Autoimmune diseases in primary sclerosing cholangitis and their first-degree relatives.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel disease (IBD). However, there is limited overlap between IBD and PSC risk genes, but a stronger association between PSC and other autoimmune conditions. We aimed to assess the coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune comorbidity on severe outcomes. APPROACH AND RESULTS: In a matched cohort study, 1378 individuals with PSC and 13,549 general population comparators and their first-degree relatives were evaluated. National registries provided data on diagnoses and outcomes (liver transplantation, hepatobiliary cancer, and liver-related death). The OR of autoimmune disease was estimated by logistic regression. The Fine and Gray competing risk regression estimated HRs for severe outcomes. The prevalence of non-IBD, non-autoimmune hepatitis, and autoimmune disease was 18% in PSC and 11% in comparators, OR: 1.77 (95% CI: 1.53-2.05). Highest odds were seen for celiac disease [OR: 4.36 (95% CI: 2.44-7.49)], sarcoidosis [OR: 2.74 (95% CI: 1.29-5.33)], diabetes type 1 [OR: 2.91 (95% CI: 2.05-4.05)], and autoimmune skin disease [OR: 2.15 (95% CI: 1.52-2.96)]. First-degree relatives of individuals with PSC had higher odds of developing IBD, autoimmune hepatitis, and any autoimmune disease than relatives of the comparators [OR: 3.25 (95% CI: 2.68-3.91); OR: 5.94 (95% CI: 2.82-12.02); OR: 1.34 (95% CI: 1.19-1.50)]. Autoimmune comorbidity in PSC was not associated with poorer outcomes [HR: 0.96 (95% CI: 0.71-1.28)]. CONCLUSIONS: Individuals with PSC and their first-degree relatives had higher odds of autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcomes.

Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?

Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 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).

Prevalence and clinical profiles of primary sclerosing cholangitis in China: Data from electronic medical records and systematic literature retrieval.

BACKGROUND & AIMS: Epidemiology of primary sclerosing cholangitis (PSC) is lacking in China. We aimed to estimate the period prevalence and depict the clinical features of PSC in China. METHODS: We identified and included PSC cases between 2000 and 2023 from two sources: electronic medical records (EMR) and systematical literature retrieval (SLR). The period prevalence of PSC was estimated by the multiplier method. Rate ratios (RRs) for PSC prevalence in relation to macroeconomic indicators were calculated by the negative binomial regression model. RESULTS: A total of 1358 PSC cases were retrieved from 299 hospitals (162 from EMR and 1196 from SLR). Males accounted for 55.7 % of the PSC cases and 25.7 % had concomitant inflammatory bowel disease (IBD). The estimated period prevalence of PSC from 2000 to 2023 was 2.36 (95 % CI: 1.82, 3.34) per 100,000. Males had a numerically higher PSC prevalence than females (2.56, 95 % CI: 1.97, 3.63 vs. 2.14, 95 % CI: 1.65, 3.04 per 100,000). The highest prevalence of PSC was in East China at 4.87 (95 % CI: 3.44, 7.18) per 100,000, followed by North China at 2.94 (95 % CI: 2.33, 3.74) per 100,000, and the lowest in South China at 0.92 (95 % CI: 0.66, 1.30) per 100,000. Regional per capita GDP (RR 1.65, 95 % CI: 1.03, 2.65) and healthcare expenditure (RR 1.94, 95 % CI: 1.13, 3.38) were identified to be associated with PSC prevalence. CONCLUSION: Our study showed the estimated PSC prevalence varied within China, but was generally lower than that in Western countries.

Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases.

BACKGROUND: Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS: A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS: We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS: We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.

The new definition of dominant stricture in primary sclerosing cholangitis: Prevalence and clinical significance.

