Faculty Bibliography

Background: Certain nutritional and herbal supplements may have potential hepatotoxic effects. With increasing use of these supplements in the general population, supplements-induced liver injury (SILI) has become a common problem clinically. However, there is not much data about the clinical and pathologic features of SILI, and pathological characteristics of SILI have not been defined. Design: All liver biopsy cases with diagnoses of hepatitis or liver injury were reviewed from our pathology database from 2014-2015. The cases of SILI were confirmed by pathological and clinical correlation. Pre-biopsy liver function tests (LFTs) were collected from the electronic medical record system. The H&E and Trichrome stain slides were re-assessed for pathologic changes. The morphologic patterns of liver injury, including bile duct injury, portal inflammation, interface hepatitis, lobular inflammation, fibrosis, presence of granulomas, and plasma cell and eosinophil infiltrates were recorded and analyzed. Results: Total 17 cases of SILI were identified from 323 liver biopsy cases of hepatitis and liver injury. Two of 17 patients with SILI developed acute fulminant hepatic failure and succumbed to the illness. The hepatotoxic nutritional/herbal supplements identified included boswellic acid, carnosyn beta-alanine, whey protein, maca extract, rhodiola, holy basil, creatine, and some unspecified tea and anti-itching supplements. Histologically, the major pattern of liver injury was combined bile duct damage and hepatitis, and the majority of cases showed significant cholestasis. Fibrosis ranged from mild portal fibrosis to cirrhosis. No granulomas were identified. Plasma cells were rare to minimal in all cases, while eosinophils ranged from none up to 12 per high power field. Serologically, the mean values of alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 625 U/L, 447 U/L, 241 U/L, and 12 mg/d, respectively. Conclusions: Nutritional and herbal supplements have become a common cause of drug induced liver injury that may be under recognized. Histologically, the pattern of SILI in this study is the combination of bile duct and hepatocytic damage, ranging from mild disease to fulminant hepatitis. Significant elevation of LFTs, in combination with mixed pattern of liver injury should trigger the consideration of SILI

A salient feature of pancreatic ductal adenocarcinoma (PDA) is an abundant fibroinflammatory response characterized by the recruitment of immune and mesenchymal cells and the consequent establishment of a pro-tumorigenic microenvironment. Here we report the prominent presence of B cells in human pancreatic intraepithelial neoplasia (PanIN) and PDA lesions as well as in oncogenic K-Ras-driven pancreatic neoplasms in the mouse. The growth of orthotopic pancreatic neoplasms harboring oncogenic K-Ras was significantly compromised in B cell-deficient mice (muMT), and this growth deficiency could be rescued by the reconstitution of a CD1dhighCD5+ B cell subset. The pro-tumorigenic effect of B cells was mediated by their expression of IL-35 through a mechanism involving IL-35-mediated stimulation of tumor cell proliferation. Our results identify a previously unrecognized role for IL-35-producing CD1dhighCD5+ B cells in the pathogenesis of pancreatic cancer and underscore the potential significance of a B cell/IL-35 axis as a therapeutic target.

PURPOSE: To assess the use of diffusion-weighted imaging (DWI) for differentiating acute from chronic cholecystitis, in comparison with conventional magnetic resonance imaging (MRI) features. MATERIALS AND METHODS: Liver MRI including DWI (b-values 0/500/1000s/mm2 ) was performed at 1.5T