ImportanceNonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice.ObservationsNASH affects an estimated 3% to 6% of the US population and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome. Although a number of noninvasive tests and scoring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosis of NASH. Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss. Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss. In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with annual all-cause mortality rate of 25.56 per 1000 person-years and a liver-specific mortality rate of 11.77 per 1000 person-years.Conclusions and RelevanceNonalcoholic steatohepatitis affects 3% to 6% of the US population, is more prevalent in patients with metabolic disease and obesity, progresses to cirrhosis in approximately 20% of cases, and is associated with increased rates of liver-specific and overall mortality. Early identification and targeted treatment of patients with nonalcoholic steatohepatitis are needed to improve patient outcomes, including directing patients toward intensive lifestyle modification to promote weight loss and referral for bariatric surgery as indicated for management of obesity and metabolic disease.

To investigate the role of donor-specific indirect pathway T cells in renal transplant tolerance, we analyzed responses in peripheral blood of 45 patients using the trans-vivo delayed-type hypersensitivity assay. Subjects were enrolled into five groups—identical twin, clinically tolerant (TOL), steroid monotherapy (MONO), standard immunosuppression (SI) and chronic rejection (CR)—based on transplant type, posttransplant immunosuppression and graft function. The indirect pathway was active in all groups except twins but distinct intergroup differences were evident, corresponding to clinical status. The antidonor indirect pathway T effector response increased across patient groups (TOL < MONO < SI < CR; p < 0.0001) whereas antidonor indirect pathway T regulatory response decreased (TOL > MONO = SI > CR; p < 0.005). This pattern differed from that seen in circulating naïve B-cell numbers and in a cross-platform biomarker analysis, where patients on monotherapy were not ranked closest to TOL patients, but rather were indistinguishable from chronically rejecting patients. Cross-sectional analysis of the indirect pathway revealed a spectrum in T-regulatory:T-effector balance, ranging from TOL patients having predominantly regulatory responses to CR patients having predominantly effector responses. Therefore, the indirect pathway measurements reflect a distinct aspect of tolerance from the recently reported elevation of circulating naïve B cells, which was apparent only in recipients off immunosuppression.

Objective: This study sought to compare trends in the development of cirrhosis between patients with NAFLD who underwent bariatric surgery and a well-matched group of nonsurgical controls. Summary of Background Data: Patients with NAFLD who undergo bariatric surgery generally have improvements in liver histology. However, the long-term effect of bariatric surgery on clinically relevant liver outcomes has not been investigated. Methods: From a large insurance database, patients with a new NAFLD diagnosis and at least 2 years of continuous enrollment before and after diagnosis were identified. Patients with traditional contraindications to bariatric surgery were excluded. Patients who underwent bariatric surgery were identified and matched 1:2 with patients who did not undergo bariatric surgery based on age, sex, and comorbid conditions. Kaplan-Meier analysis and Cox proportional hazards modeling were used to evaluate differences in progression from NAFLD to cirrhosis. Results: A total of 2942 NAFLD patients who underwent bariatric surgery were identified and matched with 5884 NAFLD patients who did not undergo surgery. Cox proportional hazards modeling found that bariatric surgery was independently associated with a decreased risk of developing cirrhosis (hazard ratio 0.31, 95% confidence interval 0.19–0.52). Male gender was associated with an increased risk of cirrhosis (hazard ratio 2.07, 95% confidence interval 1.31–3.27). Conclusions: Patients with NAFLD who undergo bariatric surgery are at a decreased risk for progression to cirrhosis compared to well-matched controls. Bariatric surgery should be considered as a treatment strategy for otherwise eligible patients with NAFLD. Future bariatric surgery guidelines should include NAFLD as a comorbid indication when determining eligibility.

Background Tolerance to non-inherited maternal antigens (NIMA) has provided clinical advantage when kidney transplants are exchanged between siblings, but not when mother herself is the donor. This paradox prompted us to revisit the “two-way” hypothesis of transplant tolerance—that the immune status of both the organ recipient and the organ donor critically influences allograft outcome. Methods We obtained PBMC from 29 living donor-recipient pairs prior to transplant and used the trans-vivo DTH assay to measure immune regulation in both the recipient anti-donor and donor anti-recipient directions. Results We found pre-existing bidirectional regulation in all HLA-identical sibling pairs tested (7/7), and half (9/18) the HLA haploidentical pairs. No significant regulation was found in 4 control living unrelated (LUR) and 2 HLA haploidentical living-related (LR) donor recipient pairs, while unidirectional regulation was found in the remaining 7 haploidentical pairs. Of the 9 HLA haploidentical transplants with unidirectional or no pre-transplant regulation, 7 had an acute rejection episode, and 4 of these experienced graft loss. In contrast, of the 9 HLA haploidentical transplants with bidirectional regulation, only 1 had rejection. Renal function for the latter group was similar to HLA-identical kidney recipients at 3 years post-transplant. Significantly (p<0.05) lower mean sCr values in bidirectional regulators were noted as early as 4 months and this difference became more pronounced at 12 (p<0.005) and 36 months (p<0.0001). Conclusions Contrary to the belief that only the recipient’s immune status matters, the data indicate that pre-transplant immune status of both donor and recipient influence post transplant outcome.

BACKGROUND Over 4% of patients undergoing colorectal surgery develop postoperative urinary tract infection (UTI). METHODS Using 2005 to 2012 American College of Surgeons National Surgical Quality Improvement Program data for 47,781 patients, we examined independent risk factors and complications associated with UTI using multivariate logistic regression. RESULTS Independent predictors of UTI included female sex (odds ratio [OR] 1.705, 95% confidence interval [CI] 1.508 to 1.928), open procedure (OR 1.419, 95% CI 1.240 to 1.624), rectal procedure (OR 1.267, 95% CI 1.105 to 1.453), age greater than 65 years (OR 1.322, 95% CI 1.151 to 1.519), nonindependent functional status (OR 1.609, 95% CI 1.299 to 1.993), steroid use (OR 1.524, 95% CI 1.116 to 2.080), higher anesthesia class, and longer operative time. Patients with UTI had longer hospital stays (7 vs 12 days), higher reoperation rates (11.9% vs 5.1%), and higher 30-day mortality (3.3% vs 1.7%). Postoperative UTI correlated with other complications, including sepsis, surgical site infections, and pulmonary embolism (P < .001). CONCLUSIONS Postoperative UTI in colorectal surgery patients correlates with increased morbidity and mortality. Patients who contract postoperative UTI may be more likely to develop multiple complications.