Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: Prevalence and diagnostic use

Abstract

Pancreatic exocrine insufficiency (PEI) frequently occurs secondary to exocrine pancreatic disease (e.g. chronic pancreatitis, cystic fibrosis, cancer) or pancreatic/gastrointestinal surgery, resulting in the maldigestion of nutrients and consequently malnutrition. Pancreatic enzyme replacement therapy (PERT) is the cornerstone of PEI management. Despite its clinical relevance, the diagnosis of PEI in clinical practice is challenging, as the current gold standard test is cumbersome, and alternatives have limited availability or accuracy. There is a need for accurate and easily applicable diagnostic modalities. We review the prevalence of clinical symptoms and changes in anthropometric measurements and laboratory nutritional markers indicative of malnutrition in patients with PEI, and the relevance of these findings in diagnosing PEI and monitoring PERT efficacy. Based on limited available evidence, assessment of clinical symptoms, body weight, body mass index and other anthropometric parameters are not sensitive methods for PEI diagnosis, owing to high variability and multiple confounding factors, but appear useful in monitoring PERT efficacy. Limited evidence precludes strong recommendations but suggests that serum levels of vitamin E, magnesium, and plasma proteins, notably retinol binding protein, albumin, and prealbumin, may have diagnostic utility in PEI. Studies show that assessment of changes in these and other nutritional parameters is helpful in monitoring PERT efficacy. Further research is needed to confirm the diagnostic accuracy of these parameters for PEI. Until such data are available, a nutritional evaluation including circulating vitamin E, magnesium, retinol binding protein, albumin, and prealbumin may be used to evaluate the probability of PEI in clinical practice when reliable pancreatic function tests are not available.

Introduction

Pancreatic exocrine insufficiency (PEI) is defined as the alteration of pancreatic function leading to maldigestion. Primary PEI results from a reduction of exocrine secretion caused by disease of the exocrine pancreas (e.g. chronic pancreatitis [CP], cystic fibrosis [CF], acute necrotizing pancreatitis, cancer), the endocrine pancreas (e.g. diabetes mellitus) or surgical resection [1]. Secondary PEI may be caused by anatomical changes following other gastrointestinal surgery (e.g. partial/total gastrectomy, gastric bypass, duodenectomy), or other digestive tract disorders (e.g. celiac disease) [1]. The main clinical consequence of PEI is malnutrition, resulting from maldigestion and poor absorption of nutrients, which frequently develops in patients with PEI. Malnutrition-related complications include cardiovascular events, osteoporosis and low-trauma fractures, and infections [2], [3], [4]. Untreated PEI was shown to be associated with high mortality after pancreatic surgery and in patients with unresectable pancreatic cancer [5], [6]. Finally, malnourished CP patients suffer more pain episodes and require more hospitalizations than those with normal nutritional status [7]. Oral pancreatic enzyme replacement therapy (PERT) is the treatment of choice for PEI, together with nutritional management and specific nutritional supplementation if required.

Despite the clinical relevance of PEI, its diagnosis in clinical practice is challenging. The gold standard is quantification of the coefficient of fat absorption (CFA) [8]; this requires patients to maintain a strict 5-day diet containing 100 g of fat/day and collection of all faeces produced over the last 3 days for faecal fat quantification. CFA values >92–93% are considered normal. However, this test is cumbersome, difficult for patients, unpleasant for laboratory technicians, and available in only very few centres worldwide, making it unfeasible in clinical practice. Furthermore, it is non-specific and the results are influenced by many different methodological issues. The ¹³C-labelled mixed triglyceride (¹³C-MTG) breath test is an accurate, reliable, clinically acceptable alternative to CFA quantification, but is not yet approved and has limited availability at present [9]. The faecal elastase-1 (FE-1) test, which quantifies faecal concentration of pancreatic elastase-1, is a widely available, non-invasive method for quantifying pancreatic secretion, and has been used successfully for the diagnosis of moderate to severe CP and PEI in other pancreatic diseases [10], [11], [12], [13]. However, its accuracy for PEI diagnosis using appropriate reference methods has been poorly investigated, with conflicting results reported [14], [15], [16], and the optimal cut-off value is unknown. Management guidelines suggest trialling PERT, with symptom improvement supporting a diagnosis of PEI [17]. This ‘PERT test’ is often used in clinical practice, although there is currently no direct evidence supporting its use in this way.

Consequently, there is a need for alternative diagnostic modalities for PEI that are accurate and easily applicable in clinical practice. As altered nutritional status is the main consequence of PEI, nutritional evaluation is proposed as an alternative to determine its presence in patients with PEI-associated diseases. Another potential use is to monitor global effects of nutritional support, i.e. PERT, dietary modifications and nutritional supplements. This narrative review examines the prevalence of clinical symptoms and anthropometric and laboratory signs of malnutrition in PEI, and evidence for the use of these markers in the diagnosis of PEI and the evaluation of PERT efficacy.