The latest advances in hepatology were presented in oral and poster presentations. In order to cover the varying subspecialties, the sessions were divided into various sections including 'Acute Liver Failure and Artificial Liver Support', 'Biliary Tract and Immunologic Liver Diseases', 'Cellular and Molecular Biology', 'Clinical and Experimental Hepatobiliary Surgery', 'Hepatotoxicity and Cell Death', 'Transport and Biliary Physiology', 'Viral Hepatitis', 'Evaluation and Treatment of Biliary Disease', 'Necrosis/Apoptosis', 'Portal Hypertension', 'Blood Flow and Vascular Disorders of Cirrhosis', 'Liver Transplantation', 'Fibrogenesis', 'Hepatocellular Carcinoma', 'Metabolism and Genetic Disease', and 'Public Policy, Epidemiology and Decision Analysis'. Drug therapy focused on treatments for viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis, and recurrent viral disease following liver transplant. High dose interferon therapy or various combinations of interferon/ribavirin (ICN Pharmaceuticals Inc) therapy seem to offer the best current therapy for chronic HCV. PEGylated interferon (F Hoffmann-La Roche Ltd) offers hope for treatment and histologic improvement in patients with chronic HCV. Following liver transplantation, combination interferon/ribavirin therapy may also find success, but caution with new potent immunosuppressant monoclonal antibodies is advised. For HBV, intramuscular H-BIG (NABI) appears to be effective and less costly than iv H-BIG administration following liver transplantation. Percutaneous radiofrequency ablation may hold promise over conventional ethanol injection therapy for small hepatocellular carcinoma. Autoimmune hepatitis may respond to tacrolimus therapy whereas budesonide therapy did not provide any advantage to prednisone therapy. For primary biliary cirrhosis, eicosapentate and ursodeoxycholic acid may provide benefit to some patients while silymarin from milk thistle did not provide any additional benefit. In primary sclerosing cholangitis, high dose ursodeoxycholic acid may provide benefit. Ursodeoxycholic acid may also provide benefit for mothers with intrahepatic cholestasis of pregnancy by decreasing pruritus, lowering laboratory values and allowing deliveries to occur closer to term.

Digestive disease week 2000. American Association for the Study of Liver Diseases

Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper

Management of toxicities of immune checkpoint inhibitors.

Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab). A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using R©, package meta. Overall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included in the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently hepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-Barre syndrome, immune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 % (95 % CI, 65–79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18–30 %). The risk of developing irAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56–66 %) for ipilimumab 3 mg/kg and 79 % (95 % CI, 69–89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 % of patients. The median time of onset of irAEs was about 10 weeks (IQR, 6–12) after the onset of treatment, corresponding with the first three cycles but varied according to the organ system involved. Such immune activation could also be indicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4 blocking in 60 % of patients. The price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting the mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a multidisciplinary approach will help to reduce morbidity and therapy interruptions.

/pdf/immune-related-adverse-events-associated-with-anti-ctla-4-2hy5cvnw3u.pdf

Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis

Incidence, Prevalence, and Temporal Trends of Microscopic Colitis: A Systematic Review and Meta-Analysis

Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary manipulation that also may present with extraintestinal manifestations. In many patients, immunosuppressive therapies are necessary. Although AIE is more common in infants, adult involvement has also been documented. Much of what is known about AIE has been gathered from case reports and small case series; therefore, more research in this evolving field is needed. IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) and APECED (autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy) are systemic forms of AIE.

/pdf/autoimmune-enteropathy-a-review-and-update-of-clinical-416tnvw4iw.pdf

Autoimmune Enteropathy: A Review and Update of Clinical Management

Summary
Background

Estimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy.



Aims

To determine the sensitivity and specificity of oesophagogastroduodenoscopy (EGD) for oesophageal narrowing when compared to a structured oesophagram.



Methods

We conducted a retrospective chart review at Mayo Clinic, Rochester of adult patients with eosinophilic oesophageal infiltration of >15 eosinophils/hpf with symptomatic dysphagia, who underwent a structured barium oesophagram. The sensitivity and specificity of EGD were evaluated against the gold standard of oesophagram. Demographic and multiple clinical factors were evaluated as potential predictors of oesophageal narrowing.



Results

Of the 58 patients identified, 34 (58.6%) had a narrowed oesophageal diameter ( 5 food impaction episodes, endoscopic rings, and female sex were the best predictors of oesophageal narrowing. 86% (6/7) patients with persistent dysphagia despite remission of histological eosinophilia responded to oesophageal dilation all of whom had radiological oesophageal narrowing and 71% of whom had no perceived oesophageal narrowing at EGD.



Conclusions

Symptomatic oesophageal narrowing identified by barium oesophagography is common and under-recognised at endoscopy in patients with oesophageal eosinophilia.

Oesophageal narrowing is common and frequently under‐appreciated at endoscopy in patients with oesophageal eosinophilia

https://www.cghjournal.org/article/S1542-3565(13)01515-2/pdf

The epidemiology of microscopic colitis in olmsted county from 2002 to 2010: A population-based study

Outcomes of Patients With Microscopic Colitis Treated With Corticosteroids: A Population-Based Study

A 62-year-old man with chemotherapy-naive, castration-resistant metastatic prostate cancer presented with refractory diarrhea despite prolonged high-dose corticosteroid treatment after receiving 3 doses of ipilimumab as part of a phase 3 clinical trial. The investigative work-up and response to a gluten-free diet essentially confirm celiac disease. Although ipilimumab-induced enterocolitis is a well-reported complication, there have been no reported cases of celiac disease with ipilimumab therapy, to our knowledge. We suspect that ipilimumab may have amplified the symptomatic presentation of previously unrecognized celiac disease or perhaps even triggered the disease itself. With ipilimumab being used more commonly in the treatment of melanoma and prostate cancer, we believe that physicians should be aware of this potential adverse outcome when evaluating a patient who experiences persistent diarrhea during or after ipilimumab treatment.

https://www.mayoclinicproceedings.org/article/S0025-6196(13)00073-6/pdf

Nicole Gentile

Papers

Autoimmune Enteropathy: A Review and Update of Clinical Management

Oesophageal narrowing is common and frequently under‐appreciated at endoscopy in patients with oesophageal eosinophilia

The epidemiology of microscopic colitis in olmsted county from 2002 to 2010: A population-based study

Outcomes of Patients With Microscopic Colitis Treated With Corticosteroids: A Population-Based Study

Association Between Ipilimumab and Celiac Disease