Management of bile acid diarrhea in Italy: a survey

The present survey investigated the knowledge and clinical attitudes of a group of Italian physicians in the management of BAD aiming to highlight the current clinical practice and guide future updates on this topic to increase awareness of this condition. To the best of our knowledge, only a previous survey was published on this topic [14]. It was carried out in the UK, including a small group of selected experts in this field (n = 21) and it was focused on improving diagnostic rates and management of BAD through a consensus on specific clinical cases. Therefore, the results are not fully comparable to our experience.

In our study we included a heterogeneous sample of physician and compared the answers from gastroenterologist to those of the remaining participant in the survey, which were mainly internal medicine doctors or surgeons. These medical specializations represent the three major types of physicians possibly facing this disease in their clinical practice. Although about half of the participants were from Northern Italy, where there is the greatest availability of 75SeHCAT test in Italy, we surprisingly found no differences in 75SeHCAT availability among the two groups.

A considerable lack of knowledge was found among gastroenterologists and other physicians with an interest in digestive diseases. Only one-third of respondents correctly estimate the actual burden of BAD. Since the prevalence of chronic diarrhea in the general population has been estimated at around 5% and BAD is responsible for 26–50% of these cases [2, 21], BAD prevalence can be estimated to affect around 1% of the general population. When patients with IBS-D are considered, this rate increases up to 28.1%, according to a meta-analysis including more than 900 patients [4]. Therefore, about half of our respondents underestimated the burden of BAD. Surprisingly, despite the higher number of visits made by gastroenterologists for patients with chronic diarrhea, the rate of BAD diagnosis was comparable between gastroenterologists and other physicians. This can be explained by a selection bias of participants with a specific interest in these topics. The most commonly reported clinical criteria for BAD diagnosis were the presence of watery stools, > 3 CSBM/day, and the exclusion of organic/drug-related diseases. This finding is in keeping with what was reported in the survey by Walters et al. since the experts reported loose stools and frequency greater than 3 times/day as common findings [14]. However, the recently published Canadian guidelines for BAD management [16] suggested against using symptom presentation for the initial assessment to identify patients with possible BAD, while recommending using risk factors (history of terminal ileal resection, cholecystectomy, or abdominal radiotherapy) for the initial assessment of patients with chronic non-bloody diarrhea. Most of the participants in our survey reported using 75SeHCAT as a gold standard method for BAD diagnosis, when available, in line with international guidelines [6, 16]. Our data underline that the prescription of 75SeHCAT in clinical practice, the perceived accuracy of this test, and the general awareness and knowledge of BAD are directly correlated with 75SeHCAT test availability in the place of origin. On this line and supporting the importance of 75SeHCAT availability, we found no difference in the number of 75SeHCAT prescribed by gastroenterologists and other physicians operating in the same area.

The variation in 75SeHCAT utilization among physicians likely reflects differences in local test availability, institutional protocols, and physician familiarity with BAD. In regions where the test is not accessible, clinicians may rely more on empirical therapy or alternative diagnostic approaches, leading to inconsistent practices [1]. This inconsistency underscores the need for standardized diagnostic pathways and wider dissemination of guideline-based approaches [14].

When the response to a cholestyramine trial was used as an ex adjuvantibus diagnosis, respondents heterogeneously reported using different doses of the drug. In BAD studies, cholestyramine was generally started at a low doses of 2 to 4 g/day and titrated based on response (maximum, 4‒24 g/day) [16]. When cholestyramine trial duration was considered, the majority of interviewed gastroenterologists reported a trial of 28 days, while other physicians reported shorter durations. Heterogeneous duration of cholestyramine trial from 4 to 12 weeks have been published [22]. However, lack of response to cholestyramine does not constitute per se exclusion of BAD and there is very little evidence to determine the relative role of 75SeHCAT testing versus using an empiric trial of BAST to make a diagnosis of BAD [22]. Therefore, in most guidelines, other factors were considered when making a recommendation for or against a diagnosis based on a cholestyramine trial [6, 16]. Despite evidence supporting the efficacy of bile acid sequestrants, treatment prescription remains suboptimal. Barriers such as perceived poor tolerability, side effects such as bloating or constipation, and uncertainties regarding dose optimization may deter clinicians from initiating therapy [12]. Patient-related concerns, including palatability and long-term adherence, may further complicate therapeutic decision-making [23].

