Annie O.O. Chan

A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy

Background and aim: Clinical data on spontaneous hepatitis B e antigen (HBeAg) seroconversion and acute exacerbation of chronic hepatitis B (CHB) virus infection from large population studies are lacking. In the present study we examined the clinical features and significance of HBeAg seroconversion and acute exacerbation in 3063 Chinese CHB patients. Methods: Clinical assessment, liver biochemistry, hepatitis B virus (HBV) serology and HBV DNA, time of HBeAg seroconversion, and acute exacerbation were monitored. Results: Median age at HBeAg seroconversion was 34.5 years. The cumulative HBeAg seroconversion rate significantly increased with alanine aminotransferase (ALT) levels on presentation (p<0.0001). For patients with ALT levels more than twice the upper limit of normal (ULN) on presentation, the HBeAg seroconversion rate at the fifth year of follow up was 72.4%. After HBeAg seroconversion, 65.2% (73/110) of patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay. Of these, 78.1% still had HBV DNA levels detectable by the Amplicor HBV Monitor Test. We found that 37.5% antibody to HBeAg (anti-HBe) positive patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay before acute exacerbation. Acute exacerbations of longer duration, with higher peak ALT, bilirubin, and α fetoprotein levels were associated with an increased HBeAg seroconversion rate (p<0.0001–0.045). Acute exacerbation with peak ALT levels more than five times the ULN carried a 46.4% chance of HBeAg seroconversion within three months. HBeAg seroreversion and mortality occurred in 2.7% and 0.7% of acute exacerbations, respectively. Conclusion: In the present study we have provided information on HBeAg seroconversion and acute exacerbation, which are important in decision making for CHB treatment and in designing clinical trials.

Serum macrophage migration‐inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer

This study aimed to determine the potential diagnostic value of migration‐inhibitory factor (MIF) for gastric cancer in patients presenting with dyspepsia and its prognostic value for gastric cancer.

Attitudes and knowledge of colorectal cancer and screening in Hong Kong: A population‐based study

Background:  Colorectal cancer (CRC) ranks third of all cancer mortalities in Hong Kong. CRC screening can reduce mortality. However, participation in the CRC screening program depends on the knowledge and attitude of the population. The aim of this study is to investigate the knowledge and attitude towards CRC screening in the Hong Kong population.

Effects of Cyclooxygenase-1 and -2 Gene Disruption on Helicobacter pylori–Induced Gastric Inflammation

BACKGROUND Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. METHODS Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1+/- and COX-2+/-), and homozygous COX-deficient (COX-1-/- and COX-2-/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. RESULTS COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B4 and LTC4 levels were increased to a similar extent in infected WT and COX-deficient mice. CONCLUSIONS COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.

Inhibition of human telomerase reverse transcriptase by nonsteroidal antiinflammatory drugs in colon carcinoma

Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT.

Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer cells.

Background/Aim: Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway. Methods: Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line. Results: SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases. Conclusion: One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.

Quality of Life and Psychological Impact in Patients With Noncardiac Chest Pain

Background Chest pain is common and data regarding noncardiac chest pain (NCCP) in Asia are lacking. Aim To determine the differences in clinical presentations, psychologic impact, and quality of life between patients with NCCP and cardiac chest pain (CCP), and to identify any factors that impacted on these patients. Methods Consecutive patients undergoing coronary angiography for the evaluation of chest pain were recruited in Hong Kong and Wuhan, China. One hundred and forty patients with abnormal and 141 patients with normal angiography were included in the study. The validated gastroesophageal reflux disease questionnaire, the Hospital Anxiety-Depression Scale, and the 12-item Short Form Health Survey (SF-12) were used for assessment. Results NCCP patients reported similar days-off work and impairment of their social life compared with those with CCP. No difference was found in the anxiety and depression scores between the 2 groups. NCCP patients with reflux symptoms had higher anxiety score (7.19 vs. 5.74, P=0.044), reported more interruption of their social life (26% vs. 5%, P<0.0001), and had taken more sick leaves (17% vs. 5%, P=0.018) compared with those without gastroesophageal reflux disease. Conclusions The quality of life and psychologic impact of patients with NCCP were as significant as those with CCP. NCCP patients with reflux symptoms were more anxious and were impaired in their productivity and social life.

Prevalence and time trend of intestinal metaplasia in Hong Kong

Background and Methods:  Upper endoscopy records from 1998 to 2003 were reviewed. The demographic data, endoscopic diagnosis, results of rapid urease test and the absence or presence of intestinal metaplasia (IM) in histology were reviewed, to evaluate the prevalence of IM and Helicobacter pylori (Hp) infection over time in Hong Kong.

Colonoscopy Demand and Practice in a Regional Hospital over 9 Years in Hong Kong: Resource Implication for Cancer Screening

Background: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain. Aim: To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years. Methods: Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared. Results: There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001). Conclusion: The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.

Symptom Resolution Does Not Predict Healing of Erosive Oesophagitis in Chinese

Background: Previous studies suggested that Chinese have a milder spectrum of gastro-oesophageal reflux disease and a lower dose of proton pump inhibitors (PPI) is sufficient for the control of symptoms as compared with the Western population. Aims: To determine if 8 weeks of esomeprazole 20 mg daily would be adequate for both symptom resolution and oesophagitis healing in Chinese patients and the predictive factors for the response. Methods: 66 patients with oesophagitis were included. Oesophagitis severity was graded by Los Angeles (LA) classification. 61 patients underwent 24-hour ambulatory pH study at baseline. All were given esomeprazole 20 mg daily for 8 weeks. Symptom response and healing of oesophagitis was assessed at the end of the treatment period. Results: 75.8% of the patients had complete reflux symptom resolution but only 48% had complete healing of the oesophagitis at endoscopy after 8 weeks of treatment. LA classification grading at baseline endoscopy (p < 0.0001) and total number acid reflux episodes on 24-hour pH monitoring prior to treatment (p = 0.007) were both good predictors of oesophagitis healing but not for symptom resolution. Conclusions: Our results suggested that 8 weeks of lower dose PPI is not sufficient for oesophagitis healing. Symptom resolution with PPI does not predict oesophagitis healing in Chinese.