Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model

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 patient

99mTc-GSA scintigraphy with SPECT for assessment of hepatic function and functional volume during liver regeneration in a rat model of partial hepatectomy

Small-animal models are crucial to gain insights in the complex recovery mechanisms of liver function during liver regeneration. (99m)Tc-Mebrofenin hepatobiliary scintigraphy (HBS) has been introduced for noninvasive assessment of liver function in the clinical setting as well as in experimental research. However, HBS is restricted to planar modalities in small animals because hepatic kinetics are generally too fast for SPECT acquisition. (99m)Tc-DTPA-galactosyl serum albumin (where DTPA is diethylenetriaminepentaacetic acid) ((99m)Tc-GSA) scintigraphy is an alternative, receptor-mediated, noninvasive liver function test. After hepatic uptake, (99m)Tc-GSA remains trapped in the liver, which readily enables additional SPECT for the assessment of both liver function and liver functional volume within one test. In this study we evaluated the use of (99m)Tc-GSA scintigraphy combined with SPECT for the assessment of liver function and liver functional volume in normal and regenerating rat livers. METHODS: The reproducibility of (99m)Tc-GSA scintigraphy and SPECT was investigated by repeated measurements within the same rat. For the assessment in a regenerating liver, (99m)Tc-GSA scintigraphy with SPECT was performed on 1, 3, 5, and 7 d (n = 6 rats per time point) after 70% partial hepatectomy (PH). RESULTS: The correlation between repeated (99m)Tc-GSA measurements was strong (r = 0.75, P = 0.019). In normal rat livers, there was a strong, significant correlation between liver functional volume and conventional liver volume (r = 0.93; < 0.0001). The correlation between (99m)Tc-GSA uptake and liver volume was moderate (r = 0.62, P = 0.043). During the regeneration process, (99m)Tc-GSA uptake was significantly lower compared with both liver volume (P < 0.001) and liver functional volume (P < 0.001), when expressed as a percentage of baseline levels. There was a strong correlation between liver functional volume and conventional liver volume in the regenerating liver (r = 0.92, P < 0.0001). CONCLUSION: (99m)Tc-GSA scintigraphy combined with SPECT is a feasible, noninvasive method to assess hepatic functional volume in normal rat liver as well as in the regenerating rat liver. However, the hepatic (99m)Tc-GSA uptake as a liver function test seems to underestimate hepatic regeneration in comparison to liver volum

Liver adenomatosis: re-evaluation of aetiology and management

BACKGROUND: Liver adenomatosis (LA) is a rare benign parenchymal liver disease with unknown aetiology. In recent reports, LA has been associated with hepatic steatosis, with potential implications for the management of this disease. The aim of this study was to determine prognosis and optimal management of patients with LA. METHODS: Clinical presentation, diagnostic studies and management of patients with LA were analysed in our centre. Furthermore, a Medline search of all published case reports and series of LA patients was performed. RESULTS: Ninety-four patients with LA have been reported in the literature. Fifty-two per cent of females had a history of oral contraceptive use. Eighteen per cent of patients had steatosis in nontumoral tissue. In our own series, five of six patients had histologically confirmed steatosis. Forty-three per cent of patients presented with acute pain, of whom 46% had a haemorrhagical complication, in contrast to 2% of nonsymptomatic patients. Tumours <5 cm tended to increase in size during follow-up and only in four patients tumour regression was observed. CONCLUSION: Liver adenomatosis is a progressive, benign parenchymal disease mainly occurring in females. There is a potential link with hepatic steatosis with implications for the management of patients with LA. Noninvasive diagnosis is difficult because of the variety of tumoral and nontumoral components. Management should primarily be conservativ