BACKGROUND AND AIMS: A new definition of dominant stricture (NDS) has recently been defined for patients with primary sclerosing cholangitis (PSC). Prevalence and clinical features of this, compared to traditional dominant stricture (TDS), have not been reported. METHODS: In this single-centre longitudinal prospective cohort study, all PSC patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between October 2021 and 2022 were recruited. Symptoms of cholestasis, laboratory values (P-alkaline phosphatase, P-Bilirubin), Helsinki PSC-score, brush cytology findings and need for endoscopic therapy (i.e. dilation, stenting) were prospectively collected. RESULTS: Overall, 228 patients with PSC underwent 248 ERCPs. NDS was detected in 43 (17%; 36 patients) and TDS without NDS (TDS group) was detected in 62 (25%; 58 patients) ERCPs, respectively; in the remaining 143 ERCPs, neither TDS nor NDS was seen (no dominant stricture [NoDS] group). PSC duration (median 8 years) and patient's age did not differ between the three groups; males presented more often with NDS. Patients with NDS were more often symptomatic, had higher cholestatic liver enzymes, advanced bile duct disease and markers of biliary inflammation (p < .001). Patients with NDS needed dilation (81%) and stenting (21%) more often than the TDS group (60% and 5%, respectively). Dysplasia in brush cytology was more common in TDS (5%) and NDS (9%) than in NoDS (3%) groups (p = .04), but did not differ between TDS and NDS groups. CONCLUSIONS: Dominant stricture according to the new definition developed in 17% of PSC patients in our cohort and identifies patients with more advanced disease, biliary inflammation and need of endo-therapy.

Association between autoimmune liver diseases and chronic hepatitis B: A multivariable Mendelian randomization study in European population.

BACKGROUND: Observational studies have indicated a link between autoimmune liver diseases (AILD) and chronic hepatitis B (CHB) through observational studies. The association between AILD and CHB remains indeterminate. METHODS: A two-sample Mendelian randomization (MR) analysis was conducted to scrutinize the causal nexus between AILD and CHB utilizing summary statistics derived from extensive genome-wide association studies (GWASs) in European populations. The primary statistical methodology employed was the inverse variance-weighted (IVW) method to deduce the causal connection of AILD on CHB. This study incorporated primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) as subtypes of AILD. Additionally, we conducted a multivariable MR (MVMR) analysis to account for the potential confounding effects of smoking, alcohol consumption, body mass index (BMI), and some autoimmune diseases. RESULTS: Our MR investigation encompassed a cohort of 725,816 individuals. The MR analysis revealed that genetically predicted PSC significantly correlated with a reduced risk of CHB (IVW OR = 0.857; 95%CI: 0.770-0.953, P = 0.005). Conversely, the reverse MR analysis suggested that genetic susceptibility to PSC might not modify the risk of CHB (IVW OR = 1.004; 95% CI: 0.958-1.053, P = 0.866). Genetically proxied PBC and AIH exhibited no discernible causal association with CHB in the MR analysis using the IVW method (P = 0.583; P = 0.425). The MVMR analysis still indicated a decreased risk of CHB associated with PSC (OR = 0.853, P = 0.003). CONCLUSION: Our study elucidates a causal relationship between PSC and a diminished risk of CHB.

Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Health-related quality of life in patients with primary sclerosing cholangitis: A longitudinal population-based cohort study.

