The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases

BACKGROUND Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases. METHODS A selective literature search was conducted in Medline and PubMed, using the terms \textquotedblnonalcoholic fatty liver disease,\textquotedbl \textquotedblalcoholic liver disease,\textquotedbl \textquotedbllipopolysaccharide,\textquotedbl \textquotedblgut barrier,\textquotedbl and \textquotedblmicrobiome.\textquotedbl RESULTS Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD. CONCLUSIONS The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated

Molecular Mechanisms of Ischaemia-Reperfusion Injury and Regeneration in the Liver-Shock and Surgery-Associated Changes

Hepatic ischemia-reperfusion injury (IRI) represents a major challenge during liver surgery, liver preservation for transplantation, and can cause hemorrhagic shock with severe hypoxemia and trauma. The reduction of blood supply with a concomitant deficit in oxygen delivery initiates various molecular mechanisms involving the innate and adaptive immune response, alterations in gene transcription, induction of cell death programs, and changes in metabolic state and vascular function. Hepatic IRI is a major cause of morbidity and mortality, and is associated with an increased risk for tumor growth and recurrence after oncologic surgery for primary and secondary hepatobiliary malignancies. Therapeutic strategies to prevent or treat hepatic IRI have been investigated in animal models but, for the most part, have failed to provide a protective effect in a clinical setting. This review focuses on the molecular mechanisms underlying hepatic IRI and regeneration, as well as its clinical implications. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes

Albumin Might Attenuate Bacteria-Induced Damage on Kupffer Cells for Patients with Chronic Liver Disease

Chronic liver diseases (CLDs) are complex diseases that cause long-term inflammation and infection, which in turn accelerate their development. The usage of albumin in patients with CLDs has been debated for years. Human serum albumin (HSA) plays a key role in immunomodulation during the process of CLDs. The correlation between albumin and C-reactive protein (CRP) in CLD patients was analyzed by linear regression with the Pearson statistic. The damage of THP-1 and primary cells was evaluated by measuring the lactate dehydrogenase (LDH) in the supernatant. Immunofluorescence staining was performed to determine underlying pathways in Kupffer cells (KCs). Albumin negatively correlated with infection in patients with CLDs. In vitro experiments with THP-1 cells and KCs showed that albumin reduced LDH release after stimulation with bacterial products, while no differences in hepatic stellate cells (HSCs) and sinusoidal endothelial cells (SECs) were detected. Moreover, immunofluorescence staining revealed an increase of p-ERK and p-NF-kB p65 density after albumin treatment of KCs stimulated by bacterial products. In conclusion, albumin could assist CLD patients in alleviating inflammation caused by bacterial products and might be beneficial to patients with CLDs by securing KCs from bacteria-induced damage, providing a compelling rationale for albumin therapy in patients with CLDs

Spindle Cell Metaplastic Breast Carcinoma with Leiomyoid Differentiation: A Case Report

Background: Metaplastic carcinoma of the breast is a rare but distinct entity within the group of undifferentiated invasive carcinomas. This entity accounts for less than 0.5% of all breast cancers and contains elements of epithelial (ductal), mesenchymal, and intermediate forms of differentiation. Of these metaplastic carcinomas, there have been reports of chondroid, squamous, osseous, and spindle differentiation. Case Report: We describe the clinical course of a 52-year-old female patient with an unusual histopathology of a spindle cell carcinoma of the breast, discuss the literature, and recommend an approach to diagnosis and treatment. The patient initially presented to an outside hospital with a rapidly growing breast mass that was originally diagnosed as a malignant phylloides tumor. She presented 11 months after the primary treatment with a local subcutaneous relapse. She later developed a local relapse of her metaplastic carcinoma in the chest wall. Extensive histopathological analysis lead to the diagnosis of a spindle cell metaplastic breast carcinoma with leiomyoid differentiation, which has not been described previously. Conclusions: Overlap in morphology can lead to a misinterpretation or underdiagnosis of metaplastic carcinomas. However, the prognosis is similar to more common types of breast adenocarcinoma