Are elevated systemic bile acids involved in the pathophysiology of sarcopenia and liver injury following gastric bypass?

Bariatric surgery is currently the most effective treatment for sustained weight loss in severe obesity. However, recent data describe the development of liver damage and in particular massive steatosis and cholangitis in some patients, for which certain pathophysiological mechanisms are suggested such as bacterial overgrowth, malabsorption or sarcopenia. We describe the case of a patient presenting with a new liver dysfunction 6 years after a gastric bypass. The work-up revealed sarcopenic obesity characterised by low muscle mass and low muscle function as well as elevated fasting bile acids, severe liver steatosis and cholangitis. The pathophysiology of this disease is complex and multifactorial but could include bile acid toxicity. Bile acids are increased in cases of liver steatosis, but also in cases of gastric bypass and malnutrition. In our opinion, they may contribute to the loss of muscle mass and the vicious circle observed in this situation. Treatment with enteral feeding, intravenous albumin supplementation and diuretics reversed the liver dysfunction and the patient was discharged from hospital.

ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology.

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.

Guidelines for an optimal management of a malignant colorectal polyp. What is essential in a pathology report ?

Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report.

The role of the pathologist and clinical implications in colorectal liver metastasis.

Colorectal liver metastases (CRLM) affect about 50% of colorectal cancer patients. With the improvement of neoadjuvant chemotherapy and the introduction of targeted therapy, resectability of CRLM and survival rates have improved over time. However, 60-70% of patients still recur. Several pathological and molecular parameters have been described as prognostic factors after CRLM resection. These parameters encompass not only tumoral features, but also non-tumoral ones, such as chemotherapy related liver injury, or factors related to tumour environment, namely Immunoscore. This review summarizes these prognostic indicators to clarify which patho-molecular parameters should be addressed in the pathological report.

Progressive Fibrosis Is Driven by Genetic Predisposition, Allo-immunity, and Inflammation in Pediatric Liver Transplant Recipients.

AIM: To determine predisposing factors of idiopathic allograft fibrosis among pediatric liver transplant recipients. BACKGROUND: Protocol biopsies (PB) from stable liver transplant (LT) recipient children frequently exhibit idiopathic fibrosis. The relation between allograft inflammation, humoral immune response and fibrosis is uncertain. Also the role of HLA-DRB1 genotype has not been evaluated, though it's associated with fibrosis in autoimmune hepatitis. PATIENTS AND METHODS: This observational study, included 89 stable LT recipient transplanted between 2004-2012 with mean follow-up of 4.3years, 281 serial PBs (3.1 biopsy/child) and human leukocyte antigen (HLA) antibody data. PBs were taken 1-2, 2-3, 3-5, 5-7, and 7-10years post-LT, and evaluated for inflammation and fibrosis using liver allograft fibrosis score (LAFSc). The evolution of fibrosis, inflammation and related predisposing factors were analysed. FINDINGS: HLA-DRB1*03/04 allele and Class II DSA were significantly associated with portal fibrosis (p=0.03; p=0.03, respectively). Portal inflammation was predisposed by Class II DSA (p=0.02) and non-HLA antibody presence (p=0.01). Non-portal fibrosis wasn't predisposed by inflammation. Lobular inflammation was associated with non-HLA antibodies. INTERPRETATION: We conclusively demonstrated that allograft inflammation results in fibrosis and is associated with post-LT Class II DSA and non-HLA antibodies. The HLA-DRB1*03/04 allele caused genetic predisposition for fibrosis. FUNDING: None.