BACKGROUND & AIMS: Data regarding health-related quality of life (HRQoL) in primary sclerosing cholangitis (PSC) are sparse and have only been studied cross-sectionally in a disease which runs a fluctuating and unpredictable course. We aim to describe HRQoL longitudinally by using repeated measurements in a population-based cohort. METHODS: Every 3 months from May 2017 up to August 2020, patients received digital questionnaires at home. These included the EQ-5D, 5-D Itch, patient-based SCCAI and patient-based HBI. The SF-36, measuring HRQoL over eight dimensions as well as a physical component summary (PCS) and mental component summary (MCS) score, was sent annually. Data were compared with Dutch reference data and a matched IBD disease control from the population-based POBASIC cohort. Mixed-effects modelling was performed to identify factors associated with HRQoL. RESULTS: Three hundred twenty-eight patients completed 2576 questionnaires. A significant reduction of small clinical relevance in several mean HRQoL scores was found compared with the Dutch reference population: 46.4 versus 48.0, p = .018 for PCS and 47.5 versus 50.5, p = .004 for MCS scores. HRQoL outcomes were significantly negatively associated with coexisting active IBD (PCS -12.2, p < .001 and MCS -12.0, p < .001), which was not the case in case of quiescent IBD. Decreasing HRQoL scores were also negatively associated with increasing age (PCS -0.1 per 10 years, p = .002), female sex (PCS -2.8, p < .001), diagnosis of AIH overlap (PCS -3.7, p = .059), end-stage liver disease (PCS -3.7, p = .015) and presence of itch (PCS -9.2, p < .001 and MCS -3.1, p = .078). The odds of reporting a clinically relevant reduction in EQ-5D scores showed seasonal variation, being lowest in summer (OR = 0.48 relative to spring, p = .037). In patients with liver transplant, HRQoL outcomes were comparable to the Dutch general population. CONCLUSIONS: PSC patients report impaired HRQoL of small clinical relevance compared with the general population. After liver transplantation, HRQoL scores are at comparable levels to the general population. HRQoL scores are associated with potentially modifiable factors such as itch and IBD activity.

Autoimmune liver diseases and diabetes: A propensity score matched analysis and a proportional meta-analysis.

BACKGROUND AND AIMS: Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS: We performed a case-control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age-, sex-, BMI- and ethnicity-matched controls. Next, we performed a systematic review and proportional meta-analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model. RESULTS: Three hundred twenty-eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%-5.7%), 1.7% (0.9%-3.1%), 3.1% (1.9%-4.8%) and of T2D 14.8% (11.1%-19.5%), 18.1% (14.6%-22.2%), 6.3% (2.8%-13.3%) in patients with AIH, PBC and PSC, respectively. CONCLUSIONS: Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.

The role of serology, liver function tests and imaging in screening of primary sclerosing cholangitis: the HelPSCreen score.

OBJECIVES: At present, no sensitive or specific screening test exists for primary sclerosing cholangitis (PSC). PSC screening is mainly based on elevated alkaline phosphatase (ALP) in patients with inflammatory bowel disease (IBD). We aimed to produce a screening score based on laboratory tests to predict the likelihood of PSC. Moreover, we evaluated the additional roles of liver histology and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of PSC. MATERIALS AND METHODS: The data of 385 patients who came for their first endoscopic retrograde cholangiography (ERC) to confirm PSC diagnosis were retrieved from the PSC registry of the Helsinki University Hospital. Overall, 69 patients referred for ERC with suspected PSC, in whom PSC was excluded by ERC or liver biopsy and MRCP, served as controls. We included patients' demographics and 13 laboratory test results in the analysis. Variables with significant odds ratios were selected for multivariate logistic regression, which was used to create a novel scoring system for PSC. The presence of IBD, serum perinuclear anti-neutrophil cytoplasmic antibodies, and ALP levels demonstrated the highest predictive value for PSC. A score was assigned for each statistically significant predictor. RESULTS: The optimal cut-off point for the score was ≥3, with an AUC of 0.83 (95%CI: 0.78-0.88). The addition of liver histology or MRCP findings to the score did not add a predictive value. CONCUSIONS: In conclusion, we created a novel, simple scoring system to screen the probability of PSC. The HelPSCreen-score may help to assess the disease prevalence and to target further investigations in patients suspected of PSC.

Incidence and adverse clinical events of primary sclerosing cholangitis with ulcerative colitis.

PURPOSE: The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. METHODS: We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. RESULTS: A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92 years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P < .001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P < .001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P < .001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P < .001) and mortality (HR, 4.257) rates than did the UC-alone group. CONCLUSION: Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services.

Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

Prevalence of Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Although the association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) is well recognized, uncertainties remain about the magnitude of this problem. We conducted a systematic review and meta-analysis assessing prevalence of PSC in IBD to investigate whether type of IBD, how presence of PSC was defined, sex, disease extent or location, time period, or geographic location influenced prevalence. METHODS: Medline, Embase, and Embase Classic were searched (from inception to April 10, 2021) to identify observational studies recruiting ≥50 adult patients with IBD and reporting prevalence of PSC. Data were extracted, and pooled prevalence, odds ratios (ORs), and 95% confidence intervals (CIs) calculated. RESULTS: Of 1204 citations, 64 studies were eligible, containing 776,700 patients. Overall, pooled prevalence of PSC in IBD was 2.16%; it was highest in South America and lowest in Southeast Asia. Pooled prevalences in patients with ulcerative colitis (UC), Crohn's disease (CD), and IBD-unclassified were 2.47%, 0.96%, and 5.01%, respectively. Pooled prevalence was significantly higher in UC versus CD (OR 1.69, 95% CI 1.24-2.29). In subgroup analyses according to method used to define presence of PSC, the highest prevalence was 2.88% in studies performing both liver biochemistry and endoscopic retrograde/magnetic resonance cholangiopancreatography and the lowest was 1.79% in studies using a clinical diagnosis. Prevalence was generally higher in men, patients with more extensive, compared with left-side, UC or ileocolonic or colonic, compared with ileal, CD. CONCLUSIONS: Our findings provide the first pooled estimates of the burden of PSC in IBD, as well as potential risk factors, which may be important in establishing a prompt diagnosis and initiating appropriate surveillance for relevant gastrointestinal malignancies.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

We Are Not Immune: Racial and Ethnic Disparities in Autoimmune Liver Diseases.

Autoimmune liver diseases are attributed to a complex interplay of biologic, acquired, and environmental factors. Increased prevalence, later stage at presentation, worse response to standard therapy, and transplant-related disparities have all been reported in racial and ethnic minorities such as Black and Latinx patients with autoimmune liver diseases. While biology and inherited genetic predispositions may partly explain these disparities, definitive and universal genetic variations underlying these differences in outcomes have not been defined. Nonetheless, socioeconomic status, access to health care, environmental and societal factors, and implicit provider bias can all contribute to poor patient outcomes. There remains an unmet need to understand and mitigate the factors contributing to health inequity in autoimmune liver diseases. In this review, we summarize the data on racial and ethnic disparities in presentation, treatment response, and outcomes pertaining to autoimmune liver diseases in minority populations, on the premise that understanding disparities is the first step toward reaching health equity.

De Novo Colorectal and Pancreatic Cancer in Liver-Transplant Recipients: Identifying the Higher-Risk Populations.

BACKGROUND AND AIMS: Gastrointestinal (GI) malignancies are common after liver transplantation. The aim of this study was to identify the risk and timing of the more common GI malignancies, colorectal and pancreatic cancer, to aid in optimizing potential posttransplant screening practices. APPROACH AND RESULTS: Data from the United Network for Organ Sharing database of all adult liver-transplant recipients from 1997 to 2017 were analyzed and a comparison made with cancer incidence from general population data using Surveillance, Epidemiology, and End Results data. Of 866 de novo GI malignancies, 405 colorectal and 216 pancreas were identified. The highest cumulative incidence for colorectal cancer occurred in recipients with primary sclerosing cholangitis (PSC), recipients over the age of 50 with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC)/cholangiocarcinoma (CCA), and females >50 years with alcohol-associated liver disease and HCC/CCA, with risk increasing above the general population within 5 years of transplant. Patients with PSC and HCC/CCA or NASH and HCC/CCA have the highest cumulative incidence of pancreatic cancer also rising within 5 years following transplant, with those patients >50 years old conferring the highest risk. CONCLUSIONS: These data identify a high-risk cohort that warrants consideration for intensified individualized screening practices for colorectal cancer after liver transplantation. In addition to recipients with PSC, further study of recipients with NASH and HCC/CCA and females with alcohol-associated liver disease and HCC/CCA may be better tailored to colorectal cancer screening ideals. Higher-risk patient populations for pancreatic cancer (PSC and NASH with HCC/CCA) would benefit from further study to determine potential screening practices. GI malignancies occur at higher rates in liver-transplant patients compared with the general population. In the era of individualized medicine, this study identifies the highest-risk transplant recipients (PSC and NASH cirrhosis with coexisting HCC/CCA) who may benefit from altered screening practices for these malignancies.

