Crohn's disease (CD) and eosinophilic gastrointestinal diseases (EGIDs) are distinct inflammatory entities, but eosinophilic disease may emerge as a paradoxical immune complication of anti-tumor necrosis factor therapy. We report a 12-year-old boy with terminal ileal CD who developed severe eosinophilic gastritis and ileitis, peripheral eosinophilia, and psoriasiform dermatitis during prolonged anti-TNF treatment, despite CD remission. Corticosteroids, dietary modification, and sequential biologic therapy resulted in incomplete or transient responses. Following anti-TNF withdrawal, eosinophilic disease persisted, prompting compassionate off-label treatment with benralizumab, an interleukin-5 (IL-5) receptor α-antagonist, alongside vedolizumab for CD maintenance. Benralizumab led to rapid normalization of peripheral eosinophil counts, resolution of gastrointestinal symptoms, improved food tolerance, and histologic remission at 6 months. This case illustrates persistent anti-TNF-associated immune deviation and supports targeted IL-5 receptor blockade as an effective strategy for refractory eosinophilic gastrointestinal disease while maintaining CD remission.

BACKGROUND:Oral vancomycin therapy (OVT) induces histological remission in children with ulcerative colitis (UC) showing primary sclerosing cholangitis (PSC)-associated features (proximally dominant or patchy inflammation, backwash ileitis, or rectal sparing). However, predictors of response and optimal treatment duration remain unclear. AIM:To evaluate segmental colonoscopy outcomes across various OVT durations. METHODS:Children with active UC receiving OVT for ≥3 months were retrospectively identified. Pre-post-OVT colonoscopies were available for 38 children, 4 had repeated examination after relapsing and re-commencing OVT, totaling 42 colonoscopy pairs. RESULTS:Pre-OVT colonoscopies showed 19 proximally dominant inflammation (more severe gradient proximal to hepatic flexure), 18 pancolitis with backwash ileitis or rectal sparing, 3 patchy colitis, and 2 distal colitis. Within 5.7 (IQR 3.5-7.5) months after OVT, follow-up colonoscopy showed mucosal healing (Mayo 0) in 27/42. Pan-colonic histological remission was achieved in 23/42, more frequently in proximally dominant colitis than in other UC types (aOR 7.50, 95% CI 1.22-46.3). Remission rate was higher after ≥4 months of therapy compared with shorter durations (aOR 7.12, 95% CI 1.14-44.7). CONCLUSIONS:Over half of post‑OVT colonoscopies showed pan‑colonic histological remission, particularly in proximally dominant UC. Treating for ≥4 months further improved outcomes, helping identify which patients may benefit from OVT.

BACKGROUND AND AIMS:Intestinal ultrasonography (IUS) is a noninvasive tool for assessing bowel inflammation. In adults, a bowel wall thickness (BWT) cutoff of 0.30 cm is used to indicate inflammation, but children do not have a widely accepted value. We propose an optimal BWT cutoff value for children. METHODS:We performed 144 IUS examinations during 2019-2024 in 133 children within 30 days before to 7 days after colonoscopy. Assessed values for the BWT from the terminal ileum to the rectum were paired with colonoscopy findings at each segment (n = 809 pairs). The cutoff value for detecting inflammation was explored with receiver operating characteristic (ROC) analysis. RESULTS:In children ≥6 years old IUS demonstrated excellent accuracy for detecting moderate/severe inflammation (area under the curve [AUC] 0.907) but poor accuracy for mild inflammation (AUC 0.690) or in children <6 years old (AUC, 0.667). The adult cutoff (0.30 cm) missed 32% of inflammation in children. In children ≥6 years old, a BWT cutoff of 0.27 cm detected 85% of moderate/severe and 43% of mild inflammation. Lower cutoff values (0.24 cm) were more optimal for girls and children weighing <40 kg. CONCLUSIONS:Although IUS is an excellent tool for detecting moderate/severe bowel inflammation, this method showed limited accuracy in children <6 years old. The adult BWT cutoff missed over 30% of bowel inflammation in children. BWT cutoff of 0.27-0.30 cm in boys and 0.23-0.25 cm in girls and/or children <40 kg indicated active gut inflammation.

