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Objective 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. Methods 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. Results 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 87622 weeks, 30 (10.0%) patients with fatty liver and 18 (11.0%) patients without fatty liver reached the composite clinical end point (p¼0.79). Conclusions 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. INSET: Significance of this study. [ABSTRACT FROM AUTHOR]

Background Patients with non-alcoholic steatohepatitis (NASH) have increased mortality and liver-related complications. In contrast, simple steatosis is considered benign and non-progressive. Objective To investigate disease progression in patients with different degrees of non-alcoholic fatty liver disease (NAFLD) activity. Design Prospective longitudinal hospital-based cohort study. Patients Fifty-two patients (age 44±9 years) with biopsy-proven NAFLD had liver biopsies repeated at month 36. Results Among 13 patients with simple steatosis at baseline, 2 (15%) had a normal liver at month 36, 3 (23%) continued to have simple steatosis, 5 (39%) developed borderline NASH and 3 (23%) developed NASH. Among 22 patients with borderline NASH at baseline, 4 (18%) had simple steatosis and 13 (59%) had borderline NASH at month 36, while 5 (23%) developed NASH. Among 17 patients with NASH at baseline, 10 (59%) continued to have NASH and 6 (35%) had borderline NASH at month 36. Only 1 (6%) patient regressed to simple steatosis. Overall, 14 (27%) patients had fibrosis progression, 25 (48%) had static disease, and 13 (25%) had fibrosis regression. Reduction in body mass index and waist circumference was independently associated with non-progressive disease activity and fibrosis. The baseline serum levels and month 36 changes in adiponectin, tumour necrosis factor a, interleukin 6 and leptin were not associated with disease progression. Serum cytokeratin-18 fragment level reflected disease activity and its change correlated with the change in NAFLD activity score (R=0.51, p<0.001). Conclusions Patients with simple steatosis may still develop NASH and fibrosis progression. Weight reduction is associated with non-progressive disease. All patients with NAFLD should undergo periodic assessment and lifestyle modification. [ABSTRACT FROM AUTHOR]

The human cathelicidin LL-37, a pleiotropic host defense peptide, is down-regulated in gastric adenocarcinomas. We therefore investigated whether this peptide suppresses gastric cancer growth. LL-37 lowered gastric cancer cell proliferation and delayed G1-S transition in vitro and inhibits the growth of gastric cancer xenograft in vivo. In this connection, LL-37 increased the tumor-suppressing bone morphogenetic protein (BMP) signaling, manifested as an increase in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of p21Waf1/Cip1. The anti-mitogenic effect, Smad1/5 phosphorylation, and p21Waf1/Cip1 up-regulation induced by LL-37 were reversed by the knockdown of BMP receptor II. The activation of BMP signaling was paralleled by the inhibition of chymotrypsin-like and caspase-like activity of proteasome. In this regard, proteasome inhibitor MG-132 mimicked the effect of LL-37 by up-regulating BMP4 expression and Smad1/5 phosphorylation. Further analysis of clinical samples revealed that LL-37 and p21Waf1/Cip1 mRNA expressions were both down-regulated in gastric cancer tissues and their expressions were positively correlated. Collectively, we describe for the first time that LL-37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome-dependent mechanism. This unique biological activity may open up novel therapeutic avenue for the treatment of gastric cancer. J. Cell. Physiol. 223: 178–186, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Chronic hepatitis B patients with diabetes and metabolic syndrome are at increased risk of cirrhosis and hepatocellular carcinoma, but the underlying mechanism is unclear. Our objective was to test whether dysregulation of adipokines contributes to liver injury. We also studied whether viral factors affected adipokines, insulin resistance, and hepatic steatosis.METHODS:A prospective cohort of 266 chronic hepatitis B patients undergoing liver biopsy was studied. Fasting blood was taken for the analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, leptin, and resistin. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Factors associated with significant necroinflammation and cirrhosis were identified.RESULTS:Histological activity index was correlated with serum TNF-α (R=0.40, P<0.0001) and IL-6 (R=0.32, P<0.0001) but not with adiponectin, leptin, or resistin. By multivariate analysis, TNF-α was associated with significant necroinflammation after adjusting for age and viral factors (odds ratio (OR) 1.041, 95% confidence interval (CI) 1.002–1.082, P=0.04). Serum adiponectin had positive correlation with hepatitis B virus DNA (R=0.17, P=0.007) and was decreased in patients with insulin resistance and hepatic steatosis. On the other hand, viral load, hepatitis B e-antigen status, and genotypes had no association with insulin resistance, hepatic steatosis, and the levels of TNF-α and IL-6. A total of 68 (25.6%) patients had cirrhosis. HOMA-IR, but not adipokine dysregulation, was independently associated with cirrhosis (OR 1.09, 95% CI 1.02–1.15, P=0.006).CONCLUSIONS:TNF-α and/or IL-6 contribute to hepatic necroinflammation in chronic hepatitis B patients. Adiponectin protects against insulin resistance and hepatic steatosis but does not affect liver injury. Adipokines and viral factors contribute to liver injury independently. [ABSTRACT FROM AUTHOR]

