Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Hepatocellular cancer (HCC) is a frequent cause of cancer death worldwide. Although successful screening programs exist in Asian countries, the role for screening in the United States is not clear. The purpose of this study is to determine if screening has an effect on survival in a predominantly Asian population in Hawaii. We retrospectively reviewed cases of HCC from 1993 to 1998 for demographic data, risk factors, symptoms, stage, treatment, and survival. Patients were divided into 3 groups according to presentation: symptomatic (S), asymptomatic (A), and asymptomatic but screened for disease (A/Sc). Kaplan-Meier analysis was performed on overall survival by group. Ninety-one patients were referred for HCC. There were 56 patients in group S, 19 patients in group A, and 16 patients in group A/Sc. Patients in group A/Sc survived significantly longer than those in group S (P= .009), with the former group having a median survival of 1,399 versus 234 days for group S. Median survival for group A was 545 days and did not differ significantly from the other groups. Patients who are asymptomatic and screened for HCC have an increased survival compared with those patients who present with symptoms. This may justify the use of a formal screening program for HCC in Hawaii, but we would need to investigate this prospectively.

Hepatocellular carcinoma (HCC) is one of the most common cancers and frequently presents with an advanced disease at diagnosis. There is only limited knowledge of genome-scale methylation changes in HCC. We performed genome-wide methylation profiling in a total of 47 samples including 27 HCC and 20 adjacent normal liver tissues using the Illumina HumanMethylation450 BeadChip. We focused on differential methylation patterns in the promoter CpG islands as well as in various less studied genomic regions such as those surrounding the CpG islands, i.e. shores and shelves. Of the 485,577 loci studied, significant differential methylation (DM) was observed between HCC and adjacent normal tissues at 62,692 loci or 13% (p<1.03e-07). Of them, 61,058 loci (97%) were hypomethylated and most of these loci were located in the intergenic regions (43%) or gene bodies (33%). Our analysis also identified 10,775 differentially methylated (DM) loci (17% out of 62,692 loci) located in or surrounding the gene promoters, 4% of which reside in known Differentially Methylated Regions (DMRs) including reprogramming specific DMRs and cancer specific DMRs, while the rest (10,315) involving 4,106 genes could be potential new HCC DMR loci. Interestingly, the promoter-related DM loci occurred twice as frequently in the shores than in the actual CpG islands. We further characterized 982 DM loci in the promoter CpG islands to evaluate their potential biological function and found that the methylation changes could have effect on the signaling networks of Cellular development, Gene expression and Cell death (p = 1.0e-38), with BMP4, CDKN2A, GSTP1, and NFATC1 on the top of the gene list. Substantial changes of DNA methylation at a genome-wide level were observed in HCC. Understanding epigenetic changes in HCC will help to elucidate the pathogenesis and may eventually lead to identification of molecular markers for liver cancer diagnosis, treatment and prognosis.

Background: Patients are living longer with cardiovascular disease managed with antiplatelet drugs. These seniors are asked to be more physically active and are prone to falls or injuries. Few have studied the mortality or morbidity from anticoagulants in patients with traumatic brain injuries (TBI). With the increasing use of clopidogrel in the elderly, studies on the consequences of TBI are warranted. Methods: This is a retrospective case-controlled study using a trauma data registry of 3,817 closed head trauma cases (2001–2005). Patients with preinjury use of clopidogrel, aspirin or warfarin, and evidence of traumatic intracranial bleeding were identified (n = 131). These were compared with a frequency-matched control group (n = 178) with similar age, gender, Glasgow Coma Scale, and Injury Severity Scores. Main outcome measure included mortality, hospital or intensive care unit duration, and discharge disposition. Results: Of 131 patients on anticoagulants, patients on clopidogrel (n = 21) were more likely to die (OR = 14.7; 95% CI: 2.3–93.6) and be discharged to an inpatient long-term facility (OR = 3.25; 95%CI: 1.06–9.96). Length of hospital stay and intensive care unit stay were not different from control. Mortality in aspirin patients (n = 90) and warfarin patients (n = 20) did not differ from control. Warfarin patients had increased hospital and ICU stay (10.6 and 5.3 days) when compared with the control (4.7 and 0.9 days, respectively). Conclusions: TBI patients on clopidogrel may have increased long-term disability and fatal consequences when compared with patients who are not on these drugs or on other anticoagulants. Patients on clopidogrel should be advised of safety when engaging in potentially dangerous activities to avoid the consequences of TBI.

Various cancer stem cell (CSC) biomarkers have been identified for hepatocellular carcinoma (HCC), but little is known about the implications of heterogeneity and shared molecular networks within the CSC population. Through miRNA profile analysis in an HCC cohort (n = 241) for five groups of CSC+ HCC tissues, i.e., EpCAM+, CD90+, CD133+, CD44+, and CD24+ HCC, we identified a 14-miRNA signature commonly altered among these five groups of CSC+ HCC. miR-192-5p, the top-ranked CSC miRNA, was liver-abundant and -specific and markedly downregulated in all five groups of CSC+ HCC from two independent cohorts (n = 613). Suppressing miR-192-5p in HCC cells significantly increased multiple CSC populations and CSC-related features through targeting PABPC4. Both TP53 mutation and hypermethylation of the mir-192 promoter impeded transcriptional activation of miR-192-5p in HCC cell lines and primary CSC+ HCC. This study reveals the circuit from hypermethylation of the mir-192 promoter through the increase in PABPC4 as a shared genetic regulatory pathway in various groups of primary CSC+ HCC. This circuit may be the driver that steers liver cells toward hepatic CSC cells, leading to hepatic carcinogenesis.Significance: miR-192-5p and its regulatory pathway is significantly abolished in multiple groups of HCC expressing high levels of CSC markers, which may represent a key event for hepatic carcinogenesis.