Purpose: This study evaluated the utility of non-invasive assessment of hepatobiliary function by 99mTc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis.
Methods: Male Wistar rats (250-300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. 99mTc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T(peak)) and the time required for peak activity to decrease by 50% (T(1/2peak)). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology.
Results: MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T(peak), T(1/2peak) prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p<0.05). There was a strong, significant correlation between the severity of steatosis (histopathology, hepatic triglyceride content) and the 99mTc-mebrofenin uptake rate (r2=0.83, p<0.0001 and r2=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-alpha, r2=0.72, p<0.0001 and r2=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r2=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r2=0.70, p<0.001).
Conclusion: Hepatobiliary function assessed by 99mTc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients.