1. Introduction
Crohn’s disease (CD) is one of the two main forms of inflammatory bowel disease (IBD) and is characterised by recurrent inflammation of the gastrointestinal tract, which can occur throughout its entire length but most commonly affects the intestines [
1]. According to the Centre for Disease Control and Prevention (CDC), the global prevalence of the disease rose to 6.8 million people in 2017 [
2]. Despite the improvement of treatment options for CD symptoms, up to 50% of patients require surgery within 10 years of diagnosis. Indications for small bowel resection include complications such as strictures, fistulas and abscesses as well as treatment resistance. They can all contribute to intestinal failure (IF), including the development of short bowel syndrome (SBS) [
3].
SBS is a malabsorptive condition that leads to diarrhoea, dehydration, electrolyte imbalances, nutrient deficiencies and weight loss, eventually leading to the development of malnutrition [
3]. Malnutrition affects 65–75% of CD patients, and can occur not only as a result of SBS but also due to the underlying disease itself as a result of reduced intestinal absorption, intestinal dysbiosis, or symptoms such as abdominal pain, loss of appetite, nausea, or vomiting [
4]. Inflammation leads to a loss of blood and proteins in the intestinal lumen, and changes in ionic transport lead to a loss of fluids and electrolytes [
5]. To meet nutritional requirements and maintain fluid and electrolyte balance in CD patients, particularly those with SBS-IF, long-term total or supplemental parenteral support (PS) is implemented. PN is a life-saving therapy in which nutrients such as amino acids, glucose, lipids, electrolytes, vitamins and trace elements are administered intravenously [
6]. The technological advances in the 20th century have made it possible to transfer this method to the home setting as home parenteral nutrition (HPN), which has greatly improved the lives of patients requiring long-term nutritional support, such as those with chronic intestinal failure [
7].
There are relatively few data on patients with CD receiving HPN. The purpose of this study was to examine the nutritional status and specific characteristics of patients with Crohn’s disease who require HPN and to analyse the HPN treatment course with regard to selected parameters. The study aims to provide evidence that can guide early nutritional interventions and improve the management of Crohn’s disease patients on HPN.
2. Materials and Methods
2.1. Study Design and Setting
This retrospective observational study was conducted in a Polish reference centre for HPN and included prospectively collected data from hospitalisation records during HPN qualification and from all medical records of outpatient visits to the HPN centre between November 2004 and April 2022. Patient follow-up extended from the first HPN hospital admission to the last visit on the day of study termination, HPN discontinuation, or death. The study protocol was approved by the Ethics Committee of the Medical University of Warsaw (AKBE/347/2023).
2.2. Study Sample
The study group consisted of all consecutive adult patients with CD who qualified for HPN between November 2004 and April 2022. The inclusion criteria required that Crohn’s disease was an initial cause for implementing PN, and patients with cancer as a concomitant disease were excluded from the analysis (N = 3). Based on these criteria, a cohort of 46 patients were included in the analysis.
2.3. Institutional Approach to HPN Procedure
The assessment of qualification for home parenteral nutrition took place in the hospital. It included a nutritional status assessment, blood tests, a full physical examination, education and training of the patient and/or carer by a trained nurse, the insertion of a tunnelled central venous catheter (CVC), and prescription and adjustment of the nutritional formula individually prepared by the hospital pharmacy or patient’s carer. The nutritional assessment, including measurements of body weight and height, calculation of body mass loss, and assessment with the SGA scale, was carried out by a trained dietitian within the first 24 h of admission to the ward and repeated every 7–14 days if necessary. After discharge, patients were required to remain in constant contact with the HPN clinic and attend all quarterly follow-up visits.
2.4. Data Collection and Nutritional Assessment
The data collected included demographic information such as gender and age at the time of HPN qualification, the date of onset and duration of HPN, and, if applicable, the date and reason for the discontinuation of HPN. Medical data, such as concomitant diseases, the indications for parenteral nutrition, and the anatomical details of the bowel, including the presence or absence of fistulas, stomas, and the type of SBS, were also collected. If the patient’s bowel anatomy changed during the study, both the initial and final parameters were recorded. The laboratory data collected included serum albumin, total protein, C-reactive protein, leukocytes, lymphocytes, and haematocrit. Anthropometric measurements such as weight and height as well as nutritional assessment data including unintentional weight loss (kg and % of body mass) were also analysed. For patients who qualified for the HPN procedure since 2012—the start of mandatory use of the Subjective Global Assessment (SGA) to assess nutritional status—scale results were collected. For patients who qualified prior to 2012, the SGA was performed by a trained clinical dietitian during data analysis based on the medical records obtained.
