Introduction

Accurate evaluation of Crohn’s disease (CD) activity is crucial to optimise and monitor treatment. Magnetic resonance enterography (MRE) has an important role in characterising disease behaviour, but its interpretation remains subjective. Currently available validated MRE activity scores such as the simplified magnetic resonance enterography index (sMARIA) often fail to capture early treatment response; changes in constituent parameters may lag behind clinical improvements by several months. Furthermore, current evaluation is based on an isolated 2D assessment of subjectively the worst area of diseased bowel rather than assessing the full disease volume. Nonetheless, reductions in bowel wall thickness are associated with treatment response, but are subjective, and small reductions may not be detected reliably. We hypothesised that disease volume may be a more responsive imaging biomarker for disease response than conventional MRE scores.

Aims & Methods

This study aimed to evaluate the technical feasibility and clinical utility of volumetric measurement of terminal ileal (TI) CD on MRE compared to an endoscopic reference standard, and sMARIA activity score. We also assessed whether volumetric changes in disease burden measured on MRE are responsive to changes induced by biologic therapy.
Patients with CD proven by histopathological analysis who prospectively underwent both MRE and ileocolonoscopy scored with Crohn's Disease Endoscopic Index of Severity (CDEIS) within 1 month were included. A board-certified abdominal radiologist placed a centreline through the lumen of the TI that defined the length of diseased bowel on the T2-weighted non-fat saturated sequence. Centrelines were used as the basis for manual segmentations of the involved bowel wall performed independently by two board-certified abdominal radiologists. If there was no disease apparent on MRE, 5 cm of “normal” bowel wall was segmented. The mean volume of disease was compared to CDEIS and sMARIA. Inter-observer agreement for segmentation was assessed using Bland-Altman analysis. We also examined a group of patients with CD who had been treated with biologics, undergone paired pre- and post- treatment MRE, and classified as treatment responders by their treating gastroenterologist based on all available clinical data (global physician assessment). We compared the volumetric burden of CD on their pre- and post- biologic treatment MRE.

Results

Thirty patients (median age of 29 (IQR 24, 34) years, 18 females) with available MRE and endoscopy were included. The mean difference of volume of disease between the 2 readers was -3.0 cm³ (limits of agreement -21.8, 15.9). The median of the mean volume of disease in those with endoscopically active terminal ileal CD (CDEIS ≥ 3, n = 15) was 20.9 cm³ (IQR 11.3, 44.0) compared to 5.7 cm³ (2.9, 9.8) with no active CD on endoscopy (n = 15). The median of the mean volume of disease of patients with active CD by sMARIA (>= 1) (n = 23) was 15.0 cm³ (8.7, 44.0) compared to 2.85 cm³ (2.6, 3.1) for those with inactive CD.
In a further group of 6 clinically responding patients, the median volume of disease on the pre-treatment scan was 28.5 cm³ (26.4, 31.3) and 11 cm³ (4.8, 16.6) on the post-treatment scan, with a median percentage difference of -110% (-147%, -51%).

Conclusion

Volumetric measurement of CD burden on MRE is a feasible method, relates to the endoscopic burden of disease, and is sensitive to changes induced by biologics. This represents a novel, objective biomarker using MRE for assessing disease activity and treatment response in CD, worthy of further validation.

References

Ordas I, Rimola J, Alfaro I, Rodriguez S, Castro-Poceiro J, Ramirez-Morros A, et al. Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease. Gastroenterology. 2019;157(2):432-9 e1.
Puylaert CAJ, Nolthenius CJT, Tielbeek JAW, Makanyanga JC, Rodriguez-Justo M, Brosens LAA, et al. Comparison of MRI Activity Scoring Systems and Features for the Terminal Ileum in Patients With Crohn Disease. AJR Am J Roentgenol. 2019;212(2):W25-W31.
Rimola J, Torres J, Kumar S, Taylor SA, Kucharzik T, Rimola J. Recent advances in clinical practice: advances in cross-sectional imaging in inflammatory bowel disease.
Gut 2022;71:2587-2597.

Disclosure

DB is the Associate Scientific Director, GI Clinical Imaging Lead at Takeda
BB and AB are employees at Motilent, a medical imaging analysis company
AM is the CEO of Motilent
S A Taylor holds shares in Motilent

Introduction

The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available.

