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Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease
IntroductionIt is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD.MethodsPrevious and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced.ResultsAmong 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3–60) g over an average of 18 years. Modest consumption (1–70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14–0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a binge-type fashion. Exclusive wine drinkers but not exclusive beer drinkers, had lower mean fibrosis stage and lower odds of advanced fibrosis (OR 0.20, 95% CI 0.06–0.69, p = 0.01), compared to lifetime abstinent subjects. No interaction between gender and alcohol quantity, type, or binge consumption on fibrosis was observed.DiscussionModest (1–70 g per week) alcohol consumption, particularly wine in a non-binge pattern, is associated with lower fibrosis in patients with NAFLD. Prospective longitudinal studies into fibrosis progression, cardiovascular outcomes, and mortality are required before clinical recommendations can be made.
Journal Article
Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles
Extracellular vesicles are encapsulated lipid nanoparticles secreted by a variety of cell types in living organisms. They are known to carry proteins, metabolites, nucleic acids, and lipids as their cargoes and are important mediators of intercellular communication. The role of extracellular vesicles in chronic liver disease has been reported. Chronic liver disease such as viral hepatitis accounts for a significant mortality and morbidity burden worldwide. Hepatic fibrosis has been commonly associated with the chronic form of viral hepatitis, which results in end-stage liver disease, including cirrhosis, liver failure, and carcinoma in some patients. In this review, we discuss the potential role of extracellular vesicles in mediating communication between infectious agents (hepatitis B and C viruses) and host cells, and how these complex cell-cell interactions may facilitate the development of chronic liver disease. We will further discuss how understanding their biological mechanism of action might be beneficial for developing therapeutic strategies to treat chronic liver disease.
Journal Article
Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease
BackgroundNon-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD.MethodsNAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3–4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs.ResultsIn 271 NAFLD patients, 83 (31%) had F3–4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all).ConclusionsHepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.
Journal Article
Hepascore: An Accurate Validated Predictor of Liver Fibrosis in Chronic Hepatitis C Infection
Background: Staging hepatic fibrosis by liver biopsy guides prognosis and treatment of hepatitis C, but is invasive and expensive. We sought to create an algorithm of serum markers that accurately and reliably predict liver fibrosis stage among hepatitis C patients. Methods: Ten biochemical markers were measured at time of liver biopsy in 117 untreated hepatitis C patients (training set). Multivariate logistic regression and ROC curve analyses were used to create a predictive model for significant fibrosis (METAVIR F2, F3, and F4), advanced fibrosis (F3 and F4), and cirrhosis (F4). The model was validated in 104 patients from other institutions. Results: A model (Hepascore) of bilirubin, γ-glutamyltransferase, hyaluronic acid, α2-macroglobulin, age, and sex produced areas under the ROC curves (AUCs) of 0.85, 0.96, and 0.94 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. In the training set, a score ≥0.5 (range, 0.0–1.0) was 92% specific and 67% sensitive for significant fibrosis, a score <0.5 was 81% specific and 95% sensitive for advanced fibrosis, and a score <0.84 was 84% specific and 71% sensitive for cirrhosis. Among the validation set, the AUC for significant fibrosis, advanced fibrosis, and cirrhosis were 0.82, 0.90, and 0.89, respectively. A score ≥0.5 provided a specificity and sensitivity of 89% and 63% for significant fibrosis, whereas scores <0.5 had 74% specificity and 88% sensitivity for advanced fibrosis. Conclusions: A model of 4 serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among hepatitis C patients.
Journal Article