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Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
Unit of Biostatistics and Epidemiology, Clinical Research Centre, University Hospital, Örebro, Sweden.
2005 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 18, no 7, 912-916 p.Article in journal (Refereed) Published
Abstract [en]

The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.

Place, publisher, year, edition, pages
2005. Vol. 18, no 7, 912-916 p.
Keyword [en]
Liver, quantification, steatosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17322DOI: 10.1038/modpathol.3800370PubMedID: 15920560OAI: oai:DiVA.org:liu-17322DiVA: diva2:208439
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Non-Alcoholic Fatty Liver Disease: A clinical and histopathological study
Open this publication in new window or tab >>Non-Alcoholic Fatty Liver Disease: A clinical and histopathological study
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fatty liver has previously often been associated with excessive alcohol consumption. During the last two decades, the interest in fatty liver occurring in non-drinkers i.e. non-alcoholic fatty liver disease (NAFLD) has increased dramatically. Today, NAFLD is considered as the most common liver disease in the developed world. It is strongly associated with obesity, insulin resistance, and hypertension. Thus, NAFLD is considered as the hepatic manifestation of the metabolic syndrome.

The spectrum of NAFLD includes: simple fatty liver without necroinflammatory activity; non-alcoholic steatohepatitis (NASH), a condition characterised by hepatocellular injury, inflammation, and fibrosis; cirrhosis; and in some individuals hepatocellular carcinoma.

The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the pathologist uses a four-graded scale: 0–3 or none, slight, moderate and severe. In this thesis we show that there is a considerable inter- and intraindividual variation in such scoring methods and that a more standardised and quantitative approach is preferable. The area/volume of fat in liver biopsies is greatly overestimated when assessed semiquantitatively. Moreover, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis.

The long-term clinical and histopathological course of 129 consecutively enrolled NAFLD patients was studied. Mean follow-up (SD) was 13.7 (1.3) years. Survival of NASH patients was reduced compared with a matched reference population. These subjects more often died from cardiovascular and liver-related causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.

During follow-up, 17 patients had been prescribed a statin. At follow-up, patients on medication with statins had significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Although patients under statin treatment exhibited a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. It is concluded that statins can be prescribed safely in patients with elevated liver enzymes because of NAFLD.

Alcohol consumption was evaluated with a validated questionnaire combined with an oral interview. In a multivariate analysis moderate alcohol consumption, particularly when frequency of heavy episodic drinking was analysed, consistent with the diagnosis of NAFLD to be set, was independently associated with fibrosis progression in NAFLD.

The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. We evaluated the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in our cohort of NAFLD patients. Although the NAS was independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score was limited due to significant overlap in clinical development between NAS-score groups.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 87 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1081
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-17220 (URN)978-91-7393-787-0 (ISBN)
Public defence
2008-10-17, Berzeliussalen, CampUS, Hälsouniversitetet, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
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Available from: 2009-03-18 Created: 2009-03-11 Last updated: 2012-03-22Bibliographically approved

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Franzén, Lennart EEkstedt, MattiasKechagias, Stergios

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Molecular and Immunological Pathology Faculty of Health SciencesDepartment of Clinical PharmacologyGastroenterology and Hepatology Department of Endocrinology and Gastroenterology UHLInternal Medicine
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