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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)

BACKGROUND AND GOALS: Data regarding the management of adefovir (ADV) resistance are still limited. The aim of this study is to investigate treatment outcomes of rescue therapy in ADV-resistant chronic hepatitis B (CHB) patients. STUDY: CHB patients who began rescue therapy due to documented genotypic resistance mutations to ADV between October 2006 and July 2012 were retrospectively reviewed. RESULTS: Sixty-three patients were included in this study. Most patients had history of lamivudine (LAM) resistance. Treatment response was evaluated at 3-month intervals up to 12 months. The cumulative rate of complete virologic response (CVR) in hepatitis B virus (HBV)-infected patients (HBV DNA

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.

The goal of the study was to compare the efficacy and safety of sorafenib with those of systemic cytotoxic chemotherapy.Sorafenib treatment has shown to improve the survival in patients with advanced hepatocellular carcinoma (HCC) when compared with placebo. However, whether sorafenib controls advanced-stage HCC better than systemic cytotoxic chemotherapy has not been elucidated.We retrospectively reviewed the medical records of 220 patients with measurable advanced HCC who had not received systemic treatment previously between January 2007 and April 2012. Among these patients, 78 had been treated with sorafenib. Another 14 patients who were treated with a 4-weekly regimen of adriamycin, cisplatin, and capecitabine were included as the historical control group for comparison. The median overall survival, the progression-free survival, response rates, and safety profiles were evaluated.Baseline characteristics were similar between the treatment groups. The median overall survival was 7.2 months [95% confidence interval (CI), 5.6-8.8] in the sorafenib group and 11.2 months (95% CI, 8.1-14.2) in the cytotoxic chemotherapy group (P=0.10). The median progression-free survival was 3.2 months (95% CI, 2.2-4.3) in the sorafenib group and 5.9 months (95% CI, 3.6-8.2) in the cytotoxic chemotherapy group (P=0.07). The deterioration of liver function and neutropenia were the most frequent serious adverse events in the sorafenib and the systemic chemotherapy group.Although a direct head-to-head comparison could not be done, there were some patients who showed a good response to systemic cytotoxic chemotherapy. Further assessment is necessary to study the role of chemotherapy in patients who are intolerant or intractable to sorafenib.

Although there are some differences in hepatitis B surface antigen (HBsAg) titers in infection with different hepatitis B virus (HBV) genotypes, the HBsAg titers for each HBV genotype have not been evaluated extensively. The aim of this study was to investigate HBsAg titers during the natural history of patients infected with HBV in Korea, where the HBV genotype C is endemic exclusively. Four hundred fifteen patients were enrolled retrospectively and classified according to definitions of the natural phases of HBV infection. In total, 73, 118, 147, and 77 patients were classified in the immune tolerance, immune clearance, low replicative, and HBeAg-negative hepatitis phases, respectively. HBsAg titers (4.35 ± 0.67, 3.74 ± 0.68, 2.39 ± 1.23, and 3.29 ± 0.64 log(10) IU/ml) were significantly different in the immune tolerance, immune clearance, low replicative, and HBeAg-negative hepatitis phases, respectively (P 0.001). The ratio of HBsAg to HBV DNA was highest in the low replicative phase (1.13 ± 0.71, all P 0.001) and second highest in the HBeAg-negative hepatitis phase (0.58 ± 0.18, all P 0.05). In multivariate analysis of all patients, the HBsAg titers did not correlate with alanine aminotransferase. However, the HBsAg titers correlated with age (P = 0.038), platelet count (P 0.001) and HBV DNA (P 0.001). In subgroup analysis, the HBsAg titers correlated with HBV DNA in all phases (P 0.001), except for the HBeAg-negative hepatitis phase. HBsAg titers were significantly different across the four phases of the natural history of the infection and correlated significantly with HBV DNA titer in genotype C chronic hepatitis B patients. The HBsAg titer could be used as a biomarker to differentiate the natural history of HBV infection.

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.