Introduction

Total abdominal proctolectomy with ileal-pouch anastomosis (IPAA) for ulcerative colitis (UC) is associated with substantial complications, including the inflammation of the pouch, namely pouchitis. Its estimated cumulative probability is 80% in 30-year1. The antibiotic therapy is highly effective2; however, up to 15-20% of patients develop chronic pouchitis (CP)3. The aim of our study is to provide new evidence about effectiveness of biologic agents to treat CP.

Aims & Methods

We performed an observational retrospective multicentre study at six Italian IBD referral units including adult patients with IPAA for UC surgery treated with biologic/small molecule therapy due to CP. Primary aim was to evaluate clinical response at 6 and 12 months (defined as a reduction of clinical Pouchitis Disease Activity Index - PDAI - sub-score by 2 points or more). Secondary aims were clinical and endoscopic response (defined as a reduction of the modified PDAI - mPDAI - by 2 points or more) at 6 and 12 months, clinical remission (defined as clinical PDAI sub-score <3) at 6 and 12 months, endoscopic remission (defined as endoscopic PDAI sub-score <2) at 12 months and rate of treatment failure, defined as need for re-intervention or change of therapy. Rate of adverse events were calculated too.

Results

77 patients (pts), male 66.2%, mean age 47.7 ± 14.6, 47 (64.4%) treated with advanced therapy before surgery, were included. Some of them has been treated with more than one advanced therapy after IPAA surgery and we used a total of 88 therapeutic lines for analyses (our population was distributed as following: 11.4% infliximab, 14.8% adalimumab, 1.1% golimumab, 54.6% vedolizumab, 14.8% ustekinumab, 2.3% tofacitinib, 1.1% upadacitinib and none with filgotinib). Amongst them, 45 pts (51.1%) reached clinical response at 6 months, whereas 50 (56.8%) at 12 months. No statistical differences were found between each drug neither at 6 (p 0.597) nor at 12 months (p0.610). However, infliximab had higher rate of response compared to the others (Table 1). Considering the mPDAI, 11 pts (44%) reached clinical and endoscopic response at 6 months, whereas 16 (47.1%) at 12 months. Moreover, 51 (58%) pts achieved clinical remission at 6 months and 54 (61.4%) at 12 months. Analyzing data about anti-TNFs, out of 19 pts with clinical and endoscopic response at 12 months, 8 failed at anti-TNFs before surgery. Therefore, 8 pts over 19 (42.1%) had a good answer to anti-TNFs even though they resulted failure before surgery. Endoscopic remission was achieved by 11/34 pts (32.4%) at 12 months. IPAA failure, with consequent ileostomy surgery was performed in just 3 pts, 2 at six months and 1 at 12 months. Adverse events occurred only in 1 pt (hitching).

	6 months	12 months
Type of advanced therapy Infliximab Adalimumab Golimumab Vedolizumab Ustekinumab Tofacitinib Upadacitnib p	6 (60%) 6 (46.2%) 1 (100%) 25 (52.1%) 6 (46.2%) 0 (0%) 1 (100%) 0.597	7 (70%) 7 (53.9%) 1 (100%) 25 (52.1%) 7 (53.9%) 2 (100%) 1 (100%) 0.610

Table 1. Clinical response at 6 and 12 months for each advanced therapy.

Conclusion

In our multicentre experience, clinical remission was achieved in 61.4% of patients with CP under advanced therapy. Infliximab in one-year therapy seems to have higher efficacy rate compared to the others.

References

1. Results up to 30 Years after ileal pouch-anal anastomosis for chronic ulcerative colitis - Lightner AI, Mathis KI, Dozonis EJ, et al. Inflamm Bowel Dis 2017;23(5);781-90
2. Systematic review with meta-analysis: the management o chrronic refractory pouchitis with an evidence-based treatment algorithm - Segal JP, Ding NS, Worley G, et al. Aliment Pharmacol Ther 2017;45:581-92
3. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Sandborn WJ. Gastroenterology 1994;107:1856-60.

Introduction

Whether using Immunomodulators (IMM) as immunosuppressors (ISS), biologics or JAK inhibitors (JAKi) after a diagnosis of cancer in Inflammatory Bowel Disease (IBD) patients (pts) may increase the risk of new or recurrent cancer is undefined.

