https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20701

Design and validation of a histological scoring system for nonalcoholic fatty liver disease

Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis

Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

Nonalcoholic fatty liver disease.

SUMMARY Background Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. Aim To review epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. Methods An in-depth search of PubMed (1980–2010) was based on five search terms: ‘nonalcoholic fatty liver disease’ OR ‘non-alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2011.04724.x

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1053/jhep.2003.50161

Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome

https://www.gastrojournal.org/article/S0016-5085(00)70364-7/pdf

Liver fibrosis in overweight patients.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510270505

Factors associated with serum alanine transaminase activity in healthy subjects: Consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C

Sensitive and accurate measurement of hepatic iron concentration (HIC) is required to investigate liver fibrogenesis (1) and its influence on the outcome of interferon therapy for chronic viral hepatitis C (2)(3). Hepatic iron content can be measured by a quantitative chemical method and/or evaluated by semiquantitative histologic scoring. Quantitative chemical methods assess all liver iron forms, whereas histologic scoring evaluates only the hemosiderin form. A colorimetric method using bathophenanthroline sulfonate as chromogen was recommended in 1978 by the International Committee for Standardization in Hematology (ICSH) for determination of serum iron (4)(5). It was adapted by Barry and Sherlock (6) to the determination of HIC, and we recently evaluated it for measurement of low HIC (7). In 1990, the ICSH replaced bathophenanthroline sulfonate with ferene, a more sensitive chromogen, in the determination of serum iron (8). The aim of the present study was to evaluate the replacement of bathophenanthroline sulfonate with ferene to improve the sensitivity of the colorimetric determination of low HIC.

We used samples of a frozen Wistar rat liver for quality control and determination of reliability criteria of both assays. We compared the results obtained with the two chromogens on 66 liver biopsies from patients with chronic liver diseases hospitalized in the Department of Hepatogastroenterology of the Pitie-Salpetriere Hospital. The clinical diagnoses of these patients are summarized in Table 1⇓ . We determined the CV for HIC measurements on two separate samples from the same liver specimen for each chromogen on 38 human liver biopsies. Histologic iron scoring was according to the method of Deugnier et al. (9); among the 66 biopsies, 20 had no stainable iron (score of 0), and the 46 others exhibited iron overload (score ≥6). Biopsies were fixed in 40 g/L formaldehyde and embedded in paraffin as part of …

Comparison of Bathophenanthroline Sulfonate and Ferene as Chromogens in Colorimetric Measurement of Low Hepatic Iron Concentration

AIMS: To validate a method of assessment of low hepatic iron concentration based on a biochemical colorimetric assay plus histological scoring. METHODS: The within-day and day to day precision of the iron colorimetric assay was determined on frozen rat liver. The coefficient of variation (CV) of iron measurement in two separate samples from the same liver was determined for 21 deparaffinised human biopsies. The intra- and interlaboratory variability of the colorimetric assay and histological scoring were assessed on 38 deparaffinised liver biopsies. RESULTS: For the within-day test, the CV was 11% (5.1 (0.6) mumol/g dry weight (dw), mean (SD) iron concentration). For the day to day test, the CV was 19.5% (8.2 (1.6) mumol/g dw). The CV was 14.7% for iron concentration determined in two separate samples from the same liver. By correlation and kappa concordance tests, the intra- and interlaboratory variability of the hepatic iron colorimetric assay and iron histological scoring was slight. Absence of stainable iron corresponded to a liver iron concentration < or = 20 mumol/g dw. CONCLUSIONS: A combination of two complementary methods, colorimetric measurement and histological scoring, is an accurate and reliable way of determining low iron concentrations in deparaffinised human liver biopsies. In secondary haemosiderosis, such methods would be essential for investigating the role of low iron overload in fibrogenesis and during the response to antiviral treatment in chronic viral hepatitis.

https://jcp.bmj.com/content/jclinpath/52/6/430.full.pdf

Lina Khalil

Papers

Liver fibrosis in overweight patients.

Factors associated with serum alanine transaminase activity in healthy subjects: Consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C

Comparison of Bathophenanthroline Sulfonate and Ferene as Chromogens in Colorimetric Measurement of Low Hepatic Iron Concentration

Low hepatic iron concentration: evaluation of two complementary methods, colorimetric assay and iron histological scoring.