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Background/Aims: α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are re-portedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC. Methods: We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic ac-curacy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The GPC3 levels in the HCC patients (75.8 ng/mL) were sig-nificantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors. Conclu-sions: The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors. (Gut Liver 2014;8:177-185)

Objectives: Interferon (IFN)-based therapy for chronic hepatitis C (CHC) is cost-effective and is associated with reduced risk of disease progression. We aimed to assess the incidence of cirrhosis and hepatocellular carcinoma (HCC) and to identify risk factors associated with disease progression. Methods: We retrospectively reviewed 280 CHC patients who were registered at our hospital between 2001 and 2010. Results: About 80% of patients received antiviral treatment. The 10-year cumulative incidence of cirrhosis was significantly lower among patients who received antiviral therapy than among those who did not (8.3 vs. 44.0%; p = 0.001). Among them, patients with sustained virological response (SVR) had a significantly lower incidence of cirrhosis than those without SVR (0.6 vs. 33.9%; p < 0.001). Cox proportional hazards regression showed that SVR was the significant independent factor for reducing the risk of cirrhosis (hazard ratio, HR = 0.03; p = 0.034). The 10-year cumulative incidence of HCC was higher among patients who did not receive antiviral therapy than among those who did (43.9 vs. 6.1%; p < 0.001). Multivariate analysis showed that underlying cirrhosis was the only independent risk factor associated with HCC development (HR = 7.70; p = 0.010). Conclusions: SVR secondary to IFN-based therapy could reduce cirrhosis development in CHC patients. Underlying cirrhosis was the strongest predictor of HCC development.

To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models.Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW.HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.

Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8×10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.

A 30-year-old man visited the emergency room for chest pain, dyspnea and fever. Despite increased serum cardiac enzymes, ST segment elevation and inferior wall akinesis in electrocardiography and echocardiography, no atherosclerosis was evident in the coronary angiography. However, radionuclide myocardial perfusion image at day 2 showed a persistent perfusion defect in the left ventricular (LV) inferior wall. At day 3, prominent myocardial edema and severe LV systolic dysfunction developed with signs of heart failure. In this case, fulminant myocarditis seemed to originate from the right coronary artery territory and simulated a ST segment elevation myocardial infarction without coronary artery obstruction. The pathogenesis of the localized perfusion defect was