Yayoi Hosoki

Induction of transferrin receptor by Ethanol in Rat primary hepatocyte culture

BACKGROUND It is not uncommon for alcoholics to have iron accumulation in the liver, a condition that may contribute to the development of alcoholic liver disease. Recently, we reported that the expression of transferrin receptor, which mediates cellular iron uptake, was increased in hepatocytes in patients with alcoholic liver disease. To elucidate the mechanism of the iron accumulation in hepatocytes in such disease, we examined whether ethanol exposure induced the transferrin receptor expression and increased the cellular iron uptake. METHODS Rat primary hepatocytes were isolated and cultured in the presence of 20 micromol/liter of iron and 25 mmol/liter of ethanol. RESULTS Ethanol exposure to the hepatocytes demonstrated an ~2-fold increase in transferrin receptor expression for 24 hr, shown by Western blot analysis and S-methionine metabolic labeling, 19% increase in Fe-transferrin uptake by hepatocytes, and 20% increase in activity of iron regulatory protein examined by band shift assay. CONCLUSION Ethanol exposure induced the transferrin receptor expression, partially through the activation of iron regulatory protein, and increased the transferrin-bound iron uptake in rat hepatocyte cultures. The induction of transferrin receptor by ethanol might be one of the mechanisms of iron accumulation in the hepatocytes in alcoholic liver disease.

Clinical utility of sequential imaging of hepatocellular carcinoma by contrast-enhanced power Doppler ultrasonograpy

The aim of this study was to investigate the clinical utility of sequential imaging of hepatocellular carcinoma (HCC) by contrast-enhanced power Doppler ultrasonograpy (CE-PDUS) to differentiate hepatocellular carcinoma from adenomatous hyperplasia (AH) and regenerated nodule (RN) and to predict the degree of differentiation of HCC. Fifty-one patients with 62 hepatic lesions including 33 moderately and poorly differentiated HCCs, 19 well-differentiated HCCs, seven AHs and three large RNs were examined by CE-PDUS. The imaging patterns during early arterial phase (tumor vessel image), late vascular phase (tumor perfusion image) and post-vascular phase (liver perfusion image) were classified as diffuse, basket, peripheral, central and no enhancement; as whole tumor, partial tumor and no enhancement; as whole tumor, partial tumor and no defect, respectively. The diffuse pattern in the tumor vessel image, the whole enhancement pattern in the tumor perfusion image and the whole defect pattern in the liver perfusion image were observed in moderately and poorly differentiated HCCs only. The basket pattern in the tumor vessel image and the partial defect pattern in the tumor perfusion image were observed in HCCs only. All AH/RNs showed no defect pattern in the liver perfusion image. The sequential imaging of HCC during early arterial, late vascular and post-vascular phases by CE-PDUS is clinically useful to differentiate HCC from AH/RN and to predict the degree of differentiation of HCC.

Usefulness of contrast-enhanced wide-band Doppler ultrasonograpy to diagnose alveolar echinococcosis of the liver and evaluate the effect of the treatment

Alveolar echinococcosis is a rare parasitic disease caused by Echinococcus multicularis and most commonly involves the liver. Early diagnosis and accurate evaluation of the effect of the treatment are essential to improve the prognosis of patients with alveolar echinococcosis of the liver (AEL). The aim of this study was to demonstrate the characteristic imaging of AEL by contrast-enhanced Dynamic Flow (CE-DF) employing a wide-band Doppler technique for the diagnosis and the accurate evaluation of the effect of the treatment. Four patients with five AEL lesions before treatment or during medication were examined by CE-DF. All of the five AEL lesions examined by CE-DF revealed a defect with an irregular and distinct margin like a worm-eaten defect appearance, which was never observed on other hepatic lesions, in liver perfusion image during post-vascular phase. In addition, CE-DF made it possible to measure the size of AEL lesions accurately because the margin was detected distinctly. These data suggest that CE-DF is clinically useful for the diagnosis of AEL and the evaluation of the effect of the treatment.

Enlarging splenic vein aneurysm associated with increasing portal hypertension

To the Editor: Since splenic vein aneurysm was initially reported by Lowenthal et al.1 in 1953, fewer than ten cases have been reported in the English-language literature. Moreover, splenic vein aneurysm that develops progressively and expands is very rare.2 Here, we report a recently observed case of splenic vein aneurysm that developed and enlarged with the advance of portal hypertension. A 48-year-old woman was admitted to Asahikawa Medical College Hospital in 1989 for the purpose of treating esophageal varices. She was diagnosed as having idiopathic portal hypertension by several examinations, including liver biopsy under laparoscopy, and angiography. The esophageal varices were treated by endoscopic injection sclerotherapy (EIS) three times in 1989 and twice in 1992. In 1992, there was no abnormal finding in the splenic vein on computed tomography (CT). However, a 15mm-diameter saccular dilatation of the splenic vein was initially detected by magnetic resonance imaging (MRI) in 1995 (Fig. 1a). Moreover, this saccular dilatation gradually enlarged, and the diameter had increased to 35 mm on contrast-enhanced CT in 1999 (Fig. 1a). This saccular dilatation of the splenic vein was confirmed as an aneurysm by gray-scale endoscopic ultrasonography (EUS) (Fig. 2a) and by portal venogram after celiac angiography (Fig. 2b). The patient has been treated for this aneurysm with the oral administration of propranolol (a b-blocker) to decrease the portal pressure. Surgical treatment, has not been performed according to the patient’s wishes, although we fully informed her of various risks, including the risk of rupture. In April 2005, the aneurysm had not changed in size compared with findings in August 1999 (Fig. 1a). The mechanism whereby aneurysm of the portal venous system develops is still unclear. Long-standing portal hypertension has been reported as one possible mechanism.3 However, aneurysm of the portal venous system has been found in younger patients without portal hypertension, so congenital vascular anomalies have been thought to be another possible mechanism.4 As shown in Fig. 1, our patient showed progression of splenomegaly on CT and MRI and thrombopenia after EIS for the treatment of esophageal varices. These phenomena suggested that the interruption of portal blood flow through the left gastric vein by EIS may have caused exacerbation of the portal hypertension and increased blood flow toward the spleen. Furthermore, development and enlargement of the splenic vein aneurysm was observed in parallel with the progression of splenomegaly and thrombopenia (Fig. 1a, b). Therefore, it was considered that the exacerbation of portal hypertension had caused the development and enlargement of the splenic vein aneurysm in our patient, although there was a possibility that she had a latent congenital vascular anomaly. The rupture1,3,5 of an aneurysm is directly connected to sudden death. However, the standards for indications and selection of treatment for portal venous system aneurysms, including surgical treatment, have not been established. We will urge our patient to undergo removal of the splenic vein aneurysm, with the formation of a spleno-renal shunt or splenectomy, if the aneurysm suddenly enlarges.