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Franzén, Lennart E
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Publications (10 of 22) Show all publications
Petersson, F., Franzén, L. E. & Borch, K. (2010). Characterization of the gastric cardia in volunteers from the general population: type of mucosa, helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis. Digestive Diseases and Sciences, 55(1), 46-53
Open this publication in new window or tab >>Characterization of the gastric cardia in volunteers from the general population: type of mucosa, helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis
2010 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 55, no 1, p. 46-53Article in journal (Refereed) Published
Abstract [en]

The aim of this research was to characterize the mucosa of the gastric cardia in relation to infection with Helicobacter pylori and the occurrence of chronic gastritis in other parts of the stomach in a sample of the general population. In this study, 80 adult volunteers underwent esophagogastroscopy with biopsies from the gastric cardia, corpus, and antrum. Gastritis was classified according to the Sydney system. Chronic gastritis (cardia excepted) was diagnosed in 35 subjects, 30 with Hpylori infection. Epithelial proliferative activity (Ki-67), p53- and p21 expression were examined quantitatively with cell counting after immunohistochemical stainings. Esophagitis was diagnosed macroscopically. Fourty eight subjects had cardia-type and 32 corpus-type mucosa in the anatomical cardia. The prevalence of esophagitis (nine cases) did not differ between these groups. Carditis was more prevalent among subjects with cardia-type mucosa (73 vs. 28%, P < 0.0001). Hpylori was present in 48% of those with cardia-type and 25% of those with corpus-type mucosa (P = 0.06). Of the 44 subjects with carditis, 31 had Hpylori in this location. The group with Hpylori infection had significantly higher mucosal proliferative activity when compared to uninfected subjects. Among the subjects with H. pylori-associated carditis, more p53-positive epithelial cells were detected compared to both the non-infected group (P = 0.0004) and to subjects with non-Hpylori-associated carditis (P = 0.03). In subjects with cardia-type mucosa, and both carditis and gastritis, the degree of chronic inflammation was higher in the cardia compared to the corpus and antrum and the p53 expression was significantly higher in the cardia compared to the corpus, but similar to that in the antrum. The proliferative activity was significantly higher in the antrum compared to the cardia and corpus, respectively. In conclusion, H. pylori infection, carditis, and increased p53 expression are more common in subjects with cardia- than corpus-type mucosa in the gastric cardia. Carditis is mainly related to Hpylori infection. There are some differences regarding inflammation, proliferative activity, and p53 expression between the cardia and other regions of the stomach, yet the significance of these differences remains to be clarified.

Keywords
Cardia, Carditis, Gastritis, Helicobacter pylori, Proliferation, Ki-67, p53, p21
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-53693 (URN)10.1007/s10620-008-0705-0 (DOI)
Available from: 2010-02-01 Created: 2010-02-01 Last updated: 2017-12-12
Ekstedt, M., Franzén, L. E., Holmqvist, M., Bendtsen, P., Mathiesen, U. L., Bodemar, G. & Kechagias, S. (2009). Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 44(3), 366-374
Open this publication in new window or tab >>Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease
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2009 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 44, no 3, p. 366-374Article 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.

Keywords
Alcoholic liver disease, fatty liver, histopathology, liver fibrosis, non-alcoholic fatty liver disease
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17133 (URN)10.1080/00365520802555991 (DOI)
Available from: 2009-03-07 Created: 2009-03-07 Last updated: 2017-12-13Bibliographically approved
Ekstedt, M., Franzén, L. E., Mathiesen, U. L., Bodemar, G. & Kechagias, S. (2008). The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression.
Open this publication in new window or tab >>The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression
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2008 (English)Article in journal (Other academic) Submitted
Abstract [en]

Objective: The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD.

Methods: One hundred and twenty-nine patients with biopsy proven NAFLD were included in a long-term histological follow-up study. Clinical and histological course were compared between NASH, “borderline NASH”, and “not NASH” patients. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up.

Results: Eighty-eight patients accepted re-evaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3-16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend towards higher baseline NAS was seen in patients (n = 7) that developed end-stage liver disease (3.1 ± 0.9 vs. 2.4 ± 1.0; P = 0.062). Baseline NAS was significantly higher in patients with progressive fibrosis (2.9 ± 0.9 vs. 2.2 ± 0.9; P = 0.017), and NAS was independently associated with significant fibrosis progression tested in a multivariate analysis (P = 0.023). However, 18% of patients without NASH progressed significantly in fibrosis stage.

Conclusion: Although the NAS is independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS-score groups.

Keywords
Steatohepatitis, Fatty liver, Fibrosis progression, Clinical follow-up, Histopathology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17325 (URN)
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2009-08-17Bibliographically approved
Ekstedt, M., Franzén, L. E., Mathiesen, U. L., Holmqvist, M., Bodemar, G. & Kechagias, S. (2007). Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study.. Journal of Hepatology, 47(1), 135-141
Open this publication in new window or tab >>Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study.
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2007 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 47, no 1, p. 135-141Article 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.

Keywords
Non-alcoholic fatty liver disease, Histology, Statin, Metabolic syndrome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17324 (URN)10.1016/j.jhep.2007.02.013 (DOI)17400325 (PubMedID)
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
Ekstedt, M., Franzén, L. E., Mathiesen, U. L., Thorelius, L., Holmqvist, M., Bodemar, G. & Kechagias, S. (2006). Long-term follow-up of patients with NAFLD and elevated liver enzymes.. Hepatology, 44(4), 865-873
Open this publication in new window or tab >>Long-term follow-up of patients with NAFLD and elevated liver enzymes.
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2006 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 44, no 4, p. 865-873Article 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.

