Introduction

Although chronic alcohol consumption has progressively decreased in recent years, a third of people over 15 years declare at least one episode of excessive use every month, which ranks Romania on second position, with a rate of 35%, far above the average registered in the EU (20%). Therefore, Romania has one of the highest incidence rates of alcohol-related liver cirrhosis, which has become a major public health problem. This study aimed to investigate the prevalence of liver fibrosis in the asymptomatic alcohol-consuming population.

Aims & Methods

The study aimed to evaluate the relationship between advanced liver fibrosis measured by transient elastography, laboratory parameters, and the amount of alcohol consumed depending on non-modifiable risk factors such as age and gender. Between January 2022 and December 2022, we examined patients with day hospitalization in the Institute of Gastroenterology and Hepatology in Iasi, without liver history, who admitted a moderate or high consumption (women <7 versus >7 drinks/week; men <14 versus >14 drinks/week) for at least one year. The classification of the fibrosis stage by transient elastography was adjusted according to transaminase values. The results were analyzed by univariate analysis and logistic regression to establish models of prediction.

Results

The study included 689 patients with an average age of 49.32±14.31 years, a proportion of 63.7% represented by men. Advanced fibrosis (³ F3) was detected in 19.30% of the examined patients, predominantly in men (14.1%) and patients over 55 years old (12.5%). Excessive alcohol consumption is associated 2 times more with advanced fibrosis in women (OR=5.08; CI 95%: 3.45-9.50, p<0,001) and the group under 40 years old (OR=6.29; CI 95%: 1.67-9.43, p<0,001) compared to men (OR=2.27; CI 95%: 1.76-3.81, p=0,012) respectively patients over 55 years old (OR=3.21; CI 95% : 2.28-4.45 p<0,001). Using logistic regression, it was demonstrated that there was a strong correlation between advanced fibrosis, excessive alcohol consumption, low serum albumin level and the reduction of triglycerides in men (R² Nagelkerke = 0.854; p<0.001) supplemented with the reduction of cholesterol in the age group 40-55 years (R² Nagelkerke = 0.785; p<0.001), respectively of ferritin in those over 55 years old (R² Nagelkerke = 0.804; p<0.001). The association of excessive alcohol consumption, age, low levels of albumin, LDL-cholesterol and C-reactive protein generated a significant predictive model (R² Nagelkerke = 0.784; p<0.001) for female patients.

Conclusion

Screening using transient elastography represents an approach that could provide early diagnosis of advanced liver fibrosis in an asymptomatic population, with the possibility to prevent the evolution of ALD and the development of complications of cirrhosis.

Clinical Case Summary

Seronegative enteropathies pose a complex diagnostic challenge, as their histology mimics celiac disease (CeD) (1). We report a 51-year-old patient with hypertension and osteoporosis, referred for abdominal pain, weight loss, and constipation. Blood tests showed no anemia; anti-transglutaminase and anti-endomysium antibodies were negative, but HLA typing was compatible with CeD. Ileocolonoscopy excluded IBD and microscopic colitis, while OEGD revealed villous atrophy (MARSH 3c). Negative anti-enterocyte antibodies, and exclusion of drugs and infections, led to a diagnosis of seronegative CeD. A gluten-free diet was started, but after 1 year, symptoms improved only partially despite good adherence. OEGD showed persistent duodenal damage with increased intraepithelial lymphocytes (IELs), CD3+ and CD8+ T-cells with monoclonal TCR expression (fig. 1), consistent with RCeD type 1, despite no overt malabsorption. The patient began prednisone 50 mg/day, then switched to open-capsule budesonide, with some clinical benefit but persistent atrophy.
A year later, his daughter was diagnosed with CVID and a heterozygous STAT3 variant (c.1252T>C, p.Cys418Arg), somatically acquired in NK-cell leukemia. A luciferase assay confirmed its gain-of-function (GOF) effect (fig. 2). Family studies revealed the same germline variant in the patient. His diagnosis was revised to STAT3 GOF-associated enteropathy. Further investigations revealed hypogammaglobulinemia, splenomegaly, bronchiectasis, and emphysema. Treatment with Ruxolitinib (a JAK1/2 inhibitor) was started, resulting in clinical and histological remission (fig. 3).
STAT3 GOF enteropathy is a very rare condition (2,3) that should be considered in the differential diagnosis of seronegative villous atrophy. Anti-JAK therapy may be effective (4).

References

References of the images:
Figure 1: Histologic aspects at diagnosis
Figure 2: Luciferase assay of STAT3
Figure 3: Histologic aspects after 1 year of therapy

1. Schiepatti A, Sanders DS, Baiardi P, Caio G, Ciacci C, Kaukinen K, et al. Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus. Gut. 2022 Jun 8;71(11):2218–25.
2. Vogel TP, Leiding JW, Cooper MA, Forbes Satter LR. STAT3 gain-of-function syndrome. Vol. 10, Frontiers in Pediatrics. Frontiers Media SA; 2023.
3. Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Allen HL, De Franco E, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet. 2014;46(8):812–4.
4. Kaneko S, Sakura F, Tanita K, Shimbo A, Nambu R, Yoshida M, et al. Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function. Immunotherapy Advances. 2023;3(1).

