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Vincent Wai-Sun Wong,
Ruth Suk-Mei Chan,
Grace Lai-Hung Wong,
Bernice Ho-Ki Cheung,
Winnie Chiu-Wing Chu,
David Ka-Wai Yeung,
Angel Mei-Ling Chim,
Jennifer Wing-Yan Lai,
Liz Sin Li,
Mandy Man-Mei Sea, Francis Ka-Leung Chan,
Joseph Jao-Yiu Sung,
Jean Woo,
Henry Lik-Yuen Chan
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ABSTRACT: BACKGROUND & AIMS: Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the efficacy of a community-based lifestyle modification programme in the remission of NAFLD. METHODS: This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy. RESULTS: 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; P<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (P<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (P<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome. CONCLUSION: The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients.
Journal of Hepatology 04/2013; · 9.26 Impact Factor
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ABSTRACT: BACKGROUND: Gastric intestinal metaplasia (IM) is considered precancerous and is difficult to differentiate upon endoscopy. Endocytoscopy enables observation at a cellular level for focused biopsy. The present study examined the use of endocytoscopy for recognition of gastric IM. PATIENTS AND METHODS: Patients with a history of gastric IM were recruited. We first carried out narrow band imaging (NBI) endoscopy to look for suspicious areas of gastric IM. A prototype endocytoscope with a magnification of 450× was used to re-examine these areas. Areas examined were biopsied for histological comparison. Presence of goblet cells was considered as representative of IM upon endocytoscopy. RESULTS: Twenty patients were recruited with NBI demonstrating 102 suspicious lesions of gastric IM. Mean age of patients was 53.9 ± 7.6 years. Upon histology, 72 biopsies were confirmed as gastric IM, 15 showed IM and low-grade dysplasia, whereas 15were diagnosed as chronic gastritis. Endocytoscopy image quality was significantly better for areas of IM as compared to gastritis (P < 0.05; OR 21.7 [95% CI 4.5-105.9]). The presence of goblet cells upon endocytoscopy achieved a diagnostic accuracy of 0.86 for gastric IM. Receiver operator characteristics curve achieved an area under curve of 0.8 with the presence of goblet cells under endocytoscopy as compared to 0.64 for NBI alone. CONCLUSIONS: Presence of goblet cells upon endocytoscopy indicates a diagnosis of gastric IM. Image quality of endocytoscopy, however, is suboptimal. Further developments in endocytoscopy should focus on image quality and staining methods to enhance differentiation between IM, dysplasia and early gastric cancer.
Digestive Endoscopy 03/2013; · 1.19 Impact Factor
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Gastroenterology 03/2013; · 11.68 Impact Factor
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Gastroenterology 11/2012; · 11.68 Impact Factor
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ABSTRACT: BACKGROUND & AIMS: Limited endoscopic sphincterotomy with large balloon dilation (ESBD) is an alternative to ES for removing bile duct stones, but it is not clear which procedure is most effective. We compared the 2 techniques in removal of bile duct stones. METHODS: Between September 2005 and 2011, 156 consecutive patients with suspected of having, or known to have, common bile duct stones were randomly assigned to groups that underwent ES or ESBD. Patients in the ESBD group received limited sphincterotomy (up to half of the sphincter), followed by balloon dilation to the size of the common bile duct or 15 mm. The ES group received complete sphincterotomy alone. Stones were then removed with standard techniques. The primary outcome was percentage of stones cleared; secondary outcomes included procedure time, method of stone extraction, number of procedures required for stone clearance, morbidities and mortality within 30 days, and direct costs. RESULTS: There was no significant difference between groups in percentages of stones cleared (ES vs ESBD: 88.5% vs 89.0%). More patients in the ES group (46.2%) than the ESBD group (28.8%) required mechanical lithotripsy (P=.028), particularly for stones ≥ 15 mm (90.9% vs 58.1%; P=.002). Morbidities developed in 10.3% in the ES group and 6.8% in the ESBD group (P=.46). The cost of the hospitalization was also significantly lower in the ESBD group (P=.034) CONCLUSIONS: ESBD and ES clear bile stones with equal efficacy. However, ESBD reduces the need for mechanical lithotripsy and is less expensive.
