A novel model of CCl4-induced cirrhosis with ascites in the mouse.

BACKGROUND/AIMS: The current approaches to study the molecular mechanisms involved in the pathophysiology of liver diseases often rely on the use of transgenic mice. However, experimental models of decompensated cirrhosis have not been clearly established in mice. Thus, we aimed to set an efficient and well-tolerated protocol to induce cirrhosis in mice able to progress up to the ascitic stage. METHODS: C57BL/6N mice received CCl(4) subcutaneously, intraperitoneally or by inhalation. In the latter group, gaseous CCl(4) was administered according to three different schedules: increasing exposure times, twice weekly (traditional protocol; TP), short inhalation cycles, twice or three times weekly. RESULTS: Portal hypertension, sodium retention, and ascites developed in all groups between 11 and 15 weeks. Mortality reached 70% in the TP group, but it was only 0-10% with all other protocols. All the inhalation groups had significantly more ascites at sacrifice than those receiving CCl(4) subcutaneously and intraperitoneally. Extensive abdominal adhesions and evidence of enhanced hepatic inflammation, as suggested by the increased gene expression of pro-inflammatory cytokines in liver tissue, were found in the intraperitoneal group, while large granulomas at the injection site and marked neutrophil infiltration of lungs developed in the subcutaneous group. No extra-hepatic damage could be detected in mice inhaling CCl(4). CONCLUSIONS: The use of short cycles of CCl(4) inhalation represents a novel, safe, and effective method to induce decompensated cirrhosis in mice. Intraperitoneal CCl(4) leads instead to abdominal adhesions precluding a correct evaluation of ascites, while subcutaneous CCl(4) causes an unwanted systemic inflammatory response.

Liver Cirrhosis in a Patient with Sickle Cell Trait (Hb Sß Thalassemia) without Other Known Causes of Hepatic Disease.

Liver involvement in patients with sickle cell anemia/trait includes a wide range of alterations, from mild liver function test abnormalities to cirrhosis and acute liver failure. Approximately 15-30% of patients with sickle cell anemia present cirrhosis at autopsy. The pathogenesis of cirrhosis is usually related to chronic hepatitis B or C infection or to iron overload resulting from the many transfusions received by these patients in their lifetime. Thus, cirrhosis has been described almost exclusively in patients with sickle cell anemia, while only mild liver abnormalities have been associated with the sickle cell trait. In the present case study, we describe a young Mediterranean man carrying a sickle cell trait (Hb Sß(+) thalassemia) who developed liver cirrhosis being negative for hepatitis C and B viruses or for other causes of cirrhosis and not receiving chronic blood transfusions.

C-11 acetate does not enhance usefulness of F-18 FDG PET/CT in differentiating between focal nodular hyperplasia and hepatic adenoma.

PURPOSE OF THE REPORT: We assessed the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and C-11 acetate PET (AC PET) in distinguishing hepatic lesions due to consequential disease (hepatocellular adenoma and malignant lesions) from focal nodular hyperplasia (FNH) in patients at low risk of malignancy. MATERIALS AND METHODS: Thirty-one patients with 43 lesions were prospectively enrolled. The diagnostic work-up included Doppler and contrast-enhanced ultrasonography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. Fine needle biopsy was performed if the imaging study was inconclusive. The work-up revealed 36 FNH and 7 consequential lesions (5 hepatocellular adenoma, 1 hepatoma, and 1 metastasis). All patients underwent FDG and AC PET. FDG PET with target/background ratio (T/Br) greater than 1.2 and AC PET with T/Br of less than 1.2 were considered positive test for consequential disease. RESULTS: On FDG PET, we had 6 true-positive out of 7 lesions due to consequential diseases, with a sensitivity of 85.7%, and 33 true-negative out of 36 lesions with FNH, with a specificity of 91.7%. Using AC PET, there were 2 true-positive lesions out of 7 caused by neoplasms, with a sensitivity of 28.6%, and 34 true-negative lesions out of 36 FNH, with a specificity of 94.4%. CONCLUSIONS: When the goal is differentiating FNH from liver neoplasms, AC PET offered no additional diagnostic advantage over what is achieved with FDG PET.