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Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease
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.
Department of Histopathology and Cytology, Aleris Medilab, Täby, 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.
Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
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2009 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 44, no 3, 366-374 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Moderate alcohol consumption has been reported to be inversely associated with cardiovascular disease and total mortality. The importance of non-alcoholic fatty liver disease (NAFLD) is increasing and many NAFLD patients suffer from cardiovascular disease. In these patients, moderate alcohol consumption could be beneficial. The aim of this study was to investigate whether low alcohol intake, consistent with the diagnosis of NAFLD, is associated with fibrosis progression in established NAFLD.

Material and methods: Seventy-one patients originally referred because of chronically elevated liver enzymes and diagnosed with biopsy-proven NAFLD were re-evaluated. A validated questionnaire combined with an oral interview was used to assess weekly alcohol consumption and the frequency of episodic drinking. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of endstage liver disease during follow-up.

Results: Mean follow-up (SD) was 13.8 (1.2) years between liver biopsies. At follow-up, 17 patients (24%) fulfilled the criteria for significant fibrosis progression. The proportion of patients reporting heavy episodic drinking at least once a month was higher among those with significant fibrosis progression (p=0.003) and a trend towards higher weekly alcohol consumption was also seen (p=0.061). In a multivariate binary logistic regression analysis, heavy episodic drinking (p0.001) and insulin resistance (p0.01) were independently associated with significant fibrosis progression.

Conclusions: Moderate alcohol consumption, consistent with the diagnosis of NAFLD to be set, is associated with fibrosis progression in NAFLD. These patients should be advised to refrain from heavy episodic drinking.

Place, publisher, year, edition, pages
2009. Vol. 44, no 3, 366-374 p.
Keyword [en]
Alcoholic liver disease, fatty liver, histopathology, liver fibrosis, non-alcoholic fatty liver disease
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17133DOI: 10.1080/00365520802555991OAI: oai:DiVA.org:liu-17133DiVA: diva2:202123
Available from: 2009-03-07 Created: 2009-03-07 Last updated: 2010-05-10Bibliographically 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, MarikaBendtsen, PrebenBodemar, GöranKechagias, Stergios

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Ekstedt, MattiasFranzén, Lennart EHolmqvist, MarikaBendtsen, PrebenBodemar, GöranKechagias, Stergios
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Gastroenterology and Hepatology Faculty of Health SciencesDepartment of Endocrinology and Gastroenterology UHLDivision of Preventive and Social Medicine and Public Health ScienceDepartment of Medical SpecialistInternal Medicine
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