Rosacea and autoimmune liver diseases: a two-sample Mendelian randomization study.

Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02-1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients.

Coexistence of metabolic-associated fatty liver disease and autoimmune or toxic liver disease.

Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH.

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.

Association between inflammatory bowel disease and primary sclerosing cholangitis: Insights from bibliometric analysis.

BACKGROUND: Crohn's disease and ulcerative colitis are forms of inflammatory bowel disease affecting approximately 1% of the population. Their typical features include chronic diarrhea, abdominal pain, and weight loss. Extraintestinal manifestations may coincide with or precede the diagnosis of these diseases. Primary sclerosing cholangitis is one such extraintestinal manifestation. Although many papers on this field have been published, bibliometric analysis still needs to be conducted. This article summarizes the current research progress through a bibliometric study, provides an overview of the research status in this field, and analyzes recent research trends. METHODS: Publications on inflammatory bowel disease and primary sclerosing cholangitis from January 1, 2008, to August 31, 2023, were extracted from the Web of Science Core Collection. VOSviewer and CiteSpace were used to perform a bibliometric and visual study. RESULTS: There are 1499 relevant articles, and the number of articles in this field has been relatively stable in recent years. The results indicate that Karlson TH from the University of Oslo has the highest cumulative number of publications. The institution with the highest publication output is the Mayo Clinic, and the United States leads in article production, occupying a dominant position. Keyword analysis reveals 4079 keywords, with primary sclerosing cholangitis, inflammatory bowel disease, and ulcerative colitis being the most frequently occurring keywords. CONCLUSION: Research on the association between inflammatory bowel disease and primary sclerosing cholangitis is steadily advancing, with the United States leading in publication output globally. China needs to invest more in research in this area, and collaboration among institutions should be strengthened. The research hotspots revolve around the association between inflammatory bowel disease and primary sclerosing cholangitis, gut microbiota, and other fields.

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.

Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database.

BACKGROUND: Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are all immune-mediated chronic inflammatory liver diseases. Autoimmune liver diseases are rare, making identification and treatment difficult. To improve clinical outcomes and enhance patient quality of life, we performed an epidemiological study of autoimmune liver diseases based on real-world comprehensive data. RESULTS: We used National Health Insurance Service claims data in Korea from 2005 to 2019. Patients were identified using the International Classification of Disease 10th Revision code, and rare intractable disease codes assigned according to the strict diagnostic criteria. In the AIH cohort, 8,572 (83.9%) were females and the mean age at diagnosis was 56.3 ± 14.3 years. PBC also showed female dominance (83.3%) and the mean age was 57.8 ± 12.6 years. Patients with PSC showed no sex predominance and had a mean age of 57.8 ± 21.5 years. During the study period, there were 10,212, 6,784, and 888 AIH, PBC, and PSC patients, respectively. The prevalence of AIH, PBC, and PSC in 2019 were 18.4, 11.8, and 1.5 per 100,000 population, while the corresponding incidences were 2.3, 1.4, and 0.3 per 100,000 population, respectively. Analysis of sex-age-standardized data showed that the annual prevalence of these diseases is increasing. The 10-year survival rates were 89.8%, 74.9%, and 73.4% for AIH, PBC, and PSC, respectively. CONCLUSIONS: The number of patients with autoimmune liver disease in South Korea is increasing over time. Further research on autoimmune liver disease is needed to fulfill unmet clinical needs.

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.

The prevalence and disease course of autoimmune liver diseases in Greenland.

Autoimmune liver diseases are rare serious diseases causing chronic inflammation and fibrosis in the liver parenchyma and bile ducts. Yet, the prevalence and burden of autoimmune liver diseases are largely unexplored in Arctic native populations. We investigated the prevalence and management of autoimmune liver diseases in Greenland using nationwide cross-sectional register data and subsequent medical chart reviews validating diagnoses and extracting liver histology examinations and medical treatments. The overall prevalence of autoimmune liver diseases in Greenland was 24.6 per 100,000 (95% CI: 14.7-41.3). This was based on 7 patients with autoimmune hepatitis (AIH) (12.3 per 100,000), 3 patients with primary biliary cholangitis (PBC) (5.3 per 100,000), 4 patients with AIH/PBC overlap disease (7.0 per 100,000), and no patients with primary sclerosing cholangitis. All diagnoses were confirmed by liver histology examinations. Medical treatments adhered to internal recommendations and induced complete remission in most patients with AIH, and complete or partial remission in 1 patient with PBC and 3 patients with AIH/PBC overlap disease. One patient had established cirrhosis at the time of diagnosis, while 2 patients progressed to cirrhosis. In conclusion, the prevalence of autoimmune liver diseases was lower in Greenland than in Scandinavia and among Alaska Inuit.

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.

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.

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).

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.

Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma.

BACKGROUND: It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS: We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS: Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS: In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT: The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.

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.

Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease.

BACKGROUND: While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. METHODS: A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. RESULTS: Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32-7.89] and PBC (aOR 4.16, 95% CI 3.46-5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88-5.92) and PBC (aOR 9.22, 95% CI 7.03-12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96-2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72-3.14). CONCLUSION: Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.

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.

Colectomy in patients with ulcerative colitis is not associated to future diagnosis of primary sclerosing cholangitis.

BACKGROUND: Primary Sclerosing Cholangitis (PSC) is a hepatobiliary disease closely related to ulcerative colitis (UC). In PSC patients, colectomy has been linked to improved prognosis, especially following liver transplantation. This suggests an involvement of the gut-liver axis in PSC etiology. OBJECTIVE: We aimed to investigate the association between colectomy and the risk of future PSC in an epidemiological setting. METHOD: Through nationwide registers, we identified all adults diagnosed with UC in Sweden 1990-2018 and retrieved information on PSC diagnosis and colectomy. Within the UC cohort (n = 61,993 patients), we matched 5577 patients with colectomy to 15,078 without colectomy. Matching criteria were sex, age at UC onset (±5 years), year of UC onset (±3 years), and proctitis at the time of colectomy. Incidence rates of PSC per 1000-person year were calculated, and the Cox proportional hazard regression model estimated hazard ratios (HRs) for PSC until 31 December 2019. RESULTS: During the follow-up, 190 (3.4%) colectomized UC patients and 450 (3.0%) UC comparators developed PSC, yielding incidence rates of 2.6 and 2.4 per 1000 person-years (HR 1.07 [95% CI 0.90-1.28]). The cumulative incidence of colectomy decreased remarkably over calendar periods, but the cumulative incidence of PSC remained unchanged. The risk of developing PSC in colectomized versus comparators changed over time (HR 0.68 [95% CI; 0.48-0.96] in 1990-97 and HR 2.10 [95% CI; 1.37-3.24] in 2011-18). CONCLUSIONS: In UC patients, colectomy was not associated with a decreased risk of subsequent PSC. The observed differences in the risk of PSC development over calendar periods are likely due to changes in PSC-diagnosis and UC-treatment.

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.

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.

Recent Insights into Pediatric Primary Sclerosing Cholangitis.

This article reviews recent literature on the pathogenesis, presentation, diagnosis, comorbidities, natural history, and management of pediatric primary sclerosing cholangitis (PSC). The authors shed light on the role of genetic and environmental factors in PSC, although recognize the limitations in the understanding of PSC pathogenesis. They reflect on presenting disease phenotypes, including the association with inflammatory bowel disease and frequent histologic presence of autoimmune hepatitis features. The current lack of effective medications is discussed, and disease complications and prognosis are described. Finally, the authors highlight available evidence while acknowledging the paucity of prospective pediatric data.