Background and Aim: Hypoadiponectinemia and high tumor necrosis factor-alpha (TNF-α) levels are associated with the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the genetic polymorphisms of adiponectin and TNF-α in Chinese NAFLD patients and their association with disease severity. Methods: Seventy-nine patients with histology-proven NAFLD (61 with simple steatosis and 18 with stage 2–4 fibrosis) and 40 controls were tested for the nucleotide polymorphisms at adiponectin −11 391, −11 377, +45, and +276 and TNF-α promoters −863, −308, and −238. Results: There was no significant deviation in the adiponectin and TNF-α gene polymorphisms between NAFLD patients and controls, or between patients with simple steatosis and those with stage 2–4 fibrosis. NAFLD patients with −11377G and +45G at the adiponectin gene were more likely to have hypertriglyceridemia. On multivariate analysis, older age, higher body mass index, and higher fasting glucose were independent factors associated with stage 2–4 fibrosis in NAFLD patients. Conclusions: Adiponectin and TNF-α gene polymorphisms were not shown to be associated with NAFLD or significant fibrosis in Chinese people. The adiponectin −11377G and +45G alleles were associated with hypertriglyceridemia in NAFLD patients. Since the current study is not adequately powered to detect smaller differences in allele frequencies, larger-sized studies in different ethnic groups are required. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Though extensive research has been performed on primary biliary cirrhosis (PBC) in Caucasian patients, little is known about the disease in the Asian population. PATIENTS AND METHODS: This was a retrospective study of Chinese patients with biopsy-proven PBC. Electronic records of results from all liver biopsies (n = 1,021) performed between January 1996 and April 2004, together with records of patients labeled as “biliary cirrhosis,” were retrieved. Patients with biopsy-proven PBC were identified, and their medical notes were reviewed. The demographic, clinical, biochemical, and histological parameters of these patients were analyzed for mortality predictors. RESULTS: Thirty-nine patients with biopsy-proven PBC and a median follow-up of 44 (range: 5–114) months were identified. Twelve patients (30.8%) were asymptomatic at diagnosis. The patients were approximately equally divided into one-thirds at stages I, II, and III of the histological disease. Hepatic decompensation or hepatocellular carcinoma developed in 14 (35.9%) patients during the follow-up period. The overall 5-yr survival probability was 81.4%. Hypoalbuminemia was found to be the only independent predictor of mortality on multivariate analysis (hazard ratio = 0.50 per 1 g/L increase, 95% CI 0.30–0.84, p= 0.008). Using the median serum albumin level as the cutoff, the 5-yr survival probability was significantly higher for patients with serum albumin levels >35 g/L than for those with serum albumin levels ≤35 g/L (100% vs 69%, p= 0.007). No significant difference was found when baseline serum albumin was compared with the Mayo Risk Score and the model for end-stage liver disease (MELD) score for prediction of patient survival ( p= 0.68) and death ( p= 0.12) at 5 yr. CONCLUSIONS: In this longitudinal cohort study of biopsy-proven PBC with up to 9 yr of follow-up, we found that Chinese patients with PBC had significant morbidity and mortality. Hypoalbuminemia at presentation was an independent and strong predictor of mortality. [ABSTRACT FROM AUTHOR]