Incidence of chronic immune-mediated inflammatory diseases after diagnosis with Kawasaki disease: a population-based cohort study.

OBJECTIVES: Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. METHODS: We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n = 3753) were matched to 5 non-KD controls from the general population (n = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. RESULTS: There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. CONCLUSION: Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD.

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Previous studies have established an association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The disease burden of IBD in PSC patients was not well estimated. The study aimed to quantify the pooled prevalence of IBD in PSC and to investigate whether subtypes of PSC and sex influence the prevalence of IBD. METHODS: PubMed, Embase, and Web of Science were searched through November 2021 for studies reporting data on IBD among PSC patients. The outcomes were the prevalence of IBD in patients with PSC, as well as the association (odds ratio [OR]) of IBD in PSC according to subtype and sex. RESULTS: Based on the analysis of 25 studies, the prevalence of IBD in patients with PSC was 71.1% (95% CI 68.2-75.1%), most commonly in UC (55.9%, 95% CI 52.5-59.3%). The pooled prevalence of IBD was 76.9% in Australia (95% CI 71.2-82.6%, 1 study), 75.9% (95% CI 69.5-82.3%, 4 studies) in North America, 70.9% (95% CI 65.8-76.0%, 17 studies) in Europe and 67.0% (95% CI 57.9-76.0%, 2 studies) in Asia. Male PSC patients had a higher prevalence of IBD (OR 1.67, 95% CI 1.52-1.83) and UC (OR 2.02, 95% CI 1.56-2.63) and a lower prevalence of CD (OR 0.77, 95% CI 0.67-0.88) than female patients. Large duct PSC patients had a higher prevalence of IBD (OR 2.57, 95% CI 2.03-3.25) and UC (OR 4.51, 95% CI 1.22-16.71) than small duct PSC patients. CONCLUSIONS: The study provided the first pooled estimates of the burden of IBD in patients with PSC and could be used as the basis for risk stratification of PSC patients.

Characteristics and impact of sex in a cohort of patients with primary sclerosing cholangitis: Experience of a transplant center in the Mediterranean basin. / Características e impacto del sexo en una cohorte de pacientes con colangitis esclerosante primaria: experiencia de un centro trasplantador de la cuenca mediterránea.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that typically affects middle-aged men with ulcerative colitis (UC). However, recent studies point out to epidemiological changes. Our aim was to determine if the epidemiology, clinical course and outcome of patients with PSC followed at a reference hepatology center resemble what is described in the literature. PATIENTS AND METHOD: Retrospective search of patients with a diagnosis of PSC treated in our center between 2000 and 2019. RESULTS: Cohort of 55 patients (mean age: 37 years), 44% women. Most were large duct type (79%). Most diagnoses were made after 2011. At time of diagnosis, 63% of patients were asymptomatic. The median time from suspicion to diagnosis was 2 years. After a mean follow-up time of 7 years, one third developed cirrhosis, and 25% required liver transplantation (LT); among these, the disease recurred in almost half. Inflammatory bowel disease (IBD) was present in 45%, especially UC. Although statistical significance was not reached, PSC in women was characterized by higher rate of asymptomatic presentation and more frequent association with UC versus other forms of IBD. Women also had more frequently cirrhosis at diagnosis and required LT more often than men. CONCLUSION: The epidemiology of PSC is changing. The number of women affected is greater than what was expected from the literature, with a recent increase in incidence. There seems to be differences between sexes in the form of presentation and disease course that should be confirmed in subsequent studies.

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. METHODS: Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. RESULTS: Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006-1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1-1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815-182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215-42.43). CONCLUSION: Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).