Early-onset hepatocellular carcinoma (HCC) accounts for 15%-20% of total HCC cases in Asia, and the incidence is increasing. The low frequency of cirrhosis and poor prognosis of early-onset HCC suggests that its mechanisms may differ from late-onset HCC. Although hepatitis B virus (HBV) infection is epidemiologically associated with HCC, the role of HBV in early-onset HCC remains poorly understood. Here, we report a comparative study of HBV subgenotypes and integration in early-( £ 30) and late-onset (70) HBV-associated HCC using a novel high-throughput viral integration detection method. We report that HBV B2 is predominantly present in early-onset HCC. HBV integration is a common phenomenon, both in early-and late-onset HCC, which favors integrating into human repeat regions. Moreover, we found a breakpoint in 8q24 located between c-Myc and plasmocytoma variant translocation 1 (PVT1), which was detected in 12.4% (14 of 113) of early-onset HCCs, but only 1.4% (2 of 145) in lateonset HCCs. HBV integrating this site results in c-MYC, PVT1, and microRNA-1204 overexpression in tumors, thereby potentially contributing to the development of earlyonset HCC. Conclusion: HBV genotype and integration patterns may be distinct in early-onset HCC. Our results may shed light on HCC risk factors in young HBV carriers. Further studies are needed to elucidate at which time in tumor development this integration event occurs and whether it plays an important, causative role in HCC development or progression. (HEPATOLOGY 2015;61:1821-1831 H epatocellular carcinoma (HCC) is a common solid tumor and the third leading cause of cancer death worldwide.1 Hepatitis B virus (HBV) is a major etiological agent in China, Southeast Asia, and sub-Saharan Africa, and individuals with chronic HBV infection are at increased risk of developing HCC, particularly those with chronic liver disease and cirrhosis.2 Average age at onset of HBVassociated HCC is 50 years 3,4 ; thus, the recommendations advise HCC screening for Asian male HBV patients older than 40 and Asian female HBV patients older than 50.5 Nonetheless, incidence of HCC in patients younger than 40, especially in high-risk populations, is relatively high. 6,7 Recent studies have reported a significant prevalence and worse prognosis in early-onset HCC patients, 8,9 suggesting that there Abbreviations: ALB, albumin; bp, base pairs; DR1/2, direct repeat 1 and 2; FN1, fibronectin 1; GATM, glycine amidinotransferase; gDNA, genomic DNA; HBV, hepatitis B virus; Hbx, HBV x gene; HCC, hepatocellular carcinoma; HIVID, high-throughput viral integration detection; kb, kilobase; LC, liver cirrhosis; LINE, long interspersed nuclear elements; miR, microRNA; MLL4, myeloid/lymphoid or mixed-lineage leukemia 4; PVT1, plasmocytoma variant translocation 1; RT-PCR, reverse-transcription polymerase chain reaction; SINE, short interspersed nuclear elements; ST18, suppression of tumorigenicity 18; STAT1, signal transducer and activator of transcription 1; SYT12, synaptotagmin XII; TERT, telomerase reverse transc...

Objective: This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Method: Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Results: Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. Conclusion: These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs). Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors. Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p ¼ .875). The 1-, 3-and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3-and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p ¼ .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p ¼ .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p ¼ .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p ¼ .001) in the ablation group. Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.