Introduction

Anti-mitochondrial antibodies (AMA) are commonly associated with Primary Biliary Cholangitis (PBC), a progressive liver disease. However, the clinical significance of AMA positivity in patients with normal liver enzymes remains poorly understood. Despite the presence of AMA, many patients maintain normal liver function, raising the question of whether these individuals are at risk for developing liver-related complications.

Aims & Methods

This study aims to evaluate the natural history, prognostic implications, and potential risk factors for disease progression in AMA-positive patients with normal liver enzymes.
A retrospective cohort study was conducted using a national healthcare database to identify patients (aged>18) with a positive AMA and normal liver enzymes between 2002 and 2023. Demographics, biochemical parameters, and liver-related complications were analyzed. Multivariate regression models assessed predictors of disease progression.

Results

Among 1,018 patients, 76 (7.5 %) developed Primary biliary cholangitis (PBC), and 30 (2.9%) progressed to cirrhosis over a median follow-up of 6.3 years. Liver-related complications were rare, with esophageal varices in 1.1%, ascites in 1.8%, hepatocellular carcinoma in 0.2%, and liver transplantation in 0.1%. Notably, higher AMA titers were strongly associated with increased risk of developing PBC, cirrhosis and liver-related complications, demonstrating a clear titer-dependent pattern.

Conclusion

Most AMA-positive patients with normal liver enzymes do not develop clinically significant liver disease. However, higher AMA titers identify a high-risk subgroup that warrants closer monitoring. These findings underscore the need for risk-stratified follow-up strategies and may influence future clinical guidelines.

Introduction

Ocular manifestations (OMs) are recognized extraintestinal complications in inflammatory bowel disease (IBD), but their incidence remains understudied. We aimed to evaluate the incidence and trends of OMs in a large population-based cohort of adults with newly diagnosed IBD over the past two decades.

Aims & Methods

We conducted a retrospective cohort study including all adults diagnosed with IBD between 2005 and 2024 in Maccabi Healthcare Services, Israel. Patients with prior OM diagnoses were excluded. The primary outcome was the development of OM (uveitis, episcleritis/scleritis, or orbital inflammation) following IBD diagnosis. Annual incidence trends were evaluated using the Cochran–Armitage test, and multivariable Cox models (stratified by IBD type) identified risk factors.

Results

Among 15,035 newly diagnosed IBD patients (51.8% Crohn’s disease [CD], 48.2% ulcerative colitis [UC]), 349 developed an OM over 119,669 person-years, corresponding to an incidence rate of 2.9 per 1,000 person-years (95% CI: 2.62–3.24), approximately 0.3% of IBD patients per year developed a new OM. By 5 years after IBD diagnosis, the cumulative incidence of OM was 1.7%, and by 10
years, it was 2.7%. The annual incidence rates of OM remained relatively stable from 2005 through 2024, with no clear upward or downward trend (Cochran–Armitage trend test p = 0.125, Table 1). OM incidence was higher in CD than UC (p < 0.001) and remained stable over time (p = 0.125). The median time to OM was 45 months. In CD, female sex (HR 1.62; 95% CI: 1.24–2.13) and systemic corticosteroid use (HR 1.62; 95% CI: 1.18–2.22) were associated with increased OM risk. In UC, corticosteroid use (HR 2.17; 95% CI: 1.40–3.37) and intestinal surgery (HR 3.50; 95% CI: 1.69–7.28) were significant predictors.

Table 1 – Incidence of OM among adults with IBD (2005-2024)

Conclusion

OMs in adult-onset IBD are infrequent but clinically relevant, particularly among CD patients and those with markers of severe disease. Clinician awareness and early referral remain essential for prompt diagnosis and management.

Introduction

Food is often reported as a trigger for symptoms in patients with irritable bowel syndrome (IBS). One of the proposed pathophysiological mechanisms is a local immune response to food antigens, triggered by a preceding infection¹.

Aims & Methods

This study aimed to investigate rectal mucosal reactions to food in patients with IBS. Therefore, patients with IBS and food-related symptoms were included. Allergies to the food items that were tested during the colonoscopic antigen provocation (COLAP) were excluded by an allergologist. The COLAP was started in the absence of macroscopic abnormalities during sigmoidoscopy. A 200 μL solution of each food antigen (wheat, gluten, soy, and milk; administered in a randomized order and blinded), a negative control (NaCl 0.9%), and a positive control (histamine) were injected in the rectal mucosa, with a positive reaction defined as mucosal edema 12 minutes after injection and judged based on a previously used semiquantitative scale ². The reaction was independently judged by two endoscopists, resulting in a positive or negative reaction when they agreed and doubtful when they did not.