INTRODUCTION:Primary sclerosing cholangitis (PSC) is a fibro-inflammatory cholangiopathy strongly associated with inflammatory bowel disease (PSC-IBD). With no approved PSC therapy, clinicians face uncertainty about oral vancomycin (OV) as a therapeutic option. This review synthesizes clinical effectiveness evidence alongside mechanistic data. AREAS COVERED:We searched PubMed/Google Scholar for studies of vancomycin in PSC from 1998 through November, 2025. OV shows consistent IBD benefits and variable liver responses. In PSC-IBD, clinical and endoscopic remission occurred in 60% at 6 months and in 71% at 12 months in a pediatric cohort; in an adult single-arm study (n = 15), 80% achieved endoscopic remission at 4 weeks with universal mucosal healing, reductions in fecal calprotectin and Mayo scores, and relapse after withdrawal. For liver disease, a pediatric open-label cohort (n = 45) reported ≥50% declines in gamma-glutamyl transferase in 82%; in an adult pilot randomized controlled trial, alkaline phosphatase fell 46% at 12 weeks. Imaging/histology improved as evidenced by MRCP in 26/34 large-duct PSC and reduced portal/periportal inflammation in 11/12 small-duct PSC. No vancomycin-resistant enterococci development has been reported. EXPERT OPINION:OV appears effective for colitis control in PSC-IBD. Differences in observed liver outcomes across studies likely reflect variation in treatment duration, dose, and endpoint selection. Liver responses may depend on higher doses. Cross-specialty guidance and pragmatic, integrated trials are needed.

BACKGROUND:Ataxia-telangiectasia (A-T) is a rare multisystem disease characterised by neurodegenerative cerebellar ataxia, lung disease, immune deficiency, high cancer risk, and mitochondrial dysfunction. A-T cells demonstrate defective endoplasmic reticulum-mitochondrial connectivity disrupting calcium homoeostasis and mitochondrial fusion, which are corrected in vitro by the triheptanoin metabolite, heptanoate. METHODS:We performed a Phase 2a/b trial of triheptanoin with a three-arm placebo-controlled dose-escalation design. Doses escalated at 2-month intervals for 12 months in the sequence 0%, 10%, 20%, 35% of calculated caloric intake. The primary outcome was cell death in respiratory epithelial cells. Key secondary outcomes included scales for assessment and rating of ataxia (SARA), international cooperative ataxia rating scale (ICARS), speech and swallowing function, and novel biomarker discovery. FINDINGS:31 participants with A-T were enrolled aged from 4 to 37 years (median 16-years). For the maximum dose vs. placebo or no dose, significant improvements was observed for the primary outcome percent nasal cell death (mean difference (MD) = -9.7%, 95% confidence interval (CI) -16.0, 4.6). The SARA subscale kinetic function improved (MD = -5.8, 95% CI -10.4, -1.2), as did ICARS subscales gait (MD = -0.5, 95% CI -0.9, -0.1) and fine motor disturbance (MD = -2.7, 95% CI -4.3, -1.1). Speech intelligibility (MD = -12.8, 95% CI -21.2, -4.3) and swallowing safety (-0.9, 95% CI -1.6, -0.3) improved. Adverse events including abdominal pain, nausea, vomiting, and diarrhoea, requiring dose capping at 20%, were observed in 12 (38%) participants. INTERPRETATION:Improvements in mitochondrial function in A-T cells in vivo in patients occurred after triheptanoin. The biomarkers neurofilament light chain and interferon signature stimulated gene scores may allow for monitoring of disease progression and treatment response. FUNDING:Funded by Medical Researcher Futures Fund Australia (GA89314), The University of Queensland, Wesley Research Institute, and BrAshA-T.

