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SUMMARY BackgroundRecent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-a ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.

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Background: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease. Aim: To assess the value of TE for predicting the stage of fibrosis. Methods: Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated.

Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration (ICa2I1I) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in ICa2`i1 followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2" channels. To analyze the temporal and spatial dynamics of Ca2" release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, ratiometric video imaging system. The rise inICa2"], was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in ICa2"1, more than fourfold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca2"-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo. (J. Clin. Invest. 1992. 90:642-646.)