Aoo Chan

Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications.

Background: Identifying risk factors for the development of complications of chronic hepatitis B (CHB) is important for setting up treatment criteria. Aim: To determine risk factors for the development of complications in Asian CHB patients. Patients and methods: A total of 3233 Chinese CHB patients (mean follow up 46.8 months) were monitored for liver biochemistry, viral serology, hepatitis B virus (HBV) DNA levels, acute exacerbation, hepatitis B e antigen (HBeAg) seroconversion, and development of cirrhotic complications and hepatocellular carcinoma. Results: Median age for HBeAg seroconversion and development of complications was 35 years and 57.2 years, respectively. Patients with alanine aminotransferase (ALT) levels of 0.5–1 times the upper limit of normal (ULN) and 1–2× ULN had an increased risk for the development of complications compared with patients with ALT levels <0.5× ULN (p<0.0001 for both). HBeAg/antibody to hepatitis B e antigen status, and number of episodes, duration, and peak ALT levels of acute exacerbations were not associated with an increased risk of complications. In patients with complications, 43.6% had HBV DNA levels less than 1.42×105 copies/ml. Male sex, stigmata of chronic liver disease, old age, low albumin, and high α fetoprotein levels on presentation were independently associated with increased cumulative risk of complications. Male sex, presence of hepatitis symptoms, old age, low albumin level, and presence of complications on presentation were independently associated with shorter survival. Conclusion: Prolonged low level viraemia causing insidious and continual liver damage, as reflected by ALT levels of 0.5–2× ULN, is the most likely pathway for the development of complications in Asian CHB patients.

Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer.

Background:E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer. Aims: This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer. Methods:E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry. Results:E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05). Conclusion:E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.

Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation

Background: E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients. Aim: To examine if eradication of H pylori could reverse E-cadherin methylation. Methods: Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing. Results: Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5). Conclusion:H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.

Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study.

Background: Functional constipation has important psychological elements.

Long-term prospective follow-up of endoscopic oesophagitis in southern Chinese - prevalence and spectrum of the disease

Aims : To study the prevalence, clinical characteristics and long‐term outcome of oesophagitis in Chinese patients.

Soluble E-cadherin is a valid prognostic marker in gastric carcinoma

BACKGROUND Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008–1.668) and palliative/conservative treatment (p=0.023, CI 1.038–2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.

A validated symptoms questionnaire (Chinese GERDQ) for the diagnosis of gastro-oesophageal reflux disease in the Chinese population

Background and aims: To develop a validated gastro‐oesophageal disease (GERD) symptom questionnaire for the Chinese population.

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection

To test the efficacy of levofloxacin‐based second‐line therapy for resistant Helicobacter pylori infection.

Trends in the prevalence of peptic ulcer disease and Helicobacter pylori infection in family physician‐referred uninvestigated dyspeptic patients in Hong Kong

Background:  Peptic ulcer disease is mainly caused by Helicobacter pylori infection and the use of non‐steroidal anti‐inflammatory drugs.

Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients: implications for screening

Aim : To compare the clinico‐pathological features of hepatitis B virus‐related hepatocellular carcinoma in young and old patients.