Understanding Fatigue in Primary Biliary Cholangitis.

BACKGROUND: Fatigue affects 50% of primary biliary cholangitis patients and is severe in approximately 20%, significantly affecting quality of life. The pathogenesis of fatigue in primary biliary cholangitis is poorly understood. This study aimed to explore subgroups of fatigue to support targeting of selected groups in future clinical trials. METHODS: Data were derived from the UK-PBC cohort. Participants completed the PBC-40, Hospital Anxiety and Depression Score, Epworth Sleepiness Scale, and Orthostatic Grading Scale for symptoms assessment. Fatigue and cognitive symptoms were regarded as clinically significant if they exceeded the previously defined cutoff for "moderate" symptom. RESULTS: Of 2002, patients for whom full PBC-40, fatigue, and cognitive symptom domain scores were available, 1203 (60%) had significant fatigue and 730 (36%) had significant cognitive symptoms. Among the 1203 patients with significant fatigue, 663 (55%) also had significant cognitive symptoms (termed fatigue with cognitive symptoms) with a significant linear association between the fatigue and cognitive symptom severity. "Fatigue with cognitive symptoms" patients were younger and more likely to have severe fatigue. They also experienced greater social and emotional impact. CONCLUSIONS: Fatigue in PBC is complex, and there has been no progress to date in identifying therapies able to improve it. One factor in slow progress may be the heterogeneity of patients describing fatigue complicating effective cohort selection for clinical trials. This study has identified potential discrete subgroups of fatigued patients with and without cognitive symptoms. The group of patients expressing "fatigue with cognitive symptoms" was homogenous and may represent a coherent cohort for clinical trials.

Emerging drugs for the treatment of primary biliary cholangitis.

INTRODUCTION: Primary biliary cholangitis (PBC) is a progressive inflammatory autoimmune cholestatic liver disease. Without treatment, it may result in fibrosis and eventually end stage liver disease. In addition to the disease burden, the symptom impact on the quality of life for PBC patients is significant. Ursodeoxycholic acid, and the second-line therapy, Obeticholic acid, are the only available licensed treatments. Although there has been rapid development of novel therapies in recent years for the treatment of PBC, there are very few symptoms directed therapies. AREA COVERED: This literature review aims to review the current treatment landscape in PBC and to explore how the next few years may unfold in the field. The current guidelines and emerging therapies in phase 2, 3 and 4 clinical trials have been included. EXPERT OPINION: The currently available therapies are effective, but their use has limitations and challenges and there is still significant unmet need. Although there have been promising therapeutic interventions in recent years, further research into personalizing therapeutic strategies with available treatments and new agents is needed.

Managing cognitive symptoms and fatigue in cholestatic liver disease.

Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.

Implementation of a care bundle improves the management of patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NAFLD 'care bundle' to standardise care; (3) to assess the impact of implementation of the NAFLD care bundle. METHODS: A retrospective review was conducted to determine baseline management of patients with NAFLD attending seven hospitals in NEE. A care bundle for the management of NAFLD was developed including important recommendations from international guidelines. Impact of implementation of the bundle was evaluated prospectively in a single centre. RESULTS: Baseline management was assessed in 147 patients attending gastroenterology, hepatology and a specialist NAFLD clinic. Overall, there was significant variability in the lifestyle advice given and management of metabolic risk factors, with patients attending an NAFLD clinic significantly more likely to achieve >10% body weight loss and have metabolic risk factors addressed. Following introduction of the NAFLD bundle 50 patients were evaluated. Use of the bundle was associated with significantly better documentation and implementation of most aspects of patient management including management of metabolic risk factors, documented lifestyle advice and provision of NAFLD-specific patient advice booklets. CONCLUSION: The introduction of an outpatient 'care bundle' led to significant improvements in the assessment and management of patients with NAFLD in the NEE and could help improve and standardise care if used more widely.

Eosinophilic gastroenteritis: a challenge to diagnose and treat.

The patient presented with bloody diarrhoea, and crampy abdominal pains. She was diagnosed with eosinophilic gastroenteritis (EGE) after the finding of persistently high peripheral eosinophil counts and histology of endoscopic biopsies. She responded to steroids but became dependent on it and her symptoms recurred on steroid tapering. There was little improvement with alternative treatment such as budesonides, azathioprine and montelukast. Surprisingly her symptoms improved significantly after she was treated with clarithromycin for chest infection and she was continued on clarithromycin. Her eosinophil counts fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the mucosal thickening had improved. She became completely free of the symptoms since she was on clarithromycin and her eosinophils counts fell within the normal range during the follow-up.