Chan HL-Y, Chui AK-K, Lau W-Y, Chan FK-L, Yui AY, Rao ARN, Wong J, Lai EC-H, Sung JJ-Y. Outcome of lamivudine resistant hepatitis B virus mutant post-liver transplantation on lamivudine monoprophylaxis. Clin Transplant 2004: 18: 295–300. © Blackwell Munksgaard, 2004 We aimed to investigate the clinical outcome of patients who develop lamivudine resistant hepatitis B virus mutants (YMDD mutants) after liver transplantation. Patients who received liver transplantation for hepatitis B-related liver diseases from 1999 to 2002 were studied. All patients received lamivudine monotherapy before and after liver transplantation. HBsAg and HBV DNA were regularly monitored, and YMDD mutation was detected by direct sequencing. Twenty patients were followed up for median 94 wk (range: 15–177 wk) post-liver transplantation. Six patients developed YMDD mutants, and the cumulative probability of developing YMDD mutations post-liver transplantation was 21% in 1 yr and 34% in 2 yr. One patient developed YMDD mutants before liver transplantation and died of hepatitis reactivation and liver failure 15 wk post-transplantation. The other five patients developed YMDD mutants 32–72 wk after liver transplantation. Two of them developed severe hepatitis which responded promptly to adefovir dipivoxil. The remaining three patients with YMDD mutants had minimal to mild hepatitis. The cumulative survival for patients with YMDD mutants was 83% and 28% at 1 and 2 yr, respectively. Only one patient who did not develop YMDD mutants died at week 119 due to chronic rejection. The post-transplant survival for patients with YMDD mutants was significantly poorer than those without YMDD mutants (log rank test p = 0.083). The emergence of YMDD mutants after liver transplantation on lamivudine monoprophylaxis had wide range of clinical presentations and was associated with increased mortality. [ABSTRACT FROM AUTHOR]

OBJECTIVES: HBeAg-negative patients constitute approximately 70% of all chronic hepatitis B virus (HBV) infections in Southeast Asia, and some of these patients continue to suffer from active disease. We aimed to study the risk of hepatitis relapse in chronic HBV-infected patients with negative HBeAg and the predictor(s) of relapses. METHODS: This was a retrospective analysis of patients carrying HBsAg but lacking HBeAg. Patients recruited were required to have been followed for ≥12 months with a minimum of three blood samples available for analysis. Patient demographic data, liver biochemistry, and HBV serology were analyzed in relation to relapses of hepatitis. Relapse was defined as an abrupt elevation of ALT >200 IU/L or >3-fold previous levels, whichever was higher. RESULTS: In a period of 3 months, 317 patients seen at the Hepatitis Clinic at the Prince of Wales Hospital in Hong Kong were recruited. The median duration of follow-up was 34 months. On initial consultation. 111 (35.0%) patients had elevated ALT (>60 IU/L). Overall, 57 (18.0%) patients developed at least one relapse, including 37 (33.3%) patients with elevated ALT and 20 (9.7%) patients with normal ALT at the first visit. Multiple logistic regression analysis showed that elevated ALT level at first presentation (odds ratio 4.17, 95% confidence interval 2.24-7.75) and male gender (odds ratio 2.83, 95% confidence interval 1.23-6.49) were the two independent factors associated with a higher risk of hepatitis relapse. The sensitivity, specificity, and positive and negative predictive values of a single ALT test for hepatitis relapse were 64.9%, 71.5%, 33.3%, and 90.3%, respectively. CONCLUSIONS: HBeAg-negative HBV carriers with normal ALT levels have a low risk of hepatitis relapse. [ABSTRACT FROM AUTHOR]

Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects. [ABSTRACT FROM AUTHOR]

Recent 16S ribosomal RNA gene (rRNA) molecular profiling of the stomach mucosa revealed a surprising complexity of microbiota. Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID) use are two main contributors to gastritis and peptic ulcer. However, little is known about the association between other members of the stomach microbiota and gastric diseases. In this study, cloning and sequencing of the 16S rRNA was used to profile the stomach microbiota from normal and gastritis patients. One hundred and thirty three phylotypes from eight bacterial phyla were identified. The stomach microbiota was found to be closely adhered to the mucosa. Eleven Streptococcus phylotypes were successfully cultivated from the biopsies. One to two genera represented a majority of clones within any of the identified phyla. We further developed two real-time quantitative PCR assays to quantify the relative abundance of the Firmicutes phylum and the Streptococcus genus. Significantly higher abundance of the Firmicutes phylum and the Streptococcus genus within the Firmicutes phylum was observed in patients with antral gastritis, compared with normal controls. This study suggests that the genus taxon level can largely represent much higher taxa such as the phylum. The clinical relevance and the mechanism underlying the altered microbiota composition in gastritis require further functional studies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Covariation of Major and Minor Viral Capsid Proteins in Norovirus Genogroup II Genotype 4 Strains," by Martin Chi-Wai Chan and colleagues is presented.