Body mass index (BMI) was calculated by dividing weight (kg) by height (m) squared [
7]. BMI categories were classified according to CDC criteria: underweight (BMI < 18.5 kg/m
2), normal weight (BMI ≥ 18.5 kg/m
2–24.9 kg/m
2), or overweight (BMI ≥ 25.0 kg/m
2). The SGA results were interpreted as follows: A—well-nourished; B—moderately malnourished (or suspected of being malnourished); C—severely malnourished; D—high risk of malnutrition. Inflammation was detected when the C-reactive protein (CRP) level exceeded 10 mg/L, and loss of muscle mass was assessed based on physical examination data via the SGA scale and deterioration of the patient’s physical condition.
Based on the serum albumin level, body weight, and ideal body weight (calculated according to the Lorentz formula [
8]), the Nutritional Risk Index (NRI) in patients under 65 years of age and the Geriatric Nutritional Risk Index (GNRI) in patients over 65 years of age were calculated according to the following formulas:
Patients with an NRI score >100 were considered to be at no nutritional risk, 97.5–100 at mild risk, 83.5–97.5 at moderate risk, and <83.5 at major nutritional risk [
9]. Patients with a GNRI score >98 were classified as at no risk, 92 to ≤ 98 as at low risk, 82 to <92 as at moderate risk, and <82 as at major risk [
10].
Total lymphocyte count (TLC) was determined according to the following formula:
The cut-off values for total lymphocyte count used for the classification of immunological depletion were as follows: <800 cells/mm
3—severe depletion, 800–1999 cells/mm
3—moderate depletion, and >2000 cells/mm
3—no immunological depletion [
11].
Also, the Prognostic Nutritional Index was calculated according the following formula:
The cutoff points for PNI were as follows: PNI <35—severe risk, PNI <38—moderate risk, PNI >38—normal risk.
2.5. Stastical Analysis
In this study, descriptive statistics were employed to succinctly summarise the characteristics and measurements of the study population. For categorical variables such as gender or specific medical indications, the analysis included the total number of observations (N) and the percentage (%). For continuous variables like body mass index (BMI) and serum levels, the mean (M) and standard deviation (SD) were calculated to describe the central tendency and dispersion, respectively. Additionally, the median (Mdn) and range (Min–Max) were determined to highlight the central value and the overall spread of data. The semi-interquartile range (IQR/2) provided a robust measure of variability.
Pearson’s chi-squared test with a continuity correction and the two-sided Fisher’s exact test were strategically employed to analyse associations among categorical variables, such as gender differences within the study groups and specific indications for home parenteral nutrition (HPN). Pearson’s test is crucial for detecting relationships and assessing the independence of these variables. For contingency tables with small sample sizes or uneven distribution among cells, Fisher’s exact test provided a more precise p-value.
For continuous data that did not meet normal distribution assumptions, the Brunner–Munzel test was applied. Utilizing random permutations, this test is essential for comparing differences between two independent samples and especially useful in the analysis of anthropometric measurements.
To investigate correlations, Spearman’s rank correlation coefficient was used to estimate the relationship between age at study enrolment and variables such as BMI and body mass. This non-parametric measure is particularly effective for data that do not exhibit linear relationships or a normal distribution, providing a reliable assessment of monotonic relationships.
For differences across multiple groups, the Kruskal–Wallis rank test was utilised. This non-parametric test is suited for assessing statistical differences across samples that do not adhere to a normal distribution and was employed to analyse variations based on factors such as the type of short bowel syndrome (SBS), the presence of a stoma, and other clinical parameters relevant to HPN. For the SBS-JC group, which consisted of only two patients, the median was calculated as the mean of the two data points, and the interquartile range (IQR) was derived by treating the two values as the first (Q1) and third quartiles (Q3). Due to the small sample size, these values should be interpreted with caution.