Gastroenterology 10/2012; · 11.68 Impact Factor
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Philip Wai Yan Chiu,
Justin Che Yuen Wu,
Anthony Yuen Bun Teoh,
Yawen Chan,
Simon Kin Hung Wong,
Shirley Yuk Wah Liu,
Man Yee Yung,
Candice C H Lam,
Joseph Jao Yiu Sung, Francis Ka Leung Chan,
James Yun Wong Lau,
Enders Kwok Wai Ng
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ABSTRACT: BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. OBJECTIVE: This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. DESIGN: Preclinical animal study and prospective clinical study. PATIENTS: Consecutive patients diagnosed with achalasia with high-resolution manometry. INTERVENTIONS: POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. MAIN OUTCOME MEASUREMENTS: Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. RESULTS: Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. LIMITATION: Small sample size. CONCLUSIONS: POEM is a feasible, safe, and effective treatment for achalasia. (Clinical trial registration number: NCT01525732.).
Gastrointestinal endoscopy 10/2012; · 6.71 Impact Factor
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ABSTRACT: BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological nonalcoholic fatty liver disease (NAFLD) activity score. METHODS: This was a placebo-controlled parallel-group double-blind randomized controlled trial. Patients with histology-proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile. RESULTS: We enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was -0.8±1.4 in the Phyllanthus group and -0.3±1.3 in the placebo group (P=0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (-0.2±0.7; P=0.039) and ballooning grades (-0.4±0.5; P<0.001), the change was small and of limited clinical significance. Furthermore, there was no significant difference in the changes in alanine aminotransferase, aspartate aminotransferase, fasting glucose and lipid profile between the two groups. CONCLUSIONS: Phyllanthus is not superior to placebo in improving NAFLD activity score in NASH patients.
Journal of Gastroenterology and Hepatology 10/2012; · 2.87 Impact Factor
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Gastroenterology 08/2012; 143(4):1114-5. · 11.68 Impact Factor
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ABSTRACT: We performed a prospective cohort study to investigate the effects of gastroprotective agents (such as proton pump inhibitors or histamine-2 receptor antagonists) on long-term clinical outcomes of patients with Helicobacter pylori-negative idiopathic bleeding ulcers.
Patients with H pylori-negative idiopathic bleeding ulcers were recruited from a single center from April 2002 to March 2009 (n = 663). Age- and sex-matched patients with H pylori-positive bleeding ulcers were used as controls (n = 633). After ulcers had healed, 566 patients in the H pylori-negative idiopathic ulcer cohort received gastroprotective agents at clinicians' discretion, whereas controls received no gastroprotective agent after H pylori eradication therapy. Patients were followed until September 2011 for end points that included recurrent ulcer bleeding and all-cause mortality.
During the exposed period of 534 person-years, the incidence rates of recurrent ulcer bleeding and death were 3.8 (95% confidence interval [CI], 2.6-5.4) and 21.8 (95% CI, 18.8-25.3) per 100 person-years among the patients given gastroprotective agents, compared with incidence rates of 2.4 (95% CI, 1.6-3.5; P = .08) and 13.8 (95% CI, 11.9-16.0; P < .001) per 100 person-years, respectively, during the unexposed period of 1588 person-years. Use of gastroprotective agents was not associated with mortality, after adjusting for confounders (hazard ratio, 1.1; 95% CI, 0.6-1.7). Incident rates of recurrent ulcer bleeding and death were significantly higher in patients with H pylori-negative idiopathic ulcers (2.9 and 17.0 per 100 person-years, respectively) than in controls (1.1 and 5.9 per 100 person-years, respectively; P < .001).