Results

Data from ten patients were available for this interim analysis. Nine were female, with a median age of 45 [range 24-58] years, and a median IBS symptom severity score of 356 [range 197-416], i.e. in the moderate to severe range. Six patients had predominant constipation, one predominant diarrhea, and three mixed bowel habits. COLAP was positive in seven patients, with a positive reaction for one food antigen in three patients and for two food antigens in four patients. In the other three patients, the test was only doubtful for one of the food antigens (n=2), or negative for all (n=1). A positive reaction to gluten was observed in five patients, to soy in three, to wheat in two, and to milk in one (Table). The reaction to histamine was positive in eight patients, with no positive reaction after injection of the negative control in all.

Conclusion

A local intestinal reaction to food antigens was seen in a subset of patients with IBS. Further research will focus on underlying pathophysiological mechanisms and clinical relevance of these findings.

References

1. Aguilera-Lizarraga J, Florens MV, Viola MF, Jain P, Decraecker L, Appeltans I, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021;590(7844):151-6.
2. Bischoff SC, Mayer J, Wedemeyer J, Meier PN, Zeck-Kapp G, Wedi B, et al. Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy. Gut. 1997;40(6):745-53.

Introduction

Gastrointestinal (GI) hemorrhage accounts for 30% of acute decompensations in cirrhotic patients, with 60% originating from variceal bleeding. Each decompensation episode carries an in-hospital mortality rate of 13%, and a 6-week mortality rate of 20%, commonly assed using Child Pugh (CP) and MELD scores. The ALBI (Albumin-Bilirubin) score, which includes only two variables, offers a simplified evaluation of liver function. However, there is limited data on its utility in predicting short-term mortality in cirrhotic patients with GI hemorrhage.

Aims & Methods

This study aimed to evaluate the association between ALBI Score with short-term mortality in cirrhotic patients with GI hemorrhage. We conducted a prospective, cross-sectional study between January and December of 2023 at Hospital Roosevelt, Guatemala, including cirrhotic patients admitted for GI hemorrhage. Informed consent was obtained from all participants. Categorical variables were analyzed using the chi-square test, normally distributed continuous variables with Student’s t-test, and non-normally distributed variables with the Mann-Whitney U test. Logistic binary regression and AUROC analysis were used to assess associations with short-term mortality. Statistical analyses were performed using SPSS.

Results

A total of 187 patients were included: 50.8% female and 49.2% male, with a mean age of 56 among survivors and 58 among non-survivors. Of these, 52.9% had a prior diagnosis of cirrhosis, while 47.1% were newly diagnosed. Cirrhosis etiology was metabolic in 50.2%, alcoholic in 42.7%, autoimmune in 4.3%, HCV in 1.6%, and HBV in 1.1%. At admission, 80.8% had no ascites and 97.3% had no hepatic encephalopathy. he causes of GI hemorrhage were 86.1% esophageal varices, 3.2% gastric varices, 9.1% gastric ulcers, and 1.6% esophagitis.
Non-survivors had significantly lower systolic blood pressure (93.90 ± 16.3 mmHg vs. 107.92 ± 17.4 mmHg; p = 0.002) and mean arterial pressure (69.50 ± 14.5 mmHg vs. 79.67 ± 11.7 mmHg; p = 0.005) compared to survivors. Non-survivors exhibited significantly higher INR (1.79 ± 0.56 vs. 1.52 ± 0.41; p = 0.026) and total bilirubin (5.85 ± 8.73 mg/dL vs. 2.02 ± 2.82 mg/dL; p = 0.031), and lower serum albumin levels (2.40 ± 0.43 g/dL vs. 3.10 ± 0.54 g/dL; p < 0.001).