In all analyses conducted within this study, a significance level of 0.05 was maintained, meaning that results were considered statistically significant if the probability of occurrence by chance was less than 5%. Additionally, the statistical analyses were performed using Jamovi (Version 2.5) [
12].
4. Discussion
This study included 46 patients with Crohn’s disease who qualified for home parenteral nutrition at a reference centre in Poland over a period of 18 years. There are relatively few data on the nutritional status of CD patients referred to long-term PN. In an observational study by Kurin et al. [
14], the authors reported that 25 of 2359 (1.1%) patients with IBD received long-term HPN between 2009 and 2015, and the group included 24 patients with CD (96%). Considering the duration of the analysis, the number appears to be higher than in this study (4 vs. 2.5 patients per year). In the study conducted in Minnesota by Bakhshi et al. [
15], less than 4% of the studied CD patients required HPN, and among them, 78.6% had moderate-to-severe CD. In a 2016 analysis by Brandt et al. [
16], CD patients accounted for 24% (N = 121) of all patients receiving HPN between 1970 and 2010 (approximately three patients per year). These results suggest that, while IBD patients requiring HPN represent only a small proportion of the total IBD population, IBD and Crohn’s disease in particular represent a significant proportion of the total HPN population. This is supported by the data from Pironi et al. [
17], who reported SBS as the most common pathophysiological mechanism of IF and Crohn’s disease as the most common underlying disease (22.4%). Accordingly, SBS was the main reason (58.7% of cases) for qualifying for HPN in this study, with SBS-I (30.43%) and SBS-J (17.39%) dominating. This is consistent with the results of the Pironi study mentioned above, where SBS-J was present in 38.6% of cases. In our experience, many hospitals referring patients for HPN do not provide sufficient information on the length of the remaining bowel and refer to the end jejunostomy as an end ileostomy. Therefore, we assume that at least some of the cases we reported as SBS-I (according to the referring hospitals’ medical documentation) were in fact SBS-J.
The assessment of nutritional status based on the SGA results revealed that 60.87% of patients were malnourished and almost half of the patients (47.83%) were severely malnourished on admission to the HPN unit. These results are worrying, especially as malnutrition is known to be associated with a poorer prognosis and higher mortality and complication rates, as well as a higher number of hospitalisations and a deterioration in quality of life [
18]. In comparison, Liu et al. [
19] reported malnutrition in 49.5% of IBD patients, but the study was conducted in an Asian population, so phenotypic differences must be taken into account. The results of Casanova et al. [
20] showed that of 333 patients with IBD, 57% of whom had CD, only 7% received SGA grade B or C and the overall prevalence of malnutrition was 16% [95% CI = 12–20%], with no significant differences between CD and UC. In the recent study by Viganò et al. [
21], the authors observed disease-related malnutrition in 26.3% of CD patients. However, the patients in both studies mentioned did not receive home parenteral nutrition, suggesting that CD patients referred for HPN are in a much more severe condition. It should also be borne in mind that SGA is based on a subjective view of the interviewer, which is another possible explanation for the differences between different studies. Therefore, we believe that double-checking with other assessment methods is of clinical importance to ensure the objectivity of the results.
