Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease

BACKGROUND: Liver biopsy is considered the gold standard for assessing histologic lesions of non-alcoholic fatty liver disease (NAFLD). The aim was to develop and validate a new biomarker of non alcoholic steato hepatitis (NASH) the NashTest (NT) in patients with NAFLD. METHODS: 160 patients with NAFLD were prospectively included in a training group, 97 were included in a multicenter validation group and 383 controls. Histological diagnoses used Kleiner et al's scoring system, with 3 classes for NASH: "Not NASH", "Borderline", "NASH"). The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV, NPV) were assessed. RESULTS: NT was developed using patented algorithms combining 13 parameters: age, sex, height, weight, and serum levels of triglycerides, cholesterol, alpha2macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase, transaminases ALT, AST, and total bilirubin. AUROCs of NT for the diagnosis of NASH in the training and validation groups were, respectively, 0.79 (95%CI 0.69–0.86) and 0.79 (95%CI 0.67–0.87; P = 0.94); for the diagnosis of borderline NASH they were: 0.69 (95%CI 0.60–0.77) and 0.69 (95%CI 0.57–0.78; P = 0.98) and for the diagnosis of no NASH, 0.77 (95%CI 0.68–0.84) and 0.83 (95%CI 0.67–0.90; P = 0.34). When the two groups were pooled together the NashTest Sp for NASH = 94% (PPV = 66%), and Se = 33% (NPV = 81%); for borderline NASH or NASH Sp = 50% (PPV = 74%) and Se = 88% (NPV = 72%). CONCLUSION: In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker reliably predicts the presence or absence of NASH

Broad-Spectrum Matrix Metalloproteinase Inhibition Curbs Inflammation and Liver Injury but Aggravates Experimental Liver Fibrosis in Mice

Background Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs). The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF)-α-converting enzyme (TACE). We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat) would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury.Methodology/Principal Findings Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4) administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-α receptors. Liver injury was quantified by alanine aminotransferase (ALT) levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-α receptors exhibited an 80% reduction of serum ALT, confirming the hepatoprotective effects of Marimastat via the TNF-signaling pathway.Conclusions/Significance Inhibition of MMP and TACE activity with Marimastat during chronic CCl4administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Since effective inhibition of MMPs accelerates fibrosis progression, MMP inhibitors should be used with caution in patients with chronic liver diseases

Demographic and clinicopathological characteristics of nonalcoholic fatty liver disease in the East-Southeastern Anatolia regions in Turkey

Objective: To identify the demographic and clinicopathological characteristics of patients diagnosed with nonalcoholic fatty liver disease (NAFLD) and the risk factors for fibrosis based on histopathological findings in East-Southeastern Anatolia regions in Turkey. Subjects and Methods: The study included a total of 93 patients diagnosed with NAFLD from 5 different centers. Histopathological findings were evaluated by dividing them into four categories using Matteoni classifications. Cases with fibrosis were further evaluated using Brunt classifications. Results: The patients with a nonalcoholic fatty liver were in the 3rd and 4th decade age groups. The mean age was 38 years, 76% of the patients were male, 85% were overweight, 37% were obese, 18% had type 2 diabetes mellitus, and 80.6% had hyperlipidemia. A multiple regression analysis showed that age, type 2 diabetes mellitus, and aspartate aminotransferase (AST) levels were linked with the severity of the disease. Of the 93 patients, 55 ( 59.1%) had fibrosis, of which 10.8% were classified as severe. The severity of fibrosis was significantly higher in obese patients. Conclusions: The risk factors for severity of NAFLD included advanced age, type 2 diabetes mellitus and serum AST level, while the risk factor for the severity of fibrosis was obesity. Copyright (C) 2006 S. Karger AG, Basel

Is ischemia-modified albumin a reliable tool for the assessment of acute pancreatitis?

Abdurrahman Sahin,1 Semra Turkoglu,2 Nurettin Tunc,1 Deccane Duzenci,3 Ozgen Arslan Solmaz,4 Ibrahim Halil Bahcecioglu,1 Mehmet Yalniz1 1Medicine Faculty, Department of Gastroenterology, Firat University, Elazig, Turkey; 2Department of Nutrition and Dietetics, Health Sciences Faculty, Firat University, Elazig, Turkey; 3Department of Internal Medicine, Elazig Education and Training Hospital, Elazig, Turkey; 4Department of Pathology, Elazig Education and Training Hospital, Elazig, Turkey Purpose: Oxidative stress has been implicated in several disorders, including acute pancreatitis (AP). Ischemia-modified albumin (IMA), which reflects the ability to bind cobalt, has been found to be elevated in conditions of oxidative stress and tissue hypoxia. This study examined IMA and adjusted IMA levels in patients with AP, and examined the associations of IMA and adjusted IMA levels to the severity of AP.Patients and methods: A total of 42 consecutive patients with AP and 43 age- and sex-matched control subjects were enrolled. Serum samples were obtained from patients with AP on admission as well as 48–72 hours after hospitalization, and from the controls, at the time of enrollment. Adjusted IMA was calculated by multiplying the IMA value of each patient with the ratio of the patient’s albumin value and the median albumin value of the study population. The severity of AP was assessed according to the modified Atlanta classification, and the patients were divided into 2 groups: mild AP and severe AP.Results: The serum IMA and adjusted IMA values of patients with AP on admission and those of the controls did not differ (p=0.86 and p=0.99, respectively). The second measurements of IMA and adjusted IMA in the AP group were higher than the first measurements of both the AP group and controls (for all, p<0.01). Among the IMA measurements, only adjusted IMA on admission had the ability to predict the severity of AP. Severe AP was correlated with albumin, and the area under the curve of adjusted IMA values on admission was 0.746 for differentiating patients with severe AP from mild AP with statistical significance (p=0.005).Conclusion: It was shown that IMA and adjusted IMA levels rise with the progression of AP. Lower levels of adjusted IMA predict the severity of AP. Further studies with serial measurements of IMA are warranted to explore the indicative role of IMA in the course of AP. Keywords: ischemia modified albumin, adjusted ischemia modified albumin, acute pancreatitis, severit

Hepatitis B virus genotype D prevails in patients with persistently elevated or normal ALT levels in Turkey

Background: The clinical relevance of hepatits B virus (HBV) genotypes are poorly understood and it is unclear if the prevalence of HBV genotypes differs with the various clinical features of HBV carriers. The aim of our study was to examine the prevalence of the HBV genotype in a group of patients with chronic hepatitis B, compared to a group with chronic inactive hepatits B surface antigen (HbsAg) carriers