Clinical Case Summary

Case report: A 47-year-old woman presented with persistent abdominal bloating, cytolysis and hyperalkaline phosphatase. The patient was underweight. Over 10 years, pancreatic hyperamylasemia (>900 U/l), thrombocytopenia and anemia with low iron and folate levels are observed. Medical history - one spontaneous abortion, 2 children conceived by in vitro fertilization. Viral, autoimmune and genetic liver diseases, autoimmune thrombocytopenia, macroamylasemia, Helicobacter pylori and Giardia lamblia infection were excluded. Immunoglobulins and calprotectin were normal. Serological tests for Celiac disease (CD) detected a positive result only for antigliadin Ig G. Abdominal tomography scan did not detect pathological changes. Duodenoscopy revealed flattening of the intestinal villi suggestive of CD. Duodenal biopsy determined a morphological picture characteristic of CD: type 3c/B2 according to the Marsh-Oberhuber criteria. It was recommended a gluten-free diet, iron and folate therapy. At repeated check-up after 3 months, the patient's condition showed significant improvement, and no changes were detected in the laboratory tests.
Discussion: CD can be diagnosed at any age and can present with a wide range of associated or isolated clinical manifestations. Evaluation of the causes of various biological abnormalities may lead to the diagnosis of CD. The presented case highlights atypical clinical presentations that can be associated with CD. Despite the evolution of serological test performances, there are significant problems regarding the diagnosis in atypical conditions, especially in the patient with intestinal atrophy. In such situations, the intestinal biopsy remains the gold standard diagnosis for CD.
Conclusion: The non-classical clinical presentation of CD is becoming increasingly common in the daily practice of the physician, which requires an awareness of its many clinical faces with atypical forms.

References

- 2 illustrative materials with fragments of biopsy from duodenal mucosa (A - complete villous atrophy, stage 3c according to Marsh-Oberhuber, cryptic hyperplasia by numeral growth and depth of the glandular layer. B - m​arked lymphocytic infiltrate within the lamina propria, minor eosinophilia, hyperplastic crypts, slightly distorted architecture, complete villous atrophy).
- 4 illustrative materials from duodenoscopy

Disclosure

None to declare.

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.

Introduction

Endoscopic submucosal dissection has become the preferred technique for managing large colonic lesions or those suspected of superficial tumor invasion. Macronodular lesions may present with a muscular retraction sign (MRS), which is associated with reduced curative resection rates due to lower R0 resection rates and increased rates of deep submucosal invasion. A few data are available about how to differentiate fibrosis and cancer and about technical and oncological outcomes of ESD in this situation.

Aims & Methods

We conducted a prospective study to evaluate the prevalence of the muscular retraction sign and its clinical outcomes in patients with colorectal macronodular lesions. This analysis utilized data from a large prospective French colorectal ESD cohort (FECCo).

Results

A total of 1,238 macronodular lesions were treated, of which 254 (20.5%) exhibited a muscular retraction sign. The prevalence of MRS increased with the size of the largest macronodule, reaching up to 50% for nodules larger than 40 mm. Enbloc, R0 and curative resection rates were significantly lower in the MRS+ group (82.68% vs 97.86%, 70.97% vs 89.76% and 56.31% vs 83.52%, p<0.001 respectively). MRS+ lesions were more frequently associated with at least submucosal cancer (30.32% vs 9.65%, p<0.001). Regardless of MRS, the presence of a nodule larger than 4cm is associated with a decrease in enbloc resection rates, particularly in the colon, as well as reductions in R0 resection rates and curative resection rates in comparison with nodules smaller than 4cm. The curative resection rate for lesions with ≥T1 cancer and presenting with MRS was 1.5% (p<0.001).
In multivariate analysis, protruding lesions (OR = 1.91 [1.19–3.06], p = 0.007) and nodules larger than 20mm (OR = 2.48 [1.74–3.52], p<0.001) or 40mm (OR 5.98 [3.55-10.08], p<0.001) were identified as risk factors for MRS. The size of the nodule did not increase the risk of submucosal cancer, unlike sigmoid location (OR 2.66 [1.15-6.17] p=0.022) and nodules classified as JNET 3 (OR 6.53 [2.07-20.57], p=0.001).

Conclusion

The prevalence of MRS is 20.5% in cases of macronodular lesions, a rate that increases significantly with the size of the macronodule. MRS negatively impacts the outcomes of ESD in terms of enbloc, R0 and curative resections. ESD should be reconsidered in cases of large macronodular colonic lesions, especially for sigmoid locations or in the presence of JNET 3 vascular pattern anomalies. For rectal large macronodular lesions, ESD should be proposed in expert centers with the option, if necessary, of intermuscular dissection to optimize the R0 resection rate and thereby improve the chances of proposing an organ-preservation strategy.

Introduction

Alternate day oral iron therapy is better than daily oral iron therapy in Iron deficiency anemia (IDA) as it increases the fractional absorption of iron. In Ulcerative colitis (UC) with IDA increased fractional absorption of iron with alternate day iron may not only be better in improvement of anemia but also results in reduced unabsorbed iron delivery to distal bowel and may hence reduce adverse effects.

Aims & Methods

In a randomized, open label trial, from February 2023 to December 2024 patients of UC in remission (Mayo ≤2 OR partial Mayo ≤1 with fecal calprotectin <150mcg/gm for last 3 months) with IDA (ferritin <30mcg/l, transferrin saturation <20%, Hb 8-12 gm/dl) were randomized to every other day 132mg (EOD group) or daily 66mg (OD group) elemental oral iron given as ferrous fumarate for 8 weeks. Primary outcome was the difference in mean change in Hemoglobin (Hb) at 8 weeks. Secondary outcomes were the difference in mean change in RBC indices, iron indices and adverse events at 8 weeks.

Results

54 patients were randomized between both groups. One patient in EOD and 2 in OD group withdrew before treatment initiation. Eleven patients had disease flare on oral iron therapy (5 in EOD and 6 in OD group) p= 0.62 and two patients in EOD group had intolerance requiring oral iron stoppage. Thirty-eight patients completed treatment. The mean change in Hb at 8 weeks in EOD and OD groups was 2.08±1.0gm/dl and 2.09±1.11gm/dl respectively in per protocol analysis (p=0.797). The mean change in serum ferritin, serum iron, transferrin saturation and total iron binding capacity in both the groups is not significant. Disease flare within 6 months prior to oral iron therapy correlated with increased incidence of flare on oral iron therapy. (P=0.04)

Conclusion

Alternate day oral iron is not better than daily oral iron in improving Hb levels, iron indices and with similar incidence of adverse events in patients of UC in remission. A recent flare has increased chances of disease flare with oral iron therapy