In the present study, the median BMI was slightly below normal values (18.35 ± 2.12 kg/m
2). Undernutrition according to BMI values was found in 50% of patients, and 32.61% of patients had a BMI of less than 17 kg/m
2, indicating severe malnutrition. In addition, six patients (13.04%) had BMI values below 15 kg/m
2 and two patients (4.35%) had BMI values below 12 kg/m
2, indicating severe malnutrition. In the study by Pironi et al. [
17], 15.1% of HPN patients with CIF were found to have a BMI between 15.1 and 18.5 kg/m
2, while a BMI < 15 kg/m
2 was found in only 2.4% of patients, but the authors did not provide a separate analysis of the distribution of BMI categories in CD patients receiving HPN. The results of the study by Xu et al. [
22] found a BMI < 18.5 kg/m
2 in 44.6% of patients with perianal fistulising CD, while Papadimitriou et. al. [
23] reported a median BMI of 25.00 kg/m
2 (23.30–29.40) in the group of 53 CD patients, of whom 79.1% were in remission, 14.6% had mild disease severity, and 6.3% had moderate. These differences support the hypothesis that the incidence of malnutrition in Crohn’s disease patients varies according to overall condition and disease severity, presenting HPN-dependent patients as “the sickest of the sick”. This is of particular concern as a low BMI (<17.0 kg/m
2) in CD patients is associated with an increased risk of postoperative infectious complications, as reported by Zhu et al. [
24]. In addition, patients with higher BMI values were found to have a lower rate of penetrating disease behaviour [
25]. Although BMI is one of the most commonly used nutritional indicators, it only takes into account the weight and height of patients and, if used alone, can lead to false-negative results in terms of the diagnosis, especially in patients with swelling. For this reason, we also included other indicators of nutritional status in this study. The analysis of another nutritional measure, Prognostic Nutritional Index, proved that the patients in the study group were at severe nutritional risk, as the mean PNI was 30.53 ± 11.03 and 63% of patients (N = 29) had a PNI below 35. Low PNI was widely reported as a poor prognostic factor in cancer patients [
26], but its use in CD is rarely discussed. The results provided by Duan et al. [
27] presented PNI as a useful indicator for predicting surgical recurrence in CD patients, but not as an indicator for predicting postoperative complications. Nonetheless, according to the data from Zhou et al. [
28], the incidence of postoperative overall and infectious complications was higher in patients with PNI < 40 than in those with PNI ≥ 40 (50.0% and 46.7% vs. 23.3% and 16.3%;
p = 0.018 and
p = 0.005, respectively). These data provide a further rationale for earlier nutritional assessment and intervention in CD patients [
19,
29]. Although the data on the use of PNI to predict complications in CD patients are inconclusive and emphasise the need for further studies, we believe that it is a valuable indicator of nutritional status that takes into account not only anthropometric variables but also reflects immunological aspects, and that its introduction into the clinical practise of nutritional risk assessment would be beneficial.
Analysis of the blood tests revealed that the majority of patients (65.20%) had inflammation (CRP > 10 g/L) on admission to hospital. This is understandable and to be expected given the mechanism of the disease itself and the fact that patients underwent bowel resection or developed fistulae. It is very likely that the presence of inflammation also contributed to the development of malnutrition in the study group, as it stimulates catabolism. The mean serum albumin level was 29.2 ± 1.09 g/L, and levels below 35 g/L were found in 71.74% of patients. This is consistent with the findings of Bakhshi et al. [
15], who reported a mean albumin level of 3.3 g/dL (95% CI: 3–3.5). Su et al. [
30] found significantly lower levels of serum albumin and CRP in CD patients compared to healthy controls. In addition, the authors reported a negative correlation between serum albumin levels and disease activity in CD patients and a positive correlation between serum CRP levels and disease activity in CD patients. Both CRP ≥ 10 mg/L and serum albumin < 33.6 g/L were found to be independent risk factors for postoperative infectious complications in the aforementioned study by Zhu et al. [
24]. The authors concluded that normalising serum albumin and CRP levels could reduce the incidence of postoperative infectious complications. Although the use of serum albumin alone as an indicator of nutritional status is not recommended, it is of value as part of the NRI, GNRI, and PNI indicators.
The composition of the parenteral admixtures was also analysed in this study. The mean daily PN volume and energy content were 2454.56 ± 469.46 mL and 1381.00 ± 203.09 kcal, respectively, and the mean energy requirement per kg body weight was 26.71± 7.42 kcal/kg bw per day. In comparison, the values in the study by Pironi et al. [
17] were 1877 ± 1016 mL/day and 1088 ± 649 kcal/day, respectively, and the patients received an average of 18.7 ± 11.9 kcal/kg bw/day. It should be remembered that the study group in Pironi’s work consisted of different patients receiving HPN due to CIF and not only CD patients. According to the ESPEN recommendations for clinical nutrition in IBD (recommendation 6, recommendation grade GPP—strong consensus (95% agreement)), energy intake should be 30–35 kcal/kg bw/day, which was not the case in the two studies compared. In contrast to Pironi et al., who observed a decrease in PN volume with increasing age category and differences in PN volume according to the pathophysiological mechanism, we reported no statistically significant differences in the composition of the PN formula according to age and indication for HPN. Nevertheless, we observed a similar trend towards higher PN volumes and energy content in patients with SBS and coexisting fistulas, and higher volume, energy, and amino acid content in patients with SBS-J. It should be noted that the methodology and statistical methods used differed between those studies.
