This Month in Gastroenterology

Abstract

Morbid obesity is a known risk factor for NAFLD. While it has been shown that significant weight loss following bariatric surgery reduces steatosis, it has been hypothesized that the rapid weight loss occurring after bariatric surgery could have adverse effects on the liver, increasing hepatic inflammation, and fibrosis. Klein et al report the results of their prospective study evaluating the changes in liver histology, hepatic inflammation, fibrogenesis, and metabolic function following gastric bypass surgery (GBP) in 7 morbidly obese patients. Prior to and one year following GBP, whole-body glucose, fatty acid and lipoprotein kinetics, liver histology, and hepatic cellular factors implicated in inflammation and fibrogenesis were evaluated. The 7 GBP patients lost a mean of 29 ± 5% of their pre-bypass body at 1 year after surgery. There was a decrease in palmitate rate of appearance in plasma (a measure of adipose tissue lipolysis) of 47 ± 4%, P<0.01, endogenous glucose production rate (−27 ± 7%, P<0.01), and VLDL-triglyceride secretion rate (−44 ± 9%, P<0.05). Liver histology from liver biopsies revealed a decrease in hepatic steatosis, although there was no change in inflammation or fibrosis. There was, however, a decrease in factors involved in hepatic fibrosis including collagen-α1, transforming growth factor-β1, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase 1 expression, and α-SMA content. Furthermore, there was a decreased expression of inflammatory factors macrophage chemoattractant protein 1, and interleukin 8. The study by Klein et al demonstrates improvement of metabolic abnormalities believed to play a role in the pathogenesis of NAFLD and a decrease in hepatic steatosis following weight loss occurring after GBP. While these authors did not see a reduction in hepatic inflammation and fibrosis, there was a decrease in the expression of factors believed to be important in the development of hepatic inflammation and fibrosis. See page 1564 Recurrence of Crohn’s disease (CD) is common after surgical resection and most commonly occurs in the margin proximal to the anastomosis. Several studies have tried to identify predictors of early postoperative recurrence, but there has been great variability in the findings of these studies. Recognized risk factors for postoperative CD recurrence include smoking, perforating disease, ileocolonic anastomosis, and restoration of fecal stream. Furthermore, previous investigators have noted changes in the enteric nervous system including neural fiber hypertrophy, hyperplasia, and inflammatory infiltrates associated with the submucosal and myenteric plexus in patients with CD. These findings have not only been reported in areas of mucosal inflammation, but have also been described in un-inflamed mucosa in margins of resected intestinal specimens, raising the possibility that neuronal inflammation precedes mucosal inflammation. Ferrante et al set out to determine if the presence of neural lesions is predictive of early postoperative recurrence of Crohn’s disease. Surgical resection specimens from 59 CD patients and 21 control patients were examined histologically. Each specimen was evaluated and graded according to the presence and severity of neural hypertrophy and inflammation involving ganglia and nerve bundles in the submucosal and myenteric plexus. Myenteric plexitis, defined as the presence of one or more inflammatory cells appositioned to or within an enteric ganglion or nerve bundle, was found in the un-inflamed proximal resection margin in 32/59 (54%) of all CD patients. The presence of myenteric plexitis at the proximal resection margin was predictive of endoscopic recurrence at 3 months (75 vs 41%, OR 4.36 [1.44–13.23], P = .008). Thirty-two patients underwent endoscopic evaluation at 1 year postoperatively. In this group of patients, the endoscopic recurrence rates were 93 vs 59% in patients with and without myenteric plexitis at the proximal resection margin respectively, OR 9.80 (1.04–92.70) P = .041 (Figure 1). The severity of plexitis correlated with the severity of endoscopic recurrence at both time points. In multiple logistic regression analysis, myenteric plexitis in the proximal resection margin, male gender, and ileocolonic involvement were all found to be independent predictors of endoscopic recurrence at 3 months postoperatively. Myenteric plexitis was the only independent predictor of disease recurrence at 1 year postoperatively. The study by Ferrante et al suggests the presence of myenteric plexitis at the proximal resection marker is a good predictor of early postoperative endoscopic recurrence of CD. See page 1595 Model for end-stage liver disease (MELD) score is the current standard used to determine which transplant candidates are highest priority for cadaveric livers. The score is based upon serum total bilirubin, the international normalized ratio (INR), and serum creatinine and has been found to correlate well with short-term mortality risk in patients with cirrhosis. Recently, several single center retrospective studies have found that serum sodium (Na) is an important additional predictor of wait-list mortality, as it is commonly associated with morbid complications of end-stage liver disease, including hyponatremia, hepatorenal syndrome, ascites, and liver-related mortality. In this study, a prospective, multi-center database of wait-listed patients from 6 transplant programs were evaluated to determine whether a refinement MELD could provide increased predictive value of wait-list mortality. The study by Biggins et al reports that after adjustment for MELD and center, there was a linear increase in the risk of death as Na decreased between 135 and 120 mEq/L. Based on these findings, a new score was developed to incorporate Na into MELD, the MELD-Na score, which is calculated from MELD + 1.59 (135-Na) with maximum and minimum Na of 135 and 120, respectively. In this cohort, MELD-Na of 20, 30, and 40 were associated with 6%, 16%, and 37% of risk of death within 6 months of listing, respectively. The study by Biggins et al estimates that if MELD-Na were used today, it would affect 27% of the transplant recipients (Figure 2). Thus, the MELD-Na provides a practical and evidence-based model that incorporates serum sodium concentration into MELD to improve prediction of liver transplant wait-list mortality. See page 1652 Ghrelin is a 28-amino-acid acylated polypeptide hormone that is primarily produced by gastric cells and appears to be involved in the control of growth hormone secretion, energy expenditure, and adiposity. However, ghrelin and its receptors also appear to be expressed by immune cells, where they may be involved in inhibiting production of proinflammatory cytokines. These observations led Gonzalez-Rey et al to investigate the possibility that ghrelin has anti-inflammatory effects in a murine model of TNBS (trinitrobenzene sulfonic acid)-induced colitis. The effects of ghrelin treatment on weight loss, diarrhea, colitis, and histopathology were measured, as well as on production of inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin significantly improved the clinical and histopathological severity of the TNBS-induced colitis, abrogating body weight loss, diarrhea, and inflammation, and increasing survival (Figure 3). In addition, an associated inhibition of both inflammatory and Th1-driven autoimmune response was observed which appeared to be associated with activation of IL-10/TGFβ1-secreting regulatory T cells. Thus, these novel anti-inflammatory actions for ghrelin provide promise for development of novel therapeutic approaches for human inflammatory bowel diseases and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. See page 1707 Gastric Bypass Surgery Improves Metabolic and Hepatic Abnormalities Associated With Nonalcoholic Fatty Liver DiseaseGastroenterologyVol. 130Issue 6PreviewBackground & Aims: Most patients with extreme obesity have nonalcoholic fatty liver disease (NAFLD). Although gastric bypass (GBP) surgery is the most common bariatric operation performed in obese patients in the United States, the effect of GBP surgery-induced weight loss on the metabolic and hepatic abnormalities associated with NAFLD are not clear. Methods: Whole-body glucose, fatty acid and lipoprotein kinetics, liver histology, and hepatic cellular factors involved in inflammation and fibrogenesis were evaluated in 7 extremely obese subjects (body mass index, 58 ± 4 kg/m2) before and 1 year after GBP surgery. Full-Text PDF The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease RecurrenceGastroenterologyVol. 130Issue 6PreviewBackground & Aims: Early ileocolonoscopy allows detection of recurrence after surgically induced remission of Crohn’s disease (CD). Unequivocal histologic markers predicting recurrence have not been identified. We assessed the predictive value of neural lesions for early endoscopic CD recurrence and long-term reintervention risk. Methods: Ileocolonic resection specimens from 59 patients with CD and 21 control patients were histologically scored for typical inflammatory bowel disease lesions, neural hypertrophy, and presence and severity of inflamed ganglia and nerve bundles. Full-Text PDF Evidence-Based Incorporation of Serum Sodium Concentration Into MELDGastroenterologyVol. 130Issue 6PreviewBackground & Aims: Serum sodium (Na) concentrations have been suggested as a useful predictor of mortality in patients with end-stage liver disease awaiting liver transplantation. Methods: We evaluated methods to incorporate Na into model for end-stage liver disease (MELD), using a prospective, multicenter database specifically created for validation and refinement of MELD. Adult, primary liver transplant candidates with end-stage liver disease were enrolled. Results: Complete data were available in 753 patients, in whom the median MELD score was 10.8 and sodium was 137 mEq/L. Full-Text PDF Therapeutic Action of Ghrelin in a Mouse Model of ColitisGastroenterologyVol. 130Issue 6PreviewBackground & Aims: Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn’s disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. Methods: We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Full-Text PDF