Gastroprotective agents do not reduce the risk of recurrent bleeding or mortality for patients with H pylori-negative idiopathic bleeding ulcers.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2012; 10(10):1124-9. · 5.64 Impact Factor
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ABSTRACT: INTRODUCTION: This study aims to compare perioperative outcomes and oncological clearance of endoscopic submucosal dissection (ESD) versus gastrectomy for treatment of early gastric cancer (EGC). METHODS: This is a retrospective cohort study including all cases of EGC or severe dysplasia treated at a university-affiliated hospital from 1993 to 2010. Preoperative endoscopic ultrasound and image-enhanced endoscopy were employed to determine depth of invasion. Clinical outcomes including baseline demographics, pathology, postoperative complication, and hospital stay, as well as 3-year survival were compared. RESULTS: From 1993 to 2010, 114 patients with severe dysplasia or EGC were treated: 40 of them received gastrectomy, while 74 received ESD. There was no difference in age, gender, comorbidity or American Society of Anesthesiologists grade between the two groups. Of patients in the gastrectomy group, 92.5 % presented with symptoms as compared with 27.0 % of those treated by ESD (p < 0.001). More patients in the ESD group had atrophic gastritis (31.1 vs 10 %; p = 0.009) and intestinal metaplasia (68.9 vs 55.0 %; p = 0.04). Patients treated by gastrectomy sustained longer operative time [265 (150-360) min] when compared with ESD [89.6 (45-360) min; p < 0.001]. They also had longer median hospital stay [9.9 (6-26) days vs 3.0 (2-10) days; p < 0.001]. There was no perioperative mortality, but the overall complication rate was significantly higher in the gastrectomy group. The 3-year survival rate was 94.6 % for ESD and 89.7 % for gastrectomy group (log-rank test, p = 0.44). CONCLUSIONS: ESD achieved similar oncological outcomes when compared with radical gastrectomy for treatment of EGC. Patients receiving ESD had better perioperative outcomes in terms of operative time, complication rate, and hospital stay.
Surgical Endoscopy 06/2012; · 4.01 Impact Factor
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Gastroenterology 05/2012; 143(1):264-5. · 11.68 Impact Factor
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Vincent Wai-Sun Wong,
Grace Lai-Hung Wong,
Winnie Chiu-Wing Chu,
Angel Mei-Ling Chim,
Arlinking Ong,
David Ka-Wai Yeung,
Karen Kar-Lum Yiu,
Shirley Ho-Ting Chu,
Hoi-Yun Chan,
Jean Woo, Francis Ka-Leung Chan,
Henry Lik-Yuen Chan
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ABSTRACT: 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.
We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy.
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.
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.
Journal of Hepatology 03/2012; 56(3):533-40. · 9.26 Impact Factor
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Jiayun Shen,
Henry Lik-Yuen Chan,
Grace Lai-Hung Wong,
Paul Cheung-Lung Choi,
Anthony Wing-Hung Chan,
Hoi-Yun Chan,
Angel Mei-Ling Chim,
David Ka-Wai Yeung, Francis Ka-Leung Chan,
Jean Woo,
Jun Yu,
Winnie Chiu-Wing Chu,
Vincent Wai-Sun Wong
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ABSTRACT: The diagnosis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is limited by the need for liver biopsy. We aimed at testing the accuracy of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) for the diagnosis of NAFLD and NASH.
146 patients with biopsy-proven NAFLD and 74 age- and gender-matched healthy controls were included. Serum CK-18, AFABP and FGF21 levels were determined by enzyme-linked immunosorbent assay.