Aims & Methods

Primary aim: to assess the frequency of new/recurrent cancer in IBD pts treated with IMM after a diagnosis of cancer. Secondary aims: to evaluate in the same population the cancer-related mortality and risk factors for recurrence or new malignancy. In a retrospective multicentre Italian study, clinical records of all IBD pts treated with IMM after a diagnosis of cancer were reviewed. Inclusion criteria: 1) Diagnosis of Crohn’s Disease(CD) or Ulcerative Colitis(UC); 2)History of cancer; 3)Clinical outcome after cancer ≥6 months (mos). Exclusion criteria: 1)IMM used for ≤3 mos or ≤3 administrations; 2)missing data. Data expressed as median[range], differences assessed with Student t-test and X-square test, univariate analysis performed to search for risk factors for new or recurrent malignancy.

Results

Study population included 122 IBD pts (84 CD, 38 UC) treated with IMM after cancer (Female 58 [47.5%]; age: 59.5[26-89] yrs). Index cancer was: genitourinary in 18(14.8%), non-melanoma skin cancer (NMSC) in 17(13.9%), breast in 15(12.3%), melanoma in 14(11.4%), thyroid in 13(10.6%), colon (CRC) in 11(9.0%), hematopoietic in 9(7.4%), prostate in 8(6.6%), neuro-endocrine in 4 (3.3%), head-neck, liver and endometrial in in 3(2.5%), other in 3(2.5%), lung in 1(0.8%). ISS used after cancer (duration: 29[4-200] mos) included: thiopurines in 10(37%), methotrexate in 14(51.9%), others in 3(11.1%) pts. Biologics or JAKi used after cancer (duration: 24[3-180] mos) included: Anti-TNF in 36(32.4%), VDZ in 60(53.6%), UST in 45(40.2%), JAKi in 9 (7.3%) and others in 6(5.4%) pts.The median time interval between cancer and IMM use was 27[0-312] and 48[1-432] mos, respectively. In a median follow up of 8[1-45] yrs after index cancer, 12 (9.8%) IBD patients developed new or recurrent malignancy after IMM use. There were 4 recurrent neoplasms (2 prostatic, 2 thyroid) and 7 new malignancy (7 NMSC,1 salivary gland carcinoma, 2 melanoma and 1 CRC). No cancer-related death occurred. No differences were observed in terms of IBD phenotype and IMM treatments between patients with vs without new/recurrent malignancy. At univariate analysis, when considering age at malignancy, smoking habits, gender, IMM treatment and duration before and after index cancer and treatment for malignancy, no predictive factors for new/recurrent malignancy were observed.

Conclusion

A low frequency of new or recurrent cancer was observed using IMM after cancer in IBD. No risk factors for new/recurrent malignancy were observed.

References

1. Gordon H. et al. ECCO Guidelines on IBD and Malignancies, Journal of Crohn's and Colitis, 2023

Introduction

Hepatic decompensation in patients with cirrhosis represents a critical point in the clinical course of the disease, associated with a significant increase in morbidity and mortality. ¹ Common clinical manifestations of decompensation include ascites, hepatic encephalopathy, and variceal bleeding.^2​ Cystatin C, a low molecular weight cysteine protease inhibitor produced by all nucleated cells, has emerged as a reliable endogenous marker of glomerular filtration rate (GFR). Unlike serum creatinine, cystatin C is not significantly influenced by age, sex, muscle mass, or dietary protein intake, making it a more precise indicator of renal function—particularly in populations with altered muscle mass, such as those with chronic liver disease.³ Beyond its role in renal assessment, cystatin C has demonstrated prognostic value in various clinical settings, including cardiovascular disease, sepsis, and general critical illness^​4,5; however, patients with liver cirrhosis have been underrepresented in these cohorts.

Aims & Methods

Prospective longitudinal study including 62 patients with confirmed Child-Pugh class A or B cirrhosis. Serum cystatin C levels were measured at baseline by ELISA (mg/L), using <0.95 mg/L as the normal cutoff. Patients were followed for 6 months to detect decompensation events. Clinical and biochemical variables (age, sex, creatinine, albumin) were analyzed using quartile stratification, linear trend tests, Pearson’s chi-squared test, and diagnostic performance metrics (odds ratio, sensitivity, specificity, likelihood ratios).

