Introduction

Advanced chronic liver disease (ACLD) may present in different stages with distinct prognoses. Child-Pugh and MELD scores are commonly used models for predicting liver-related mortality and decompensation, but they have several limitations. An alternative or complementary tool that is simple and cost-effective would be invaluable. Recently, some studies identified a potential role of ammonia in predicting liver-related outcomes.

Aims & Methods

Our primary objective was to explore the predictive role of plasma ammonia levels regarding liver-related complications and mortality. Our secondary aim was to validate a new measure that corrects baseline ammonia levels to the upper limit of normal (AMM-ULN) and test a cut-off which was proposed in the literature to define patients at higher risk of such outcomes (AMM-ULN ≥ 1.4).
This retrospective study included 278 patients with ACLD who had an ammonia measurement in our hospital between 2018 and 2022. ACLD patients were divided into compensated and decompensated stages, with the latter being subdivided into three stages, according to the type of decompensation. Outcomes of liver-related decompensation and mortality were assessed in each group. AMM-ULN was evaluated as a predictor of these outcomes both in compensated and decompensated patients. The predictive accuracy of AMM-ULN was then determined by identifying the best cut-off.

Results

Plasma ammonia levels and AMM-ULN were predictors of hepatic decompensation (HR = 1.453, 95%CI 1.085 – 1.945, p = 0.012) and mortality (HR = 1.010, 95%CI 1.003 – 1.017, p < 0.001) at 12 months, in the compensated patient group. The AUROC for AMM-ULN was 67.4% in 1-year decompensations and 69.5% in 1-year mortality, with similar results for ammonia levels. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months (p = 0.009 and p = 0.020, respectively).

Conclusion

Both ammonia levels and AMM-ULN were predictors of hepatic decompensation and liver-related mortality in compensated patients, at 12 months of follow-up. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months.

References

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Shalimar, Sheikh, M. F. et al (2019). Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology, 70(3), 982–994. https://doi.org/10.1002/hep.30534
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Elzeftawy, A. et al (2018). Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding. The Turkish Journal of Gastroenterology. https://doi.org/10.5152/tjg.2018.17894

Introduction

Nutritional deficiencies are common in IBD patients and have been widely reported in Crohn's disease (CD) patients in particular. Nonetheless micronutrient screening is not routine in all centres in the UK. Body Mass Index (BMI) is widely used for detecting malnutrition in clinical practice but it is not sensitive marker of muscle mass. Hand grip strength (HGS) is quick to perform and may be an effective parameter to predict muscle function and health in IBD patients in busy outpatient settings. Different cut points are used in clinical practice to determine muscle weakness and may yield different results.

Aims & Methods

The aims of this study were (1) To examine micronutrient status (2) To establish the incidence of over- and under-weight and (3) To measure hand grip strength to determine the frequency of dynapenia in stable patients with IBD referred to specialist dietitian clinic for advice.
A baseline micronutrient screen including 9 vitamin and minerals (Vitamins A,D, E, folate, B12, ferritin, selenium, copper and zinc as well as haemoglobin) was performed on all consenting patients at initial dietitian appointment. Inflammatory marker, C reactive protein, was also checked. Patients with raised CRP, were excluded from the micronutrient analysis. All patients were weighed, height measured and BMI calculated. Hand grip strength was measured using Marsden hand grip dynamometer. The maximum result of 6 trials was recorded and its corresponding percentile (1). Dynapenia was defined as HGS<16kg for females and <27kg for males (2) . Results of Ulcerative colitis (UC) and Crohn’s disease (CD) patients were compared.

Results

A total of 292 consecutive patients, (108m, 184 f) referred for dietitian input from April 2023 to March 2025 were included. Mean age was 45 years (SD18). 201 patients with CD and 91 with UC were included. Results are presented in Table 1. No difference in micronutrient status was found between CD and UC patients apart from vitamin D where a higher incidence of deficiency was found in UC compared with CD patients (p=0.045). Contrary to widespread belief incidence of underweight was low in both CD and UC with a higher incidence of obesity in both groups than underweight. Over a quarter of the IBD population had muscle weakness defined by both Dodds et al (2014) and Cruz-Jentofft et al (2019) which is concerning (1,2).

Conclusion

Vitamin D status in particular should be monitored in all stable patients with IBD. A high proportion of both UC and CD patients were found to have weak muscle strength. HGS is a readily obtainable measure quick to perform and could be easily incorporated into routine clinical practice. Further research is needed to establish its clinical significance for stable IBD patients.

References

1. Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM, Der G, Gale CR, Inskip HM, Jagger C, Kirkwood TB, Lawlor DA, Robinson SM, Starr JM, Steptoe A, Tilling K, Kuh D, Cooper C, Sayer AA. Grip strength across the life course: normative data from twelve British studies. PLoS One. 2014 Dec 4;9(12):e113637. doi: 10.1371/journal.pone.0113637. PMID: 25474696; PMCID: PMC4256164.
2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601. doi: 10.1093/ageing/afz046. PMID: 30312372; PMCID: PMC6322506.

Disclosure

No conflict of interest to disclose

Clinical Case Summary

29-year-old male with bloating, early satiety and frequent stools for last 8 years. He reported loss of around 30 kg weight in the past 6-8 years. His physical examination showed gross emaciation and BMI of 11.75 kg/m². He had pallor, oedema and bradycardia with heart rate of 46–54 per minutes.
Blood investigations showed Hemoglobin 8 gm%, total protein 4.8 gms with albumin 2.1 gms. Serum tissue transglutaminase antibody was negative. Contrast enhanced CT showed multifocal symmetric mural thickening involving short segment of small bowel with proximal dilatation and mild thickening of ileocecal junction. Barium meal-follow through and enteroclysis corroborated these findings. Colonoscopy and upper GI endoscopy were normal.
Diagnosis of Crohn’s Disease was considered and oral prednisolone and mesalamine were started. He continued to be symptomatic over next two years. Laparotomy showed multiple dilated small bowel loops and no stricture. Ileal biopsy showed lipofuscinosis.
The final diagnosis was confirmed to be Brown Bowel Syndrome. Patient was then started on Vitamin E, multivitamins, anti-oxidants and mesalamine.
Intestinal lipofuscinosis is a rare disorder that presents as brown pigmentation, occasionally with bowel dilatation and pseudo-obstruction. It co-exists with malabsorption of fat soluble vitamins, especially Vitamin-E. Pathologically, mitochondrial malfunction and degeneration lead to lipofuscin deposition followed by smooth muscle mitochondrial myopathy. Clinical features show motility disorders along with malabsorption features. Treatment involves treating the underlying cause and early initiation of Vitamin-E supplementation.
Conclusion
We present a rare intestinal disorder, Brown bowel syndrome, characterised by the deposition of lipofuscin in the intestinal cells following chronic malabsorption syndrome and vitamin E deficiency.