Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease

Tannapfel, Andrea; Denk, Helmut; Dienes, Hans‐Peter; Langner, Cord; Schirmacher, Peter; Trauner, Michael; Flott-Rahmel, B.

doi:10.1007/s00428-011-1066-1

Cited by 120 publications

(77 citation statements)

References 79 publications

(57 reference statements)

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“…Values for albumin, aspartate transaminase (AST/GOT), alanine transaminase (ALT/GPT), total bilirubin, thromboplastin time (Quick), gamma glutamyl transpeptidase (gamma-GT), lactate dehydrogenase (LDH), cholineesterase (CHE), alpha-1-fetoprotein (AFP), volume of resected tissue, resection weight, and the diameter of the largest tumor were provided as continuous variables, while the categorical variables were defined as follows (as provided by the tumor register database)-carcinoembryonic antigen (CEA): normal (<5 ng/ml), intermediate (5-10 ng/ml), high (>10 ng/ml), carbohydrate antigen 19-9 (CA19-9): normal (<40 IE/ml), intermediate (40-50 IE/ml), high (>50 IE/ml), invasion of lymphatic vessels (yes, no), intrahepatic (yes, no), or extrahepatic blood vessels (no, microscopic, macroscopic), cirrhosis at the time of surgery (yes, no), hepatic steatosis (none: <5% of hepatocytes, slight: 5-33%, strong: >34%, which corresponds with the Brunt steatosis grades 0, 1, and 2/3) [22] and were provided as such by the tumor registers.…”

Section: Discussionmentioning

confidence: 95%

Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC

et al. 2011

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Histone deacetylases (HDAC) are responsible for the transcriptional control of genes through chromatin remodeling and control tumor suppressor genes. In several tumors, their expression has been linked to clinicopathological factors and patient survival. This study investigates HDACs 1, 2, 3, and 7 expressions in hepatocellular carcinoma (HCC) and their correlation with clinical data and patient survival. Tissue microarrays of 170 surgically resected primary HCCs and adjacent uninvolved tissue were evaluated immunohistochemically for the expression of HDACs 1, 2, 3, 7, and Ki-67 and were analyzed with respect to clinicopathological data and patient survival. HDACs 1, 2, 3, and Ki-67 were expressed significantly higher in cancer cells compared to normal tissue (HDAC1: p = 0.034, HDACs 2 and 3 and Ki-67: p < 0.001), while HDAC7 expression did not differ between HCC and non-cancerous liver tissue. In tumor tissue HDACs 1-3 expression levels showed high concordance with each other, Ki-67 and tumor grade (p < 0.001). High HDAC2 expression was associated with poor survival in low-grade and early-stage tumors (p < 0.05). The expression of the HDACs 1, 2, and 3 (but not HDAC7) isoenzymes correlates with clinicopathological factors, and HDAC2 expression has an impact on patient survival.

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Section: Discussionmentioning

confidence: 95%

Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC

et al. 2011

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“…Non-invasive assessment of hepatic steatosis is possible and should be standardized [7]; both T1-weighted dualecho magnetic resonance (MR) imaging and one-proton MR spectroscopy have excellent diagnostic accuracy as compared to ultrasonography and computed tomography [8]. Still, a liver biopsy is used to establish or confirm the diagnosis of a particular type of liver disease, as well as for staging disease severity.…”

Section: Introductionmentioning

confidence: 99%

“…Still, a liver biopsy is used to establish or confirm the diagnosis of a particular type of liver disease, as well as for staging disease severity. Although a liver biopsy is considered the "gold standard" to assess hepatic steatosis and steatohepatitis, it is not without practical difficulties and controversies [7,9]. Overall, a biopsy is still very useful because it provides information about the prognosis of the disease its proper clinical management [10,11].…”

