galactomannan and Liver-Diseases

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Topics: Aged; Amphotericin B; Antifungal Agents; Autopsy; Fatal Outcome; Ferritins; Galactose; Humans; Invasive Fungal Infections; Liver Diseases; Male; Mannans; Mucormycosis; Primary Myelofibrosis; Spleen

Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA) and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan). In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis.

Topics: Animals; Apoptosis; Blotting, Western; Cell Line; Cell Proliferation; Fibrosis; Galactans; Galactose; Galectins; Humans; Liver Cirrhosis; Liver Diseases; Male; Mannans; Pectins; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Thioacetamide

We present a case of primary hepatic and possible splenic invasive aspergillosis (IA), which progressed under anti-CD20 B cell treatment for posttransplantation lymphoproliferative disease following allogeneic stem cell transplantation, to highlight the clinical value of a positive galactomannan-antigen test, an intestinal portal of entry of Aspergillus, and the detrimental effect of B lymphocyte depletion in IA.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Galactose; Graft vs Host Disease; Humans; Liver Diseases; Lymphoproliferative Disorders; Mannans; Middle Aged; Pyrimidines; Rituximab; Splenic Diseases; Stem Cell Transplantation; Transplantation, Homologous; Triazoles; Voriconazole

The performance of different in vitro diagnostic tests for the diagnosis of invasive aspergillosis (IA) was investigated in a transiently neutropenic rat model. Rats were immunosuppressed with cyclophosphamide and then inoculated intravenously with 1.5 x 10(4) CFU Aspergillus fumigatus spores. Animals were then either treated with caspofungin acetate, 1 mg/kg/day for 7 days, or not treated. PCR-enzyme-linked immunosorbent assay (ELISA), real-time PCR, and galactomannan (GM) detection were performed on postmortem blood samples, along with culture of liver, lung, and kidney homogenate. Caspofungin-treated animals showed a decrease in residual tissue burden of A. fumigatus from organ homogenate compared to untreated animals (P < 0.002). PCR-ELISA returned positive results for 11/17 animals treated with antifungal agents and for 10/17 untreated animals. Galactomannan was positive in 8/17 caspofungin-treated animals and 4/17 untreated animals. Real-time PCR was positive in 2/17 treated and 3/17 untreated animals. This study demonstrates that PCR-ELISA is a more sensitive test than either GM detection (P = 0.052) or real-time PCR (P < 0.01) for diagnosis of IA but that any of the three tests may return false-negative results in cases of histologically proven disease. Galactomannan indices from animals treated with antifungal agents showed a trend (P = 0.1) towards higher levels than those of untreated animals, but no effect was observed with PCR-ELISA indices (P = 0.29). GM detection, as previously described, may be enhanced by the administration of caspofungin, but PCR-ELISA appears not to be affected in the same way. We conclude that PCR-ELISA is a more sensitive and reliable method for laboratory diagnosis of IA.

Topics: Animals; Antifungal Agents; Aspergillosis; Caspofungin; Disease Models, Animal; Echinocandins; Enzyme-Linked Immunosorbent Assay; Galactose; Lipopeptides; Liver Diseases; Male; Mannans; Neutropenia; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction

The monoclonal antibody EB-A1 to galactomannan is apparently specific for detecting Aspergillus species and Penicillium marneffei in formalin-fixed, paraffin-embedded tissues. It reveals hyphae, remnants of filaments, and organisms in the cytoplasm of some phagocytic cells.

Topics: Antibodies, Monoclonal; Aspergillosis; Cell Wall; Cytoplasm; Dermatomycoses; Galactose; Humans; Immunohistochemistry; Liver Diseases; Lung Diseases, Fungal; Mannans; Phagocytes