Aims & Methods

This systematic review and meta-analysis synthesised randomised controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints in moderate to severe UC. A systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science and grey literature was conducted through November 2024. Separate meta-analyses were performed for induction and maintenance. A random-effects model was used to estimate relative risks (RR), with 95% confidence intervals (CI) and confidence in estimates was evaluated with the GRADE approach (Grading of Recommendation Assessment, Development and Evaluation).

Results

We included 40 RCTs (13 therapies , 14,369 patients). Thirty-two trials provided data in induction phase and twenty-eight in maintenance phase. During induction phase, all biologic therapies except for mirikizumab and filgotinib 100 mg demonstrated superiority over placebo (RR 2.02, 95% CI:1.76–2.31, I²=72%) for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 5.53, 95% CI: 3.78-8.09). In biologic-naive patients and in patients with no previous biologic failure status upadacitinib 30mg had the highest efficacy (RR 4.07, 95% CI:2.69-6.16). In biologic-exposed patients or those with previous biologic failure, upadacitinib 30mg also showed the greatest benefit (RR 10.52, 95% CI:4.55-24.34). For induction of mucosal healing, all interventions were superior to placebo (RR 2.95, 95% CI:2.11–4.13,I²=61%), except for filgotinib 100 mg. Risankizumab showed the highest efficacy (RR 10.25, 95% CI:2.49-42.11). In maintenance phase, all therapies showed superiority over placebo for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 4.18, 95% CI: 2.79–6.27). In biologic-naïve patients or those without prior biologic failure, all interventions—except filgotinib 100 mg and vedolizumab—were significantly superior to placebo, with etrasimod showing the highest efficacy (RR 3.12, 95% CI: 1.79–5.43). Among biologic-exposed patients or those with prior biologic failure, upadacitinib, mirikizumab, ustekinumab, etrasimod, tofacitinib, and risankizumab 180 mg were significantly superior to placebo. Upadacitinib showed the highest efficacy (RR 7.58, 95% CI: 3.42–16.8). For mucosal healing all therapies were superior to placebo, except for risankizumab. Upadacitinib showed the highest efficacy (RR 4.01 ,95% CI: 1.81–8.87). In biologic-naïve patients or those without prior biologic failure, only etrasimod, mirikizumab, upadacitinib 30 mg and subcutaneous infliximab were significantly superior to placebo, with upadacitinib showing the highest efficacy (RR 3.02, 95% CI: 1.18–7.71). Among biologic-exposed patients or those with prior biologic failure, only etrasimod, mirikizumab, and upadacitinib were significantly superior to placebo, with etrasimod demonstrating the highest efficacy (RR 9.45, 95% CI: 1.31–68.36).

Conclusion

Biologic and small-molecule therapies demonstrated substantial efficacy in achieving key endoscopic and histologic endpoints in moderate to severe UC. Upadacitinib consistently showed the highest efficacy across both induction and maintenance phases. Stratified analyses revealed enhanced response rates in biologic-naïve patients, supporting early initiation of advanced therapies. Our findings highlight the importance of individualised treatment strategies and the urgent need for standardised endpoint definitions to enhance comparability across future trials.

Introduction

The decompensation occurrence constitutes the main factor affecting survival for compensated advanced chronic liver disease (cACLD) patients. Based on the type of first decompensation event (DE), two distinct modalities of progression, with relatively different prognostic implications, have been described: “Non-Acute” (NAD) [slow ascites onset, mild hepatic encephalopathy (HE), or progressive jaundice] or “Acute” (AD) [grade 2/3 ascites within 2 weeks, severe HE, or acute bleeding]. Clinically significant portal hypertension (CSPH), defined by Hepatic Venous Pressure Gradient (HVPG) values > 10 mmHg, represents the best predictor for decompensation. However, it’s affected by the invasiveness, the general availability, and the relative strict operator dependence. Alternatively, various noninvasive tools (NITs), usually adopted to estimate liver function and hepatic fibrosis, have been proposed to predict decompensation.
Red cell distribution width (RDW)/Platelet ratio (RPR) has recently been suggested as a routinely assessable NIT predicting fibrosis severity in chronic hepatopathies. However, its predictive role in ACLD patients has never been explored.

Aims & Methods

We aimed to evaluate the accuracy of the RPR in predicting the occurrence and modalities (NAD or AD) of the first DE in cACLD patients.
In this observational study, 140 controls and 680 cACLD patients of various etiologies were prospectively enrolled and followed up (FU) semiannually for 7 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM) data were collected, as well as the Child-Pugh (CP), MELD, AST/Platelet Ratio Index (APRI), Fibrosis-4 score (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were calculated. CSPH was defined by the presence of endoscopic esophageal varices and/or assumed for LSM values > 25 kPa. During FU the DEs were recorded.

