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. (HEPATOLOGY 2006;44:865–873.)
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 x 10) and group A (carrageenan x 5) there were no changes in the tendons. In group B (carrageenan x 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 fibrocartilaginous metaplasia. The results showed that iatrogenic bursitis after carrageenan subacromial injections was associated with marked changes of the supraspinatus tendon.
The aim of this study was to see if nodular cells in Dupuytren’s disease differed from dermal cells in their contractile capacity and motility. Ten surgical specimens from patients with Dupuytren’s disease and contracture of the finger of more than 45° were harvested and the nodular cells were explanted and cultured. Dermal fibroblasts from the forearm were used as control cells. Both types of cell had the same growth pattern. The morphology on confocal laser scanning microscopy was also similar in both types of cell. Dermal control cells caused significantly more contraction of collagen lattices compared with fibroblasts from nodules of Dupuytren’s contracture. The F-actin content was equal in both groups. Platelet derived growth factor, PDGF-BB (but not PDGF-AA), increased the chemotactic activity of both cell types, but there were no differences between them. The results indicate that at a late state of the disease cells from Dupuytren’s nodules lose their contractile capacity and regain a phenotype resembling that of dermal fibroblasts.
The healing of perforated mesenterial window is delayed in insulin‐deficient rats after 4 weeks of streptozoticin‐induced diabetes (25). In the present study we investigated the mitogenic capacity of the two predominating cell types in the healing mesenterial window in such rats. The labelling index (LI) in fibroblasts and mesothelial cells, normally constituting approximately 96% of all tissue‐bound cells, was estimated in early and later phases of healing within (a) a 1 mm‐wide zone surrounding the perforation and (b) centrally in wounds after healing by closure. The mitotic index (MI) of these cells was estimated at various distances from the perforation. Adjacent unperforated control mesenteric windows served as internal controls. Proliferation increased on days 1 and 2 post‐perforation, whereafter it gradually diminished, fibroblasts showing a higher LI than mesothelial cells days 3–7 after closure. On day 1 post‐perforation the relative increase of LI was greatest in diabetic mesenteries. During the period just preceding healing by closure, LI of both fibroblasts and mesothelial cells was, however, significantly reduced in diabetic animals. The impaired mitogenesis in these wound‐healing cells in diabetic rats may thus be of pathogenic significance in the delayed healing in such animals.
Recently a new reference interval for serum ALT, based on samples from up to 3000 healthy adult reference persons, was proposed. In the present study we performed a retrospective analysis of biochemical and histological data from 178 asymptomatic patients currently considered to have increased ALT. Forty-five patients (25%) had serum ALT levels within the new proposed reference interval. Of those, only one had normal liver histology. Of the remaining 44 patients with abnormal liver histology, 34 exhibited fatty infiltration. It is concluded that if the new proposed reference interval for serum ALT is used as "healthy" ranges, the sensitivity of this test in identifying subclinical liver disease will be decreased.
ABSTRACT The effect of drug‐induced mast cell secretion on proliferation was studied in fibroblast‐like and mesothelial‐like cells in organ‐cultured rat mesentery. Mast cell degranulation achieved by Compound 48/80 was followed by a marked mitogenic reaction in the surrounding tissue cells. The drug itself lacked mitogenic effect on cultured guinea‐pig mesentery, the mast cells of which are unresponsive to the drug, and on a human normal fibroblast‐like cell line. In contrast, histamine at about 10 −10 M, a major mast cell component, induced marked mitogenesis in guinea‐pig mesentery without causing degranulation of mast cells. It is concluded that secreting rat‐tissue mast cells release a mitogenic factor or factors acting locally on nearby tissue cells.
Five of 72 patients dialysed at the same dialysis unit developed elevated alanine aminotranspherase (ALT) levels attributed to acute non-A, non-B hepatitis (NANBH). Histopathologic findings consistent with NANBH were present in four of them. Serological screening for antibodies to hepatitis C virus (anti-HCV) was performed in all 72 cases. Three of the patients with NANBH and 2 of the other 67 patients had positive tests. Low and transient levels of anti-HCV were noted in 2 patients with NANBH in spite of chronic hepatitis. Only 1 of 5 patients with NANBH was known to have had blood transfusions indicating other, as yet undefined, modes of transmission of HCV for the others. Although antibody responses to HCV might be transient or low, testing for anti-HCV should be considered in dialysis populations.
Radiologic examinations preceding the diagnosis of colorectal carcinomas were retrospectively scrutinized in 708 patients with 731 carcinomas that were radiographically investigated 741 times. Sixty-four lesions were missed 74 times, giving a 90% sensitivity of the radiographic methods used. Of the errors, 82% were perceptive, and 3% were interpretative. Eleven examinations in nine patients revealed no lesions, although the examinations were done within 2 years of the diagnosis of a carcinoma. Missed lesions were more common than expected in the cecum and the ascending colon (P less than 0.001), and 18% of the patients had multiple tumors (expected incidence 3.6%, P less than 0.001). The median delay in diagnosis was 20 months, and patients whose diagnosis was delayed for a long time tended to have more advanced carcinomas at diagnosis. As a lesion was identified either at the initial examination or retrospectively 730 of 741 times, the potential sensitivity of the radiographic methods used was 99%. It is concluded that barium enema is still an excellent method for the detection of colorectal carcinoma provided that perceptive errors can be minimized.
