F. K. L. Chan

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.

Summary.  The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications--review and recommendations based on risk assessment.

The incidence of non‐steroidal anti‐inflammatory drug‐related ulcer complications remains high despite the availability of potent anti‐ulcer drugs and selective cyclo‐oxygenase‐2 inhibitors. Non‐steroidal anti‐inflammatory drug‐related ulcer complications can be minimized by prospective assessment of patients’ baseline risk, rational choice and use of non‐steroidal anti‐inflammatory drugs, and selective use of co‐therapy strategies with gastroprotectives. Current recommendations regarding strategies using anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors for prevention of clinical non‐steroidal anti‐inflammatory drug upper gastrointestinal events are largely derived from studies using surrogates such as endoscopic ulcers, erosions, and symptoms in low‐ to average‐risk patients. Conclusions based on surrogate and potentially manipulatable end‐points are increasingly suspect with regard to applicability to clinical situations. This article reviews the risks associated with non‐steroidal anti‐inflammatory drugs including aspirin and includes the effect of the patients’ baseline risk, and the confounding effects of Helicobacter pylori infection. In addition, uncertainties regarding the clinical efficacy of anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors against non‐steroidal anti‐inflammatory drug‐related ulcer complications are put into perspective. We propose management strategies based on the risk category: low risk (absence of risk factors) (least ulcerogenic non‐steroidal anti‐inflammatory drug at lowest effective dose), moderate risk (one to two risk factors) (as above, plus an antisecretory agent or misoprostol or a cyclo‐oxygenase‐2 inhibitor), high risk (multiple risk factors or patients using concomitant low‐dose aspirin, steroids, or anticoagulants) (cyclo‐oxygenase‐2 inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton pump inhibitors or misoprostol with aspirin), and very high risk (history of ulcer complications) (avoid all non‐steroidal anti‐inflammatory drugs, if possible or a cyclo‐oxygenase‐2 plus a proton pump inhibitors and/or misoprostol). The presence of H. pylori infection increases the risk of upper gastrointestinal complications in non‐steroidal anti‐inflammatory drug users by two‐ to fourfold suggesting that all patients requiring regular non‐steroidal anti‐inflammatory drug therapy be tested for H. pylori.

Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions

Background:Helicobacter pylori blood group antigen binding adhesin (BabA) mediates bacterial adherence to human blood group antigens on gastric epithelium. Although strains harbouring babA2 were recently found to be associated with peptic ulcer and gastric cancer, the role of babA2 in cellular turnover, severity of gastritis, and premalignant changes is poorly understood. Aim: We correlated H pylori babA2, vacuolating toxin (vacA), and cytotoxin associated gene A (cagA) genotypes with the severity of gastric inflammation and epithelial cell turnover in a group of Chinese patients from an area with a high incidence of gastric cancer. Patients and methods:H pylori isolates were obtained from 104 Chinese patients who participated in a gastric cancer prevention programme. Genotype variants of babA2, vacA, and cagA were determined by polymerase chain reaction. Antrum and corpus histopathology was examined according to the updated Sydney classification. Apoptosis was scored by terminal uridine deoxynucleotidyl nick end labeling (TUNEL) and proliferation by Ki-67 immunostaining. Results: Of the 104 patients, 102 (98.1%) harboured cagA+ strains and all had vacA s1 genotype. The babA2+ strains were found in 83 (79.8%) patients and were associated with higher lymphocytic infiltration (p=0.028), presence of glandular atrophy (odds ratio (OR) 7.5, 95% confidence interval (CI) 2.3–24.3), and intestinal metaplasia (OR 7.4, 95% CI 2.2–25.3) in the antrum. Increased epithelial proliferation was also noted in individuals infected with babA2+ strains (p=0.025). Strains harbouring cagA+/vacA s1 genotypes lacked this association in the absence of babA2. Conclusions: The presence of babA2+H pylori strains alone or in combination with cagA+ and vacA s1 was associated with the presence of preneoplastic gastric lesions.

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Objective To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes. Design We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls. Results Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I–II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. Conclusions We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.

Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease.

Non‐alcoholic fatty liver disease is prevalent in affluent countries and is strongly associated with metabolic syndrome.

Histological progression of non‐alcoholic fatty liver disease in Chinese patients

Background : Non‐alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non‐alcoholic fatty liver disease is not well understood especially in Asian populations.

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti‐inflammatory drug (NSAID)‐associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID‐associated bleeding peptic ulcers.

Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

Background  Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear.

Systematic review: the efficacy of herbal therapy in inflammatory bowel disease

Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited.

Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: a double blind, placebo controlled, randomised trial

Background: The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H pylori eradication leads to worsened control of reflux disease. Methods: Consecutive patients with weekly reflux symptoms were prospectively recruited for endoscopy and symptom evaluation. Patients were enrolled if they had H pylori infection and required long term acid suppressants. Eligible patients were randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given for eight weeks for healing of oesophagitis and symptom relief. This was followed by a maintenance dose of 10 mg daily for up to 12 months. The primary study end point was the probability of treatment failure within 12 months, which was defined as either incomplete resolution of symptoms or oesophagitis at the initial treatment phase, or relapse of symptoms and oesophagitis during the maintenance phase. Predictors of treatment failure were determined by Cox’s proportional hazards model. Results: A total of 236 GORD patients were screened and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group). Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15 patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had treatment failure. The 12 month probability of treatment failure was 43.2% (95% confidence interval (CI) 29.9–56.5%) in the HpE group and 21.1% (95% CI 9.9–32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional hazards model, after adjustment for the covariates age, sex, erosive oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at baseline, H pylori eradication was the only predictor of treatment failure (adjusted hazard ratio 2.47 (95% CI 1.05–5.85)). Conclusion:H pylori eradication leads to more resilient GORD.