Results

208 (30.5%) cACLD patients progressed to decompensated ACLD (dACLD): 141 (67.8%) presented NAD and 67 AD (32.2%) as first DE. Baseline RPR resulted significantly higher in dACLD patients compared to cACLD and controls, as well as in AD patients compared to NAD (all p<0.0001). RPR positively correlated with APRI, FIB-4, ALBI, ALBI-FIB-4, MELD, CP, and LSM [R:0.88, R:0.81, R:0.61. R:0.74, R:0.68, R:0.75, R:0.74, R:0.94; all p<0.0001]. ROC analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs [AUC: 0.95; AUC: 0.94] in the prediction respectively of 7-year first DE and relative modality (AD), as well as better predictive performance if compared to APRI [AUC:0.87; AUC:0.90], FIB-4 [AUC: 0.71; AUC:0.80], ALBI [AUC:0.90; AUC:0.77], ALBI-FIB-4 [AUC: 0.93; AUC:0.79], MELD [AUC:0.78; AUC:0.89], CP [AUC:0.77; AUC:0.71], and LSM [AUC:0.87; AUC:0.94] for both first DE and AD occurrence (all p<0.0001). Multivariable analysis revealed the RPR [adjusted hazard ratio (aHR): 2.24[MD1] [MR2] ] and the presence of baseline CSPH (aHR:1.84) as the variables independently and significantly influencing both outcomes (all p <0.0001). The Kaplan-Meier Log-Rank Test analysis on DE occurrence showed HR:4.62 [C.I. 95% 3.110-5.810] for baseline RPR > 0.472 and HR: 5.10 [C.I. 95% 3.481-6.125] for patients presenting simultaneously baseline RPR >0.472 and CSPH.

Conclusion

The availability of a non-invasive tool predicting the decompensation is an unmet need. RPR non-invasively predicts the timing and modalities of decompensation in cACLD patients representing a potential clinically useful biomarker in this context.

References

1. Taefi, Amir, et al. “Red cell distribution width to platelet ratio, a useful indicator of liver fibrosis in chronic hepatitis patients.” Hepatology international vol. 9,3 (2015): 454-60. doi:10.1007/s12072-015-9638-9
2. Abraldes, Juan G, and Guadalupe Garcia-Tsao. “Simple Clinical Tools to Predict Decompensation in Patients With Compensated Cirrhosis: An Unmet Need.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association vol. 17,11 (2019): 2179-2181. doi:10.1016/j.cgh.2019.04.026
3. D'Amico, Gennaro et al. “Towards a new definition of decompensated cirrhosis.” Journal of hepatology vol. 76,1 (2022): 202-207. doi:10.1016/j.jhep.2021.06.018

Introduction

Standard treatment of autoimmune hepatitis (AIH) typically includes a combination of azathioprine and corticosteroids. However, approximately 20% of patients do not respond well to this conventional therapy. In this scenario, mycophenolate mofetil (MMF) may be used as an alternative treatment for patients with intolerance or non-response to first-line options.

Aims & Methods

This study aims to evaluate the performance of MMF in intolerant or non-responders patients with AIH previously treated with conventional therapy. We performed a systematic review in PubMed, Embase, and Cochrane databases. We analyzed overall remission, remission at AZA intolerance, and remission at AZA non-response. We also compared the outcome of overall remission in patients with AZA intolerance vs. AZA non-response. Statistical analyses were performed using R language 4.3.1.

Results

21 studies and 646 patients were included. The pooled overall remission rate was 62.21 (95% CI 54.31, 70.10). We found an overall remission rate of 66.74 (95% CI 57.48, 76.00) in patients intolerant to AZA, and 27.80 (95% CI 11.56, 44.04) in AZA non-responders. The comparison of overall remission in both groups favored the intolerance group (OR 4.98; 95% CI 1.69, 14.72; p = 0.004).

Conclusion

MMF is effective in inducing remission in patients with AIH who failed the first-line treatment. The overall effect is more prominent in patients who failed conventional therapy due to intolerance. Non-response to AZA may be correlated to suboptimal response to MMF as well.