Serum CK-18, AFABP, and FGF21 increased in a stepwise fashion in control subjects (median 103 U/L, 15.4 ng/ml, and 104 pg/ml), patients with non-NASH NAFLD (263 U/L, 18.9 ng/ml, and 249 pg/ml) and NASH (418 U/L, 19.4 ng/ml, and 354 pg/ml) (p<0.001, 0.060, and 0.016, respectively). The area under receiver-operating characteristics curve to diagnose NAFLD and NASH was 0.91 and 0.70 for CK-18, 0.66 and 0.59 for AFABP, and 0.84 and 0.62 for FGF21. At cut-offs of 203 and 670 U/L, CK-18 had 71% negative predictive value (NPV) and 77% positive predictive value (PPV) to exclude and diagnose NASH. A 2-step approach measuring CK-18 followed by FGF21 further improved the NPV to 74% and PPV to 82%. In a validation cohort of 51 patients with paired liver biopsies, the NPV and PPV of the 2-step approach were 67% and 78%, respectively.
CK-18 is the most accurate biomarker for NAFLD and NASH. A two-step approach using CK-18 and FGF21 further improves the accuracy in diagnosing NASH.
Journal of Hepatology 02/2012; 56(6):1363-70. · 9.26 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVES: Gastric MALToma is difficult to recognize upon endoscopy. The aim of this study is to evaluate the application of microstructural and microvascular patterns in recognizing gastric MALToma on magnifying endoscopy. METHOD: All patients with diagnosis of gastric MALToma upon histology were recruited. They received magnifying endoscopy to observe for changes in microstructural and microvascular patterns. For patients with H pylori, eradication therapy would be given. For those without, appropriate treatments including gastrectomy or chemotherapy were commenced accordingly. Patients treated with H pylori eradication and non-operative treatments received follow-up magnifying endoscopy, and the same features were observed to predict the response to these treatments. RESULTS: From 2004 to 2007, nine patients presented to with epigastric pain, dyspepsia and belching. All patients were confirmed to have MALToma upon initial biopsy. Five patients had H pylori infection and received eradication. Two patients without H pylori were treated with Laparoscopic total gastrectomy. Two patients had pulmonary metastasis and treated with chemotherapy. Under magnifying endoscopy, all the lesions demonstrated either absence or irregular gastric pits. Moreover, there was consistently appearance of spider-shaped vascular pattern. Five patients with H pylori eradication had follow-up magnifying endoscopy, four of them showed resolution of abnormal vascular pattern and recovery of gastric pits. CONCLUSION: Abnormal spider like vasculature and disappearance of gastric pits are diagnostic features upon magnifying endoscopy for gastric MALToma. These features enhanced the diagnosis and assessment of extent of involvement during primary endoscopy, as well as follow-up surveillance for response to non-operative treatments.
Journal of interventional gastroenterology. 01/2012; 2(1):3-7.
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ABSTRACT: Complete colonoscopy examination cannot be performed in as many as 10% of cases. The new 9.2-mm ultrathin colonoscope (UTC) with an extra bending section may improve procedure tolerance and allow improvement in colonoscopy completion rate compared with a 12.9-mm standard colonoscope (SC).
To compare the performance of the 9.2-mm UTC with that of the 12.9-mm SC.
Prospective, randomized, controlled trial.
Academic endoscopic unit.
Subjects 18 years and older undergoing their first colonoscopy.
Subjects were randomized to either the UTC or SC group.
First and rescue successful cecal intubation rates, subject satisfaction scores, and sedation requirements were compared.
A total of 1121 patients (56% women, mean age 53.6 years) were randomized to the UTC group (n = 551) or the SC group (n = 570). There was no statistically significant difference in the first successful cecal intubation rate between the UTC and SC groups (98.9% vs 97.4%, P = .057). The mean (standard deviation) dose of midazolam and pethidine used was significantly lower in the UTC group (2.65 [0.65] mg vs 2.82 [0.85] mg, P < .001 and 27.6 [7.4] mg vs 29.7 [9.6] mg, P < .001, respectively). The mean (standard deviation) patient satisfaction score was similar between groups (6.99 [2.89] vs 7.04 [3.06], P = .762). Of the 21 patients (1.9%) with an incomplete initial colonoscopy (6 in the UTC group and 15 in the SC group), all 6 in the UTC group had their procedure completed with an SC. Eleven of 15 patients in the SC group had their procedures completed with a UTC in the same session.
