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Rhus verniciflua is commonly known as a lacquer tree in Korea. The bark of R. verniciflua has been used as an immunostimulator in traditional medicine, but also causes allergic dermatitis due to urushiol derivatives. For the development of active natural resources with less toxicity, the antibacterial activity of various parts of R. verniciflua such as bark, lignum, leaves and fruit, together with chemical composition, were investigated. Among the various parts of R. verniciflua, lignum showed the most potent antibacterial activity against fish pathogenic bacteria such as Edwardsiella tarda, Vibrio anguillarum and Streptococcus iniae. Measurement of total phenolic content and flavonoid content clearly showed a high content of phenolic and flavonoids in lignum among the various parts of R. verniciflua. Further analysis showed a close correlation between antibacterial activity and phenolic content. In addition, methyl gallate and fustin, the major constituents of bark and lignum, showed antibacterial activity, which suggested phenolic constituents as active constituents. The content of urushiols, however, was highest in bark, but there was a trace amount in lignum. LC-MS-MS and PCA analysis showed good discrimination with the difference of phenolic composition in various parts of R. verniciflua. Taken together, phenolic compounds are responsible for the antibacterial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antibacterial activity with less toxicity. Therefore, the lignum of R. verniciflua is suggested as a good source for antibacterial material to use against fish bacterial diseases. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection causes chronic liver diseases leading to hepatocellular carcinoma (HCC) and liver failure. We have previously shown that HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for cancer therapy, their potential against HCC with chronic HCV infection has not been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of caspase-8 leading to elevation of apoptotic signaling in infected cells and also present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8, caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV-induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8 signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase (PARP), a substrate for caspase-3 during apoptosis, indicating the functional role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating the effect of TRAIL for the induction of selective apoptosis of HCC cells infected with HCV. Given the importance of apoptosis in HCC development, our data suggest that HCV-induced DR4 and DR5 may be considered as an attractive target for TRAIL therapy against HCC with chronic HCV infection. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) recurrence after liver resection depends upon the stage and histological grade of the tumor and the expression of certain biomarkers. However, it remains unclear which of these factors has the highest predictive value regarding HCC recurrence after surgical resection. Methods: This study investigated the associations among clinicopathological characteristics, expression of biomarkers, and HCC recurrence after liver resection. Fifty-four patients having undergone liver resection for HCC were enrolled prospectively, and their data were analyzed retrospectively. Evaluated variables were clinical data, laboratory findings, modified Union for International Cancer Control (UICC) stage, vascular invasion, histological differentiation, and immunohistochemical staining for fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor, and tumor-necrosis-factor-related apoptosis-inducing ligand receptors 1 and 2. Results: Mean patient age was 58.6 years (range, 30–71), and the mean and SD for follow-up duration were 51.2 ± 34.8 months. Cumulative 1-, 3-, and 5-year recurrence rates were 32.9%, 53.6%, and 68.1%, respectively. In univariate analysis, FGFR2 (p = 0.026) and Edmonson-Steiner grade (E-S grade) (p = 0.030) were associated with recurrence after resection in HCC patients. In multivariate analyses, increased FGFR2 expression (p = 0.017) was the only significant predictor of HCC recurrence. Conclusions: High FGFR2 expression had marginal association with poor E-S grade (p = 0.056). More intensive surveillance of HCC recurrence is warranted in HCC patients with increased FGFR2 expression. [ABSTRACT FROM AUTHOR]

Background/aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease. [ABSTRACT FROM AUTHOR]

Background: Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. Methods and findings: We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56–1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36). Conclusion: The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis and hepatocellular carcinoma (HCC) are often ineligible for resection or local ablation therapy due to poor liver function and/or difficult location. The aim of this study is to evaluate therapeutic outcomes of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) compared with TACE alone for HCC measuring less than 5 cm. From March 2011 to December 2016, 85 patients underwent SBRT with TACE (SBRT-TACE group) and 114 underwent TACE (TACE group) at 4 tertiary hospitals. Local control rate (LCR), progression-free survival (PFS) and overall survival (OS) were compared after propensity-score matching (1:1 ratio). The SBRT-TACE group showed significantly higher 1- and 3-year LCR than the TACE group (91.1% and 89.9%, respectively vs 69.9% and 44.8%, respectively; P < 0.001). The SBRT-TACE group showed better 1- and 3-year PFS than the TACE group (56.5% and 32.3%, respectively vs 42.2% and 21.6%, respectively; P = 0.022). However, 1-, 3- and 5-year OS was not different between the SBRT-TACE and TACE groups (98.8%, 89.1% and 80.7%, respectively vs 99.7%, 83.3% and 71.0%, respectively; P = 0.206). In multivariate analysis, the overall SBRT added to TACE did not contribute to extend PFS. However, in patients with less than 2 tumors, the combined therapy was effective (HR 0.590, 95% CI 0.392–0.889, P = 0.012). SBRT-TACE is superior to TACE in terms of LCR. Particularly, SBRT-TACE may be an effective alternative in patients with HCC number (≤2), which is not indicated for resection or local ablation. [ABSTRACT FROM AUTHOR]

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532–27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548–18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT. [ABSTRACT FROM AUTHOR]

Background/aims: Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. Methods: A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. Results: There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κCAP = 0.77, P<0.001; κultrasonography = 0.60, P<0.001; κHSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826–0.972)], 0.859 (95% CI = 0.779–0.939), and 0.766 (95% CI = 0.655–0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. Conclusion: The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages. [ABSTRACT FROM AUTHOR]

Background/aims: The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). Methods: The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. Results: The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P<0.001) and fibrosis (r = 0.714, P<0.001), respectively. The optimal cut-off values for steatosis were 247 dB/m for S1, 280 dB/m for S2, and 300 dB/m for S3. Based on the independent predictors derived from multivariate analysis [P = 0.044, odds ratio (OR) 4.133, 95% confidence interval (CI) 1.037–16.470 for AP>250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295–8.291 for S>7.0 kPa; and P<0.001, OR 7.557, 95% CI 2.997–19.059 for lanine aminotransferase>60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724–0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740–0.893). Conclusion: This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation. [ABSTRACT FROM AUTHOR]

Background & Aim: To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods: We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. Results: Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391). Conclusions: The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF. [ABSTRACT FROM AUTHOR]