BACKGROUND & AIMS: We assessed associations of time-weighted average haemoglobin A (HbA), time-to-target HbA, HbA variability, and individual HbA trajectories with liver-related events (LREs) in type 2 diabetes mellitus...BACKGROUND & AIMS: We assessed associations of time-weighted average haemoglobin A (HbA), time-to-target HbA, HbA variability, and individual HbA trajectories with liver-related events (LREs) in type 2 diabetes mellitus (T2DM). METHODS: A territory-wide cohort of adults newly diagnosed with T2DM (Jan 2000-Dec 2016) was identified in Hong Kong. HbA trajectories were identified via time series clustering and externally validated in UK Biobank. Their associations with LREs were estimated in the Hong Kong territory-wide cohort using cause-specific hazards models, with non-liver-related death as competing risk. RESULTS: Among 294,096 patients identified (mean age, 60.6 years; 50.6% males), 3,438 (1.2%) developed LREs at a median 7.4 (IQR, 4.5-10.0) years follow-up. Higher time-weighted average HbA (adjusted cause-specific hazard ratio [aCSHR] 1.12 per 1%, 95%CI 1.08-1.16, p<0.001) and high variability were associated with a higher risk of LREs, while more years with HbA<7% were associated with a lower risk (aCSHR 0.95 per year, 95%CI 0.93-0.96, p<0.001). Three trajectories were identified: rapid decreasing (n=43,712; 14.9%), mild decreasing (n=114,413; 38.9%), and increasing (n=135,971; 46.2%). Compared with rapid decreasing, mild decreasing (aCSHR 1.30, 95%CI 1.13-1.50, p<0.001) and increasing (aCSHR 1.37, 95%CI 1.16-1.61, p<0.001) trajectories conferred higher risks. Compared with patients with baseline HbA<7% and mild decreasing trajectory, those with baseline HbA≥9% and mild decreasing (aCSHR 1.27, 95%CI 1.08-1.50, p<0.001) or increasing (aCSHR 1.84, 95%CI 1.45-2.34, p<0.001) trajectories had higher LRE risks; whereas rapid decreasing trajectory was not associated with a higher risk (aCSHR 1.05, 95%CI 0.90-1.22, p=0.57). CONCLUSIONS: Time-weighted average HbA, cumulative duration of good glycaemic control, HbA variability and trajectories correlated with LREs in T2DM. Rapid decreasing trajectory may mitigate LRE risk in patients with high baseline HbA. IMPACT AND IMPLICATIONS: The relationship between long-term glycaemic control and liver-related events (LREs) in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this real-world territory-wide cohort study of 294,096 patients with newly diagnosed T2DM, patients with higher average HbA, cumulative exposure to high HbA and high HbA variability had a higher risk of LREs. Among patients with baseline HbA ≥9%, a rapid decreasing HbA trajectory was associated with a lower risk of LREs, with no statistically significant difference compared to patients whose baseline HbA was <7% and had a mild decreasing HbA trajectory, while those with baseline HbA ≥9% and mild decreasing or increasing HbA trajectories were associated with increased risk of LREs. Our findings suggest that patients with rapid glycaemic control of newly diagnosed T2DM could benefit from reduced risk of LREs, and careful monitoring and intensified intervention should be maintained for patients who develop mild decreasing or increasing HbA trajectories.
