ObjectiveKnowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New ...non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population.MethodsSubjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively.ResultsOverall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54).ConclusionNAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.
Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for ...colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
.
Bacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in ...CRC.
Faecal shotgun metagenomic sequences of 184 patients with CRC, 197 patients with adenoma and 204 control subjects from Hong Kong were analysed (discovery cohort: 73 patients with CRC and 92 control subjects; validation cohort: 111 patients with CRC, 197 patients with adenoma and 112 controls from Hong Kong). CRC-associated fungal markers and ecological changes were also validated in additional independent cohorts of 90 patients with CRC, 42 patients with adenoma and 66 control subjects of published repository sequences from Germany and France. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.
Principal component analysis revealed separate clusters for CRC and control (p<0.0001), with distinct mycobiomes in early-stage and late-stage CRC (p=0.0048). Basidiomycota:Ascomycota ratio was higher in CRC (p=0.0042), with increase in Malasseziomycetes (p<0.0001) and decrease in Saccharomycetes (p<0.0001) and Pneumocystidomycetes (p=0.0017). Abundances of 14 fungal biomarkers distinguished CRC from controls with an area under the receiver-operating characteristic curve (AUC) of 0.93 and validated AUCs of 0.82 and 0.74 in independent Chinese cohort V1 and European cohort V2, respectively. Further ecological analysis revealed higher numbers of co-occurring fungal intrakingdom and co-exclusive bacterial-fungal correlations in CRC (p<0.0001). Moreover, co-occurrence interactions between fungi and bacteria, mostly contributed by fungal Ascomycota and bacterial Proteobacteria in control, were reverted to co-exclusive interplay in CRC (p=0.00045).
This study revealed CRC-associated mycobiome dysbiosis characterised by altered fungal composition and ecology, signifying that the gut mycobiome might play a role in CRC.
ObjectiveUsing faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential ...antitumourigenic role of L. gallinarum in colorectal tumourigenesis.DesignThe tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.ResultsL. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo.ConclusionL. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.
Summary
Background
Patients with a history of Helicobacter pylori–negative idiopathic bleeding ulcers have an increased risk of recurring ulcer complications.
Aim
To build a machine learning model to ...identify patients at high risk for recurrent ulcer bleeding.
Methods
Data from a retrospective cohort of 22 854 patients (training cohort) diagnosed with peptic ulcer disease in 2007‐2016 were analysed to build a model (IPU‐ML) to predict recurrent ulcer bleeding. We tested the IPU‐ML in all patients with a diagnosis of gastrointestinal bleeding (n = 1265) in 2008‐2015 from a different catchment population (independent validation cohort). Any co‐morbid conditions which had occurred in >1% of study population were eligible as predictors.
Results
Recurrent ulcer bleeding developed in 4772 patients (19.5%) in the training cohort, during a median follow‐up period of 2.7 years. IPU‐ML model built on six parameters (age, baseline haemoglobin, and presence of gastric ulcer, gastrointestinal diseases, malignancies, and infections) identified patients with bleeding recurrence within 1 year with an area under the receiver operating characteristic curve (AUROC) of 0.648. When we set the IPU‐ML cutoff value at 0.20, 27.5% of patients were classified as high risk for rebleeding with a sensitivity of 41.4%, specificity of 74.6%, and a negative predictive value of 91.1%. In the validation cohort, the IPU‐ML identified patients with a recurrence ulcer bleeding within 1 year with an AUROC of 0.775, and 84.3% of overall accuracy.
Conclusion
We developed a machine‐learning model to identify those patients with a history of idiopathic gastroduodenal ulcer bleeding who are not at high risk for recurrent ulcer bleeding.
A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by ...transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1β/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D
, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.
Dietary pattern analysis is an alternative approach to examine the association between diet and nonalcoholic fatty liver disease (NAFLD). This study examined the association of two diet-quality ...scores, namely Diet Quality Index-International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence. Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above were recruited through a population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. DQI-I and MDS, as well as major food group and nutrient intakes were calculated based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at ≥5% by proton-magnetic resonance spectroscopy. Multivariate logistic regression models were used to examine the association between each diet-quality score or dietary component and prevalent NAFLD with adjustment for potential lifestyle, metabolic and genetic factors. A total of 220 subjects (27.6%) were diagnosed with NAFLD. DQI-I but not MDS was associated with the prevalence of NAFLD. A 10-unit decrease in DQI-I was associated with 24% increase in the likelihood of having NAFLD in the age and sex adjusted model (95% CI: 1.06-1.45, p = 0.009), and the association remained significant when the model was further adjusted for other lifestyle factors, metabolic and genetic factors OR: 1.26 (95% CI: 1.03-1.54), p = 0.027. Multivariate regression analyses showed an inverse association of the intake of vegetables and legumes, fruits and dried fruits, as well as vitamin C with the NAFLD prevalence (p<0.05). In conclusion, a better diet quality as characterized by a higher DQI-I and a higher consumption of vegetables, legumes and fruits was associated with a reduced likelihood of having NAFLD in Hong Kong Chinese.
Background & Aims In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection ...in the general population. Methods We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy. Results One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2–33.3) in HBV patients and 2.1% (0–44.2) in controls ( p <0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval CI 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls ( p = 0.003). The fatty liver prevalence differed in HBV patients and controls aged 40–59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p = 0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p = 0.034), but the difference was mainly attributed to lower triglyceride levels. Among HBV patients, viral genotypes, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver. Conclusions HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies.
Correspondence to Professor Siew Chien Ng, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong 999077, Hong Kong; siewchienng@cuhk.edu.hk We recently published in ...Gut to show that gut dysbiosis persisted for at least 6 months in patients with post-acute COVID-19 syndrome (PACS).1 Murine and human studies have also reported microbial alterations associated with different PACS symptoms.2 3 With the pandemic entering its third year, PACS could potentially affect recovered individuals for over 1 year.4 It remains unknown whether PACS-associated gut dysbiosis would also linger for such a long time. A total of 155 patients with COVID-19 in Hong Kong were followed up for an average of 14 months after SARS-CoV-2 viral clearance, and 155 age-matched, sex-matched and body mass index-matched subjects without COVID-19 were recruited as controls. Consistent with the key microbial species identified thus far,1–3 the enrichment of potentially pathogenic bacteria including R. gnavus, Clostridium bolteae, Flavonifractor plautii and E. ramosum was associated with the majority of the PACS symptoms. ...effective elimination or inhibition of these bacteria via dietary intervention, microbiota modulation or drugs may also have significant implications for alleviating PACS.
ObjectiveTo present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction ...of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis.DesignTwenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto.ResultsAll 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection.ConclusionsA global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.
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