Use of Biomarkers of Inflammation in the Differentiation of Iron Deficiency and Anaemia-Lessons from Inflammatory Bowel Disease.

Iron deficiency and iron deficiency anaemia are common in inflammatory bowel disease (IBD), to the detriment of the patients' quality of life. Since ferritin, as an acute-phase protein (APP), has limited diagnostic value in IBD, concurrent assessment of C-reactive protein (CRP) is recommended. The World Health Organization suggests using α1-acid glycoprotein (AGP) as an additional biomarker due to its differing half-life. This study aimed to evaluate ferritin levels in patients with IBD using CRP and AGP, individually and in combination. A total of 118 patients with IBD (mean age: 45.48 ± 15.25 years, 47.46% female) were recruited, including 38 with Crohn's disease, 47 with ulcerative colitis, and 33 controls. The results showed that while CRP alone detected an inflammatory increase in ferritin of 29.76%, this increased to 82.14% when AGP or both AGP and CRP were considered (p < 0.05). Elevated AGP levels were more prevalent in patients with ulcerative colitis. However, concordance between high CRP and AGP levels was confirmed in only 55% of cases. Correcting for inflammation using CRP and/or AGP significantly improved the diagnostic accuracy of ferritin levels in patients with IBD, highlighting the challenge posed by inflammation when assessing iron deficiency.

Diagnostic utility of low hemoglobin density to detect iron deficiency in patients with inflammatory bowel disease.

BACKGROUND: In the absence of a feasible noninvasive gold standard, iron deficiency (ID) anemia (IDA) is best measured using multiple indicators. However, the choice of an appropriate single iron biomarker for ID screening continues to be debated. Low hemoglobin density (LHD%) from Coulter counters has been suggested as a useful tool to detect ID. This study investigated the reliability of LHD% for the assessment of iron status in patients with inflammatory bowel disease (IBD) and IDA, anemia of chronic disease (ACD) or mixed anemia (MIX). METHODS: The study population consisted of 143 patients with IBD (aged 39.03±12.53 years, 61.5% female). Blood count, transferrin saturation, serum ferritin, and C-reactive protein were determined by routine assays. Patients with anemia were divided into 3 groups: IDA, ACD and MIX, according to specific criteria. Receiver operator characteristic (ROC) curves were constructed. RESULTS: ROC analysis for LHD% in the detection of ID yielded a cutoff value of 3.8%. In anemic patients, LHD% values did not differ statistically significantly between groups (IDA, ACD, MIX) and no significant difference in LHD% values was observed between patients with IDA and ID. CONCLUSIONS: These results demonstrate that LHD% is a reliable biomarker for the detection of iron deficiency in patients with IBD and anemia, regardless of whether inflammation is present. Our findings indicate that LHD% can provide added value in diagnosing iron deficiency.

Chronic intestinal failure and short bowel syndrome in Crohn's disease.

Chronic intestinal failure (CIF) is a rare but feared complication of Crohn's disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.

Flipside of the Coin: Iron Deficiency and Colorectal Cancer.

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.

Zinc Protoporphyrin Is a Reliable Marker of Functional Iron Deficiency in Patients with Inflammatory Bowel Disease.

Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%); fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC; 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.

Short and Long-Term Effectiveness of Ustekinumab in Patients with Crohn's Disease: Real-World Data from a German IBD Cohort.

: Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn's disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey-Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

Serum Hepcidin Levels Predict Intestinal Iron Absorption in Patients with Inflammatory Bowel Disease.