Introduction

Acute esophageal variceal bleeding (EVB) typically requires initial treatment involving pharmacotherapy and endoscopy, particularly endoscopic variceal ligation (EVL). In cases of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) is recommended, but in regions with limited TIPS access, repeated endoscopic therapy is common. This study evaluates the outcomes of EVL in managing rebleeding and mortality in resource-constrained settings.

Aims & Methods

Patients experiencing acute EVB and undergoing EVL were followed for up to five years or until death. Treatment involved vasoactive drugs and EVL until variceal eradication was achieved. Primary endpoints included bleeding control effectiveness and the need for a second EVL session to manage rebleeding. Rebleeding and mortality rates at 6 weeks and 5 years were analyzed. Logistic regression analysis identified risk factors associated with rebleeding and mortality.

Results

Among 118 patients with acute EVB undergoing EVL, no treatment failures occurred within five days. Eighty-three percent were successfully controlled with one EVL session, while 17% required at least two sessions for recurrent bleeding. In the rebleeding group, no patients rebled within five days after the first EVL, but 75% rebled within 6 weeks. Second EVL was performed for these patients, with a failure rate of 25%. Recurrent EVBs were ultimately controlled by other endoscopic therapy. There was no significant difference in 6-week mortality between rebleeding (15%) and non-rebleeding (18%) groups (p=0.72). Factors associated with 6-week mortality included age, hepatocellular carcinoma, post-bleeding beta-blocker use, creatinine, bilirubin, albumin, Child-Pugh class, and MELD score (Table). Beta-blocker use was associated with preventing recurrent EVB within six months (OR 0.053, 95% CI: 0.004-0.687, p = 0.025). Over five years, the rebleeding group showed a higher mortality trend (90%) compared to the non-rebleeding group (68.8%), though not statistically significant (p=0.06).

Conclusion

In resource-limited settings, multiple attempts of EVL demonstrate success in controlling rebleeding. Long-term trends indicate higher mortality in rebleeding cases, although not statistically significant.

Disclosure

The authors declare that they have no conflict of interest.

Introduction

Chronic liver disease, particularly cirrhosis, leads to significant morphological and psychological endocrine changes, which can have an impact on patients' sexual health. Although sexual health is an important parameter of quality of life, it remains little studied in hepatology.

Aims & Methods

The aim of our work is to study the prevalence and degree of sexual dysfunction in male patients with chronic liver disease, and the associated risk factors.
This is a monocentric, comparative, descriptive and analytical study conducted during the year 2023.We included male patients followed for chronic hepatopathies (group 1 (G1)) as well as a control group of subjects followed in gastroenterology consultation presenting no hepatic pathology (group 2(G2)). Exclusion criteria were the existence of overt hepatic encephalopathy, cognitive disorders or active alcohol abuse, limiting the reliability of the survey.
Sexual health was assessed using the IIEF (International Index of Erectile Function) questionnaire, which covers five domains: erection, orgasm, desire, satisfaction with intercourse and overall satisfaction. Two software packages were used for statistical analysis: Jamovi version 2.3.28 and Microsoft Excel.

Results

Our study included 120 patients, 60 followed for chronic liver disease, and 60 without liver pathology (control group).
Mean age was 44.6 years (21-73 years).
In the group of patients with hepatopathies, we found:
34 (65%) cirrhotics, 24 (40%) of whom had a history of decompensation.
18 (30%) HBV, 11(18%) HCV, 5 (8%) NAFLD, 5 (8%) of undetermined cause, 5 (8%) portal hypertension, 4 (6.6%) portal thrombosis, 12 (19.8%) others.
Patients in the liver disease group had more erectile dysfunction, orgasmic dysfunction, disorders of desire, disorders of sexual satisfaction and disorders of overall satisfaction compared with the control group, with respectively 40/60 (66. 6%) vs 16/60 (26.6%) p 0.003; 35/60 (58.3%) vs 14/60 (23.3%) p 0.012; 41/60 (68.3%) vs 10/60 (16.6) p <.001; 38/60 (63.3%) vs 18/60 (30%) p <.001; and 45/60 (75%), vs 17/60 (28.3%) p <.001.
After statistical analysis, cirrhosis was the only statistically significant risk factor for sexual dysfunction in our study (OR 7.9 ;p 0.012).
Moreover, 100% of patients said they had never been asked about their sexual health during a consultation.

Conclusion

Sexual dysfunction is common in patients followed for liver disease, with cirrhosis as the main risk factor. Sexual dysfunction should be systematically screened, with a multidisciplinary approach to the management of these patients.