Low failure rate may mask any difference between the 2 colonoscopes as a rescue instrument.
The 9.2-mm UTC has performance characteristics similar to those of an SC in Chinese subjects undergoing their first colonoscopy performed by experienced and trainee endoscopists. (Clinical trial registration number: NCT01142167.).
Gastrointestinal endoscopy 09/2011; 75(3):484-90. · 6.71 Impact Factor
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Vincent Wai-Sun Wong,
Winnie Chiu-Wing Chu,
Grace Lai-Hung Wong,
Ruth Suk-Mei Chan,
Angel Mei-Ling Chim,
Arlinking Ong,
David Ka-Wai Yeung,
Karen Kar-Lum Yiu,
Shirley Ho-Ting Chu,
Jean Woo, Francis Ka-Leung Chan,
Henry Lik-Yuen Chan
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ABSTRACT: Knowledge 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.
Subjects 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.
Overall, 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).
NAFLD 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 08/2011; 61(3):409-15. · 10.11 Impact Factor
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Vincent Wai-Sun Wong,
Grace Lai-Hung Wong,
Gabriel Wai-Kwok Yip,
Angeline Oi-Shan Lo,
Jenny Limquiaco,
Winnie Chiu-Wing Chu,
Angel Mei-Ling Chim,
Cheuk-Man Yu,
Jun Yu, Francis Ka-Leung Chan,
Joseph Jao-Yiu Sung,
Henry Lik-Yuen Chan
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is associated with cardiovascular risk. The aim of this study was to determine the role of fatty liver in predicting coronary artery disease and clinical outcomes in patients undergoing coronary angiogram.
This was a prospective cohort study carried out in a University hospital. Consecutive patients who underwent coronary angiogram had ultrasound screening for fatty liver. Significant cardiovascular disease was defined as ≥50% stenosis in at least one coronary artery. The primary outcome was a composite end point comprising cardiovascular deaths, non-fatal myocardial infarction and the need for further coronary intervention during prospective follow-up.
Among 612 recruited patients, 356 (58.2%) had fatty liver by ultrasonography, 318 (52.0%) had elevated serum alanine aminotransferase and 465 (76.0%) had significant coronary artery disease. Coronary artery disease occurred in 84.6% of patients with fatty liver and 64.1% of those without fatty liver (p<0.001). After adjusting for demographic and metabolic factors, fatty liver (adjusted OR 2.31; 95% CI 1.46 to 3.64) and alanine aminotransferase level (adjusted OR 1.01; 95% CI 1.00 to 1.02) remained independently associated with coronary artery disease. At a mean follow-up of 87±22 weeks, 30 (10.0%) patients with fatty liver and 18 (11.0%) patients without fatty liver reached the composite clinical end point (p=0.79).
In patients with clinical indications for coronary angiogram, fatty liver is associated with coronary artery disease independently of other metabolic factors. However, fatty liver cannot predict cardiovascular mortality and morbidity in patients with established coronary artery disease.
Gut 05/2011; 60(12):1721-7. · 10.11 Impact Factor
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ABSTRACT: Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G(0)/G(1)-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D(3) and p21(Waf1), which stabilizes cyclin D/cdk4 complex for G(1)-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.
Experimental Cell Research 03/2011; 317(10):1353-8. · 3.58 Impact Factor
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Vincent Wai-Sun Wong,
Grace Lai-Hung Wong,
Steven Woon-Choy Tsang,
Tina Fan,
Winnie Chiu-Wing Chu,
Jean Woo,
Anthony Wing-Hung Chan,
Paul Cheung-Lung Choi,
Angel Mei-Ling Chim,
James Yun-Wong Lau, Francis Ka-Leung Chan,
Joseph Jao-Yiu Sung,
Henry Lik-Yuen Chan
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) affects 20-40% of the general adult population. Due to shared risk factors, it is postulated that NAFLD patients have an increased risk of colorectal neoplasm and should be a target group for screening. The aim of this study was to examine the prevalence of colorectal neoplasm in NAFLD patients and the risk of colorectal neoplasm in relation to the severity of NAFLD histology. Design Cross-sectional study.