Section: Introductionmentioning

confidence: 99%

A critical analysis of three quantitative methods of assessment of hepatic steatosis in liver biopsies

et al. 2011

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The issue of adequately quantitatively evaluating hepatic steatosis is still unresolved. Therefore, we compared three methods of quantitative assessment. Two groups of mice (n = 10 each) were fed standard chow (10% fat, SC group) or a high-fat diet (60% fat, HF group) for 16 weeks, and hepatic triglyceride (HT) and liver tissue were then studied. Paraplast-embedded tissues stained by hematoxylin and eosin (H-E) were compared to frozen sections stained by Oil Red-O (ORO). In addition, the volume density of steatosis (Vv[steatosis, liver]) was measured by point counting (P-C, sections H-E or ORO) or by image analysis (I-A, sections ORO). HT was significantly higher in the HF group (104% greater, P = 0.0004) than in the SC group. With P-C and H-E, Vv[steatosis, liver] was 4.80 ± 0.90% in the SC group and 33.50 ± 3.17% in the HF group (600% greater, P < 0.0001). With P-C and ORO, Vv[steatosis, liver] was 4.86 ± 0.89% in the SC group and 25.21 ± 1.27% in the HF group (420% greater, P < 0.0001). With I-A and ORO, Vv[steatosis, liver] was 4.17 ± 0.85% in the SC group and 23.35 ± 1.58% in the HF group (460% greater, P < 0.0001). Correlations between Vv[steatosis, liver] and HT were strong and significant in all methods. In conclusion, all methods were appropriate and reproducible. In P-C and H-E, there is a slight overestimation of steatosis in the HF animals in comparison to frozen sections and ORO; in frozen sections, differences between P-C and I-A are insignificant.

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“…According to the modified two-hit hypothesis (Dowman et al 2010), the accumulation of liver TAG may actually be protective by preventing NEFA-induced inflammation and oxidative stress. Benign fatty liver has been shown to be reversible in humans (Mantena et al 2008;Tannapfel et al 2011) and our results demonstrate that liver recovery is possible in the mink even after 7 days of food deprivation.…”

Section: Discussionmentioning

confidence: 55%

Evidence of endoplasmic reticulum stress and liver inflammation in the American mink Neovison vison with benign hepatic steatosis

et al. 2014

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We investigated the presence of inflammatory signs in the progression of fatty liver disease induced by fasting. Sixty standard black American mink (Neovison vison) were fasted for 0, 1, 3, 5, or 7 days and one group for 7 days followed by re-feeding for 28 days. Liver sections were evaluated histologically and liver mRNA levels indicating endoplasmic reticulum (ER) stress, adipogenic transformation, and inflammation were assessed by quantitative real-time PCR. After 3 days of fasting, the mink had developed moderate liver steatosis. Increased hyaluronan reactivity in lymphocytic foci but no Mallory-Denk bodies were seen in livers of the mink fasted for 5-7 days. Up-regulation of glucose-regulated protein, 78 kDa was observed on day 7 indicating ER stress, especially in the females. Liver lipoprotein lipase and monocyte chemoattractant protein 1 mRNA levels increased in response to 5-7 days of food deprivation, while tumor necrosis factor α (TNF-α) was the highest in the mink fasted for 5 days. The expression of the genes of interest, except for TNF-α, correlated with each other and with the liver fat content. The mRNA levels were found to change more rapidly below n-3/n-6 polyunsaturated fatty acid ratio threshold of 0.15. Following re-feeding, hepatocyte morphology and mRNA abundance returned to pre-fasting levels. Within the studied timeframe, evidence for ER stress, adipogenic transformation, and liver inflammation suggested incipient transition from steatosis to steatohepatitis with potential for development of more severe liver disease. This may present a possibility to influence disease progression before histologically observable steatohepatitis.

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Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease

Cited by 120 publications

References 79 publications

Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC

Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC

A critical analysis of three quantitative methods of assessment of hepatic steatosis in liver biopsies

Evidence of endoplasmic reticulum stress and liver inflammation in the American mink Neovison vison with benign hepatic steatosis

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