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BackgroundHepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC.Methods1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC.Results85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10–4.14, P = 0.025). HBcrAg above 2.9 log10 U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (P = 0.024 by Kaplan–Meier analysis), and possibly in cirrhotic patients (P = 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups.ConclusionSerum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.

Background Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancers. We aimed to evaluate the incidence and prognostic impact of hepatic adverse events (AEs) in a territory‐wide cohort of patients who received ICIs. Methods Patients were identified from a territory‐wide database who received ICIs in 2014‐2018. Hepatic AEs were defined as any elevation of liver biochemistries including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels. Hepatic AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results Total of 1480 patients were identified (mean age 60 years, male 65.5%) and the commonest malignancies being lung cancer (39.6%), liver cancer (16.5%), and gastrointestinal cancer (10.0%). Grade 1‐2 and grade 3‐4 hepatic AEs occurred in 41.3% and 14.9% of patients during ICI treatment, respectively. Patients with liver cancer had the highest rate of hepatic AEs (grade 1‐2:54.1%; grade 3‐4:32.8%). Among 711 patients with hepatic AEs, 383 (53.9%) had raised ALT/AST only, and 328 (46.1%) had concomitant raised ALT/AST and bilirubin levels. In the whole cohort, median overall survival of patients without any hepatic AEs, grade 1‐2 and grade 3‐4 hepatic AEs during ICI treatment was 9.0 months, 7.2 months, and 3.3 months (P < .001), respectively. Similar results on overall survival were obtained among different types of cancers. Conclusions Hepatic AEs occur in more than half of patients receiving ICIs for cancer treatment, with approximately 15% being grade 3‐4 AEs. Occurrence of hepatic AEs is associated with worse prognosis. Hepatic adverse events are common and may occur in more than half of patients receiving immune checkpoint inhibitors for cancer treatment. Severe hepatic adverse events of grade 3‐4 occur in 15% and are associated with worse prognosis.

The discovery of new tumor subtypes has been aided by transcriptomics profiling. However, some new subtypes can be irreproducible due to data artifacts that arise from disparate experimental handling. To deal with these artifacts, methods for data normalization and batch-effect correction have been utilized before performing sample clustering for disease subtyping, despite that these methods were primarily developed for group comparison. It remains to be elucidated whether they are effective for sample clustering. We examined this issue with a re-sampling-based simulation study that leverages a pair of microRNA microarray data sets. Our study showed that (i) normalization generally benefited the discovery of sample clusters and quantile normalization tended to be the best performer, (ii) batch-effect correction was harmful when data artifacts confounded with biological signals, and (iii) their performance can be influenced by the choice of clustering method with the Prediction Around Medoid method based on Pearson correlation being consistently a best performer. Our study provides important insights on the use of data normalization and batch-effect correction in connection with the design of array-to-sample assignment and the choice of clustering method for facilitating accurate and reproducible discovery of tumor subtypes with microRNAs.

Background Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. Methods We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. Results We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0–13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28–1.57, P  < 0.001). The SIR was highest in patients with drug-induced (SIR 3.18, 95% CI 2.41–4.11, P  < 0.001) and alcohol-induced mental disorders (SIR 2.98, 95% CI 2.30–3.81, P  < 0.001), but was also increased in patients with psychotic disorders (SIR 1.39, 95% CI 1.16–1.65, P  < 0.001) and mood disorders (SIR 1.16, 95% CI 1.00–1.34, P  = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26–83] years) was older and the median overall survival (8.0 [95% CI 5.0–10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. Conclusions HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.