BACKGROUND: Hepcidin has been shown to be inversely associated with iron absorption and the expression of iron transport proteins in healthy females and patients with iron deficiency. Data describing the relationship between hepcidin expression and iron absorption in patients with inflammatory bowel disease (IBD) are lacking. The objective of this study was to assess the relationship between serum concentrations of hepcidin and iron absorption in patients with IBD and iron deficiency by means of an oral iron absorption test. METHODS: This study was conducted as a comparative, single-centered, open clinical trial. After overnight fasting, an oral iron absorption test was performed, serum iron concentrations were measured 60, 90, 120, 180, and 240 minutes. Changes in iron levels between baseline and the 2-hour timepoint were calculated and recorded. RESULTS: Both ferritin and serum hepcidin levels are found to be good predictors of iron malabsorption, with sensitivity and specificity both at levels > 95%. When the two markers are compared, in our analysis, serum hepcidin levels (AUC: 0.817) tended to predict iron malabsorption slightly better than serum ferritin (AUC: 0.788). CONCLUSIONS: The evidence from our study suggests that serum hepcidin levels are a promising predictor of absorptive capacity in patients treated with oral iron compounds.

Is Early Reimplantation of the Duodenal-Jejunal Bypass Liner Viable?

The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an impermeable fluoropolymer device which prevents food making contact with the proximal intestine, thus inducing weight loss and improvement of type 2 diabetes mellitus (T2DM). However, weight and HbA1c levels generally increase post explantation. This study investigated the safety and feasibility of early DJBL reimplantation in five patients with obesity whose glucose levels had relapsed post explantation, examining the effect of reimplantation on weight loss, BMI and T2DM management. All DJBL implantation and explantation procedures were performed without complications. Despite reduction of T2DM medications, reduction in body weight and HbA1c levels resumed after reimplantation. In conclusion, early reimplantation of DJBL appears feasible, safe and effective.

Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice.

AIMS: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD), who are often treated with intravenous iron. This observational study aimed to investigate the effectiveness and safety of iron isomaltoside in routine practical care of IDA in IBD patients. METHODS: The study included 197 IBD patients designated for treatment with iron isomaltoside. Treatment was administered according to routine practice. Data were recorded at baseline and after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb) levels and haematinics, while safety data included adverse drug reactions and safety laboratory variables. RESULTS: Patients received a mean (range) cumulative dose of 1304 (100-3500) mg iron isomaltoside. Hb increased from 10.7(±1.6) g/dL at baseline to 13.1(±1.5) g/dL at the final visit. In addition, serum iron, ferritin and transferrin saturation increased and soluble transferrin receptor decreased. Calprotectin decreased, as did IBD symptom scores, Harvey-Bradshaw Index (Crohn's disease) and partial Mayo score (Ulcerative colitis). About 8% of patients reported transient adverse reactions, most commonly skin reactions, nausea and vomiting, and 2% SAEs, most frequently tachycardia. CONCLUSION: Iron isomaltoside was demonstrated to be effective and had a good safety profile in IBD patients in everyday clinical practice in Germany.

Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions.

Patients with inflammatory conditions such as inflammatory bowel disease (IBD), chronic heart failure (CHF), and chronic kidney disease (CKD) have high rates of iron deficiency with adverse clinical consequences. Under normal circumstances, serum ferritin levels are a sensitive marker for iron status but ferritin is an acute-phase reactant that becomes elevated in response to inflammation, complicating the diagnosis. Proinflammatory cytokines also trigger an increase in hepcidin, which restricts uptake of dietary iron and promotes sequestration of iron by ferritin within storage sites. Patients with inflammatory conditions may thus have restricted availability of iron for erythropoiesis and other cell functions due to increased hepcidin expression, despite normal or high levels of serum ferritin. The standard threshold for iron deficiency (<30 µg/L) therefore does not apply and transferrin saturation (TSAT), a marker of iron availability, should also be assessed. A serum ferritin threshold of <100 µg/L or TSAT < 20% can be considered diagnostic for iron deficiency in CHF, CKD, and IBD. If serum ferritin is 100-300 µg/L, TSAT < 20% is required to confirm iron deficiency. Routine surveillance of serum ferritin and TSAT in these at-risk groups is advisable so that iron deficiency can be detected and managed.

Management of inflammatory bowel disease-related anemia and iron deficiency with specific reference to the role of intravenous iron in current practice.

INTRODUCTION: Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.