Clinical Case Summary

Diseases damaging the enteric mucosa cause malabsorption that may trigger neurologic symptoms, both by immune-related processes and impaired absorption of essential vitamins.
Celiac disease (CD) is found in patients presented with nonhereditary ataxia. In these patients, abnormalities referred to as “gluten ataxia”, are probably the result of immunologic damage to the CNS and peripheral nerves.
B1 is an essential vitamin which its deficiency has broad clinical spectrum; thus, its diagnosis is challenging, and a sensitized clinician is needed to prompt identification. The encephalopathic form of adult thiamine deficiency is called Wernicke-Korsakoff syndrome.
A 40-y/o/w, G4P2, suffered from severe hyperemesis gravidarum resistant to antiemetics during trimester 1.
On 13^th week of pregnancy, she went to the ER, d/t confusion & extensive weakness. Her lab tests showed severe electrolytes deficiencies with transaminitis and elevated CPK levels. She was diagnosed with rhabdomyolysis secondary to her continuous vomiting. On her neurological examination psychomotor slowness and ataxia were found. Thus, Wernicke encephalopathy was suspected and her B1 level was tested and found low: 12 ug/L. She was hospitalized in the ICU to get electrolytes replacement and intravenous thiamine. To confirm the diagnosis, brain MRI was performed and demonstrated a classic picture of Wernicke encephalopathy (1).
6m later she gave birth, but her neurological deficits got worse. TTG level was tested and found positive. Gastroscopy showed duodenal scalloping (2) and Marsh 3C on biopsy (3). She started GFD and neurological rehabilitation. On repeated anamnesis she had abdominal pain before the pregnancy, but her investigation was negative.
This case illustrates a rare herald of CD and increases the awareness of possible manifestation of B1 def.
Points to discuss:

1. Two-hit theory of B1 def. (hyperemesis gravidarum and CD)
2. Neurologic manifestation of CD & B1 def.
3. Vitamins’ malabsorption in CD

References

1. Brain MRI with classic picture of Wernicke encephalopathy
2. Endoscopic picture of duodenal scalloping
3. H&E staining that demonstrates Marsh 3C in duodenal biopsy

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.