Osman, Karim T.

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Liver transplant (LT) has become increasingly common among reproductive-aged women. The effect of the type of liver donor, either a living donor LT (LDLT) or a deceased donor LT, on pregnancy outcomes is unknown. As such, we aim to review the available literature and assess obstetric, pregnancy, or delivery outcomes in LDLT. We conducted a comprehensive literature review of MEDLINE, EMBASE, Cochrane, and Scopus databases. Random-effect meta-regression assessed the association between the percentage of women who underwent LDLT (independent variable) and the proportion of outcomes. Meta-regression results were expressed as a regression coefficient, which transforms the proportion of outcomes of interest associated with a 1% increase in the percentage of LDLT patients. A value of 0 denotes no relationship between the outcomes and LDLT. A total of 6 articles (438 patients) were included, with a total of 806 pregnancies. Eighty-eight (20.09%) patients underwent LDLT. None of the studies segregated the data based on the type of donor LT. The median time from LT to pregnancy was 4.86 (4.62–5.03) years. Twelve (1.5%) stillbirths were reported. LDLT was statistically significantly associated with a higher rate of stillbirths (coefficient 0.002, p < 0.001; I2 0%). The type of donor LT was not associated with an increased risk of other obstetric, pregnancy, or delivery complications. This is the first meta-analysis to evaluate the effect of the type of donor LT on pregnancy outcomes. This study highlights the lack of robust literature addressing this important topic. The results suggest that pregnancy outcomes after LDLT and deceased donor LT are comparable. Despite LDLT being statistically significantly associated with a higher rate of stillbirths, the association is weak and is unlikely to be clinically significant.

There is no clear consensus regarding the optimal approach for secondary prophylaxis of gastric variceal bleeding (GVB) in patients with cirrhosis. We conducted a systematic review and network meta‐analysis (NMA) to compare the efficacy of available treatments. A comprehensive search of several databases from each database's inception to March 23, 2021, was conducted to identify relevant randomized controlled trials (RCTs). Outcomes of interest were rebleeding and mortality. Results were expressed as relative risk (RR) and 95% confidence interval (CI). We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to rate the certainty of evidence. We included 9 RCTs with 647 patients who had histories of GVB and follow‐ups >6 weeks. A total of 9 interventions were included in the NMA. Balloon‐occluded retrograde transvenous obliteration (BRTO) was associated with a lower risk of rebleeding when compared with β‐blockers (RR, 0.04; 95% CI, 0.01‐0.26; low certainty), and endoscopic injection sclerotherapy (EIS)–cyanoacrylate (CYA) (RR, 0.18; 95% CI, 0.04‐0.77; low certainty). β‐blockers were associated with a higher risk of rebleeding compared with most interventions and with increased mortality compared with EIS‐CYA (RR, 4.12, 95% CI, 1.50‐11.36; low certainty), and EIS‐CYA + nonselective β‐blockers (RR, 5.61; 95% CI, 1.91‐16.43; low certainty). Analysis based on indirect comparisons suggests that BRTO may be the best intervention in preventing rebleeding, whereas β‐blocker monotherapy is likely the worst in preventing rebleeding and mortality. Head‐to‐head RCTs are needed to validate these results.

The differential diagnosis for ulcerating small bowel strictures is extensive and includes exposure to non-steroidal anti-inflammatory drugs (NSAIDs), Crohn’s disease, infections, gastrointestinal lymphoma and vasculopathy. It also encompasses the exceptionally rare and poorly understood diagnosis of cryptogenic multifocal ulcerative stenosing enterocolitis (CMUSE), often a diagnosis of exclusion and considerable difficulty. We present a case of persistent proximal jejunal ulcerating stenoses in a 75-year-old Caucasian man, which continued despite cessation of NSAIDs. After extensive clinical, radiographic, laboratory and ultimately surgical pathological appraisal—as well as failure to improve with both misoprostol and budesonide—he was diagnosed with CMUSE and managed with limited small bowel resection. In the presentation of this case, we aim to underscore the diagnostic challenges that clinicians face in differentiating CMUSE from other more common diagnoses, particularly NSAIDs-induced enteropathy.