A case of sarcoidosis with isolated hepatosplenic onset and development of inflammatory bowel disease during recovery stage

Sarcoidosis is a systemic disease characterized by an immune-mediated disorder, which leads to the development of non-caseating granulomas in the involved organs. More than 90% of patients with sarcoidosis present lungs and lymphatic system involvement at onset, while less than 10% has an isolated extrapulmonary localization. Here, we describe the case of an elderly patient with isolated hepato-splenic onset (multiple splenic lesions at imaging and cholestasis), and subsequent pulmonary involvement. The liver biopsy showed the presence of noncaseating granulomas, suggesting sarcoidosis. Despite the complete recovery was obtained with steroid therapy, after dosage reduction the patient presented watery diarrhea. Endoscopic investigations with biopsies were performed, describing the presence of an important lympho-plasmacytic infiltrate of terminal ileum mucosa with typical aspects of inflammatory bowel disease. The symptomatology completely disappeared after steroid dosage increase. This case confirms that sarcoidosis could present in a very atypical way, involving several organs in a different manner at the same time and that every symptom should not be underestimated, despite the rare presentation

High total cholesterol in peripheral blood correlates with poorer hearing recovery in idiopathic sudden sensorineural hearing loss

Idiopathic sudden sensorineural hearing loss (ISSHL) is a common otologic emergency whose cause is still unclear. The importance of blood lipids in the pathogenesis of ISSHL is widely reported in literature. In fact elevated levels of low density lipoprotein cholesterol (LDL), total cholesterol (TC) and apolipoprotein B (Apo-B) have been proposed as risk factors for this pathology. No correlation has been described between serum lipid parameters and the prognosis of ISSHL. Aim of the present study was to identify prognostic factors associated with hearing recovery in a group of patients affected by ISSHL. Ninety-four patients with the diagnosis of ISSHL hospitalized between March 2013 and October 2014 were included in this study. Patients' blood sampling and hearing assessments were carried out. Patients were divided into two groups as "recovered" and "unrecovered", according to their response to the treatment. We found a statistically significant higher level of total cholesterol in the unrecovered group compared to the recovered one (p = 0.03). None of the other routine laboratory parameters have shown a statistically significant difference between the patients successfully treated and patients with poor outcomes. Total cholesterol concentrations may be a prognostic factor for recovery in ISSHL and should be assessed together with routine tests in patients with this condition. The other routine laboratory parameters seem to have no effect on the development and prognosis of this pathology

Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet.

Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient

Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs

Introduction and objectives: Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course. Patients and methods: Hepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24. Results: Viral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover. Conclusions: Although viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development

The GLP-1 receptor agonist Exendin-4 modulates hippocampal NMDA-receptor signalling in aged rats and improves cognitive impairment in diabetic elderly patients

n/

High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases

Aim Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with (reverse transcription-polymerase chain reaction) RT-PCR of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. The presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as well. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death

Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet.

Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient

Liver Ultrasound Elastography in Non-Alcoholic Fatty Liver Disease: A State-of-the-Art Summary

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease which is currently the most common hepatic disorder affecting up to 38% of the general population with differences according to age, country, ethnicity and sex. Both genetic and acquired risk factors such as a high-calorie diet or high intake of saturated fats have been associated with obesity, diabetes and, finally, NAFLD. A liver biopsy has always been considered essential for the diagnosis of NAFLD; however, due to several limitations such as the potential occurrence of major complications, sampling variability and the poor repeatability in clinical practice, it is considered an imperfect option for the evaluation of liver fibrosis over time. For these reasons, a non-invasive assessment by serum biomarkers and the quantification of liver stiffness is becoming the new frontier in the management of patients with NAFLD and liver fibrosis. We present a state-of-the-art summary addressing the methods for the non-invasive evaluation of liver fibrosis in NAFLD patients, particularly the ultrasound-based techniques (transient elastography, ARFI techniques and strain elastography) and their optimal cut-off values for the staging of liver fibrosis

Pseudocirrhosis and portal hypertension in patients with metastatic cancers: a systematic review and meta-analysis

Pseudocirrhosis is a clinical and radiological entity mimicking liver cirrhosis in patients without a history of chronic liver disease. We performed a systematic review and meta-analysis of the current literature to evaluate the state-of-the-art and investigate the epidemiology and clinical features of pseudocirrhosis. We searched PubMed, Web of Science and Scopus for literature published until February 28, 2022. We included in the final analysis 62 articles (N = 389 patients): 51 case reports (N = 64 patients), 5 case series (N = 35 patients) and 6 observational studies (N = 290 patients). About 80% of patients included in the case reports and case series had breast cancer. Most patients had at least one clinical sign of portal hypertension and ascites was the most common clinical manifestation of portal hypertension. The median time from pseudocirrhosis to death was 2 months (IQR 1-7 months). Alkylating agents and antimitotics were the most common classes of anticancer drugs reported in our study population. Notably, about 70% of patients received three or more anticancer drugs. Finally, pseudocirrhosis is a condition that occurs in patients with hepatic metastases and may have a negative impact on survival and clinical management of patients because of the potential development of portal hypertension and its complications