In this second major US series, we confirm several findings previously reported in AIP. Our study highlights the presence of vascular complications in a subset of patients with AIP. The current diagnostic criteria may not identify all AIP patients.

Background and ObjectivesWhile animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis.MethodsThis prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival.ResultsLevels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH.ConclusionSevere AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH.

ANP significantly impacts long-term survival. A high proportion of patients develop functional derangement and disability following ANP.

Patients with upper gastrointestinal obstructions were previously managed with gastric decompression and parenteral feeding. The authors present their experience in 50 patients with obstructions chiefly due to complicated severe acute (n = 31) or chronic cystic pancreatitis (n = 11) using a double-lumen nasogastric decompression and jejunal feeding tube system (NGJ) held in place with a nasal bridle that passes through the obstructed gastroduodenal segments, allowing distal jejunal feeding, and at the same time decompresses the stomach to prevent vomiting and aspiration. The tip of the jejunal tube was placed approximately 40 cm down the jejunum to maintain pancreatic rest. Duration of feeding ranged from 1-145 days (median 25 days); 19 patients were discharged home with tube feeds. Only 1 patient could not tolerate feeding and needed to be converted to parenteral feeding. Average tube life was 14 days, with replacement being needed most commonly for kinking or clogging of the jejunal tube (56%) or accidental dislodgement (24%). The obstruction resolved spontaneously in 60%, allowing resumption of normal eating. Of the patients with severe acute pancreatitis or pancreatic pseudocysts, pancreatic rest resulted in resolution of the disease without surgery in 87%, and need for surgery in the remainder was put off for 31-76 days. Seven patients died predominantly of complications of acute pancreatitis between 1 and 31 days. In conclusion, NGJ feeding provides a relatively safe conservative management for critically ill patients with upper gastrointestinal obstructions, reducing the need for surgery and parenteral feeding.

Early initiation of DJF in the ICU was associated with reduced mortality in this cohort of patients with SAP. Early achievement of jejunal feeding goal early was associated with a shorter ICU length of stay, irrespective of the severity of SAP.

IgG4 plasma cells are significantly increased in a subset of patients with IBD suggesting the possibility of a B-cell-mediated mechanism in these patients.

Background: Dysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis (AAH) and determine their utility to predict survival in severe AAH. Methods: A prospective, case control study design was used. Seventy-six patients hospitalized with severe AAH and twenty-five ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180 days after enrollment to determine survival. Results: AAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose-specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor-1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor α (TNF- α), interleukin (IL)-6, IL-8 and IL-15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180 days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL-6, and TNF-α were associated with 180-day survival, and all five markers demonstrated accuracy by area under receiver-operator curve (AUC) analysis. Serum IL-6 levels ≥ 38.66 pg/ml most precisely identified deaths in severe AAH. Patients with IL-6 ≥ 38.66 pg/ml had significantly decreased mean survival compared to those with lower levels. Conclusions: AAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL-6 may be a useful biomarker to risk-stratify severe AAH patients at the highest risk of mortality.

Autoimmune pancreatitis (AIP) is a benign, IgG4-related, fibroinflammatory form of chronic pancreatitis that can mimic pancreatic ductal adenocarcinoma both clinically and radiographically. Laboratory studies typically demonstrate elevated serum IgG4 levels and imaging studies reveal a diffusely or focally enlarged pancreas with associated diffuse or focal narrowing of the pancreatic duct. The pathologic features include periductal lymphoplasmacytic inflammation, obliterative phlebitis, and abundant IgG4-positive plasma cells. The treatment of choice for AIP is steroid therapy. Diagnostic criteria for AIP have been proposed that incorporate histologic, radiographic, serologic, and clinical information.