Electron microscopic findings in non‐alcoholic fatty liver disease: Is there a difference between hepatosteatosis and steatohepatitis?

Abstract

Background and Aims: Non-alcoholic fatty liver disease has long been accepted as benign; however, recent evidence suggests that the disease may progress to cirrhosis and hepatocellular carcinoma, although the natural course of the disease is still unclear. This study was designed to comparatively evaluate electron microscopic features of nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Methods: Quantitative and semi-quantitative ultrastructural evaluations were performed on liver biopsies from 23 patients, 10 with NAFL and 13 with NASH. Results: No statistically significant difference was noted between NAFL and NASH patients in ultrastructural features of hepatocytes including megamitochondria, intramitochondrial crystalline inclusions, mitochondrial matrix granules, foamy cytoplasmic appearance, electron-lucent and glycogen-containing nuclear regions, lipofuscin granules, or an increased frequency of vesicles containing electron-dense material in peribiliary Golgi zone; however, the mitochondrial diameter was significantly higher in the NASH patients. Intercellular distance and microvilli between hepatocytes, collagen and electron-dense material accumulation in the space of Disse, electron-dense material accumulation and microvillus density in bile canaliculi did not differ significantly between the groups. Conclusions: Our data show that, although NAFL and NASH can be distinguished by their distinct light microscopic features, ultrastructural characteristics are similar, which suggests that NAFL may also have the potential to progress to fibrosis and cirrhosis like NASH.

Loss of PDGF-B activity increases hepatic vascular permeability and enhances insulin sensitivity

“…Ultrastructural changes to the hepatic sinusoids are common in NAFLD (3), and this may explain why reduced PDGF-B signaling actually improves hepatic sinusoidal structure in the B6 background. Indeed, black and tan, tufted mice are resistant to the development of fatty liver, and they display reduced sinusoidal alterations compared with B6 mice (data not shown).…”

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

“…To complicate matters, there are also spaces in the hepatocytes in places once occupied by glycogen. Thus, not all the spaces observed with H-E staining are unequivocally the remains of vesicles of steatosis [23,24]. It is well understood that there are difficulties in detecting lipid microvesicles after paraffin embedding, and this can cause both an underestimation of the degree of fatty change and a misdiagnosis of "normal" liver that, in fact, contains high levels of microsteatosis [25].…”

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

“…Decreased activity of the mitochondrial respiratory chain was reported in overweight/obese patients with NASH compared to controls [97, 98], and alterations in mitochondrial ultrastructure have been observed prior to NAFLD development in the Otsuka Long–Evans Tokushima Fatty rat [99] as well as in patients with steatosis preceding progression to NASH [100]. The decrease in mitochondrial function may result in the utilization of alternative FAO pathways.…”