Objectives Atypical ulcerative colitis (UC) presenting reverse gradient colitis, backwash ileitis, or rectal sparing and/or positive atypical antineutrophil cytoplasmic antibody serology is often associated with primary sclerosing cholangitis (PSC) and can be resistant to conventional medical therapies (CMT) for inflammatory bowel diseases. We report short-term and long-term outcomes of oral vancomycin therapy (OVT) in children with atypical UC and confirmed PSC in imaging/biopsy (PSC-UC) or treatment-resistant atypical UC without detectable PSC (aUC-non-PSC).Methods In this retrospective real-world observational study from a tertiary paediatric centre in Brisbane, Australia, 44 children with aUC (29 PSC-UC, 15 aUC-non-PSC) received 79 OVT courses between 2014 and 2023. Pre–post-OVT characteristics were compared and relapses/repeated courses were recorded.Results Pre-OVT, all had active colitis by Paediatric Ulcerative Colitis Activity Index (PUCAI), Feacal Calprotectin (FC) and/or colonoscopy. Post-OVT, PUCAI reduced from 15 (IQR 5–33) to 0 (IQR 0–5); 85% of children with pre-OVT PUCAI ≥10 achieved clinical remission (100% PSC-UC vs 64% aUC-non-PSC, p=0.019). FC reduced from 995 (IQR 319–1825) to 44 (IQR 16–79) µg/g; 83% of children with pre-OVT FC ≥100 µg/g achieved biochemical remission (92% PSC-UC vs 64% aUC-non-PSC, p=0.063). Colonoscopy confirmed Mayo 0 healing in 62% (67% PSC-UC vs 54% aUC-non-PSC, p=0.443) and 46% achieved pan-colonic histological remission (54% PSC-UC vs 31% aUC-non-PSC, p=0.173). All pre–post-OVT changes in these four markers were significant in both groups. After ceasing first OVT, 25/44 relapsed within 8.2 (IQR 1.9–14.5) months. Recommencing OVT regained biomarker remission in 13/25. During 3.8 (IQR 2.0–5.3) years of follow-up, 79 OVT courses in conjunction with CMT maintained deep remission in 67%. Routine stool testing (n=138) detected no vancomycin-resistant Enterococcus (VRE).Conclusions OVT induced and reinduced remission in children with atypical UC. Relapse often followed ceasing vancomycin, half responded to reinduction. No VRE was developed.

Background Cystic fibrosis-related liver disease(CFLD) has long been thought to be secondary to CFTR dysfunction in the biliary epithelial cells causing hepatobiliary complications,eventually progressing to cirrhosis. However, in more recent studies, non-cirrhotic portal hypertension(NCPH) has been postulated as a possible alternative mechanism contributing to CFLD. Methods We collected clinical information pertaining to the status of their liver disease from children with CFLD who underwent liver transplant at the 3 paediatric liver transplant centres in Australia- Melbourne, Sydney and Brisbane. Explant histopathology slides were independently reviewed by 2 experienced pathologists based at two different anatomical pathology centres. Results Data was collected from 18 children (including 10 females, median age 13 years) making this the largest paediatric series reported. Pre-transplant, all had evidence of portal hypertension with splenomegaly and thrombocytopenia. Median bilirubin, ALT, ALP, GGT levels and PELD/MELD, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores were recorded to ascertain pre-transplant status. All explanted livers had evidence of variable degree of biliary cholestasis/cirrhosis as the predominant histopathological feature, whereas 11 out of the 18 explants (61%) also had patchy/focal areas of NCPH, mostly within the less fibrous or macro nodular areas. Conclusions Data from this series reinstates the longstanding observation that focal biliary fibrosis/biliary cirrhosis seems to be the predominant pathophysiology in this condition, and NCPH, if present, is mostly focal, representing overlap features in a percentage of these patients. As such, NCPH may represent an early feature in CFLD before progressing to biliary stasis and cirrhosis.

Objective Paediatric acute severe colitis (ASC) is a life-threatening gastroenterological emergency and a predictor of poor long-term inflammatory bowel disease outcomes. We report our experience with oral antibiotic combination therapy as rescue therapy for children with ASC failing to respond to conventional medical therapy (CMT). Methods We analysed data of children admitted with ASC between January 2020 and January 2023 who failed steroids and infliximab and received the oral antibiotic combination therapy (vancomycin, amoxicillin, metronidazole and doxycycline). Treatments and responses including Paediatric Ulcerative Colitis Activity Index (PUCAI), biochemical markers, intestinal ultrasound (IUS) and colectomy rates (acute and deferred) were collated. Results Oral antibiotic combination therapy was prescribed in 12 episodes of ASC in 11 children following failure of CMT. Improvements were seen in PUCAI (mean difference = −27.86, 95% confidence interval = −43.43 to −12.28, P < 0.001), albumin (mean: 29.5–33.6) and CRP (mean: 12–4), as well as in IUS (bowel wall thickening, extent of involvement or vascularity in five of seven). Five of 11 children were colectomy free at a maximum follow-up of 24 months. Three children had acute colectomy during index admission and three underwent deferred colectomy at a mean of 4 months. Conclusion Oral antibiotic combination therapy shows promise in deferring and, in some cases, averting the need for acute colectomy in medically refractory ASC. This notable finding warrants confirmation in larger studies.