Introduction

At the time of treat to target, endoscopic healing is the goal to achieve in ulcerative colitis (UC). Colonoscopy (CO), rectosigmoidoscopy (RS) or rectoscopy can be performed to assess endoscopic healing. The objective of this study was to compare the performance of rectosigmoidoscopy with colonoscopy to predict endoscopic healing (EH) and histological healing.

Aims & Methods

This is a monocentric, prospective cohort of UC patients. All UC patients with a total colonoscopy were included between January 2021 and January 2023. Endoscopic and histological activity were measured using the MAYO endoscopic scores on each colonic segment and the Nancy Score, respectively. The correlation between RS or rectoscopy alone and CO in terms of endoscopic and histological mucosal healing was assessed using Cohen's kappa coefficient.
The study population was calculated according to the following assumptions: (1) absence of rectosigmoidoscopy lesions if absence of total colonoscopy lesions (0%), (2) 10% of lesions not seen in RS, (3) expected difference of 10% between CT and RS. 80 patients had to be included to demonstrate a significant difference in terms of EH between RS and CT with a bilateral alpha risk of 5% and a power of 81%.

Results

80 patients were included. 34 patients were MAYO 0 in RS and CO, 44 were not healed in RS and CO.. The correlation between the two exams was almost perfect with an index к of 0.949 (p=0) for MAYO 0 (2 patients misclassified), and к of 0.945 (p=0) for MAYO 0-1. The correlation between histological healing in RS and CO was almost perfect (к=0.877, p<0.001). Additionally, the correlation between rectoscopy and CT for the evaluation of mucosal healing MAYO 0 and histological healing was almost perfect (к=0.826 (p < 0.001) and к=0.8 (p < 0.001), respectively.

Conclusion

RS is sufficient in UC to assess both endoscopic mucosal healing (whether defined by a Mayo score of 0 or 1) and histological healing. With a false negative rate < 10%, rectoscopy could be a less invasive exam to assess healing in UC.

Introduction

Piecemeal endoscopic mucosal resection (pEMR) is the preferred treatment for large non-pedunculated colorectal polyps (LNPCPs)[1,2]. A major limitation of pEMR is residual or recurrent adenoma (RRA), which was reported to in 15%-30% of cases at first surveillance colonoscopy (SC1)[3], performed 3-6 months after the index procedure, but is reduced to the range of 3%-5% by applying ablative measures to the post-EMR resection margin[4].

Aims & Methods

This study aimed to evaluate the effects of late SC1 on RRA.
This is an analysis of a prospectively collected cohort of adult patients referred for pEMR at two academic centers in Israel, from 2016 to 2023. We included all patients who underwent pEMR of LNCPCs and completed SC1.
We compared outcomes between patients who completed early SC1 at 3-6 months following the index procedure with patients who completed late SC1 later than 6 months. All procedures and surveillance colonoscopies were performed by experienced endoscopists trained in pEMR using high-definition scopes. EMR was followed by thermal ablation of the entire mucosal defect margin with snare soft tip coagulation, as previously described[4].
Scar evaluation at SC1 was performed with high-definition white light and chromoendoscopy. Our primary endpoint was RRA at SC1.
Analyses were performed per lesion. We compared baseline parameters and outcome rates between groups, and performed multivariate analysis to assess the adjusted association of months to SC1 with RRA.

Results

We analyzed 516 lesions that underwent index pEMR resection and subsequent SC1. Baseline parameters and recurrence rates are presented in Table 1. The early SC1 group (n=371) underwent SC1 at a mean of 5.1 months versus a mean of 11.1 months in the late SC1 group (p<0.01; Table 1). Polyp size in the early SC1 group was significantly larger than that in the late SC1 group (mean size 35.9 mm [SD 13.9] vs. 32.1 mm [SD 12.4], p<0.01; Table 1). The distribution of lesion location, granularity differed between the groups (Table 1). However, there were no significant differences in lesion Paris classification or rates of high grade dysplasia (Table 1).
We found no statistically significant difference in the rate of recurrence at SC1 between the two groups (6.3% in the standard group versus 4.8% in the delayed group, p=0.64). Additionally, a sub-analysis comparing the early SC1 group to patients with very late SC1 (>12 months – mean time to SC1 17.9 (SD [5.4] months) and did not reveal significant difference in recurrence at SC1 (6.2% in the early SC1 vs 6.3% in the very late group, p=1).
Multivariate analysis, adjusted for lesion size, location, and high-grade dysplasia, showed that time to SC1 was not significantly associated with RRA (odds ratio 1.05, 95% confidence interval 0.98-1.13).

TABLE 1. Comparison of baseline variables and outcome between the early and late SC1.

Conclusion

Late SC1 is not associated with an increased RRA. Hence, we suggest that high-quality pEMR with margin ablation may alleviate the need for early SC1, thereby reducing healthcare and patient burdens. Further interventional studies are required.

References

[1] Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270–297. doi:10.1055/S-0043-102569/ID/JR15335-1/BIB
[2] Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 159: 1916-1934.e2. doi:10.1053/j.gastro.2020.08.050
[3] Belderbos TDG, Leenders M, Moons LMG, et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: Systematic review and meta-analysis. Endoscopy 2014; 46: 388–400. doi:10.1055/S-0034-1364970/ID/JR910-7/BIB
[4] Klein A, Tate DJ, Jayasekeran V, et al. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology 2019; 156: 604-613.e3. doi:10.1053/j.gastro.2018.10.003

Disclosure

The authors report no conflict of interests