Recurrent HBV Integration Targets as Potential Drivers in Hepatocellular Carcinoma.

Chronic hepatitis B virus (HBV) infection is the major etiology of hepatocellular carcinoma (HCC), frequently with HBV integrating into the host genome. HBV integration, found in 85% of HBV-associated HCC (HBV-HCC) tissue samples, has been suggested to be oncogenic. Here, we investigated the potential of HBV-HCC driver identification via the characterization of recurrently targeted genes (RTGs). A total of 18,596 HBV integration sites from our in-house study and others were analyzed. RTGs were identified by applying three criteria: at least two HCC subjects, reported by at least two studies, and the number of reporting studies. A total of 396 RTGs were identified. Among the 28 most frequent RTGs, defined as affected in at least 10 HCC patients, 23 (82%) were associated with carcinogenesis and 5 (18%) had no known function. Available breakpoint positions from the three most frequent RTGs, TERT, MLL4/KMT2B, and PLEKHG4B, were analyzed. Mutual exclusivity of TERT promoter mutation and HBV integration into TERT was observed. We present an RTG consensus through comprehensive analysis to enable the potential identification and discovery of HCC drivers for drug development and disease management.

A retrospective study on the incidences of adverse drug events and analysis of the contributing trigger factors.

OBJECTIVES: To retrospectively determine the extent and types of adverse drug events (ADEs) from the patient cases sheets and identify the contributing factors of medication errors. To assess causality and severity using the World Health Organization (WHO) probability scale and Hartwig's scale, respectively. METHODS: Hundred patient case sheets were randomly selected, modified version of the Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to identify the ADEs; causality and severity were calculated utilizing the WHO probability scale and Hartwig's severity assessment scale, respectively. RESULTS: In total, 153 adverse events (AEs) were identified using the IHI Global Trigger Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60 adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were identified in 15 patient records. The percentage of AE/100 patients is 17%. The average ADEs/1000 doses is 2.03% (calculated). CONCLUSION: The IHI Global Trigger Tool is an effective method to aid provisionally-registered pharmacists to identify ADEs quicker.