AIMS:Atypical colitis (presenting reverse gradient colitis, backwash ileitis or rectal sparing) is associated with primary sclerosing cholangitis-ulcerative colitis (PSC). Oral vancomycin has been used to manage paediatric atypical colitis with/without confirmed PSC. Different preparations had shown different efficacy. We compared oral vancomycin solution to capsules in inducing remission in children with atypical colitis, while assessing other potential confounders. METHODS:Children using oral vancomycin for at least 3 months to manage atypical colitis were retrospectively identified. Factors associated with colitis remission (Paediatric Ulcerative Colitis Activity Index [PUCAI], faecal calprotectin, colonoscopy and histology) were explored. RESULTS:Of 32/48 children with elevated PUCAI, 27/32 achieved PUCAI < 10 (20/23 after solution vs. 7/9 after capsules, P = .520). Faecal calprotectin <100 μg/g was achieved in 35/48 (28/35 after solution vs. 6/13 after capsules, P = .022). Follow-up colonoscopy during treatment (n = 25) showed reduced Mayo from median 2 to 0 (P < .001) after solution vs. from 2 to 1 (P = .257) after capsules. Pan-colonic histological remission was seen in 14/25 (12/20 after solution vs. 1/5 after capsules, P = .109). In adjusted analysis, use of oral vancomycin solution was a significant predictor for biomarker (adjusted odds ratio 23.1, 95% confidence interval 2.11-253) and pan-colonic histological remission (adjusted odds ratio 900, 95% confidence interval 1.61-504 929). No other predictors were identified. Within 12 months after ceasing oral vancomycin in children who achieved remission, 52% relapsed. No clinical predictors, including vancomycin preparation, were established. CONCLUSION:Oral vancomycin solution was superior to capsules for inducing biomarker and colonoscopic remission in children with atypical colitis with/without confirmed PSC. This finding warrants further investigation to ensure optimal use.

BACKGROUND:Perianal fistulas and abscesses occur commonly as complications of pediatric Crohn's disease (CD). A validated imaging assessment tool for quantification of perianal disease severity and activity is needed to evaluate treatment response. We aimed to identify magnetic resonance imaging (MRI)-based measures of perianal fistulizing disease activity and study design features appropriate for pediatric patients. METHODS:Seventy-nine statements relevant to MRI-based assessment of pediatric perianal fistulizing CD activity and clinical trial design were generated from literature review and expert opinion. Statement appropriateness was rated by a panel (N = 15) of gastroenterologists, radiologists, and surgeons using modified RAND/University of California Los Angeles appropriateness methodology. RESULTS:The modified Van Assche Index (mVAI) and the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD) were considered appropriate instruments for use in pediatric perianal fistulizing disease clinical trials. Although there was concern regarding the use of intravascular contrast material in pediatric patients, its use in clinical trials was considered appropriate. A clinically evident fistula tract and radiologic disease defined as at least 1 fistula or abscess on pelvic MRI were considered appropriate trial inclusion criteria. A coprimary clinical and radiologic end point and inclusion of a patient-reported outcome were also considered appropriate. CONCLUSION:Outcomes of treatment of perianal fistulizing disease in children must include MRI. Existing multi-item measures, specifically the mVAI and MAGNIFI-CD, can be adapted and used for children. Further research to assess the operating properties of the indices when used in a pediatric patient population is ongoing.

