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Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study.
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 Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
Department of Internal Medicine, County Hospital, Oskarshamn, Sweden.
Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
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2007 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 47, no 1, 135-141 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aims: The effect of statins on hepatic histology in non-alcoholic fatty liver disease (NAFLD) is not known. This study explores hepatic histology in NAFLD patients before and after initiation of statin therapy and compares histological outcome with NAFLD patients who had not been prescribed statins.

Methods: Sixty-eight NAFLD patients were re-evaluated. Follow-up ranged from 10.3 to 16.3 years. Subjects were clinically investigated and a repeat liver biopsy was obtained. No patient was taking statins at baseline while 17 patients were treated with statins at follow-up.

Results: At baseline, patients that later were prescribed statins had significantly higher BMI and more pronounced hepatic steatosis. At follow-up patients on medication with statins continued to have 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. Despite exhibiting a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage.

Conclusions: Statins can be prescribed in patients with elevated liver enzymes because of NAFLD.

Place, publisher, year, edition, pages
2007. Vol. 47, no 1, 135-141 p.
Keyword [en]
Non-alcoholic fatty liver disease, Histology, Statin, Metabolic syndrome
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17324DOI: 10.1016/j.jhep.2007.02.013PubMedID: 17400325OAI: oai:DiVA.org:liu-17324DiVA: diva2:208533
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)
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Available from: 2009-03-18 Created: 2009-03-11 Last updated: 2012-03-22Bibliographically approved

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Ekstedt, MattiasFranzén, Lennart EHolmqvist, MarikaBodemar, GöranKechagias, Stergios

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Gastroenterology and Hepatology Faculty of Health SciencesDepartment of Endocrinology and Gastroenterology UHLMolecular and Immunological Pathology Department of Clinical Pathology and Clinical GeneticsDivision of Preventive and Social Medicine and Public Health ScienceInternal Medicine
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