Topala M, Ionescu V, Cojocaru M
… +4 more, Iacob R, Gheorghe LS, Vadan R, Gheorghe C
Medicina (Kaunas)
· 2026 Jun · PMID 42356205
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: In recent years, frailty has emerged as a prognostic factor in inflammatory bowel diseases (IBD), particularly among patients with active disease. However, evidence regarding its reversibility after treatment optimizat...: In recent years, frailty has emerged as a prognostic factor in inflammatory bowel diseases (IBD), particularly among patients with active disease. However, evidence regarding its reversibility after treatment optimization remains limited. This study aimed to assess frailty in active IBD and determine whether frailty status improved after 6 months of clinical management and the achievement of clinical remission. : This prospective, single-center, observational cohort study included adults with active IBD requiring escalation to advanced therapy who achieved clinical remission at the 6-month follow-up. Patients were evaluated at baseline and after 6 months using a modified Fried frailty phenotype. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Univariate and multivariate logistic regressions were utilized to identify independent factors associated with frailty improvement. : The analysis included 54 patients (61.1% male; 42.6% with Crohn's disease). At baseline, 20.4% were classified as frail, 72.2% as pre-frail, and 7.4% as robust. Following 6 months of clinical management and the achievement of clinical remission, a 100% resolution of frailty was observed, with the robust cohort expanding to 42.6%. Significant improvements occurred across clinical parameters, including handgrip strength, 400 m walk times, and median SIBDQ scores (increasing from 4.4 to 5.9, < 0.001) alongside a substantial decline in CES-D scores ( = 0.017). Multivariate logistic regression revealed that severe disease at baseline (aOR = 4.51, 95%CI: 1.26-16.18, = 0.020), anti-TNF therapy initiation (aOR = 3.69, 95%CI: 1.04-13.18, = 0.044), and higher baseline CES-D scores (aOR = 1.06, 95%CI: 1.00-1.13, = 0.038) were independently associated with higher odds of frailty improvement. : Among patients who achieved clinical remission, frailty and pre-frailty demonstrate substantial short-term improvement following advanced therapy. Functional and psychological recoveries are associated with successful control of baseline disease severity and systemic inflammation.
Medicina (Kaunas)
· 2026 Jun · PMID 42356190
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: Human immunodeficiency virus (HIV) infection is associated with immune dysregulation, which may influence the development of autoimmune diseases. However, population-based evidence on the prevalence of autoimmune disea...: Human immunodeficiency virus (HIV) infection is associated with immune dysregulation, which may influence the development of autoimmune diseases. However, population-based evidence on the prevalence of autoimmune diseases in individuals living with HIV remains limited, particularly in Asian populations. This study aimed to evaluate the prevalence of autoimmune diseases in individuals living with HIV in Korea using nationwide population-based data. : We conducted a cross-sectional analysis using the Health Insurance Review and Assessment Service National Patient Samples from 2012 to 2015, including 4,851,064 individuals aged ≥15 years. HIV infection and autoimmune diseases were identified using ICD-10 codes. The prevalence of autoimmune diseases in individuals with HIV infection was compared with that in the general population. Antiretroviral therapy (ART) status was determined based on prescription records. : A total of 1023 individuals were identified with HIV infection, all of whom were receiving antiretroviral therapy. The overall prevalence of autoimmune diseases was 4.4% in males and 3.6% in females with HIV, without significant differences compared to controls. However, the prevalence of ulcerative colitis in males ( = 0.030) and of dermatomyositis in females ( = 0.011) was higher in individuals with HIV. : Although the overall prevalence of autoimmune diseases was not significantly increased in individuals living with HIV, certain autoimmune diseases-particularly ulcerative colitis in men and dermatomyositis in women-showed a higher prevalence. As these findings were based on small case numbers, they should be approached with caution. The results are best regarded as hypothesis-generative observations that warrant further investigation rather than findings on which clinical practice should currently be based. Further research using large datasets is warranted to confirm these associations and clarify the underlying immunological mechanisms.