Background & Aims Intestinal ultrasound (IUS) is increasingly used to assess Crohn’s disease (CD) activity in clinical practice. However, application in clinical trials has been limited by heterogeneous scoring methods and concerns about reliability. We aimed to determine the inter- and intra-rater reliability of locally- and centrally-read IUS parameters for evaluating CD using prospectively performed scans. Methods Twenty-four participants with CD and 6 gastroenterologists participated in a 2-day workshop where each participant underwent 6 IUS scans in total. Eight IUS parameters (bowel wall thickness [BWT], bowel wall stratification [BWS], color Doppler signal [CDS], inflammatory mesenteric fat [i-fat], submucosal prominence, submucosal layer thickness, haustra coli/peristalsis, and affected segment length) and an overall measure of sonographic disease activity were blindly assessed by the 6 local readers and 4 central gastroenterologist-sonographers. Reliability was quantified using intraclass correlation coefficients (ICCs). Institutional review board approval was granted for this study (12938). Results Five IUS parameters demonstrated at least moderate (ICC >0.41) inter- and intra-rater reliability when local and central reading was performed (BWT, CDS, i-fat, submucosal prominence, and affected segment length). Reliability was generally better with central, in distinction to local, reading. ICCs for BWS and i-fat were highest when evaluated as binary outcomes. Sensitivity analyses demonstrated that IUS parameters are most reliable when evaluated in the worst affected segment. Fair reliability was observed when local readers identified the worst affected segment. Conclusions Local and central reading of IUS demonstrated at least moderate inter- and intra-rater reliability for several parameters. This study supports refining existing activity indices and incorporating IUS central reading into clinical trials.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD. What is Known The spectrum of Fontan-associated liver disease (FALD) may vary from abnormal liver function tests to fibrosis and even cirrhosis. The role of elastography for the monitoring of FALD is unclear.What is New The median liver stiffness measurement value in children with FALD is much higher than values in normal children. There is a poor correlation between elastography values and ultrasound evidence of advanced liver disease in this population. Further studies are required to determine the precise role of shear-wave elastography as a noninvasive marker of liver fibrosis in FALD.

Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intrahepatic and extrahepatic bile ducts of unclear etiology. PSC is commonly (in 60%-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation. Here, we review recent epidemiologic observations and highlight that PSC-IBD and PSC-AIH overlap appear to represent aspects of a common PSC clinico-pathological pathway and manifest in an age-of-presentation-dependent manner. Particularly from the pediatric experience, we hypothesize that all cases of PSC likely originate from a complex "Early PSC"-"IBD"-"AIH" overlap in which PSC defines the uniquely and variably associated "AIH" and "IBD" components along an individualized lifetime continuum. We speculate that a distinctly unique, "diverticular autoimmunity" against the embryonic cecal- and hepatic diverticulum-derived tissues may be the origin of this combined syndrome, where "AIH" and "IBD" variably commence then variably fade while PSC progresses with age. Our hypothesis provides an explanation for the age-dependent variation in the presentation and progression of PSC. This is critical for the optimal targeting of studies into PSC etiopathogenesis and emphasizes the concept of a "developmental window of opportunity for therapeutic mitigation" in what is currently recognized as an irreversible disease process. The discovery of such a window would be critically important for the targeting of interventions, both the administration of current therapies and therapeutic trial planning.

Conclusion : Four in fi ve patients with IEI reported cutaneous features associated with their disease. These results may serve as the foundation for future prospective studies which aim to identify patients with IEI from der-matological consultations and clinics.

Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. The severe CFLD variant with cirrhosis or portal hypertension has a poor prognosis and life expectancy. CFTR modulator therapies are now available for people with CF and eligibility for such treatment is based on their CFTR genotype. We evaluated the genetic eligibility for elexacaftor, tezacaftor, ivacaftor (ETI), and ivacaftor (IVA) monotherapy in a previously reported CF cohort of 1591 people with CF of whom 171 with severe CFLD. Based on their CFTR mutations, 13% (N=184/1420) of subjects without CFLD and 11% (N=19/171) of those with severe CFLD are not eligible for either ETI or IVA therapy. The non-eligible patients without CFLD or with severe CFLD can currently not take advantage of the potential benefits of these new treatments. Although this study cannot provide any data regarding the effect of ETI or IVA on the progression of severe CFLD, the consequences for ineligibility of patients with extreme liver phenotype may be even more significant because of their poorer disease risk profile.

