BACKGROUND & AIMS: Cachexia is prevalent and prognostically adverse in decompensated cirrhosis. Diagnosis is challenging, especially in Asian populations, due to limitations of current criteria and scoring systems. This...BACKGROUND & AIMS: Cachexia is prevalent and prognostically adverse in decompensated cirrhosis. Diagnosis is challenging, especially in Asian populations, due to limitations of current criteria and scoring systems. This study aimed to develop and validate a biomarker-based model for predicting cachexia defined by the Asian Working Group for Cachexia (AWGC) in cirrhotic patients. METHODS: In this retrospective cohort study, 420 patients with decompensated cirrhosis were enrolled (295 in the training cohort, 125 in the external validation cohort). Cachexia was diagnosed according to AWGC criteria. LASSO regression selected predictive serum biomarkers. A nomogram-derived GDF-15-Albumin-CRP score was constructed, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). RESULTS: In the training cohort, 158 patients (53.56%) had cachexia. LASSO regression identified serum growth differentiation factor-15 (GDF-15), albumin, and C-reactive protein (CRP) as the strongest predictors. The resulting GDF-15-Albumin-CRP score achieved an AUC of 0.736 (95% CI: 0.680-0.792) for cachexia prediction, significantly outperforming Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and MELD-Na scores (all P < 0.05). DCA demonstrated clinical net benefit across a wide range of threshold probabilities. The score exhibited a strong risk gradient for cachexia (adjusted OR for the high- vs. low-risk group: 7.58; 95% CI: 2.68-21.46). External validation confirmed its performance (AUC = 0.723, 95% CI: 0.630-0.810). CONCLUSIONS: The GDF-15-Albumin-CRP score is a validated and clinically feasible tool predicting AWGC-defined cachexia in Asian cirrhotic patients, superior to traditional severity scores and potentially enabling earlier targeted intervention.
Holst JP, Christensen ME, Lang NR
… +2 more, Mehlsen MY, Tobberup R
Support Care Cancer
· 2026 May · PMID 42154240
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PURPOSE: This review aims to identify and synthesize existing literature on non-pharmacological interventions in cancer patients in which perceived appetite was assessed as a specific outcome, either alone or as part of...PURPOSE: This review aims to identify and synthesize existing literature on non-pharmacological interventions in cancer patients in which perceived appetite was assessed as a specific outcome, either alone or as part of broader symptom or quality-of-life measures. METHODS: Systematic searches were performed using Embase, PubMed, CINAHL, and PsycINFO databases. Eligible studies included quantitative research involving adult cancer patients with poor appetite. All records were screened independently by two reviewers. RESULTS: A total of 3021 records were screened, and 29 studies met the inclusion criteria. These studies were grouped into four categories: mindfulness and relaxation, psychological or psychosocial, education and self-care, and multicomponent/comprehensive supportive-care programs. Interventions were heterogeneous in type, intensity, and delivery. Across categories, structured, repeated, and actively guided interventions were more consistently associated with improvements in perceived appetite, whereas brief or passive interventions showed limited effects. Interventions that incorporated personalization and required active patient engagement demonstrated greater effectiveness, suggesting the importance of sustained and individualized support. To support interpretation of these heterogeneous findings, results were synthesized using a conceptual framework linking intervention characteristics to psychological, sensory, physiological, and behavioral mechanisms influencing appetite perception. Within this framework, non-pharmacological appetite support appears to operate indirectly through pathways such as emotional regulation, sensory engagement, stress reduction, and active coping, rather than through appetite-specific mechanisms alone. CONCLUSION: Structured, actively guided, and repeated non-pharmacological interventions show potential to improve perceived appetite in cancer patients, whereas brief or passive interventions appear less effective. Findings suggest that appetite support operates primarily through indirect psychological, sensory, and behavioral pathways, as captured in a conceptual framework. Further research should develop and evaluate well-defined, mechanism-informed interventions.
BACKGROUND AND AIMS: Although spleen stiffness measurement (SSM) via 100 Hz probe shows promise in predicting hepatic decompensation, its prognostic value across different etiological backgrounds remains insufficiently v...BACKGROUND AND AIMS: Although spleen stiffness measurement (SSM) via 100 Hz probe shows promise in predicting hepatic decompensation, its prognostic value across different etiological backgrounds remains insufficiently validated. We evaluated its efficacy in patients with compensated advanced chronic liver disease (cACLD) in a Chinese cohort. METHODS: This retrospective study included 713 cACLD patients. The optimal SSM cut-off was derived using the Fine-Grey competing risk model and validated by bootstrapping. The SSM-based model was compared against established models using time-dependent area under the curve (AUC), C-index, and decision curve analysis (DCA). RESULTS: During a median follow-up of 36.6 months, 28 patients (3.9%) developed decompensation. SSM was an independent predictor (sHR 1.03, 95% CI 1.02-1.05, p < 0.001). An SSM threshold of > 55 kPa was identified and demonstrated excellent stability (bootstrap 95% CI 39.8-57.3 kPa). The SSM > 55 kPa showed comparable discriminative ability to the multivariate NICER model at 1 year (AUC: 0.820 vs. 0.868, p = 0.328) and 2 years (AUC: 0.809 vs. 0.851, p = 0.271). Notably, SSM > 55 kPa significantly outperformed albumin-combined models (LSM-ALB, NICER-ALB) at 1-year prediction (all p < 0.05). DCA revealed that SSM > 55 kPa provided the highest net clinical benefit across all models. Patients with SSM > 55 kPa had a markedly higher decompensation risk (sHR 8.69, 95% CI 4.15-18.23, p < 0.001), with decompensation incidences of 15.2% vs. 2.0% compared to those below the threshold. CONCLUSION: In cACLD patients, a simple 100-Hz SSM threshold (> 55 kPa) effectively predicts hepatic decompensation with performance rivalling more complex models, offering a practical, non-invasive tool for risk stratification.
Weiss M, Rossignol J, Campeotto F
… +23 more, Foy E, Elbany C, Jaume L, Geroux L, Debeaupuis O, Neuraz A, Bekel L, Lezmi G, Bellon N, Méni C, Livideanu C, Madrange M, Condé D, Agopian J, Michot C, Villard-Truc F, Lachaux A, Greco C, Hadj-Rabia S, Dubreuil P, Hermine O, Bodemer C, Polivka L
Pediatr Allergy Immunol
· 2026 May · PMID 42149735
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BACKGROUND: Mast cell (MC) activation (MCA) disorders (MCAD) include diseases in which MCs excessively release mediators leading to recurrent manifestations of MCA. MCAD encompasses MCA syndrome (MCAS) which is defined b...BACKGROUND: Mast cell (MC) activation (MCA) disorders (MCAD) include diseases in which MCs excessively release mediators leading to recurrent manifestations of MCA. MCAD encompasses MCA syndrome (MCAS) which is defined by (i) documented systemic symptoms of MCA, (ii) a 20% increase in serum tryptase level from the individual's baseline plus 2 ng/mL and (iii) a symptom response to MC-stabilizing drugs. MCAD not fulfilling mastocytosis or all MCAS criteria are referred to as MCAD not otherwise specified (MCAD-NOS). The aim was to describe the clinical, laboratory characteristics and outcomes of the first pediatric-onset non-mastocytosis MCAD cohort. METHODS: All children with the criteria of non-mastocytosis MCAD managed at the French National Referral Center for MCAD were included. Clinical, laboratory data, and outcomes were recorded. RESULTS: Forty-four MCAD patients (mean age at onset: 4.3 years) were identified including 36 MCAD-NOS and 8 idiopathic MCAS. Hereditary-α-tryptasemia was identified in 5/33 (15.2%) patients. The spectrum of symptoms concerned most frequently both the skin (100% of children, with urticaria, angioedema, pruritus, and/or flushing) and the gastrointestinal tract (93% patients). We identified two clinical profiles, according to the age at onset. Before 3 years of age, MCAD was associated with persistent gastrointestinal symptoms triggered by various foods (leading to a drastically limited diet), and after 3 years of age with episodic, recurrent, idiopathic, anaphylactic reactions. The administration of H1 and/or H2 antihistamines drugs +/- a leukotriene receptor antagonist resulted in a marked reduction in symptoms. CONCLUSION: The description of the clinical profiles of pediatric-onset non-mastocytosis MCAD may help to avoid diagnostic delay.
van Elst JM, Beukers K, Beijer S
… +4 more, Janssen-Heijnen M, Reyners AKL, Jager-Wittenaar H, de Haan JJ
J Hum Nutr Diet
· 2026 Jun · PMID 42144986
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BACKGROUND AND AIMS: Enjoying food is related to the taste, smell and texture of food, ambience during meals, presentation of the meals, and freedom to choose meals. A decrease in food enjoyment can lead to decreased foo...BACKGROUND AND AIMS: Enjoying food is related to the taste, smell and texture of food, ambience during meals, presentation of the meals, and freedom to choose meals. A decrease in food enjoyment can lead to decreased food intake, undesired weight loss, and reduced quality of life. Cancer and cancer treatment can induce symptoms that affect food enjoyment. To optimise food enjoyment and intake, insight in the experiences and preferences of hospitalised patients with cancer is essential. This qualitative study aimed to explore the perspectives of patients with cancer on the experience of food and drinks, ambience during meals, timing of the meals, and the freedom to choose one's own meals, during hospital admission. METHODS: In hospitalised patients with cancer treated with systemic therapy, 12 semi-structured interviews were performed. Nutritional status was subjectively assessed, and taste and smell objectively to characterise the study population. Thematic analysis was used to identify key themes. RESULTS: Three selective codes emerged: (1) the quality of hospital food and drinks, (2) the presentation of hospital food and drinks, and (3) meeting patients' preferences. Patients described hospital food, and in particular main meals, as bland, overcooked, and repetitive. Autonomy in meal choices and flexibility in portion sizes were appreciated but inconsistently facilitated. Ambiance was moderately important, with suggestions for communal dining areas. Presentation issues, including plastic odours and inconsistent meal temperatures, were mentioned. Patients valued personalised options such as additional seasonings or sauces. CONCLUSIONS: The eating experience of hospitalised cancer patients is shaped by various factors including quality of food, its presentation, and the ability to cater to individual preferences. By addressing these aspects and implementing a patient-centred food service, care could be optimised in oncology wards.
Yoshida M, Urabe Y, Kadota T
… +12 more, Nonaka S, Ohno K, Kitamura Y, Takahashi H, Yoshio T, Sasaki F, Ono Y, Igarashi K, Hirasawa D, Takeuchi M, Mori K, Ishihara R
OBJECTIVES: To investigate whether considering the B2 vessel area (B2VA) size and macroscopic type improves diagnostic performance. METHODS: In total, 136 esophageal squamous cell carcinoma (ESCCs) with B2 but not B3 ves...OBJECTIVES: To investigate whether considering the B2 vessel area (B2VA) size and macroscopic type improves diagnostic performance. METHODS: In total, 136 esophageal squamous cell carcinoma (ESCCs) with B2 but not B3 vessels were prospectively enrolled. Tumor invasion depth was assessed using the standard Japan Esophageal Society (JES) classification and a "B2VA-based" method that incorporates B2VA size and macroscopic type. Lesions with B2VA ≤ 4 mm (B2-narrow) were classified as cEP/LPM; B2VA ≥ 10 mm (B2-wide) or type 0-I or 0-III within the B2VA were classified as cSM2-3; intermediate lesions were classified as cMM/SM1. All lesions underwent endoscopic resection or esophagectomy with histopathological confirmation. The primary endpoint was diagnostic accuracy, and positive likelihood ratios (+LRs) were calculated for each endoscopic feature. RESULTS: Among the 136 ESCCs, 27.2% were pEP/LPM, 49.3% were pMM/SM1, and 23.5% were pSM2-3. The overall diagnostic accuracy was 49.3% for the standard JES evaluation and 50.0% for the B2VA-based evaluation (p = 1.00). B2VA size correlated with pathological depth, with median values of 3, 5, and 10 mm for pEP/LPM, pMM/SM1, and pSM2-3, respectively. B2-narrow predicted pEP/LPM (+LR 2.26), whereas B2-wide predicted pSM2-3 (+LR 3.45), and type 0-I within the B2VA predicted pSM2-3 (+LR 4.47). Combination of B2-wide and 0-I demonstrated the highest predictive value for pSM2-3 (+LR 9.75). CONCLUSIONS: B2VA-based evaluation incorporating B2VA size and macroscopic type did not improve the diagnostic accuracy compared with that of the standard JES evaluation for predicting invasion depth in ESCC with B2 vessels. TRIAL REGISTRATION: Registry and registration number: UMIN000051145.
BACKGROUND & AIMS: HDV requires HBsAg for viral assembly. The siRNA JNJ-73763989 (JNJ-3989) targets all HBV transcripts and reduces HBsAg in patients with chronic hepatitis B. We evaluated whether HBsAg reduction with JN...BACKGROUND & AIMS: HDV requires HBsAg for viral assembly. The siRNA JNJ-73763989 (JNJ-3989) targets all HBV transcripts and reduces HBsAg in patients with chronic hepatitis B. We evaluated whether HBsAg reduction with JNJ-3989 leads to a decline in HDV RNA and ALT in patients with chronic hepatitis D (CHD). METHODS: REEF-D, a two-part, phase II, randomized, double-blind, placebo-controlled study, enrolled 22 adults with CHD in Part 1. Participants were randomized 4:1 to receive JNJ-3989 (100 mg subcutaneously every 4 weeks) + nucleos(t)ide analogue (NA) for 144 weeks (active arm, n = 17) or for 96 weeks after 52 weeks of placebo + NA (deferred treatment arm, n = 5). During the 48-week follow-up period, NA therapy was continued. The primary endpoint was achievement of a ≥2 log IU/ml reduction of HDV RNA from baseline (or <LLOQ) and normal ALT at treatment week (TW) 48. RESULTS: The primary endpoint was achieved by 4/17 (24%) participants in the active arm and 0/5 in the deferred treatment arm. ALT elevations leading to treatment discontinuation occurred in 12/17 (71%) active-arm participants. Among those on JNJ-3989 treatment at TW48 (n = 9) mean (SE) reductions from baseline were 1.75 (0.29) log IU/ml vs. 0.07 (0.04) log IU/ml for HBsAg and 1.52 (0.38) log IU/ml vs. 0.23 (0.15) log IU/ml for HDV RNA in active and deferred treatment arms, respectively. Four of five participants in the control arm rolled-over to JNJ-3989 at TW52 including two experiencing subsequent ALT elevations. No ALT elevations were seen in the seven participants with screening HBsAg <10,000 IU/ml. CONCLUSION: This is the first study showing that the HBsAg-targeting siRNA JNJ-3989 can reduce HDV RNA and HBsAg in patients with CHD. Unexpected ALT elevations were seen in 14 of 21 (67%) participants receiving JNJ-3989 (immediate or deferred). GOV IDENTIFIER: NCT04535544 IMPACT AND IMPLICATIONS: In the REEF-D study of patients with chronic hepatitis D, the reduction of HBsAg with the HBsAg-targeting siRNA JNJ-73763989 (JNJ-3989) led to HDV RNA decline, and in some participants, to prolonged HDV RNA suppression. Participants with high HBsAg levels (>10,000 IU/ml) at screening experienced unexpected ALT elevations, sometimes severe, with a return to baseline levels after discontinuation of JNJ-3989. Both HDV RNA reduction and ALT elevation are critical observations for a better understanding of HDV biology and the interplay between viral antigens and the infected hepatocyte. Despite the low sample size and majority of participants not completing the planned treatment course, these findings are important for caregivers and researchers developing novel treatment strategies for patients with chronic hepatitis D.
Schramm C, Hehn C, Curth H
… +17 more, Scheller I, Weingaertner JH, Reichert MC, Kasper P, Bozal D, Allo G, Casper M, Adams T, Jochheim L, Zeller A, Rahe G, Zeeh J, Neumann-Haefelin C, Lammert F, Schmidt H, Friedrich CM, Buerger M
BMJ Open Gastroenterol
· 2026 May · PMID 42134870
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OBJECTIVE: Inadequate bowel preparation impairs the accuracy of colonoscopy and increases the burden on patients and healthcare systems. Consequently, the quality of bowel preparation is an important quality indicator. W...OBJECTIVE: Inadequate bowel preparation impairs the accuracy of colonoscopy and increases the burden on patients and healthcare systems. Consequently, the quality of bowel preparation is an important quality indicator. We aim to develop and validate multivariable prognostic models for the identification of patients at risk of inadequate bowel preparation using machine learning (ML). METHODS: Demographic and clinical data from consecutive patients ≥18 years of age who underwent colonoscopy at six centres in Germany were prospectively collected. Adequate bowel preparation was defined as Boston Bowel Preparation Scale ≥6 with a value ≥2 in each colonic segment. We used statistical and ML methods to build prognostic models and to compare them to published models. RESULTS: Overall, we analysed 2652 patients, including 699 (26.4%) inpatient procedures. The mean patient age was 57.6 years (SD 16 years), and 48.9% were women. In 1401 (52.8%) patients, the indication was screening or surveillance, and 1035 (39%) patients had a first-time colonoscopy. The rate of inadequate bowel preparation was 16%. Sensitivities, specificities and areas under the curve of predictive models obtained by generalised boosting models, Ranger, support vector machine (radial), CatBoost and Net Regularised Generalised Linear Models were 0.51-0.86, 0.52-0.83 and 0.71-0.74, respectively. They were only marginally superior to a logistic regression model. All models had high negative predictive values >0.9 for inadequate bowel preparation. To detect one patient with inadequate bowel preparation, 8-10 patients need to be evaluated. CONCLUSIONS: Predictive models to identify patients at risk for inadequate bowel preparation obtained by ML showed comparable results compared with a logistic regression model. TRIAL REGISTRATION NUMBER: DRKS00018878.
Randomised trials provide the strongest evidence to guide clinical care and typically generate detailed data on large numbers of patients. These individual patient data (IPD) should be used to their full potential, inclu...Randomised trials provide the strongest evidence to guide clinical care and typically generate detailed data on large numbers of patients. These individual patient data (IPD) should be used to their full potential, including for research questions beyond the original trial objectives. To achieve this, IPD must be shared with other researchers. In this article, we review the history of IPD sharing, report past and current proportions of hepatology trials declaring their willingness to share IPD, and present our own experience of reusing IPD from hepatology trials.
Liver sinusoidal endothelial cells (LSECs) are specialised endothelial cells that orchestrate hepatic homeostasis within the liver sinusoid. Besides their key role in regulating intrahepatic vascular tone, trafficking an...Liver sinusoidal endothelial cells (LSECs) are specialised endothelial cells that orchestrate hepatic homeostasis within the liver sinusoid. Besides their key role in regulating intrahepatic vascular tone, trafficking and cellular crosstalk, their scavenging and immune-regulatory role makes them central to the development of liver disease. LSEC dysfunction includes loss of fenestrae, inflammatory activation and the gain of vasoconstrictive and prothrombotic functions. Robust evidence has demonstrated how preserving LSECs is crucial in a pathological context, placing LSECs at the centre of novel therapeutic and diagnostic strategies. Despite innovative tools supporting the dissection of LSEC heterogeneity, our understanding of LSEC pathobiology remains limited and characterised by important gaps. This review highlights recent discoveries and examines possible innovative therapeutic strategies targeting LSECs in liver disease.
Wang SR, Wang SC, Yi ZX
… +3 more, He EH, Zhao JF, Hu XD
Ultrasound Med Biol
· 2026 Aug · PMID 42128721
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BACKGROUND: Graft fibrosis is a critical pathological endpoint of chronic injury after liver transplantation (LT). While serum-based scores are validated in native liver diseases, their efficacy in LT recipients remains...BACKGROUND: Graft fibrosis is a critical pathological endpoint of chronic injury after liver transplantation (LT). While serum-based scores are validated in native liver diseases, their efficacy in LT recipients remains controversial. This study compared the diagnostic performance of shear wave elastography (SWE) with common serological indices (APRI, FIB-4, GPR) for detecting significant graft fibrosis (≥S2) in adult and pediatric recipients. METHODS: We retrospectively analyzed 111 LT recipients (63 adults, 48 children) who underwent liver biopsy and concurrent SWE/biochemical testing. Fibrosis was staged by the Scheuer classification. Diagnostic accuracy was evaluated using Spearman correlation and receiver operating characteristic (ROC) curves, stratified by recipient and graft age. RESULTS: SWE demonstrated the strongest correlation with histological fibrosis stage (ρ = 0.76, p < 0.001), significantly outperforming all serological indices. For the detection of significant fibrosis, SWE achieved an AUC of 0.927 (95% CI: 0.879-0.975), superior to GPR (0.759), APRI (0.691), and FIB-4 (0.594). Notably, FIB-4 showed no significant correlation with fibrosis (ρ = -0.02, p = 0.818). SWE maintained high diagnostic accuracy across adult and pediatric recipients, with optimal cut-off values of 10.14 kPa and 10.92 kPa. Moreover, SWE exhibited stable performance across different graft ages, whereas serological indices showed marked variability in the early post-transplant period. CONCLUSION: SWE provides a superior and more stable assessment of graft fibrosis compared to conventional serological models in both adult and pediatric LT recipients. Given its high NPV, SWE serves as a robust first-line tool for long-term non-invasive graft surveillance.
BACKGROUND & AIMS: Microbiome-derived deoxycholic acid (DCA) elevates serum 5-hydroxytryptamine (5-HT), a mediator of portal hypertension (PH). Rifaximin, a non-absorbable antibiotic, is known to reduce DCA levels. We ai...BACKGROUND & AIMS: Microbiome-derived deoxycholic acid (DCA) elevates serum 5-hydroxytryptamine (5-HT), a mediator of portal hypertension (PH). Rifaximin, a non-absorbable antibiotic, is known to reduce DCA levels. We aimed to elucidate the role of DCA in cirrhotic PH and evaluate the therapeutic potential of rifaximin. METHODS: PH was induced in mice by thioacetamide (TAA) injection or bile duct ligation (BDL). Mice were treated with antibiotics (ABX) or rifaximin, with or without exogenous DCA supplementation. A cohort of 51 patients with cirrhosis and 19 healthy controls was analyzed to validate correlations among DCA, 5-HT, and hepatic venous pressure gradient (HVPG). Mice with tissue-specific knockout of gut epithelial Tph1 (Tph1), vascular smooth muscle cell Htr1a (Htr1a), or Kcnj9 (Kcnj9) were used for mechanistic studies. RESULTS: Fecal DCA positively correlated with portal pressure (PP) in TAA-induced PH mice (r = 0.631, p <0.001) and with HVPG in patients (r = 0.5874, p <0.001). ABX treatment reduced fecal DCA, serum 5-HT, and PP in TAA- or BDL-induced PH mice. Exogenous DCA reversed the ABX-induced reductions in serum 5-HT and PP, an effect abolished in Tph1 mice. GIRK3 (encoded by Kcnj9) was upregulated in portal veins from PH mice and patients. VSMC-specific Kcnj9 deletion attenuated PH and prevented 5-HT-induced PP elevation. Mechanistically, 5-HT triggered portal vein smooth muscle cell contraction via the HTR1A-GIRK3-Ca-MLC2 pathway. Rifaximin alleviated PH by reducing DCA in wild-type mice but showed no additional PP reduction in Tph1, Htr1a, or Kcnj9 mice. CONCLUSIONS: Microbiome-derived DCA exacerbates PH by enhancing TPH1-dependent 5-HT biosynthesis, which activates portal vein smooth muscle cell contraction via HTR1A-GIRK3 signaling. Rifaximin alleviates cirrhotic PH by reducing DCA levels, highlighting a potential therapeutic strategy for clinical PH management. IMPACT AND IMPLICATIONS: Portal hypertension is a key driver of cirrhosis-related complications, yet current therapies exhibit suboptimal efficacy. Herein, we elucidate the role of the gut microbial metabolite deoxycholic acid in the pathophysiology of cirrhotic portal hypertension through the TPH1-5-HT/HTR1A-GIRK3 axis and provide preclinical evidence that rifaximin ameliorates cirrhotic portal hypertension by reducing deoxycholic acid. These insights may open a new avenue for the clinical management of cirrhotic portal hypertension.
Chung AH, Tan JJ, Yap RXJ
… +10 more, Loo JH, Tay WX, Singh CL, Ong SJ, Low AYJ, Lin Y, Lytvyak E, Mason A, Montano-Loza AJ, Wong YJ
Hepatol Commun
· 2026 Jun · PMID 42118984
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BACKGROUND: Patients with primary biliary cholangitis (PBC) often suffer from debilitating symptoms, yet the overall symptom burden has not been systematically quantified. This study aims to systematically review the pre...BACKGROUND: Patients with primary biliary cholangitis (PBC) often suffer from debilitating symptoms, yet the overall symptom burden has not been systematically quantified. This study aims to systematically review the prevalence and severity of the symptom burden in PBC patients. METHODS: We conducted a systematic search of 3 electronic databases to include studies that reported the prevalence and severity of PBC symptoms. Subgroup analyses were performed based on study type, publication year, risk of bias, study location, sex, and latitude. RESULTS: A total of 25 studies involving 13,178 patients were included. Fatigue was the most common symptom, affecting 51% of patients, followed by pruritus at 33%. Severe fatigue and severe pruritus were reported in 23% and 10% of patients, respectively. The prevalence of fatigue was significantly higher in more recent studies, those with smaller sample sizes, and studies published as abstracts. Fatigue score was significantly higher in female patients compared with males. Severe fatigue was more prevalent in studies conducted in North America/Europe than those from Asia (26% vs. 8%, p=0.0005), and in studies with a higher proportion of patients with cirrhosis (28% vs. 8%, p=0.0005). Despite the high burden, only 36% of PBC patients with pruritus received anti-pruritic treatment, with antihistamines being the most frequently prescribed medication. CONCLUSIONS: Over half of PBC patients experience significant symptom burden, with substantial ethnic disparities identified. The proportion and quality of appropriate symptom management in PBC are suboptimal. There remains an unmet need for standardized assessment, consistent reporting, and improved management strategies for PBC-related symptoms in future research.
We report a rare case of type 1 autoimmune pancreatitis (AIP) forming a polypoid mass at the major duodenal papilla in continuity with a cystic lesion of the pancreatic head, initially misdiagnosed as an intraductal papi...We report a rare case of type 1 autoimmune pancreatitis (AIP) forming a polypoid mass at the major duodenal papilla in continuity with a cystic lesion of the pancreatic head, initially misdiagnosed as an intraductal papillary mucinous neoplasm (IPMN). A man in his 70s underwent pancreaticoduodenectomy after imaging revealed a mural nodule within a cystic lesion. Gross examination revealed a papillary polypoid lesion with continuity to a firm nodule in the pancreatic head. Histologically, the lesion exhibited glandular proliferation with pyloric and Brunner's gland-like differentiation in the fibrotic stroma, with dense IgG4-positive plasma cell infiltration and obliterative phlebitis. An incidental 6-mm high-grade pancreatic intraepithelial neoplasia was also identified adjacent to the IgG4-rich fibroinflammatory lesion. The surrounding pancreas showed acinar atrophy, vanishing duct change, and features consistent with resolving inflammation. The postoperative serum IgG4 levels remained elevated. Awareness of this unusual papillary, lumen-extending morphology may prompt consideration of type 1 AIP in the differential diagnosis and guide preoperative evaluation, including serum IgG4 testing and tissue sampling when clinically feasible.
Mwenda M, Mosler K, Bohmeier B
… +46 more, Chomba M, van Loon W, Mambwe B, Gaye A, Olorunfemi A, Suliman S, Yanogo NJ, Sow D, Ngom B, Zoure OAZ, Tibiri YNG, Ojeniyi F, Zongo A, Anoh EA, Achi V, Chiyesu C, Otieno S, Ogola B, Niangaly M, Carrasquilla M, Goboto DK, Feldt T, Tufa TB, Oliveira R, Schallenberg E, Sogoba Y, Ntalla C, Ouedraogo O, Otieno K, Opaleye O, Olowe A, Gibbons M, Drakeley C, Schubert G, Mockenhaupt FP, Portugal S, Deme AB, Soulama I, Ndiaye D, Ojurongbe O, Kariuki S, Shi YP, Schultz JS, Hawela M, Bridges DJ, Hendry JA
In sub-Saharan Africa, continental-scale genomic surveillance of Plasmodium falciparum malaria is needed to track the spread of drug and diagnostic resistance, as well as monitor parasite evolutionary responses to vaccin...In sub-Saharan Africa, continental-scale genomic surveillance of Plasmodium falciparum malaria is needed to track the spread of drug and diagnostic resistance, as well as monitor parasite evolutionary responses to vaccine rollout. Yet continental-scale implementation is hindered by a lack of genomic approaches suitable for local laboratories, and the vastness of the continent. Here, we initiate a decentralised scale-up of P. falciparum genomic surveillance by locally sequencing and analysing 1065 samples across six African countries in one year. We achieve this with a novel nanopore sequencing protocol that is rapid (~5 hr) and cost-effective (<$25 USD/sample), providing surveillance of antimalarial drug resistance genes, hrp2/3 deletions, the vaccine target csp, and the polymorphic gene ama1. We couple this to a laptop-based bioinformatics dashboard that runs offline and displays mapping and variant calling results in real-time. We demonstrate robust sequencing coverage across parasitemia levels and laboratories, accurate identification of antimalarial resistance markers and hrp2/3 deletions; and, with a novel variant caller, sensitive detection of mutations carried by minor clones. Our approach will accelerate genomic surveillance of P. falciparum malaria across sub-Saharan Africa at a time of urgent need.
