Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during ILC 2016 in Berlin. Since then, not much has changed unfortunately, largely due to the still elusive pathophysiology of the disease. One of the most striking features of PSC is its association with inflammatory bowel disease (IBD), with the majority of patients with PSC being diagnosed with extensive colitis. This review describes the epidemiology of IBD in PSC, its specific phenotype, complications and potential pathophysiological mechanisms connecting the two diseases. Whether PSC is merely an extra-intestinal manifestation of IBD or if PSC and IBD are two distinct diseases that happen to share a common susceptibility that leads to a dual phenotype is debated. Implications for the management of the two diseases together are also discussed. Overall, this review summarises the available data in PSC-IBD and discusses whether PSC and IBD are one or two disease(s).

Although patients with PSC are increasingly diagnosed at earlier stages of disease based on asymptomatic serum liver enzyme abnormalities, at least 45% of patients PSC present with symptoms on either a constant or intermittent basis, which significantly reduces quality of life.¹⁰ Broome U. Olsson R. Lööf L. et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996; 38 : 610-615 Crossref PubMed Google Scholar Furthermore, more than 22% of asymptomatic patients may develop symptoms within 5 years. The most common clinical symptoms associated with PSC are fatigue; pruritus; right upper quadrant (RUQ) abdominal pain; and emotional distress, which may include anxiety and depression symptoms. Pruritus and abdominal pain can fluctuate dramatically, and this may be suddenly worsened because of the development of a biliary obstruction or acute bacterial cholangitis. Therefore, clinical evaluation with laboratory testing and imaging may be necessary in the event of the sudden appearance or worsening of symptoms. Emotional distress for many patients is attributable to chronic anxiety about the uncertain etiology of the disease, the lack of effective therapy, and the risk of malignancy, among others.¹¹ Ranieri V. Kennedy E. Walmsley M. et al. The Primary Sclerosing Cholangitis (PSC) Wellbeing study: understanding psychological distress in those living with PSC and those who support them. PLoS One. 2020; 15 e0234624 Crossref PubMed Scopus (0) Google Scholar

Liver diseases are currently diagnosed through liver biopsy. Its invasiveness, costs, and relatively low diagnostic accuracy require new techniques to be sought. Analysis of volatile organic compounds (VOCs) in human bio-matrices has received a lot of attention. It is known that a musty odour characterises liver impairment, resulting in the elucidation of volatile chemicals in the breath and other body fluids such as urine and stool, which may serve as biomarkers of a disease. Aims: This study aims to review all the studies found in the literature regarding VOCs in liver diseases, and to summarise all the identified compounds that could be used as diagnostic or prognostic biomarkers. The literature search was conducted on ScienceDirect and PubMed, and each eligible publication was qualitatively assessed by two independent evaluators using the SANRA critical appraisal tool. Results: In the search, 58 publications were found, and 28 were kept for inclusion: 23 were about VOCs in the breath, one in the bile, three in urine, and one in faeces. Each publication was graded from zero to ten. A graphical summary of the metabolic pathways showcasing the known liver disease-related VOCs and suggestions on how VOC analysis on liver impairment could be applied in clinical practice are given.

Background Work-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients. Aims We aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL. Methods Employed IBD patients of two tertiary and two secondary referral hospitals were included. QWL (range 0–100) was measured using the Quality of Working Life Questionnaire (QWLQ). Work productivity (WP), fatigue, and health-related quality of life (HRQL) were assessed using the Work Productivity and Activity Impairment questionnaire, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire, respectively. Active disease was defined as a score > 4 for the patient-reported Harvey–Bradshaw index in Crohn’s disease (CD) or Simple Clinical Colitis Activity Index in ulcerative colitis patients. Results In total, 510 IBD patients were included (59% female, 53% CD, mean age 43 (SD 12) years). The mean QWLQ score was 78 (SD 11). The lowest subscore (54 (SD 26)) was observed for “problems due to the health situation”: 63% reported fatigue-related problems at work, 48% agreed being hampered at work, 46% had limited confidence in their body, and 48% felt insecure about the future due to their health situation. Intermediate/strong associations were found between QWL and fatigue (r = − 0.543, p < 0.001), HRQL (r = 0.527, p < 0.001), WP loss (r = − 0.453, p < 0.001) and disease activity (r = − 0.331, p < 0.001). Independent predictors of impaired QWL in hierarchical regression analyses were fatigue (B = − 0.204, p < 0.001), WP loss (B = − 0.070, p < 0.001), and impaired HRQL (B = 0.248, p = 0.001). Conclusions IBD-related problems at work negatively influence QWL. Fatigue, reduced HRQL, and WP loss were independent predictors of impaired QWL in IBD.

Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials.

Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC), yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition. MEDLINE, Embase and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with Joanna Briggs tools and a composite critical appraisal-score. Additionally, species-level data from two landmark FMT-trials (TURN and FOCUS) were re-analyzed from a compositional perspective. Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high diversity composition with abundant but not excessive levels of Prevotella copri. This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.