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BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients. ispartof: Gastroenterology vol:163 issue:6 pages:1630-1642.e3 ispartof: location:United States status: published

The near-fatal occurrence of achalasia in a patient with pre-existing bulimia nervosa is described. The case emphasizes the critical importance of being alert to the development of new pathology in individuals with chronic symptoms, especially in the presence of psychological illness. It also raises the possibility of an additional mechanism by which achalasia could be initiated.

Extra-hepatic bile duct compression is encountered commonly among patients with pancreatic disease, primary sclerosing cholangitis, and cholangiocarcinoma. However, in an elderly lady with predominantly cholestatic liver test abnormalities, magnetic resonance cholangiopancreatography (MRCP) demonstrated a large abdominal aortic aneurysm that was causing extra-hepatic bile duct compression and concomitant proximal bile duct dilatation. This unusual and uncommon finding was almost certainly the explanation for her liver test dysfunction. This report draws attention to the increasing role for MRCP as an accurate, but non-invasive means of appraisal of the pancreatico-biliary tree. In addition, an unusual and uncommon cause of extra-hepatic bile duct compression is discussed.

Editor—We appreciated the report by O'Beirne and Cairns concerning a patient with liver test dysfunction in the setting of treatment with the COX 2 inhibitor celecoxib.1 We are, however, concerned at their use of “cholestatic hepatitis” as the most appropriate description of the pattern of liver test abnormality observed. The patient they described had a maximal aspartate transaminase concentration of 1650 IU/l (reference range 10-40 IU/l), a maximal alkaline phosphatase concentration of 232 IU/l (25-115 IU/l), and peak total serum bilirubin of 123 μmol/l (5-20 μmol/l). In broad terms, two categories of drug associated liver injury are encountered commonly, namely cholestatic and hepatocellular.2 Cholestatic injury has been defined further as occurring when the peak transaminase concentration is less than eight times the upper limit of normal, and the corresponding ALP is greater than threefold normal, whereas hepatocellular injury has been defined as being present when the peak transaminase concentration is greater than eight times the upper limit of normal and the concomitant alkaline phosphatase concentration is less than threefold normal. A mixed pattern of injury, showing features of both, may also be found.3 According to these criteria the patient of O'Beirne and Cairns had evidence of hepatocellular injury primarily, rather than a mixed pattern as the term “cholestatic hepatitis” suggests. Liver biopsy might have helped to emphasise this distinction. The article by Maddrey et al referred to in their report was misquoted4: where the term alkaline phosphatase was used, it should have read alanine aminotransferase. In that study only 0.4% and 0.3% respectively of 6376 patients treated with celecoxib had maximal alanine aminotransferase and aspartate transaminase concentrations greater than or equal to three times the upper limit of normal. None of these transaminase elevations was greater than eight times the upper limit of normal, in contrast to that found in the patient of O'Beirne and Cairns (about 41 times upper normal limit). Therefore, although we disagree with the view that this patient had cholestatic hepatitis on the basis of data quoted, the case does represent the first reported instance of severe hepatocellular liver dysfunction in association with celecoxib treatment.