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Long-term follow-up of patients with NAFLD and elevated liver enzymes.
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 Care. Linköping University, Faculty of Health Sciences.
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2006 (English)In: Hepatology, ISSN 0270-9139, Vol. 44, no 4, 865-873 p.Article in journal (Refereed) Published
Abstract [en]

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. 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.

Place, publisher, year, edition, pages
2006. Vol. 44, no 4, 865-873 p.
Keyword [en]
Liver, quantification, steatosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17323DOI: 10.1002/hep.21327PubMedID: 17006923OAI: oai:DiVA.org:liu-17323DiVA: diva2:208441
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2009-08-18Bibliographically 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 EThorelius, LarsHolmqvist, MarikaBodemar, GöranKechagias, Stergios

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Ekstedt, MattiasFranzén, Lennart EThorelius, LarsHolmqvist, 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 GeneticsDepartment of Medicine and CareDivision of Preventive and Social Medicine and Public Health ScienceInternal Medicine
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