About one out of five respondents among gastroenterologists and those with the 75SeHCAT availability believed that 7αC4 or FGF19 are accurate enough for BAD diagnosis. However, although these tests may have a good specificity for identifying patients with moderate BAD (75SeHCAT < 10%), they have insufficient sensitivity as diagnostic tests to be used alone and they are not widely available [24].

Notably, no difference was found in the reported satisfaction among physicians regarding therapies available for BAD, with a rate of satisfaction of about 31–34%. Furthermore, all respondents reported efficacy of therapies for BAD of less than 30%. Indeed, besides the high rates of remissions reported for BASTs in observational studies [2, 25], the few placebo-controlled trials available did not show that colestyramine or colesevelam were superior to placebo regarding bowel movements, although secondary non-clinical outcomes improved [15, 26,27,28]. However, the response to cholestyramine may vary according to the BAD etiology and its degree of severity. A metanalysis published in 2009 reported that in the pooled data from 15 studies there was a correlation between the severity of malabsorption and response to BAST: response to colestyramine occurred in 96% of patients with < 5% retention, 80% at < 10% retention and 70% at < 15% retention [2]. Long-term efficacy of BASTs may be hampered by several factors, such as uncertainty on the optimal dose to be used, different individual responses, side effects such as bloating and constipation, vitamin and concomitant drug malabsorption [23]. Colesevelam seems to gain some therapeutic response in BAD in patients nonrespondent to cholestyramine according to a trial published in 2015, where colestyramine was unsuccessful in 44% of cases, 47% of which responded to colesevelam [29]. Recently, a diagnostic and therapeutic RCTs assessing C4 accuracy vs 75SeHCAT and the therapeutic response to colesevelam found that colesevelam was superior to placebo at inducing remission of BAD diagnosed with C4 concentration greater than 46 ng/mL [30]. Secondary outcome data suggested similar efficacy in treating 75SeHCAT-defined BAD [30].

Finally, we found that more than half of the participants were not satisfied with their own knowledge of BAD and this gap significantly increased when 75SeHCAT test was not available in the place of origin. Almost all participants reported the need for updates on this condition. These findings suggest a critical need for targeted educational initiatives and broader access to diagnostic tools to reduce disparities in care [16, 22].

Our study has some limitations: first, the sample size was rather low leading to a possible error type II when performing comparison among groups, although the response rate was satisfying. Second, the overall knowledge of BAD may have been positively influenced by a selection bias, since most gastroenterologists and other physicians participating in the meeting expressed an interest in gastroenterological diseases. Also, it was not possible to use validated questionnaires or to use questions with pre-validated scales in order to explore BAD knowledge and management, thus influencing the reliability of our questions. Furthermore, some heterogeneity in our results may be influenced by the different training and clinical experience. However, our survey also has several strengths: it is the first report describing the knowledge and awareness of BAD in Italy and more generally in a European country among practicing physicians. These data may be used in the future to improve the awareness and knowledge of this condition, e.g. with focused updating courses. Moreover, we provided real-life data regarding the current epidemiology and management of patients with BAD in Italy according to tests and drugs availability, and its burden on healthcare resources.

In conclusion, BAD is a common condition with a multifaceted etiology. At least one-third of patients with IBS suffer from this condition. 75SeHCAT testing is the gold standard method for the diagnosis of BAD, although available only in a few Italian centers. 75SeHCAT availability influences the awareness and knowledge of this disease, possibly leading to a faster diagnosis and consequently reducing the burden of this disease for the patient and healthcare facilities. Therapies currently available for the treatment of BAD are often not able to guarantee adequate symptom relief. Updates on BAD are needed to fill in this knowledge gap, especially in geographic areas where 75SeHCAT is not available.

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