Med Sci (Basel)
· 2026 Jun · PMID 42346848
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BACKGROUND: Whether the fatal and non-fatal composition of aggregate pancreatitis burden has changed over time remains unclear. We assessed long-term changes in the fatal-to-non-fatal composition of aggregate pancreatiti...BACKGROUND: Whether the fatal and non-fatal composition of aggregate pancreatitis burden has changed over time remains unclear. We assessed long-term changes in the fatal-to-non-fatal composition of aggregate pancreatitis burden using Global Burden of Disease (GBD) 2023 estimates. METHODS: We conducted a systematic descriptive and trend analysis using publicly available estimates from the GBD 2023 Results Tool for incidence, prevalence, deaths, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) across 204 countries and territories from 1990 to 2023. Because GBD reports pancreatitis as an aggregate cause category, the analysis could not distinguish acute pancreatitis, recurrent acute pancreatitis, chronic pancreatitis, or acute exacerbations of chronic pancreatitis. Primary analyses used age-standardised rates per 100,000 population. Four burden-composition metrics were derived within each location-year stratum: the YLL:YLD ratio, YLD:DALY proportion, deaths-to-incidence ratio, and prevalence-to-incidence ratio. Temporal trends were modelled in R version 4.5, using segmented regression, with up to three joinpoints selected by a Bayesian information criterion. RESULTS: Globally, all six age-standardised native GBD measures declined between 1990 and 2023. The age-standardised incidence rate decreased from 37.62 (95% UI 32.20-43.11) to 32.91 (28.84-37.17) per 100,000, prevalence from 93.78 (69.26-126.25) to 68.92 (52.53-90.32), deaths from 1.76 (1.49-2.16) to 1.40 (1.21-1.66), YLDs from 5.70 (2.75-9.45) to 4.34 (2.18-7.04), YLLs from 55.96 (46.50-69.72) to 43.60 (36.89-53.53), and DALYs from 61.66 (50.62-75.61) to 47.94 (40.57-58.16). However, the fatal-to-non-fatal composition changed little: the global YLL:YLD ratio was 9.82 in 1990 and 10.04 in 2023, while the YLD share of DALYs was 0.092 and 0.091, respectively. Joinpoint modelling showed fluctuation rather than a sustained shift toward disability-dominant burden: the global YLL:YLD ratio was stable until 1998, increased from 1998 to 2002 (annual percent change [APC] 1.38%, 95% CI 0.42 to 2.36), and then declined modestly thereafter (APC -0.13%, -0.20 to -0.06). Burden remained higher in males, whereas females had a greater non-fatal share of total burden (YLD:DALY in 2023: 0.134 vs. 0.073). All sociodemographic index strata remained mortality-dominant in both 1990 and 2023; low-SDI settings had the greatest fatal dominance (YLL:YLD 34.94 in 1990; 24.72 in 2023). Using a descriptive YLD:DALY ≥ 0.50 benchmark, 203 of 204 countries and territories remained below the disability-dominant threshold in both years, no country crossed from below to above this benchmark, and only Georgia moved from above to below the benchmark. CONCLUSIONS: Despite declines in global incidence, mortality, and DALY rates, the aggregate GBD pancreatitis burden remained overwhelmingly mortality-dominant from 1990 to 2023. Because GBD pancreatitis combines acute and chronic pancreatitis, this finding should be interpreted as describing the modelled aggregate pancreatitis cause category rather than proving subtype-specific mortality dominance. The intensity of fatal dominance varied by sex, SDI, region, age, and country, but a structural shift toward disability-dominant aggregate burden was not observed.
Cirrhosis prevalence and mortality continue to rise globally, with a >50% increase in cases since 1990, imposing a growing burden through chronic healthcare needs, recurrent hospitalisation, and liver transplantation, wh...Cirrhosis prevalence and mortality continue to rise globally, with a >50% increase in cases since 1990, imposing a growing burden through chronic healthcare needs, recurrent hospitalisation, and liver transplantation, which remains the only definitive cure for advanced disease. Long regarded as a fixed end-stage, cirrhosis is now recognised as a dynamic and modifiable disease state. Sustained aetiological control can induce meaningful architectural remodelling, and single-cell and spatial analyses show that cirrhosis is a heterogeneous fibrotic niche shaped by context-specific fibrogenic, immune, and vascular cell phenotypes. Thus, reversibility is determined not simply by fibrosis stage, but by the biological state of the scar and its microenvironment. Nevertheless, recent disappointing antifibrotic trials, particularly in MASH-related cirrhosis, highlight the structural resilience of advanced disease and the limited sensitivity of conventional histological endpoints. Moreover, although structural improvement appears to confer measurable prognostic benefit, regression does not equate to complete restoration of tissue homeostasis, and residual vascular dysfunction and oncogenic risk often persist. Translating emerging mechanistic insights into precise measurement tools and effective therapies for cirrhosis regression now represents a central challenge in hepatology.