Results

Table 1. Clinical and Biochemical Characteristics According to Hepatic Decompensation During Follow-Up.

Variable	Total (n = 62)	With decompensation (n =27)	Without decompensation (n = 35)
Age (mean ± SD, years)	58.05 ± 11.4	59.1 ± 10.9	57.2 ± 11.9
Male sex, n (%)	32 (51.6%)	14 (43%)	18(56%)
Serum cystatin C (mg/L, mean ± SD)	1.07 ± 0.42	1.25 ± 0.40	0.90 ± 0.40
Elevated cystatin C (>0.95 mg/L), n (%)	35 (56.4)	22 (81.5)	20 (57.1)
Serum albumin (g/dL, mean ± SD)	3.1 ± 0.5	2.8 ± 0.5	3.4 ± 0.4
Creatinine/cystatin C ratio (mean ± SD)	8.7 ± 5.8	7.6 ± 5.1	9.7 ± 6.1
Main etiology: Alcoholic liver disease, n (%)	26 (41.9)	12 (44.4)	14 (40.0)

Of 62 patients (32 men, 51.6%; mean age 58.05 ± 11.4 years), major etiologies were alcohol use (41.9%), metabolic liver disease (38.7%), and autoimmune disease (19.3%). Patients with infectious or undefined etiologies were excluded.
During follow-up, 27 patients (43.5%) developed at least one decompensation event (ascites, encephalopathy, or variceal bleeding). Among them, 81.5% had elevated cystatin C (mean 1.25 ± 0.40 mg/L) versus non-decompensated (mean 0.9 ± 0.40 mg/L, p<0.001). Chi-square analysis showed a significant association (χ² = 4.132; p = 0.042), supported by likelihood ratio (χ² = 4.293; p = 0.038) and linear-by-linear association (χ² = 4.065; p = 0.044). The estimated OR was 3.3.
Decompensated patients had a lower creatinine/cystatin ratio (mean 7.6 ± 5.1 vs 9.7 ± 6.1), though not statistically significant (p=0.162). Albumin levels were lower (2.8 ± 0.5 g/dL vs 3.4 ± 0.4 g/dL, p<0.001).
Quartile analysis showed a higher risk of decompensation in the highest cystatin C quartile (>1.25 mg/L; p<0.001, linear trend), even after excluding patients with eGFR <60 mL/min/1.73 m². This trend was confirmed by linear-by-linear association (χ² = 39.88; df = 1; p < 0.001).

Conclusion

Cystatin C is significantly associated with the development of decompensation events in patients with chronic liver disease, providing an OR of 3.3 and a consistent dose-response trend across quartiles. Although the final sample size was relatively small due to exclusions for loss to follow-up or incomplete biochemical studies, the results were statistically significant and clinically relevant. These findings, based on a prospective design and strict follow-up, suggest that cystatin C could be a prognostic marker, and its inclusion in clinical practice warrants prospective validation.

References

1. Zhai M, Long J, Liu S, Liu C, Li L, Yang L, Li Y, Shu B. The burden of liver cirrhosis and underlying etiologies: results from the global burden of disease study 2017. Aging (Albany NY). 2021 Jan 12;13(1):279–300. doi: 10.18632/aging.104127.
2. D'Amico G, Bernardi M, Angeli P. Towards a new definition of decompensated cirrhosis. J Hepatol. 2022 Jan;76(1):202–207. doi: 10.1016/j.jhep.2021.06.018.​
3. Chen DC, Potok OA, Rifkin D, Estrella MM. Ventajas, limitaciones y consideraciones clínicas en el uso de la cistatina C para estimar la TFG. Riñón360. 2022;3(10):1807-14.
4. Wang Y, Li W, Yang J, Zhang M, Tian C, Ma M, Zhang Q. Association between cystatin C and the risk of ischemic stroke: a systematic review and meta-analysis. J Mol Neurosci. 2019;69(3):444–449. doi:10.1007/s12031-019-01373-1.
5. Luo J, Wang LP, Hu HF, Zhang L, Li YL, Ai LM, et al. Cystatin C and cardiovascular or all-cause mortality risk in the general population: a meta-analysis. Clin Chim Acta. 2015 Oct 23;450:39–45. doi: 10.1016/j.cca.2015.07.016.

Disclosure

I declare that I have no conflicts of interest related to this work.