Use of Non-Invasive Parameters of Non-Alcoholic Steatohepatitis and Liver Fibrosis in Daily Practice - An Exploratory Case-Control Study

Background

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of a metabolic syndrome. To date, liver biopsy has been the gold standard used to differentiate between simple steatosis and steatohepatitis/fibrosis. Our aim was to compare the relevance of serum non-invasive parameters and scoring systems in the staging of liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with NAFLD.

Methods and Findings

A total of 112 consecutive patients diagnosed with NAFLD were included. A liver biopsy was performed on 56 patients. The Kleiner score was used for the staging and grading of the histology. Non-invasive parameters for fibrosis (hyaluronic acid; AST/ALT; fibrosis scoring indexes OELF, ELF, BARD score, APRI, NAFLD fibrosis score); and inflammation (M30 and M65 cytokeratin-18 fragments) were measured and calculated. The same analyses were performed in 56 patients diagnosed with NAFLD, who were not indicated for liver biopsy. Based on the liver histology, NASH was diagnosed in 38 patients; simple steatosis in 18 patients. A cut-off value of 750 U/L of serum M65 discriminated patients with and without NASH with a 80% sensitivity and 82% specificity (95% CI:57–95). Fibrosis stage F0–F2 was present in 39 patients; F3–F4 in 17 patients. Serum concentrations of hyaluronic acid were higher in patients with advanced fibrosis (p<0.01); a cut-off value of 25 µg/l discriminated patients with F3–F4 with a 90% sensitivity and 84% specificity from those with F0–F2 (95% CI:59–99). When applying the non-invasive criteria to those patients without a liver biopsy, NASH could only be diagnosed in 16%; however, advanced fibrosis could be diagnosed in 35% of them.

Conclusions

In patients with NAFLD, non-invasive serum parameters with a high accuracy can differentiate those patients with NASH and/or advanced fibrosis from those with simple steatosis. A substantial portion of those patients not indicated for liver biopsy might have undiagnosed advanced fibrosis.     

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review.Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger''s tests.A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82–17.03) and ovarian tumors (OR 7.83; 1.09–56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03–0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08–2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03–2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47–2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer.Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.     

Archaeobotany of the Old Prague Town defence system, Czech Republic: archaeology, macro-remains, pollen, and diatoms

The stone fortification of Prague Old Town was constructed shortly after A.D. 1230. Large-scale archaeological and archaeobotanical research has been carried out in this area in recent years. The deep moat and the drainage ditch have been excavated at several places in front of a line of former ramparts. During the initial period of their existence, the moat and the ditch contained only minimal waste. A sudden change in the management of these features occurred at the beginning of the 14th cent., when they started to be filled with large amounts of rubbish. This article concentrates on the evaluation of these rubbish strata at three profiles through the drainage ditch and one profile through the dry moat. The results of plant macro-remains (including wood), pollen, and diatom analyses clearly demonstrate the development of the local (aquatic) environment from being relatively clean to highly polluted. An actualistic (phytosociological) approach was adopted to reconstruct the local environment of the town periphery in detail, and to distinguish a variety of habitats that were situated in the economic hinterland of the city. Some species from the rich assemblages of plant remains are interpreted in terms of their use in High Medieval households. Diatom analysis completes the picture by providing the proxy data on water quality history in the drainage ditch. Received September 15, 2001 / Accepted May 21, 2002     

Flow Injection Fluorescence Microscopy: A Novel Tool for the Study of Cells through Controlled Perfusion

Current methods of microscope stage perfusion do not take full advantage of existing technology for precise fluid control. The concept of flow injection, used extensively by analytical chemists, is described and its application to the fluorescence microscopic study of cultured cells is proposed. Using this technique, cells may be exposed to single or multiple reagent zones of almost any profile, sequence, and duration, with computer-controlled precision. A flow injection system is employed in conjunction with a novel perfusion chamber—the fountain cell. The ability of the flow injection system to perfuse cells with a reagent with a reproducibility of 1% RSD is demonstrated. The system was used to monitor changes in calcium levels in baby hamster kidney cells loaded with FURA-2 as a result of stimulation with a precisely timed concentration of ionomycin. The unique feature of the technique is that it allows a series of responses of a given cell to be directly compared to each other.     

A Complex Model for Gene Effects taking into Account Selection and Crossing Over

A general model for gene effects including the influence of selection and crossing over is presented. It is shown, how gene frequencies of alleles in two loci system are changed in selected populations in the presence of crossing over. This is used for estimation of gene effects.