The Many Faces of Primary Sclerosing Cholangitis: Controversy Abounds.

Primary sclerosing cholangitis (PSC) is notoriously challenging to manage given its heterogeneity with regard to diagnosis, management, and progression. The lack of disease-modifying therapy and variable rate of onset of cirrhosis, portal hypertension-related decompensating events, jaundice, pruritus, biliary complications, and need for liver transplantation is deeply unsettling to clinicians and patients alike. Recent updated practice guidance by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver endeavored to highlight some of these challenges. However, these references only briefly address clinical dilemmas that providers face on a daily basis. This review aims to further discuss these controversial topics, including providing insight into the utility of ursodeoxycolic acid, the significance of alkaline phosphatase normalization, when to consider PSC variants and mimickers, and the implications of continuous hepatobiliary malignancy screening. In particular, there has been a growing body of literature raising concern about repeat exposure to gadolinium-containing contrast. Patients with PSC are potentially at risk for large lifetime exposure to gadolinium related to frequent magnetic resonance imaging scans and whether this carries any negative long-term adverse effects remains unknown.

Pearls and pitfalls in nonalcoholic fatty liver disease: tricky results are common.

Interpretation of diagnostic and surveillance laboratory results and imaging in liver disease is fraught with misinterpretation and/or uncertainty. Nonalcoholic fatty liver disease (NAFLD) represents an ever-growing proportion of liver disease cases but presents unique challenges for the clinician. Given the necessity of excluding other etiologies of liver disease, NAFLD can at times represent a challenging diagnosis as non-invasive assessment and biopsy are imperfect tests with important limitations. Similarly, cautious review of laboratory reports is necessary to avoid missing abnormal pathophysiology. The presence of lab values within the standard reference range may be concerning in the setting of chronic liver disease ("abnormally normal") and conversely results flagged as abnormal may not necessarily be of great concern ("normally abnormal"). This review provides a framework for the clinician to review common diagnostic challenges in NAFLD and enhance patient care.

Systematic review with meta-analysis: risk of hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis compared to other liver diseases.

BACKGROUND: Given the lack of long-term prospective studies, it is challenging for clinicians to make informed decisions about screening and treatment decisions regarding the risk of hepatocellular carcinoma (HCC) in patients with non-alcoholic steatohepatitis (NASH) who do not have cirrhosis. AIM: To characterise the pooled risk of HCC in the non-cirrhosis population. METHODS: Published studies were identified through April 2016 in MEDLINE, Scopus, Science Citation Index, AMED and the Cochrane Library. Two independent reviewers screened citations and extracted data. Random effect odds ratios (OR) were calculated to obtain aggregate estimates of effect size between NASH and non-NASH groups. Between-study variability and heterogeneity were assessed. RESULTS: Nineteen studies with 168 571 participants were included. Eighty-six per cent of included subjects had cirrhosis. The prevalence of HCC in non-cirrhotic NASH was 38.0%; among other aetiologies in non-cirrhotics, it was 14.2% (P < 0.001). Non-cirrhotic NASH subjects were at greater odds of developing HCC than non-cirrhotic subjects of other aetiologies (OR 2.61, 95% CI 1.27-5.35, P = 0.009). When examining all NASH subjects either with or without cirrhosis, those with NASH as the underlying liver disease did not have a significantly increased risk of HCC (OR 1.43, 95% CI 0.77-2.65, P = 0.250). CONCLUSIONS: In non-cirrhotic subjects, those with NASH have a higher risk of HCC compared to other aetiologies of liver disease. Further study investigating the risk factors of HCC among non-cirrhotic NASH patients is needed.

Nonadherence to Biologic Therapies in Inflammatory Bowel Disease.

BACKGROUND: Nonadherence to medications is common with patients with inflammatory bowel disease (IBD). The aim of this study was to assess adherence to biologic medications prescribed for IBD and to identify risk factors for biologic nonadherence. METHODS: This was a single center retrospective cohort study investigating IBD patient adherence to biologic therapies over a 2-year period from September 2014 to September 2016. Specialty pharmacy and infusion center records were obtained and a modified medication possession ratio was calculated. Patient characteristics associated with nonadherence in a univariate model were placed into a multivariate logistic regression to assess independent predictors of nonadherence. RESULTS: Three hundred sixty-five patients met inclusion criteria; 63 patients were on vedolizumab. Three hundred and one patients (82%) had Crohn's disease. The pooled 24-month adherence rate was 66%; adherence to individual biologic therapy included vedolizumab 83%, infliximab 70%, adalimumab 57%, and certolizumab pegol 50%. Facility-administered biologics were independently associated with higher adherence than self-administered biologics (OR 2.39, 95% CI 1.50 - 3.80). Additional risk factors for nonadherence included younger age (OR 1.22, 95% CI 1.01-1.47) and noncommercial insurance (OR 1.78, 95% CI 1.01 - 3.13). CONCLUSIONS: This is the first study to assess adherence to vedolizumab in IBD patients, which was higher than 3 other commonly prescribed biologic medications. Self-administered injections were strongly associated with biologic nonadherence. Younger age and noncommercial insurance also were associated with biologic nonadherence. Modality of administration should be taken into account when selecting a biologic agent for treatment of IBD.