Jaber, Fouad

ABSTRACTObjectiveAlcohol‐related liver disease (ALD) has emerged as a significant public health concern, particularly among younger populations. ALD remains the leading cause of alcohol‐attributable deaths. This study aims to forecast ALD mortality trends up to 2030, focusing on individuals under 55 years.MethodsWe utilized data from the CDC WONDER database (1999–2022) to examine ALD‐related deaths, identified by ICD‐10 codes (K70.0–K70.9). Crude mortality rates (CMRs) per 100 000 were analyzed and temporal trends were assessed using annual and average annual percent changes (APC/AAPC) with empirical quantile confidence intervals. An Autoregressive Integrated Moving Average (ARIMA) model was employed to project mortality rates until 2030, validated through time series cross‐validation.ResultsFrom 1999 to 2022, there were 181 862 ALD‐related deaths among individuals under 55, with mortality rates increasing from 3.9 per 100 000 in 1999 to 9.7 per 100 000 in 2022 (AAPC 4.66%, 95% CI: 3.90%–5.86%). Projections suggest rates will continue to rise, reaching 14.4 per 100 000 by 2030. From 1999 to 2022, the 25–34 age group experienced the highest increase, with an AAPC of 10.27% (95% CI: 9.19%–11.35%), while the 35–44 and 45–54 age groups showed more moderate increases, with AAPCs of 5.03% and 4.38%, respectively. Projections indicate an AAPC of 3.86% for ages 25–34, 3.90% for ages 35–44, and 6.17% for ages 45–54 by 2030.ConclusionForecasts indicate a continued rise in ALD mortality among individuals under 55, necessitating immediate public health strategies to mitigate this trend.

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). Study Question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? Data Sources: MEDLINE, Embase, Scopus, and Cochrane databases. Study Design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

Abstract Introduction Pouchitis is the most common complication in patients with ileal pouch-anal anastomosis (IPAA), which can develop in up to 66% of patients. There is limited data on the effect of orthoptic liver transplantation (OLT) on the risk of developing pouchitis. We aimed to objectively assess whether OLT itself significantly modifies the risk of developing pouchitis in patients with overlap PSC and inflammatory bowel disease (IBD). Method We searched Medline, Scopus, and Embase databases from inception through September 2023 for studies that describe the outcomes of IPAA in patients with PSC and IBD who also have a history of OLT. Pooled proportions, Odds Ratio (OR), and 95% confidence intervals (CI) for data were calculated utilizing a random effects model. Using the Freeman-Turkey double arcsine transformation (FTT) method, the pooled weight-adjusted estimate of event rates for clinical outcomes in each group was also calculated. Heterogeneity between studies was assessed using the Cochrane Q statistic (I2). Results Seven studies with a total of 291 patients with a history of PSC, IBD, and OLT were identified. The pooled overall risk of pouchitis in PSC/IBD patients with a history of OLT was 65% (95% CI: 0.57–0.72), with no heterogeneity observed in the analysis (I2 = 0%). In a subgroup analysis of patients who had IPAA followed by OLT, 3 studies with 28 patients were included; the pooled risk of pouchitis after IPAA and OLT was 83% (95% CI: 0.71–0.94; I2 = 0%), which was significantly higher (P < .001) than the OLT followed by IPAA group (59%; 95 CI: 0.48–0.71; I2 = 0%). There was no difference in the risk of pouchitis between OLT and non-OLT groups (OR = 1.36; 95% CI: 0.37–5.0). Conclusions Our meta-analysis revelaed that pouchitis is common in patients who underwent OLT for PSC, especially in those who had IPAA before the OLT. OLT before IPAA may reduce the risk of pouchitis. Further larger studies are warranted to reproduce this and investigate the reason behind this difference.