Nonalcoholic steatohepatitis is associated with an atherogenic lipoprotein subfraction profile

Background: Nonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk. Findings: Ion mobility analysis was performed on 78 individuals with obesity undergoing weight loss surgery. All individuals had standard of care liver biopsies performed during surgery. Patients with NASH had significantly smaller peak LDL diameter (P = 0.02, 219.0 Å vs. 222.6 Å), and levels of IDL2 (P = 0.01, 104. nmol/L vs. 133.4 nmol/L) and HDL2b (P = 0.05, 676.7 nmol/L vs. 880.1 nmol/L) compared to those without NASH. NASH patients had significantly higher LDL-IVb levels than those without NASH (P = 0.02, 49.0 nmol/L vs. 37.1 nmol/L). The inverse association of LDL peak diameter with NASH remained significant after adjustment for diabetes (P = 0.02). HDL2b levels were inversely correlated with hepatocyte ballooning and NASH and these remained significant after adjustment for diabetes (P = 0.0017 and P = 0.007, respectively). IDL2 levels were inversely correlated with NASH, hepatocyte ballooning and fibrosis stage but these were not significant after adjustment for diabetes. Conclusions: The lipoprotein subfraction profile in subjects with NASH is characterized by small peak LDL diameter, reduced HDL2b levels and elevated LDL-IVb levels. These changes may contribute to the increased CVD seen in patients with NASH

The Absence of Obstructive Sleep Apnea May Protect against Non-Alcoholic Fatty Liver in Patients Undergoing Bariatric Surgery

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development. Aim This study sought to identify factors predictive of normal liver histology in a bariatric cohort. Methods: Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded. Results: One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR) of 6.8, 95% confidence interval (CI) 2.4–18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03–1.9). In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05–0.83). Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA) was strongly associated with normal histology (OR 5.6, 95% CI 2.0–16.1). In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85. Conclusions: Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD

The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease

Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets

Primary Follicular Lymphoma of the Gastrointestinal Tract

BACKGROUND: Follicular lymphoma (FL), a common nodal lymphoma, is rare in the gastrointestinal (GI) tract. We report our experience with primary FL of the GI tract. METHODS: The surgical pathology computer files at the Massachusetts General Hospital were searched for cases of FL involving the GI tract. Patients were included if on staging, the major site of disease was the GI tract. Thirty-nine cases were identified. Clinical data were collected from electronic medical records. RESULTS: The 27 women and 12 men ranged in age from 29 to 79 years (median, 59 y). Thirty tumors involved the small bowel (19 the duodenum); 8 involved the colon; and 1 involved the stomach. Eight of 10 tumors that were resected involved the small bowel (jejunum and/or ileum without duodenum) of which 5 presented with intestinal obstruction. All tumors were grade 1 or 2. Immunostains showed consistent expression of CD20 (100%), CD10 (97%), and Bcl-2 (97%). Among the 34 cases with Ann Arbor staging information, 22 were stage I, 10 were stage II, and 2 were (6%) stage IV. Of 36 cases with follow-up (median, 4.5 y), 27 patients are alive without disease, 7 are alive with disease, and 2 died of other causes. No lymphoma-related deaths were recorded. CONCLUSIONS: Primary FL of the GI tract occurs most often in middle-aged adults with a 2:1 female preponderance. The most frequent site of involvement is the duodenum, followed by the ileum and colon. Distal small bowel involvement is more likely to present as bowel obstruction requiring resection. The disease is localized in the bowel and regional lymph nodes in the vast majority of cases. The prognosis is favorable even when the disease is disseminated

Nonalcoholic steatohepatitis is associated with an atherogenic lipoprotein subfraction profile.

BackgroundNonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk.FindingsIon mobility analysis was performed on 78 individuals with obesity undergoing weight loss surgery. All individuals had standard of care liver biopsies performed during surgery. Patients with NASH had significantly smaller peak LDL diameter (P = 0.02, 219.0 Å vs. 222.6 Å), and levels of IDL2 (P = 0.01, 104. nmol/L vs. 133.4 nmol/L) and HDL2b (P = 0.05, 676.7 nmol/L vs. 880.1 nmol/L) compared to those without NASH. NASH patients had significantly higher LDL-IVb levels than those without NASH (P = 0.02, 49.0 nmol/L vs. 37.1 nmol/L).The inverse association of LDL peak diameter with NASH remained significant after adjustment for diabetes (P = 0.02). HDL2b levels were inversely correlated with hepatocyte ballooning and NASH and these remained significant after adjustment for diabetes (P = 0.0017 and P = 0.007, respectively). IDL2 levels were inversely correlated with NASH, hepatocyte ballooning and fibrosis stage but these were not significant after adjustment for diabetes.ConclusionsThe lipoprotein subfraction profile in subjects with NASH is characterized by small peak LDL diameter, reduced HDL2b levels and elevated LDL-IVb levels. These changes may contribute to the increased CVD seen in patients with NASH

Obstructive Sleep Apnea Is Associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology.

Background and aimsNonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis.MethodsTwo hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject.ResultsSubjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 vs. 37.7 U/L, P = 0.0007; AST 31.7 vs. 20.5 U/L, P = 0.0007). OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P = 0.03 OR 2.01; 95 %, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment.ConclusionsOSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH

Sessile Serrated Adenoma: Challenging Discrimination From Other Serrated Colonic Polyps

Sessile serrated adenoma (SSA) is the proposed precursor for microsatellite unstable colorectal carcinomas and some authorities recommend that SSAs should be managed similar to adenomas. The aim of our study was to determine whether serrated polyps can be classified with sufficient consistency to support current treatment recommendations. One hundred eighty-five serrated polyps were classified as hyperplastic polyp (HP), SSA, or traditional serrated adenoma (TSA) by 5 pathologists blinded to clinical data. The observers documented which histologic features they considered most helpful in reaching their diagnosis in each case. In a second round, the observers were provided with polyp site and size. After reaching a consensus on minimum criteria for SSA and TSA, the pathologists classified another set of 50 polyps. The interobserver concordance was calculated using kappa statistics. In the first round, the overall interobserver agreement was moderate (kappa=0.55). Concordance for HP and SSA was moderate whereas it was nearly perfect for TSA. In the second round, there was no improvement in the concordance. All observers relied more often on architectural features than on cytologic ones to distinguish SSA from HP and agreement was reached that architectural features should provide the basis for the diagnosis of SSA. Subsequently, interobserver concordance was slightly improved but remained moderate (kappa=0.58). Interobserver agreement for the diagnosis of serrated polyps is moderate. However, this level of variability is acceptable because the presence of SSA indicates increased risk of developing additional serrated polyps and carcinoma, and surveillance is appropriate