Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.
The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo
Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.
Plexiform angiomyxoid myofibroblastic tumor of the stomach is a unique mesenchymal tumor that we first described in 2007. The tumor is very rare, and to date, only 18 cases confirmed by immunohistochemistry have been reported in the literature. The patients' ages ranged from 7 to 75 years (mean, 43 years), and the male-to-female ratio was approximately 1:1. Representative clinical symptoms are ulceration, associated upper gastrointestinal bleeding (hematemesis), and anemia. The tumors are located at the antrum in all cases, and grossly, the tumor is whitish to brownish or reddish, and forms a lobulated submucosal or transmural mass. Microscopically, the tumor is characterized by a plexiform growth pattern, the proliferation of cytologically bland spindle cells, and a myxoid stroma that is rich in small vessels and positive for Alcian blue stain. Immunohistochemically, the tumor cells are positive for alpha-smooth muscle actin and negative for KIT and CD34. Differential diagnoses include gastrointestinal stromal tumor and other mesenchymal tumors of the gastrointestinal tract. Some authors proposed that this tumor should be designated as "plexiform fibromyxoma", but this designation might cause confusion. The tumor is probably benign and thus far, neither recurrence nor metastasis has been reported.
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