Efficacy and safety of biologics in primary sclerosing cholangitis with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics. CONCLUSIONS: Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

Cost-effectiveness of taurolidine-citrate in a cohort of patients with intestinal failure receiving home parenteral nutrition.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) in patients receiving home parenteral nutrition (HPN) for chronic intestinal failure (CIF) are associated with significant morbidity and financial costs. Taurolidine is associated with a reduction in bloodstream infections, with limited information on the cost-effectiveness as the primary prevention. This study aimed to determine the cost-effectiveness of using taurolidine-citrate for the primary prevention of CRBSIs within a quaternary hospital. METHODS: All patients with CIF receiving HPN were identified between January 2015 and November 2022. Data were retrospectively collected regarding patient demographics, HPN use, CRBSI diagnosis, and use of taurolidine-citrate. The direct costs associated with CRBSI-associated admissions and taurolidine-citrate use were obtained from the coding department using a bottom-up approach. An incremental cost-effective analysis was performed, with a time horizon of 4 years, to compare the costs associated with primary and secondary prevention against the outcome of cost per infection avoided. RESULTS: Forty-four patients received HPN within this period. The CRBSI rates were 3.25 infections per 1000 catheter days before the use of taurolidine-citrate and 0.35 infections per 1000 catheter days after taurolidine-citrate use. The incremental cost-effectiveness ratio indicates primary prevention is the weakly dominant intervention, with the base case value of $27.04 per CRBSI avoided. This held with one-way sensitivity analysis. CONCLUSION: Taurolidine-citrate in the primary prevention of CRBSIs in patients with CIF receiving HPN is associated with reduced hospital costs and infection rates.

How frequent are vancomycin-resistant enterococci in patients with primary sclerosing cholangitis and ulcerative colitis treated with oral vancomycin?

In patients with primary sclerosing cholangitis (PSC), antimicrobial therapy with oral vancomycin (OV) is increasingly used to prevent progression of the liver disease and control concomitant ulcerative colitis (UC); however, there are concerns regarding the risk of development of vancomycin-resistant enterococci (VRE). Thus, we aimed to determine the incidence of VRE in PSC-UC patients. We conducted a retrospective study of PSC-UC patients, treated with OV at the Department of Gastroenterology at the Princess Alexandra Hospital. VRE testing was performed utilizing rectal swabs. We included 7 PSC-UC patients (age 22-53 years, 2 females) treated with OV with daily dose ranging from 250 to 1500 mg. All patients were treated for at least 6 months with OV (range 9-31 months, mean 32.1 months). All patients achieved complete clinical remission of the UC, with mean reduction of fecal calprotectin by 634 µg/mg (87.3%), mean reduction in the C-reactive protein by 21.9 mg/L (74.2%), and mean reduction in the total Mayo score by 9.3 (93.3%). With regard to the liver parameters, mean improvement in alkaline phosphatase enzyme and total bilirubin was -48.7 U/L (-19.7%) and -2.7 mg/dL (-19.6%), respectively. No patient treated with OV developed VRE or reported any adverse events. This cohort study including PSC-UC patients did not provide evidence for development of VRE, while treatment with vancomycin was associated with clinical and endoscopic remission of the UC. Larger, prospective trials are required to define the efficacy and safety of antimicrobial therapy in PSC-UC, while the risk of VRE appears small.

Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia.

BACKGROUND AND AIMS: Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS. METHODS: Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured. RESULTS: Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5). CONCLUSIONS: In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms.