Scandinavian Journal of Gastroenterology最新文献

Background: Dubin-Johnson Syndrome (DJS; OMIM 237500) is a rare autosomal recessive disorder caused by pathogenic variants in the ABCC2 gene, encoding for the multidrug resistance protein 2 (MRP2), resulting in impeded biliary excretion of bilirubin metabolites. It is typically characterized by chronic or intermittent jaundice and conjugated hyperbilirubinemia.

Case presentation: We report the case of a 54-year-old male with hyperbilirubinemia (mostly conjugated) and hypertransaminasemia. Hypertransaminasemia was due to presence of Metabolic dysfunction-associated fatty liver disease (MASLD), while whole-genome sequencing revealed a homozygous missense variant affecting ABCC2 (c.3893G > A, p.Gly1298Asp), a previously undescribed variant likely linked to hyperbilirubinemia. It is an extremely rare genetic variant (allele frequency = 6.2 × 10^-7). In silico analyses predicted the variant to be highly pathogenic (CADD score 29; AlphaMissense score 0.978; PhyloP 8.87; DynaMut ΔΔG = -0.765 kcal·mol^-1 and ΔΔSVib = -0.234 kcal·mol^-1·K^-1). Structural modeling suggested no gross conformational changes but potential effects local conformation and overall function of the protein.

Conclusions: We describe a novel ABCC2 mutation associated with Dubin-Johnson Syndrome. This finding expands the spectrum of ABCC2 variants to evaluate in case of hyperbilirubinemia and highlights the importance of genetic testing in unexplained cases of conjugated hyperbilirubinemia.

Introduction: Faecal elastase-1 testing is the most commonly used method for diagnosing pancreatic exocrine insufficiency (PEI), but has poor diagnostic precision and cannot guide titration of pancreatic enzyme replacement therapy (PERT). An alternative is ¹³C-mixed triglyceride breath test. We investigated concordance between breath test and faecal elastase-1, and response to bicarbonate-buffered enzymes.

Methods: In this prospective study, adults with faecal elastase <100 µg/g using PERT performed a baseline breath test without enzyme treatment. Participants with normal baseline exhalation (≥29%) were enrolled in Substudy I, where they discontinued pancreatic enzyme replacement therapy (PERT) and were clinically reassessed after 6 months. Participants with abnormal exhalation (<29%) were enrolled in Substudy II, a three-arm crossover study where breath test was repeated on three separate days while receiving 24,000, 48,000, and 72,000 IU PERT, in random order. Primary outcomes were PERT reinstatement at follow-up (substudy I) and differences in cumulative ¹³CO2 exhalation (substudy II).

Results: Baseline tests where performed in 25 participants. Thirteen participants had normal breath test, 11 agreed to pause PERT, but only five participants did not reinitiate treatment (substudy I). 12 participants were included in substudy II (mean age 65, all males). All had significant breath test improvements on lowest enzyme dose (24,000 IU) versus baseline (mean difference 21.5%, p < 0.001), yet higher enzyme doses did not improve results significantly.

Discussion: About half of participants previously categorised with PEI had normal ¹³C-mixed triglyceride breath test, questioning diagnosis. Most participants demonstrated normal breath test with lowest enzyme dose during standardised test meal. However, this finding may not generalise to habitual meals.

Background: Severe alcohol-associated hepatitis (AH) remains a major challenge in clinical practice due to its limited treatment options and high short-term mortality. Although corticosteroids have long been the mainstay of treatment, their use has been declining because of concerns about side effects and contraindications.

Aim: We aimed to summarize the current standards for corticosteroid use in severe AH, with a specific focus on differentiating absolute from relative contraindications.

Methods: This narrative review integrates evidence from randomized clinical trials, observational cohort studies, and contemporary guideline statements pertaining to corticosteroid therapy in severe alcohol‑associated hepatitis.

Results: The majority of individuals with severe AH present with concomitant complications such as infection, acute kidney injury, or gastrointestinal bleeding. Emerging data indicates that, with the developments in diagnostic methods, treatment strategies, and supportive care, that were previously considered absolute contraindications are now being recognized as relative. Corticosteroid treatment can be administered safely once certain concomitant conditions have been stabilized or resolved. On the other hand, such severe presentations, as identified by markedly elevated Maddrey's discriminant function, MELD score, or acute-on-chronic liver failure (ACLF) grade, determine a poor response to corticosteroid treatment and high risk of complications.

Conclusions: In the setting of severe AH, while certain conditions require a temporary corticosteroid treatment delay, others necessitate alternative approaches. Individuals with a low likelihood of responding, early liver transplantation, extracorporeal therapy, microbiota-based therapeutics, or palliative care should be considered in the earlier settings.

Objectives: The real-world clinical course of hepatocellular carcinoma (HCC) remains poorly understood. We aimed to describe the prognosis of Danish patients with HCC treated with curative-intent resection or ablation strategies.

Methods: This was a population-based, historical cohort study of all patients with HCC within two Danish regions (population 2 million). Information was extracted from patients' medical records. Patients diagnosed with HCC in 2013-2023 and treated first-line with resection/ablation with curative intent were included. We used multistate models, competing risk analyses, and cause-specific Cox models to describe the clinical course and examine risk factors for recurrence.

Results: The cohort comprised 296 patients [79% male; median age 69 years (IQR 62-76); 60% (n = 179) with cirrhosis (alcohol-related, n = 76; viral hepatitis-related, n = 57)] treated first-line with resection (40%; n = 117) or ablation (60%; n = 179). The risk of early recurrence (within 2 years) was 55% (95% CI 50-61) and similar for resection- and ablation-treated patients. Five years post resection/ablation, 10% of patients remained alive and recurrence-free. Alpha-fetoprotein was a strong predictor of recurrence, and a high Child-Pugh score and high comorbidity burden were predictors of death without recurrence. The 10-year probability of receiving systemic treatment was 24%. For the total cohort, the median survival time was 3.5 years (IQR 1.5-5.9) and the median recurrence-free survival time was 1.1 years (IQR 0.5-2.4).

Conclusion: This population-based real-world study demonstrated that current curative-intent treatment strategies for early HCC are insufficient for long-term disease control, and that we need more effective management and follow-up of patients with HCC.

Background and aims: Long-term outcomes for Crohn's disease (CD) patients treated with infliximab (IFX) remain suboptimal. We developed and validated a clinical decision support tool (CDST) to predict sustained remission in CD patients treated with infliximab (IFX).

Methods: This multicenter observational study analyzed 746 CD patients across three cohorts. Sustained clinical remission (CREM) was defined as steroid-free Crohn's Disease Activity Index (CDAI) <150 at week 104. Using logistic regression, predictors were weighted by inverse variance. The CDST was internally validated (Cohort I, n = 113) and externally validated (Cohort II, n = 367).

Results: Key predictors of CREM included: prior biologic exposure (-18 points), penetrating disease (B3 phenotype, -7 points), albumin (+0.5/gL), younger age (-0.3/year), and absence of antibody to infliximab formation (ATI, +17 points). The model demonstrated strong discrimination (AUC 0.791 [95% CI 0.708-0.875]) and calibration (Brier score: 0.191). External validation AUC was 0.611 (95% CI 0.546-0.675), indicating modest generalizability. Risk stratification via CDST categorized patients into low- (<6 points), intermediate- (6-25), and high-risk (>25) groups. A cutoff of 25 points predicted 2-year CREM with 60% (95%CI 53.2%-66.5%) sensitivity and 52% (95% CI 41.2%-1.8%) specificity.

Conclusions: We developed and validated a CDST to identify CD patients likely to achieve sustained remission on IFX therapy. By stratifying patients into distinct risk profiles, it guides personalized therapy initiation and monitoring.

Background: To evaluate the efficacy and safety of potassium-competitive acid blockers (P-CABs) versus proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux disease (GERD) through a meta-analysis, explores the preliminary pharmacoeconomic advantages.

Methods: Randomized controlled trials (RCTs) comparing P-CABs and PPIs for GERD treatment were identified from database, up to July 2025. After processing the studies and extracting the data. RevMan and Stata was used for data analysis. A preliminary pharmacoeconomic analysis was performed based on market survey data.

Results: A total of 10 RCTs (5133 participants) were included. P-CABs demonstrated better overall efficacy than PPIs [risk ratio (RR) = 0.72, P = 0.02]. Sensitivity analysis indicated higher applicability in Asian populations (RR = 0.69, P = 0.01). Subgroup analysis showed P-CABs had a significant advantage over lansoprazole (P < 0.001, RR = 0.50), but not over esomeprazole (P = 0.93). P-CABs were superior in the low-dose group, 2-week and 8-week treatment courses group. In the high-dose P-CABs group, 4-week treatment courses group, heartburn relief group and adverse event rates were comparable to PPIs. Pharmacoeconomic analysis revealed that CER_P-CABs ≈ 0.1 CNY/day (d)/1%cure rate (1%CR); CER_PPIs ≈ 0.01 CNY/d/1%CR; ICER = 3.125 CNY/d/1%CR.

Conclusions: P-CABs demonstrate relatively greater efficacy than PPIs, especially in Asian populations. However, in terms of symptom relief, mid-term efficacy and safety both classes show comparable effects. PPIs are more cost-effective in specific contexts. Due to the limited follow-up duration in the included studies, the conclusions are applicable only to short-term symptom control.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease globally, strongly linked to obesity, insulin resistance, and metabolic syndrome. Inflammation plays a central role in MASLD progression, with interferon gamma-induced protein 10 (IP-10/CXCL10) emerging as a key chemokine implicated in immune cell recruitment, hepatic injury, and fibrosis. However, its level in obese non-diabetic MASLD patients remains underexplored. This study aimed to evaluate serum IP-10 levels in obese, non-diabetic MASLD patients and explore their association with anthropometric, metabolic, and hepatic parameters.

Patients and methods: We conducted a case-control study, including 120 participants, divided into 60 obese non-diabetic MASLD patients (diagnosed clinically and radiologically) and 60 age- and sex-matched healthy controls. Serum IP-10 was measured by ELISA. Correlations with anthropometric indices, biochemical markers, insulin resistance, and hepatic steatosis (HSI) and fibrosis stiffness (FIB-4) scores were analysed. Diagnostic accuracy of IP-10 was assessed using ROC curve analysis.

Results: Serum IP-10 levels were significantly higher in MASLD patients compared to controls. IP-10 correlated positively with BMI, waist circumference, ALT, AST, fasting insulin, HOMA-IR, and hepatic steatosis stage, and negatively with HDL-C. ROC analysis showed that an IP-10 cutoff > 830.1 pg/mL discriminated obese MASLD with an AUC of 0.805, sensitivity of 61.7%, and specificity of 86.7%.

Conclusion: Serum IP-10 is significantly elevated in obese non-diabetic MASLD patients and strongly associated with metabolic derangements, insulin resistance, and hepatic steatosis. These findings suggest that IP-10 may serve as a promising early non-invasive risk stratification tool or an adjunctive biomarker for MASLD.

Background: Perihilar cholangiocarcinoma (pCCA) is a rare malignancy originating from the bile duct bifurcation which is often diagnosed in an advanced stage. At presentation, most patients present with jaundice requiring biliary drainage. Palliative chemotherapy (pCTx) has a positive impact on survival and quality of life. The primary aim of this study was to investigate the impact of biliary drainage on pCTx initiation in patients with non-resected pCCA.

Methods: Individual patient data from all Dutch patients diagnosed with non-resected pCCA between 2015 and 2020 were retrieved from the Netherlands Cancer Registry. Primary outcome were factors associated with initiation of pCTx, analysed by multivariable competing risk regression analysis.

Results: A total of 1265 patients were included, of whom 242 patients (19.1%) received pCTx after a median interval of 72 days [IQR 43-110 days] after initial presentation. Patients who underwent biliary drainage did not receive pCTx more often. If performed, drainage at a referral hospital (HR:0.65, 95%CI: 0.42-0.99), ≥3 drainage procedures performed (HR:0.53, 95%CI: 0.32-0.88), and drainage performed ≥14 days after presentation (HR:0.70, 95%CI: 0.49-0.99) were associated with no pCTx. Median overall survival for those who received pCTx and those who did not was 12.8 months [95%CI: 11.7-14.2] and 2.7 months [95%CI: 2.4-3.1].

Conclusion: The need for biliary drainage did not affect the initiation of pCTx. When indicated, biliary drainage should be performed as quick as possible in an academic center to improve the rate of patients receiving pCTx.

Background: Iron deficiency is common in patients with inflammatory bowel disease (IBD) and may lead to a variety of distressing symptoms negatively impacting quality of life.

Aims: This prospective observational cohort study aimed to assess quality of life, measured using the Short Form-36 (SF-36) questionnaire before and after treatment with high-dose intravenous iron in patients with IBD and iron deficiency.

Materials and methods: Over a 15-month period, 130 patients with a well-established diagnosis of IBD (either ulcerative colitis (UC) or Crohns disease (CD)) and confirmed iron deficiency were consecutively assessed for study eligibility at two university hospitals in South-Eastern Norway. Of these, 112 patients were included in the per protocol set. Demographic characteristics were recorded at study inclusion. Clinical, and biochemical variables, as well as SF-36 questionnaires were collected just before and 5-7 weeks after treatment with intravenous iron.

Results: An improvement was observed in six of the eight SF-36 domains six weeks after treatment with intravenous iron. Females had lower scores compared to males at both visits, but there were no differences between UC and CD patients. Both sexes and the two diagnoses had a significant increase in vitality scores. Haemoglobin level was a significant predictor for improvement of quality of life.

Conclusions: Treatment with high dose intravenous iron improves quality of life in IBD patients and iron deficiency and particularly in those with anaemia. The most significant improvements were observed in vitality and energy levels, suggesting a clinically meaningful change.

Objectives: Systemic mastocytosis (SM) is a rare hematopoietic disease, in which gastrointestinal (GI) problems are common. There are no valid instruments for assessing GI problems in patients with SM. As the symptoms often mimic irritable bowel syndrome (IBS), the objective was to assess the validity of instruments designed to measure IBS related GI problems in this group of patients.

Methods: The study was performed as an exploratory multimethod study. The Gastrointestinal Symptom Rating Scale (GSRS) and the Visceral Sensitivity Index (VSI) were found to be the most appropriate and were administered to 393 adults with SM. The response rate was 78%. Of these, 147 (48%) reported having GI-problems due to SM and were thus included in this study. Reliability was assessed using Cronbach's alpha, whereas construct validity was examined through exploratory factor analysis.

Results: Internal consistency measured with Cronbach's alpha coefficient was overall good/excellent for the GSRS total scale (α = 0.88) and subscales (α = 0.72-0.84) and for the VSI (α = 0.93). The exploratory factor analysis revealed four factors for the GSRS (indigestion, diarrhea, constipation, pain/reflux) and two factors for the VSI (worries related to internal GI symptoms, external factors related to GI problems).

Conclusions: Based on our results, we propose using the GSRS for measuring physical GI problems and the VSI for measuring psychosocial consequences and/or worries related to GI problems in the SM population. The instruments could be used to highlight GI problems in both clinical care and research.

Clinical trial.gov registration: Trial registration number: NCT06065007.