Why are rare diseases underdiagnosed? A clinical management study on detection of primary biliary cholangitis in primary care.

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process. Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines. Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%). Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Quality of Life and Its Psychosocial Predictors among Patients with Disorders of Gut-Brain Interaction: A Comparison with Age- and Sex-Matched Controls.

The disorders of gut-brain interaction (DGBIs) are a heterogeneous group of chronic conditions that greatly reduce patients' quality of life (QoL). To date, biopsychosocial factors (such as gastrointestinal symptoms, alexithymia, and interpersonal problems) are believed to contribute to the development and maintenance of DGBIs, but their role in affecting patients' QoL is still under investigation. Out of 141 patients seeking treatment for their gastrointestinal symptoms, 71 were diagnosed with a DGBI (47 females, 66.2%; Mage: 41.49 ± 17.23 years) and were age- and sex-matched to 71 healthy controls (47 females, 66.2%; Mage: 40.45 ± 16.38 years) without any current gastrointestinal symptom or diagnosis. Participants completed a sociodemographic and clinical questionnaire and a survey investigating several psychosocial risk factors. We found greater symptom severity and difficulties in identifying feelings among patients compared to controls. Further, multiple linear regression analyses evidenced that, among patients, higher expressive suppression of emotions, difficulties in identifying feelings and interpersonal problems, and a lower cognitive reappraisal of emotions predicted lower QoL. Data suggest that the QoL of patients with DGBIs is affected not only by common risk factors (e.g., interpersonal problems) but also by specific difficulties in processing and regulating emotions. The implications of these findings are discussed.

Mediterranean-Oriented Dietary Intervention Is Effective to Reduce Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: Results from an Italian Clinical Trial.

Results: One hundred and fifty five subjects aged 20-59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions: Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661.