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), represent a global health challenge intr...BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), represent a global health challenge intricately linked to lipid dysregulation and systemic inflammation. Identifying biomarkers and causative molecules involved in disease progression is therefore essential. N-acyl taurines (NATs) are endogenous metabolites involved in whole-body metabolic regulation, but their roles in liver disease have not been elucidated. METHODS: To study the relationship between NATs and MASLD, we analyzed NAT profiles in human blood samples from individuals with clinical MASLD or short-term overfeeding-induced hepatic steatosis. Mouse models of MASLD and MASH were used to determine the effects of these alterations and to investigate the underlying mechanisms of action. RESULTS: We identified an endogenous, uncharacterized arachidonic acid (ARA)-derived metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating steatotic liver disease and reducing hepatic inflammation. ARA-T levels increased in human plasma from individuals with chronic and overfeeding-induced liver steatosis, and its abundance was increased in both humans and mice by dietary ARA supplementation. Despite ARA's association with pro-inflammatory mediators, administration of ARA-T reduced hepatic lipid deposition and inflammation. Chronic elevation through genetic and dietary models mitigated the development of steatosis and fibrosis through increased hepatic oxidation of fatty acids. CONCLUSIONS: ARA-T is an endogenous metabolite that increases with human hepatic steatosis and reduces murine hepatic lipid content independent of weight loss, demonstrating its direct action and potential to reverse the progression of liver disease. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most prevalent forms of liver disease worldwide and is likely to affect more than half of the global population in the next decade, with limited treatment options available. Here, we identified an endogenous, uncharacterized omega-6 fatty acid metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating steatotic liver disease and reducing hepatic inflammation by increasing hepatic fatty acid oxidation. This study positions ARA-T as an endogenous molecule with hepatoprotective effects and a potential therapeutic target for MASLD.
Lynch syndrome is an autosomal dominant cancer predisposition syndrome and the most common cause of hereditary colorectal cancer. In addition to colorectal cancer, it confers substantially increased risks for several ext...Lynch syndrome is an autosomal dominant cancer predisposition syndrome and the most common cause of hereditary colorectal cancer. In addition to colorectal cancer, it confers substantially increased risks for several extracolonic malignancies. While there is broad consensus regarding the effectiveness of endoscopic colorectal surveillance, recommendations for surveillance of gastric, small bowel, and pancreatic cancers vary considerably among guidelines issued by leading professional societies. These discrepancies largely reflect the limited availability of robust, high-quality evidence. In this narrative review, we summarize the cancer risks for gastric, small bowel, and pancreatic malignancies in Lynch syndrome carriers, discuss recent studies evaluating the outcomes of surveillance strategies, and provide an overview of current guideline recommendations. Furthermore, we highlight emerging approaches that may enhance surveillance strategies in the future. In recent years, increasing research efforts have focused on surveillance for less frequent Lynch syndrome-associated malignancies, however, prospective data from large, well-characterized cohorts remain scarce. Such data are essential to harmonize existing guidelines and to enable the development of personalized surveillance strategies for individuals affected by Lynch syndrome.
Front Public Health
· 2026 · PMID 42110297
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BACKGROUND: Hepatitis B virus (HBV) infection is widespread in Asia. Of the many chronic diseases linked to HBV, among the most important is liver cancer. This study analysed the disease burden of chronic hepatitis B-ass...BACKGROUND: Hepatitis B virus (HBV) infection is widespread in Asia. Of the many chronic diseases linked to HBV, among the most important is liver cancer. This study analysed the disease burden of chronic hepatitis B-associated liver cancer in Asia from 1990 to 2021. METHODS: Data were obtained from the 2021 Global Burden of Disease study. We analyzed incidence, prevalence, deaths and disability-adjusted life years (DALYs) in Asian regions and countries from 1990 to 2021 by age and sex. Data processing and graph construction were performed using RStudio and BioWinford. The Joinpoint regression model was used to analyse the temporal data trends. RESULTS: From 1990 to 2021, the disease burden of hepatitis B-related liver cancer in Asia decreased. A decline was observed in the rates of incidence (AAPC: -0.6), prevalence (AAPC: -0.1), deaths (AAPC: -1.0), and DALYs (AAPC: -1.2), even though their absolute numbers all increased. The number of incidence, prevalence, deaths and DALYs is highest among the middle-aged and older adults, and the highest rate is found among the older adults. Both the number and rate are highest in East Asia. Disease burdens differ by country. DISCUSSION: The burden of hepatitis B-associated liver cancer in Asia has decreased over the past three decades, but remains non-negligible. Asian countries need to take corresponding measures against hepatitis B.