Identification of hepatitis B virus DNA reverse transcriptase variants associated with partial response to entecavir

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COLD-PCR for early detection of hepatitis B virus antiviral drug resistance mutations

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White blood cell count and risk of incident lung cancer in the UK Biobank

Background The contribution of measurable immunological/inflammatory parameters to lung cancer development remains unclear, particularly among never-smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK). Methods We evaluated 424,407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered/collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference. Results There were 1,493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was significantly associated with elevated lung cancer risk (HRQ4=1.67, 95% CI:1.41-1.98). Among women, increased risks were found in current-smokers (ncases/n=244/19,464, HRQ4=2.15, 95% CI:1.46-3.16), former-smokers (ncases/n=280/69,198, HRQ4=1.75, 95% CI:1.24-2.47), and never-smokers without environmental tobacco smoke exposure (ncases/n=108/111,294, HRQ4=1.93, 95% CI:1.11-3.35). Among men, stronger associations were identified in current-smokers (ncases/n=329/22,934, HRQ4=2.95, 95% CI:2.04-4.26) and former-smokers (ncases/n= 358/71,616, HRQ4=2.38, 95% CI:1.74-3.27) but not in never-smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions. Conclusions Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men

Defining normal liver stiffness range in a normal healthy Chinese population without liver disease

BACKGROUND: For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. AIMS: To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. METHODS: This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. RESULTS: Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89). The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p55 years (p=0.001). CONCLUSIONS: The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness.published_or_final_versio

Sequence Variations of Full-Length Hepatitis B Virus Genomes in Chinese Patients with HBsAg-Negative Hepatitis B Infection

BACKGROUND: The underlying mechanism of HBsAg-negative hepatitis B virus (HBV) infection is notoriously difficult to elucidate because of the extremely low DNA levels which define the condition. We used a highly efficient amplification method to overcome this obstacle and achieved our aim which was to identify specific mutations or sequence variations associated with this entity. METHODS: A total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance were amplified by rolling circle amplification followed by full-length HBV genome sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The effects of pivotal mutations identified on regulatory regions on promoter activities were analyzed. RESULTS: 22 and 11 full-length HBV genomes were amplified from HBsAg-negative and control subjects respectively. HBV genotype C was the dominant strain. A higher mutation frequency was observed in HBsAg-negative subjects than controls, irrespective of genotype. The nucleotide diversity over the entire HBV genome was significantly higher in HBsAg-negative subjects compared with controls (p = 0.008) and compared with 49 reference sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had significantly higher amino acid substitutions in the four viral genes than controls (all p<0.001). Many mutations were uniquely found in HBsAg-negative subjects, including deletions in promoter regions (13.6%), abolishment of pre-S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%), nucleotide duplications (9.1%), and missense mutations in "alpha" determinant region, contributing to defects in HBsAg production. CONCLUSIONS: These data suggest an accumulation of multiple mutations constraining viral transcriptional activities contribute to HBsAg-negativity in HBV infection.published_or_final_versio

High false positivity in positron emission tomography is a potential diagnostic pitfall in patients with suspected adrenal metastasis

BACKGROUND: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) is a potentially powerful, non-invasive imaging tool in differentiating adrenal metastasis from benign disease, some adenomas also exhibit high FDG uptake, therefore mimicking metastasis (i.e., false positives). We aimed to evaluate the accuracy of FDG-PET/CT based exclusively on histology and to identify risk factors for adrenal metastasis. METHODS: Among the 289 consecutive patients who underwent adrenalectomy, 39 (78.0 %) patients had suspected solitary adrenal metastasis and had a positive preoperative FDG-PET/CT. The FDG-PET/CT findings were correlated with the histology of the excised adrenal gland. To identify risk factors for adrenal metastasis, characteristics were compared between patients with histologically proven adrenal metastasis and those without. Youden's index was used to calculate the optimal cut-off value for predicting adrenal metastasis. RESULTS: Histology of the excised adrenal tumor confirmed adrenal metastasis in 28/39 (71.8 %) patients while non-metastatic lesions comprised mostly benign adrenal cortical adenoma (n = 10) and one non-functional pheochromocytoma. Therefore, the overall false-positive rate of FDG-PET/CT was 28.2 %. History of primary lung malignancy [odds ratio (OR) (95 % CI) 20.00 (1.01-333.3), p = 0.049] and SUVmax > 2.65 [OR (95 % CI) 31.606 (2.46-405.71), p = 0.008] were independent risk factors for adrenal metastasis. CONCLUSIONS: Single adrenal uptake on FDG-PET/CT in suspected solitary adrenal metastasis was associated with a high false-positive rate (28.2 %). Risk factors associated with adrenal metastasis included a history of known primary lung malignancy and a SUVmax > 2.65 at the adrenal lesion of interest on FDG-PET/CT. Based on these findings, a new algorithm was constructed.postprin

Artificial neural network accurately predicts hepatitis B surface antigen seroclearance

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) seroclearance and seroconversion are regarded as favorable outcomes of chronic hepatitis B (CHB). This study aimed to develop artificial neural networks (ANNs) that could accurately predict HBsAg seroclearance or seroconversion on the basis of available serum variables. METHODS: Data from 203 untreated, HBeAg-negative CHB patients with spontaneous HBsAg seroclearance (63 with HBsAg seroconversion), and 203 age- and sex-matched HBeAg-negative controls were analyzed. ANNs and logistic regression models (LRMs) were built and tested according to HBsAg seroclearance and seroconversion. Predictive accuracy was assessed with area under the receiver operating characteristic curve (AUROC). RESULTS: Serum quantitative HBsAg (qHBsAg) and HBV DNA levels, qHBsAg and HBV DNA reduction were related to HBsAg seroclearance (P<0.001) and were used for ANN/LRM-HBsAg seroclearance building, whereas, qHBsAg reduction was not associated with ANN-HBsAg seroconversion (P = 0.197) and LRM-HBsAg seroconversion was solely based on qHBsAg (P = 0.01). For HBsAg seroclearance, AUROCs of ANN were 0.96, 0.93 and 0.95 for the training, testing and genotype B subgroups respectively. They were significantly higher than those of LRM, qHBsAg and HBV DNA (all P<0.05). Although the performance of ANN-HBsAg seroconversion (AUROC 0.757) was inferior to that for HBsAg seroclearance, it tended to be better than those of LRM, qHBsAg and HBV DNA. CONCLUSIONS: ANN identifies spontaneous HBsAg seroclearance in HBeAg-negative CHB patients with better accuracy, on the basis of easily available serum data. More useful predictors for HBsAg seroconversion are still needed to be explored in the future.published_or_final_versio

Identification of Hepatitis B Virus DNA Polymerase Sequences to Predict Virological Response to Entecavir Therapy

Poster Presentations: Emerging / Infectious DiseasesConference Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma

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Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B

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