University hospital with case recruitment from the community and clinics.
Subjects aged 40-70 years were recruited for colonoscopic screening from two study cohorts: (1) community subjects; and (2) consecutive patients with biopsy proven NAFLD. In the community cohort, hepatic fat was measured by proton-magnetic resonance spectroscopy.
Prevalence of colorectal adenomas. Advanced colorectal neoplasm was defined as cancer or adenomas with villous architecture or high grade dysplasia.
NAFLD patients (N=199) had a higher prevalence of colorectal adenomas (34.7% vs 21.5%; p=0.043) and advanced neoplasms (18.6% vs 5.5%; p=0.002) than healthy controls (N=181). Thirteen of 29 (45%) NAFLD patients with advanced neoplasms had isolated lesions in the right sided colon. Among patients with biopsy proven NAFLD, patients with non-alcoholic steatohepatitis (N=49) had a higher prevalence of adenomas (51.0% vs 25.6%; p=0.005) and advanced neoplasms (34.7% vs 14.0%; p=0.011) than those with simple steatosis (N=86). After adjusting for demographic and metabolic factors, non-alcoholic steatohepatitis remained associated with adenomas (adjusted OR 4.89, 95% CI 2.04 to 11.70) and advanced neoplasms (OR 5.34, 95% CI 1.92 to 14.84). In contrast, the prevalence of adenomas and advanced neoplasms was similar between patients with simple steatosis and control subjects.
Non-alcoholic steatohepatitis is associated with a high prevalence of colorectal adenomas and advanced neoplasms. The adenomas are found more commonly in the right sided colon. Colorectal cancer screening is strongly indicated in this high risk group.
Gut 02/2011; 60(6):829-36. · 10.11 Impact Factor
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ABSTRACT: The performance of liver stiffness measurement (LSM) to monitor the changes in the severity of liver fibrosis in chronic hepatitis B (CHB) patients on antiviral treatment is uncertain.
We prospectively studied CHB patients undergoing paired liver biopsy and transient elastography before and at week 48 of antiviral treatment. Based on our previously reported LSM algorithm, advanced liver fibrosis (F3-4) could be excluded or confirmed at >90% confidence.
A total of 71 CHB patients were studied. The median alanine aminotransferase (ALT) level decreased from 99I U/l to 33I U/l, and the median LSM decreased from 8.8 kPa to 6.6 kPa, respectively, from baseline to week 48. Overall, 17 and 11 patients had regression and progression of histological fibrosis, respectively. Areas under the receiver operating characteristics curves of the LSM algorithm at baseline and week 48 for advanced fibrosis were 0.80 (95% confidence interval [CI] 0.69-0.90) and 0.78 (95% CI 0.64-0.92), respectively. The sensitivity of LSM algorithm to exclude advanced fibrosis was 100% at baseline and 75% at week 48. The specificity of the LSM algorithm to diagnose advanced fibrosis was 84% at baseline and 91% at week 48. Overall, 11/28 (39%) patients with LSM that decreased by >30%, 28/41 (68%) of patients with LSM that changed within 30% and 1/2 (50%) patients with LSM that increased by >30% had decreased, unchanged and increased histological fibrosis stages, respectively.
LSM could predict advanced fibrosis during antiviral therapy according to the ALT-based algorithm. Decrease in absolute LSM value, which could be related to ALT normalization, was unreliable to indicate regression of liver fibrosis.
Antiviral therapy 01/2011; 16(2):165-72. · 3.16 Impact Factor