In this study, we report a median duration of HPN of 1759 ± 1754.29 days. The first patient with CD qualified for HPN in 2004 and was still receiving parenteral support at the time of data analysis. Weaning from parenteral support was possible after 560 ± 380.9 days of HPN in 41.30% of patients, mostly (63.16%) due to the achievement of gastrointestinal autonomy. Restorative surgery was performed in seven patients (15%), corresponding to 58.33% of patients who regained intestinal autonomy. In comparison, 24% of IBD patients were weaned from HPN in the Danish study by Brandt et al. [
16], and 8% of IBD patients regained bowel autonomy after 124 days of HPN treatment following restorative surgery, while spontaneous adaptation was the cause of weaning from HPN at 318 days after the last bowel resection in 19% of IBD patients. The authors reported that 29% of IBD patients died during HPN treatment of approximately 1811 days over an observation period of 40 years, while in our study, 13.04% of patients died over a period of 18 years after receiving HPN for 535 ± 77.1 days. In the study by Watanabe et al. [
31], the mortality rate was reported to be 9% of patients over a period of 19 years after a median of 14.9 HPN years. It should be noted that the authors provided data on causes of death, whereas we were not able to do so, as the patients’ relatives are not obliged to provide such information to the HPN centre, so our data on this topic are limited. In addition, the data from the Danish study refers to IBD patients with both CD and ulcerative colitis, whereas our study only included CD patients. In the study by Watanabe et al., 57% of patients with CD who were weaned off HPN achieved this after at least 2 years (730 days) of HPN treatment.
Over an observation period of 18 years, we reported that HPN-related complications occurred in 56.53% of patients, with septic complications reported in 43.47% of patients. These figures are lower than in the study by Bakhshi et al. [
15], who reported a total of 71.4% of patients with CRBSI over a 31-year observation period. The authors also reported an average of six hospitalisations, which is more than twice as high as in our study. In addition, no cases of CVC-related thrombosis or parenteral nutrition-associated liver disease (PNALD) were observed in this study, whereas Bakhshi et al. reported these in 21.4% and 21% of patients, respectively. Similar data came from a study by Watanabe et al. [
13], who analysed the outcomes of HPN in CD patients over 19 years. They reported that CRBSI occurred in 61% of the 21 patients who made up the study group and had an incidence of 0.32/1000 catheter days. More than half of the patients received PN via a central venous port device, whereas in our study, all patients had a tunnelled CVC implemented on initial hospitalisation. The authors reported liver disease as the second most common complication, occurring in 38% of patients. The difference in the incidence of complications between the studies may be related to many factors, such as the type of intravenous lines used, the type of parenteral nutrition admixtures administered (ready-to-use vs. individually prescribed formulas), their composition, and differences in the training of carers and the institutional approach to HPN, which were not described in the aforementioned papers. We believe that the significantly lower incidence of liver complications compared to other studies is due to the better tailored dosing of fat emulsions (median: 100 ± 25 mL of a 20% emulsion).
The strengths of our study include its duration and a well-described cohort of CD patients receiving HPN from a specific geographic area that is likely representative of the general population. The treatment of the patients was standardised as the work originated from one centre (there are few HPN centres with such a scope). The study was comprehensive and considered multiple clinical parameters. Nevertheless, our study had some limitations, such as its retrospective nature, which meant that we did not have access to detailed medical records from other medical institutions, including the CD treatments used and detailed information regarding the patients’ oral diet.
The sample size is relatively small; however, no better evidence exists. Therefore, the results should be interpreted with caution. In particular, regarding patients with SBS-JIC, the median and interquartile range (IQR) were calculated from only two data points, which is unconventional and offers limited statistical insight.