Keywords
Liver, quantification, steatosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17323 (URN)10.1002/hep.21327 (DOI)17006923 (PubMedID)
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
Sjöstedt, C., Hannestad, U., Franzén, L., Söderholm, J. D. & Borch, K. (2005). Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation. Digestion, 72(4), 201-206
Open this publication in new window or tab >>Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation
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2005 (English)In: Digestion, ISSN 0012-2823, E-ISSN 1421-9867, Vol. 72, no 4, p. 201-206Article in journal (Refereed) Published
Abstract [en]

Background: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. Methods: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. Results: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%, p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%, p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. Conclusion: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis. Copyright © 2005 S. Karger AG.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31495 (URN)10.1159/000089145 (DOI)17290 (Local ID)17290 (Archive number)17290 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
Franzén, L. E., Ekstedt, M., Kechagias, S. & Bodin, L. (2005). Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.. Modern Pathology, 18(7), 912-916
Open this publication in new window or tab >>Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.
2005 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 18, no 7, p. 912-916Article 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.

Keywords
Liver, quantification, steatosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17322 (URN)10.1038/modpathol.3800370 (DOI)15920560 (PubMedID)
Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
Veress, B., Franzén, L., Bodin, L. & Borch, K. (2004). Duodenal intraepithelial lymphocyte-count revisited. Scandinavian Journal of Gastroenterology, 39(2), 138-144
Open this publication in new window or tab >>Duodenal intraepithelial lymphocyte-count revisited
2004 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 2, p. 138-144Article in journal (Refereed) Published
Abstract [en]

Background: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. Methods: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron-deficiency (9 cases) and B12-deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. Results: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. Conclusion: Two-step analysis of intraepithelial lymphocyte-determination is suggested: (a) semi-quantitative estimate on H&E-stained sections (normal ratio of 1:5 between lymphocytes and enterocytes, upper normal limit 20 lymphocytes) and (b) CD3-staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as 'borderline' and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.

Keywords
duodenum, immunohistochemistry, intraepithelial lymphocytes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-46278 (URN)10.1080/00365520310007675 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Borch, K., Skarsgard, J., Franzén, L., Mårdh, S. & Rehfeld, J. (2003). Benign gastric polyps - Morphological and functional origin. Digestive Diseases and Sciences, 48(7), 1292-1297
Open this publication in new window or tab >>Benign gastric polyps - Morphological and functional origin
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2003 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 48, no 7, p. 1292-1297Article in journal (Refereed) Published
Abstract [en]

The most common types of benign gastric polyps are fundic gland polyps, hyperplastic polyps, and adenomas. The aim of this study was to determine on which morphological and functional background benign gastric polyps develop. The study includes 85 consecutive patients with gastric polyps and sex and age-matched controls without polyps selected at random from a general population sample. The type of polyp was hyperplastic in 52 (61%), fundic gland in 18 (21%), adenoma in 10 (12%), carcinoid in 2 (2%), hamartoma in 2 ( 2%), and inflammatory fibroid in 1 (1%) of the cases. Routine biopsies from the gastric corpus and antrum were examined for presence of gastritis and H. pylori. Blood samples were analyzed for H. pylori antibodies, H+, K+-ATPase antibodies, gastrin, and pepsinogen I. Patients with hyperplastic polyps had increased P-gastrin concentrations and S-H+, K+-ATPase antibody titers and decreased S-pepsinogen I concentrations with a high prevalence of atrophic corpus gastritis or pangastritis. A similar pattern was observed among patients with adenomas, whereas patients with fundic gland polyps had normal serology and a lower prevalence of gastritis and H. pylori infection than controls. In conclusion, hyperplastic polyps and adenomas are generally associated with atrophic gastritis. Patients with fundic gland polyps seem to have a sounder mucosa than controls. Whereas the risk of malignant gastric neoplasia is increased in patients with hyperplastic polyps or adenomas, this does not seem to be the case in patients with fundic gland polyps.

Keywords
gastrin, gastritis, Helicobacter pylori, H+, K+-ATPase antibodies, morphology, pepsinogen I, polyps, stomach
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-48631 (URN)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Tillander, B., Franzén, L., Nilsson, E. & Norlin, R. (2001). Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff. Journal of Orthopaedic Research, 19(3), 441-447
Open this publication in new window or tab >>Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff
2001 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, Vol. 19, no 3, p. 441-447Article in journal (Refereed) Published
Abstract [en]

This study was designed to investigate the histologic expression of the rat's supra- and infraspinatus tendons in carrageenan-induced subacromial bursitis. Thirty-two rats received subacromial injections with carrageenan (n = 28) or saline (n = 4). The tendons were analysed microscopically after staining with hematoxyline eosin, Van Giesons hematoxyline and immunofluorescent staining of fibronectin and fibrinogen. In the controls (saline × 10) and group A (carrageenan × 5) there were no changes in the tendons. In group B (carrageenan × 10) 3/8 rats showed macrophages between the collagen fibres and an increased staining of fibronectin. In group C (double dosis carrageenan) all rats had signs of fibrocartilaginous metaplasia in the supraspinatus tendon. In eight of these specimens even bony metaplasia was seen. The infraspinatus tendon showed fibrosis but no fibro-cartilaginous metaplasia. The results showed that iatrogenic bursitis after carrageenan subacromial injections was associated with marked changes of the supraspinatus tendon.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13705 (URN)10.1016/S0736-0266(00)90022-6 (DOI)
Available from: 2001-11-27 Created: 2001-11-27 Last updated: 2009-08-21
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