Prognostic scores were significantly higher among non-survivors: MELD (19.25 ± 10.09 vs. 13.57 ± 5.47; p = 0.002), MELD-Na (20.35 ± 9.76 vs. 14.44 ± 6.42; p = 0.002), Child-Pugh (9.15 ± 2.21 vs. 7.18 ± 1.90; p < 0.001), and ALBI score (-0.96 ± 0.51 vs. -1.76 ± 0.58; p < 0.001). Additionally, the length of hospital stay was significantly shorter among non-survivors (3.90 ± 3.82 days) compared to survivors (6.59 ± 5.58 days; p = 0.001).

• Higher ALBI score was significantly associated with mortality (Risk Ratio 25.80; 95% CI: 6.75–98.67; p < 0.001),
• Hospital stay <5 days (RR 9.91; 95% CI: 2.07–47.47; p = 0.004),
• Endoscopy performed within 12 hours (RR 7.53; 95% CI: 2.01–28.15; p = 0.003).

Conclusion

The ALBI score outperforms CP and MELD scores in predicting short-term mortality (in-hospital, 4 weeks, and 6 weeks) in cirrhotic patients with GI hemorrhage. Observed mortality was 10% in-hospital, 13% at 4 weeks, and 16% at 6 weeks.

Introduction

Post endoscopy upper gastrointestinal cancers (PEUGIC) are often missed opportunities to diagnose earlier or even prevent cancer. Up to 71% of PEUGIC are potentially avoidable, but identifying and investigating them can be challenging. A national process for identifying all PEUGIC in the English National Health Service and performing root cause analysis was developed.

Aims & Methods

Potential PEUGIC between 2017 and 2023 occurring 3-36 months after an index endoscopy which did not result in a cancer diagnosis were identified from National Cancer Registration Dataset and Hospital Episode Statistics held by the National Cancer Registration and Analysis Service. Data from local root cause analysis were uploaded onto a secure portal for national analysis. PEUGIC following surveillance endoscopies were excluded from this analysis. Logistic regression analysis was used to identify associations with outcomes of interest.

Results

3151 potential PEUGIC were examined by local reviewers in 144 English hospitals. 635 (20%) were excluded on local review and data were available for 2516 PEUGIC. 1897 (75.4%) PEUGIC followed diagnostic, follow-up or screening endoscopies. PEUGIC sites were oesophagus 61%, stomach 34% and duodenum 5%.
Table 1 shows the summary PEUGIC root cause results analysis based on the World Endoscopy Organisation categorisation. Categories C and D were associated with poor outcomes with 29% and 23% of cases receiving curative treatment, respectively. Compared to categories A and B receiving curative treatment in 53% and 37% of cases, respectively. Squamous cell cancers accounted for 37.5% of oesophageal PEUGIC and were associated with no lesion being detected (category C or D) in the PEUGIC segment OR 1.71 (95% CI 1.21-2.43).
Findings on index endoscopy (category A or B) at later oesophageal PEUGIC: pre-malignant lesion 23% (e.g. Barrett’s), cancer associated lesion 20% (e.g. ulcer) and other oesophageal focal lesions 15%. Findings on index endoscopy in gastric PEUGIC: cancer associated lesion 26%, pre-malignant lesion 7% and other gastric focal lesions 18%. 45% of the index endoscopies were classified as inadequate. Patient harm and adverse treatment outcomes were associated with an inadequate index endoscopy OR 1.56 (95% CI 1.28-1.91). The most common reason for inadequate endoscopy was inadequate management of lesions identified, which were most likely to be cancer associated lesions OR 1.43 (95% CI 1.11-1.69), specifically oesophageal strictures (24%) and gastric ulcers (23%).
Gastric diagnostic PEUGIC were diagnosed with more advanced cancer (40% stage 4 at diagnosis vs 30% oesophageal PEUGIC). Treatment following cancer diagnosis was adversely affected in 42% of PEUGIC. Reviewers considered that 57% of PEUGIC were at least possibly avoidable and 9% led to premature death.

Table 1 Root causes of all diagnostic PEUGIC

Conclusion

Abnormalities in the area of the later cancer were detected at index endoscopy in 59% of PEUGIC. Inadequate lesion assessment, endoscopy and/or decision making was noted in 45% of PEUGIC, which adversely affected treatment outcome. Oesophageal squamous cell cancer was a common cause of PEUGIC, suggesting issues with lesion recognition in this cancer. Many patients had incurable disease when diagnosed and treatment was adversely affected in 42%.