-13 and -2 mRNA expression increased maximally from day 10 to 21, but tended to decrease by day 42. TIMP-1 mRNA expression was significant on day 21 and was sustained until day 42. The DNA microarray revealed genes significantly increased on day 10, including calgranulin B, solute carrier family 34, thymosin and tubulin, but not fibrogenesis-related cytokines or MMPs/TIMPs. In conclusion, the enhanced gene expression of collagen-I, TGF-β1, CTGF and TIMP-1 and the decreased gene expression of MMP-13 and -2 was noted on day 42 in BDL-induced liver fibrosis.