We refer to the excellent, timely review by Lisman et al.1 on “Haemostatic alterations and management of haemostasis in patients with cirrhosis”. Children with advanced liver disease awaiting liver transplantation or close to listing are at high risk of losing portal venous flow and developing portal thrombosis because of high hepatic resistance and a fragile, rebalanced haemostatic state. Loss of portal flow is reported to herald irreversible portal thrombosis, hepatocyte extinction with worsening hepatocyte function and risk of portal vein clot extension.

BACKGROUND AND AIMS:Early identification of risk factors for the development of severe fibrosis in children with cystic fibrosis-related liver disease (CFLD) is crucial as promising therapies emerge.METHODS:This multi-center cohort study of children with a priori defined CFLD from 1999 to 2016, was designed to evaluate the clinical utility of CF-specific characteristics and liver biomarkers assessed years prior to liver biopsy-proven CFLD to predict risk of developing severe fibrosis (F3-4) over time. Fibrosis was staged by Metavir classification.RESULTS:The overall study cohort of 42 patients (F0-2 (n = 22) and F3-4 (n = 20)) was 57% male (n = 24) with median age of 7.6 years at baseline visit versus 10.3 years at biopsy. Median FEV1 % predicted was lower in F3-4 participants at baseline versus F0-2 (59% vs. 85%; p = .002), while baseline FIB-4, APRI and GGT were higher in F3-4. Median splits for FIB-4 (≥.13), APRI (≥.36), GPR (≥.09), GGT (≥25.5), and FEV1 % (<64%) were associated with more rapid progression to F3-4 (p < .01 for all). Using a combination of change/year in FIB-4, APRI, and GPR to predict F3-4, the AUROC was .81 (95% CI, .66, .96; p < .0001). For up to 5.8 years prior, thresholds for GPR were met 6.5-fold more rapidly, and those for APRI and FIB-4 were met 2.5-fold more rapidly, in those who progressed to F3-4 than those that did not.CONCLUSIONS:This study suggests mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.

To the editor, Health care insurers should cover the costs of oral vancomycin (OV) for the treatment of primary sclerosing cholangitis (PSC). AASLD’s 2022 PSC Practice Guidance (Guidance)1 combined with the AASLD separate Supporting Statement2 are helpful. While the Guidance doesn’t recommend OV for PSC.1 AASLD published a separate Supporting Statement stating: “The Guidance notes the insufficiency of the evidence and accordingly does not make a recommendation for or against the use of OV for the treatment of PSC. In the absence of a definitive clinical trial, the decision to use an off-label medication should remain between the doctor and the patient. Larger clinical trials or studies are needed to conclusively assess the efficacy and safety of vancomycin in PSC. Although there is not sufficient evidence to make a formal recommendation regarding the use of OV for PSC, it should not be used as justification to restrict coverage of this treatment if a physician feels it is the right course of action”. Although large, controlled trials are not yet completed, 2 small, controlled trials and evidence from multiple cohort studies are summarized in a systematic review and meta-analysis demonstrating OV has beneficial effects on liver functions in PSC patients. These robust findings are further supported by a recent pediatric/adult cohort study where OV showed benefits in lowering cholestatic enzymes and improving MRCP findings of bile duct dilatation and stenoses.3,4 This might translate to fewer liver transplants, fewer hospitalizations for acute cholangitis, and other expensive consequences of not treating this devastating disease. In addition, OV has beneficial effects on PSC-associated colitis with the improvement of diarrhea and other symptoms.3,4 The medical community desires better treatments at lower costs. For responsive PSC/inflammatory bowel disease patients, insurers stand to benefit financially by allowing OV to be substituted for biologic drugs. The beneficial effects of OV on colitis are its most reliable effects. Biologics typically cost 5 times more than OV, and the gain over placebo is small. Some surgeries might also be avoided; our patients have avoided colectomies with OV. While OV does not work for all PSC patients, no other treatment (besides liver transplantation) has proven effective in even a subgroup of PSC patients. Medical and financial reasons for insurers to cover OV for PSC are compelling as long as the physician and patient can demonstrate that OV benefits the patient.