Jeffrey R. Lewis

Nonalcoholic Fatty Liver Disease: A Review and Update

The spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from asymptomatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Hepatic steatosis occurs when free fatty acids, released in the setting of insulin resistance and the metabolic syndrome, are taken up by the liver. Additional biochemical insults, including oxidative stress, upregulation of inflammatory mediators, and dysregulated apoptosis, can result in inflammation (producing NASH) and fibrosis. Noninvasive methods (e.g., abdominal ultrasonography) are safe ways to support a diagnosis of hepatic steatosis, but advanced liver histopathologic findings including NASH and fibrosis cannot be identified without pursuing liver biopsy. Recent advances in serologic and imaging methods aim to determine severity of inflammation and fibrosis noninvasively. Currently, therapeutic options for NAFLD are limited to medications that reduce risk factors, but the future holds promise for therapies that might slow the progression of this increasingly prevalent disorder.

Predictors of adalimumab dose escalation in patients with crohn's disease at a tertiary referral center

Background: Pivotal trials for adalimumab (ADA) demonstrated effectiveness versus placebo for induction and maintenance of remission in moderate to severely active Crohns disease (CD). Although the approved maintenance regimen in the U.S. is 40 mg subcutaneously every 14 days, some patients require dose‐escalation ([DE] either an increase in the delivered dose or decrease in the interval of treatment). Our objective was to determine which patient‐, disease‐, and therapy‐related factors were associated with DE in CD patients treated with ADA. Methods: This retrospective medical record review of patients included all patients treated with ADA for CD at the University of Chicago Inflammatory Bowel Disease Center between 2003 and 2008. Patient‐related factors, disease‐related factors, and therapy‐related factors were analyzed. Survival and logistic regression analyses were performed. Results: In all, 75 patients treated with ADA between December 2003 and June 2008 were identified. Thirty‐one subjects (41%) required DE (32% male, median age 37.6, median disease duration 22.7 years) after a median 20 weeks of therapy (range 2–75). Patient‐, clinical‐, and therapy‐related factors were similar between DE and non‐DE. Need for DE was predicted by a family history of inflammatory bowel disease (IBD) (P = 0.0187). Time to DE was predicted by male gender, isolated colonic disease, and smoking history (all P < 0.05); however, only male gender was an independent predictor of time to DE. Conclusions: In all, 41% of CD patients required ADA DE, with shorter time to DE in smokers, men, and patients with isolated colonic disease. Patients, caregivers, and insurers should anticipate DE when utilizing ADA in CD. (Inflamm Bowel Dis 2011;)

Genetic Testing for Inflammatory Bowel Disease: Focus Group Analysis of Patients and Family Members

BACKGROUND Inflammatory bowel disease (IBD) is a chronic gastrointestinal illness with complex genetic underpinnings. Genetic testing for IBD, in particular, for high-risk alleles, is not currently used in clinical practice. Further, preferences and concerns of patients and their family members regarding a genetic test for this condition are not well studied. METHODS Thirty IBD patients and eighteen unaffected first-degree family members or spouses listened to a general educational session about IBD and then participated in one of eight focus groups in order to identify themes of concern and interest regarding a genetic test for IBD. Participants also completed demographic, attitude, and knowledge surveys prior to the focus group sessions. Qualitative analysis of transcripts was performed, and simple comparative statistics of survey data were calculated. RESULTS There were few differences between the responses of patients and unaffected family members. Participants were interested in undergoing genetic testing for IBD despite the fact that information at this time cannot be clinically applied in the diagnosis, prognosis, or treatment of the disease. Advantages of genetic testing commonly identified included benefit to themselves and family members through the possibility of earlier diagnosis and targeted therapies. Disadvantages commonly cited were discrimination by insurance companies and employers and concerns about protection of information. In general, participants were interested in receiving both pre- and posttest information from an informed gastroenterologist, which included a clear basis for testing and the implications of the results for themselves and for family members. CONCLUSIONS The results of the first focus group assessment about genetic testing for IBD reveal themes that are similar in interests and concerns to other genetic diseases. These findings will aid in the construction of patient-centered models of genetic testing that emphasize patient education and interpretation of results.

A case of biliopleural fistula in a patient with hepatocellular carcinoma

Background. A 66-year-old white man with a history of cryptogenic cirrhosis complicated by hepatocellular carcinoma, ascites and hepatic encephalopathy presented with a productive cough and pleuritic chest pain on his right side. He underwent transarterial chemoembolization for hepatocellular carcinoma 6 months before presentation. The patient had a history of coronary artery disease, type 2 diabetes mellitus and hypertension.Investigations. Medical history and physical examination, laboratory investigations, diagnostic thoracentesis, bacterial culture and Gram staining studies, abdominal MRI with magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, infused chest CT and examination of the thorax during open thoracotomy.Diagnosis. Biliopleural fistula with connections between the right pleural space and a branch of the right intrahepatic biliary tree.Management. antibiotics, placement and removal of a chest tube, endoscopic retrograde cholangiopancreatography to guide biliary sphincterotomy with placement and removal of a hepatic-duct stent, open thoracotomy with decortication, percutaneous transhepatic cholangiography and placement of a catheter.

Sa1829 Detection of Colonic Adenomas Using a Low-Cost, High Resolution Microendoscope: Assessment of Accuracy and Interobserver Variability

istry (IHC). IECs were isolated and fractionated into cytosolic and nuclear fractions. p53 levels were assessed using WB and RT-PCR. Cleaved caspase-3 protein levels were assessed by WB. Target genes of p53 including survivin, p21, and Perp were measured using RTPCR. Results: WB of purified IECs 5 days after ICR revealed that nuclear p53 levels in the ICR mice were decreased compared to sham operated mice. Survivin, which is repressed by p53 transcription, was increased by RT-PCR (2-fold) and most dramatically by IHC with (3-5 fold) more survivin positive IEC staining through the lower to mid crypt regions in the ICR mice. We next examined other p53 target genes. Perp and p21 mRNA showed a 1.5 and 2 fold respective decreases in the RT-PCR of WT ICR as compared to sham surgery. Cleaved caspase-3 protein levels demonstrated a 2-fold decrease in the WT ICR as compared to sham surgery.Conclusions : The post-surgical epithelial responses after intestinal resection continue to be poorly understood. We demonstrated the importance of the down-regulation of p53 after ICR. As expected, survivin levels increased in the ICR mouse consistent with the notion that p53 repression and survivin induction contribute to the expanded surface area in ICR mice.