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Aim The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) with Sonazoid (perfluorobutane) in patients with liver abscess. Sonazoid is a contrast agent with a low mechanical index and is phagocytosed by Kupffer cells. Methods Twenty-two patients with liver abscess were evaluated with conventional US, real-time CEUS with Sonazoid, and enhanced computed tomography (CT). After 0.5 mL of Sonazoid was administrated i.v., CEUS images in the vascular and post-vascular phases were observed. Results Conventional US showed hypoechoic lesions in 13 (59.1%), isoechoic in four (18.2%), hyperechoic in two (9.1%), mixed echoic in two (9.1%) and undetected in one (4.8%) patient. CEUS showed perilesional enhancement in 19 (86.4%) lesions in the vascular phase and well-defined unenhanced areas in 22 (100%) lesions in the post-vascular phase. CEUS revealed that 18 abscesses were cystic type and three were honeycomb type. Twenty-one abscesses (95.5%) had clearer appearances on CEUS than on conventional US in regard to the extent of necrotic or liquefied lesions seen. We could confirm reduction of the lesions after therapy in 13 (92.9%) of 14 patients followed up by CEUS. Conclusion Most of the liver abscesses showed perilesional enhancement in the vascular phase and unenhanced areas in the post-vascular phase. The appearance of liver abscesses was clearer on CEUS than on conventional US. CEUS with Sonazoid can be a more effective diagnostic and therapeutic tool for liver abscess.

Aim Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin–angiotensin system (RAS) appears to play important roles in NASH. Direct renin inhibitors (DRI) reduce plasma renin activity (PRA) through interaction with the active site of the enzyme and reduce the formation of angiotensin-II (AT-II). Therefore, the DRI aliskiren may further suppress the RAS. This study examined the effects of aliskiren on NASH in fatty liver Shionogi (FLS)-ob/ob male mice that are the closest animal model of metabolic syndrome-related NASH in humans. Methods Aliskiren (100 mg/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight FLS-ob/ob mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups. Results Amounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of α-smooth muscle actin positivity, the numbers of F4/80 positive, 8-hydroxy-2-deoxyguanosine positive cells and immunohistochemical staining of 4-hydroxynonenal were also significantly decreased in the aliskiren group. Levels of RNA expression for transforming growth factor-β1, connective tissue growth factor and monocyte chemoattractant protein-1 were significantly lower in the aliskiren group. Conclusion Aliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.

Aim The fatty liver Shionogi (FLS) mouse develops hereditary fatty liver without obesity. The FLS-ob/ob mouse made by transferring the leptin(ob) gene demonstrates several metabolic disorders and marked fat deposition in the liver. The aim was to evaluate which mouse model, the FLS or FLS-ob/ob, is more useful for non-alcoholic steatohepatitis research. Methods FLS (n = 40) and FLS-ob/ob (n = 40) mice were fed a standard diet for 12, 24, 36 and 48 weeks, and then killed. The degree of fat deposition, oxidative stress, fibrosis and apoptosis were analyzed in the liver. Hepatic mRNA expression of fibrogenic and pro-inflammatory cytokines was measured. Results FLS mice developed hepatic steatosis and slight fibrosis without obesity between 12 and 48 weeks of age. Conversely, FLS-ob/ob mice developed severe steatosis at 12 weeks of age, and steatohepatitis with increased oxidative stress and advanced fibrosis between 24 and 36 weeks of age. At 48 weeks of age, some FLS-ob/ob but not FLS mice, progressed to cirrhosis. Transforming growth factor-β1, connective tissue growth factor and tumor necrosis factor-α mRNA expression levels were greater in FLS-ob/ob than FLS mice between 24 and 48 weeks of age. The number of apoptotic cells in the liver was greater at 12 weeks of age in FLS mice and at 48 weeks of age in FLS-ob/ob mice. Conclusion FLS-ob/ob mice developed more severe steatohepatitis with fibrosis than FLS mice, and had increased oxidative stress and apoptosis. These findings indicate that the FLS-ob/ob mouse is a more useful model for steatohepatitis research.

Aim: An effective therapy for non-alcoholic steatohepatitis has yet to be defined. This study examined the therapeutic effects of ezetimibe, a lipid-lowering medication, on steatosis and hepatic fibrosis in fatty liver Shionogi ob/ob (FLS-ob) mice. Methods: Low-dose (0.2 mg/kg body weight) and high-dose (1.0 mg/kg body weight) of ezetimibe were administered to FLS-ob mice orally for 12 weeks. Results: Administration of ezetimibe significantly and dose-dependently decreased liver cholesterol content. The area of hepatic fibrosis and hepatic hydroxyproline content in the low- and high-dose groups were significantly decreased compared with controls. Areas of α-smooth muscle actin positivity and F4/80 positivity were significantly decreased in a dose-dependent manner. Percentages of 8-hydroxy-2-deoxyguanosine-positive cells in low- and high-dose groups were significantly decreased compared with those in controls, and 8-hydroxy-2-deoxyguanosine DNA content and thiobarbituric acid reactive substances in the high-dose group was also significantly decreased compared to controls. Gene expression levels of procollagen I and transforming growth factor β1 mRNA levels were lower in the low- and high-dose groups than in controls. Tumor necrosis factor-α and sterol regulatory element-binding protein 1c mRNA levels were also lower in the low- and high-dose groups than in controls. Conclusions: Ezetimibe attenuated steatosis and liver fibrosis by reducing oxidative stress and lipid peroxidation and suppressing activated hepatic stellate cells and Kupffer cells.

There is currently no report that has documented hepatocellular carcinoma (HCC) in a case of Cowden syndrome. Here, we present the first reported case of HCC in a 60-year-old female patient with Cowden syndrome. We diagnosed the patient using a pathognomonic criterion of the International Cowden Consortium Operational Diagnostic Criteria and performed genetic analysis. Enhanced computed tomography demonstrated a hypervascular tumor in segment VII of the liver. The patient was diagnosed with Cowden syndrome because her mucocutaneous lesions met the pathognomonic criterion. Mutational analysis confirmed a heterozygous germ line TGT→TAT transition at nucleotide 407 in exon 5 of the phosphatase and tensin homolog detected on the chromosome 10 (PTEN) gene. Needle biopsy showed a poorly differentiated HCC. We also diagnosed non-alcoholic steatohepatitis (NASH) from hepatic histological findings of Mallory's bodies and ballooning cells. PTEN-deficient mice reportedly develop HCC through NASH. This is the first reported case of Cowden syndrome complicated with HCC possibly originating from NASH.