New paradigms of USP53 disease: normal GGT cholestasis, BRIC, cholangiopathy, and responsiveness to rifampicin.

Biallelic variants in the USP53 gene have recently been reported to segregate with normal gamma glutamyltransferase (GGT) cholestasis. Using whole-exome sequencing (WES), we detected two USP53 homozygous variants (c.951delT; p. Phe317fs and c.1744C>T; p. Arg582*) in five additional cases, including an unpublished cousin of a previously described family with intractable itching and normal GGT cholestasis. Three patients, a child and two adults, presented with recurrent episodes of normal GGT cholestasis, consistent with a diagnosis of benign recurrent intrahepatic cholestasis (BRIC). Cholangiopathic changes, possibly autoimmune in origin, were recognized in some patients. Additional phenotypic details in one patient included an enlarged left kidney, and speech/developmental delay. Notably, two patients exhibited a complete response to rifampicin, and one responded to ursodeoxycholic acid (UDCA). Two adult patients were suspected to have autoimmune liver disease and treated with steroids. This report describes new cases of USP53 disease presenting with normal GGT cholestasis or BRIC in three children and two adults. We also describe the novel finding of a dramatic response to rifampicin. The association of cholangiopathy with normal GGT cholestasis provides a diagnostic challenge and remains poorly understood.

Time trends of causes of upper gastrointestinal bleeding and endoscopic findings.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a frequent cause for emergency endoscopy and, in a proportion, requires the application of endotherapy. We aim to evaluate the proportion of variceal and nonvariceal upper gastrointestinal bleeding (NVUGIB), the endoscopic findings that were detected, as well as the temporal trends of endoscopic findings over a period of 13 years. METHODS: This is a retrospective study of patients who underwent an esophagogastroduodenoscopy with an indication of UGIB or presented with hematemesis, melena, or both, as well as those who had hematochezia, from January 2004 to December 2016 (13 years). RESULTS: A total of 2075 patients were included with a mean age of 56.8 years (range 18-113) and males constituted 67.9%, while 65.9% had at least one comorbidity. Symptoms on presentation included hematemesis (52.5%), melena (31.2%), both hematemesis & melena (15.1%), and hematochezia (1.2%). The majority of UGIB were from a NVUGIB source (80.5%) and a variceal source was found in 13.1%, while no endoscopic findings were found in 6.4% of cases. The most common endoscopic diagnosis was gastroduodenal erosions (23.8%), duodenal ulcers (23.5%), reflux esophagitis (16.0%), esophageal varices (12.1%), and gastric ulcers (10.8%). There was no change in the endoscopic findings over the time period of the study. A third of duodenal ulcers (33.3%) as well as 21.9% of gastric ulcers were actively bleeding at the time of endoscopy, while 3.3% of duodenal ulcers had an adherent clot. CONCLUSIONS: NVUGIB composed the majority of cases presenting with UGIB and variceal bleeding was lower than that described in prior studies, but there were no clear trends in the proportion of causes of UGIB during the study duration.

Upper gastrointestinal bleeding: Causes and patient outcomes.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) remains a healthcare burden and is associated with considerable morbidity and mortality. We aim to describe the presentation, clinical, and laboratory characteristics of patients presenting with UGIB as well as important patient outcomes. METHODS: This is a retrospective study performed at a tertiary care university hospital in Riyadh. Electronic endoscopic reports of patients undergoing gastroscopies for the indication of UGIB from January 2006 to January 2015 were included. Demographic data, past medical conditions, medications used, symptoms on presentation, as well as the patients' hemodynamic status, laboratory investigations on presentations, the need for blood products, the need for admission to an intensive care unit, rebleeding, and in-hospital mortality rates were retrieved from medical records. RESULTS: Two hundred fifty-nine patients were included with a mean age of 57.1 years and males constituted 66.8% of the study cohort. At least one comorbidity was present in 88.2%, while 20.7% had a history of prior UGIB, 12.6% had a history of peptic ulcer disease, and 9.2% had known esophageal varices. A nonvariceal source represented 80.1% of the causes (95% CI: 75.4 to 85.3%), 15.5% required admission to the intensive care unit (ICU), the rebleeding rate was 8.9% (95% CI; 5.7% to 12.2%) while the in-hospital mortality was 4.4% (95% CI; 2.4% to 6.9%). The mean pre-endoscopic Rockall score was 2.6 (range: 0 to 5), while the total Rockall score was 4.4 (range: 1 to 9). There was no association between the pre-endoscopic Rockall score and rebleeding (3.0 vs. 2.5, P = 0.27) or need for ICU admission (3.2 vs. 2.4, P = 0.08), the total Rockall score and rebleeding (5.0 vs. 4.4, P = 0.58) or need for ICU admission (5.0 vs. 4.3, P = 0.36). CONCLUSION: Causes of UGIB in this patient population were predominantly nonvariceal and the rebleeding and mortality rates resembled those of other studies.