Dasarathy D, Luk JW, Shui AM
… +9 more, Wong RJ, Cheung R, Monto A, Ostacher MJ, Batki SL, Snyder HR, Peluso MJ, Satre D, Khalili M
Alcohol Alcohol
· 2026 May · PMID 42341208
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BACKGROUND: Patient-reported symptoms following COVID-19 exposure have been understudied in cirrhosis. This study evaluated type, severity, and persistence of symptoms along with impact on quality of life (QOL) post-SARS...BACKGROUND: Patient-reported symptoms following COVID-19 exposure have been understudied in cirrhosis. This study evaluated type, severity, and persistence of symptoms along with impact on quality of life (QOL) post-SARS-CoV-2 infection in a cohort with and without alcohol-related cirrhosis. METHODS: Patients with cirrhosis receiving care in hepatology clinics at three institutions were surveyed for symptoms and liver disease QOL (LDQOL) using standardized instruments following SARS-CoV-2 infection. Acute (<30 days), post-acute (≥30 days since onset), and Long COVID (≥3 months) symptoms were compared by cirrhosis etiology and decompensated status. Associations between severe COVID-19 symptoms and LDQOL were examined using multivariable models. RESULTS: 156 patients with prior COVID-19 exposure had a median age of 66.5 years; 18% were female; 43% had alcohol-related liver disease (ALD); and 42% decompensated cirrhosis. Among 208 surveys conducted, the median (Q1, Q3) number of symptoms reported was 6 (3, 10), with 66% reporting at least one severe/very severe symptom and 21% had Long COVID. There were no significant differences in symptoms by cirrhosis etiology or decompensation except those with ALD had higher post-acute symptoms compared to non-ALD (RR 2.17, P = .04). Moreover, the total number of severe symptoms was inversely associated with LDQOL. For each additional severe symptom reported, LDQOL decreased by 1.12 points after adjusting for age, sex, ALD, decompensated cirrhosis, and MELD-Na score (95% CI -1.70 to -0.53, P = .001). CONCLUSIONS: Assessing severity and persistence of post-COVID-19 exposure symptoms can help clinicians address patient-reported QOL concerns, optimize cirrhosis management, and inform integrated care for ALD and AUD.
Soliman MY, Elsalahi M, Mattar A
… +25 more, Abd Elrazik OM, Ali RF, Mohamed MG, Ghazy AM, Almasabi SHA, Ghoname M, Afifi E, Basabein A, Abdellatif MA, Elolimy ASE, Ayaad A, Ahmed FAM, Metwally ASAA, Mousa WM, Zidan MHS, Sharawy MT, Hegab SMEA, Zayed Z, Sadek SA, Al-Shahed FAN, Abd ElRazek HE, Abdalgaleel MA, Shehata MS, Ahmed A, Orabi IA
BACKGROUND: Pancreaticobiliary lesions represent a wide clinical range ranging between harmless inflammatory diseases up to aggressive cancers. Accurate differentiation remains challenging and none of the modalities is p...BACKGROUND: Pancreaticobiliary lesions represent a wide clinical range ranging between harmless inflammatory diseases up to aggressive cancers. Accurate differentiation remains challenging and none of the modalities is predictive enough to predict malignancy. This study compared the combined diagnostic usefulness of the clinical, radiological, laboratory, and histopathological data to predict malignancy. METHODS: Group I (n=26) and Group II (n=34) were formed of 60 patients with pancreaticobiliary lesions who were assessed in a tertiary care hospital in this retrospective analytical study. Proper statistical tests were used to compare clinical symptoms, radiological results of transabdominal ultrasonography, contrast-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), serum biomarkers and histopathology. RESULTS: Anorexia (88.5% vs 29.4%, p<0.001), weight loss (69.2% vs 26.5%, p=0.002), and jaundice (69.2% vs 38.2%, p=0.034) were significantly more prevalent in malignant cases. EUS demonstrated sensitivity of 96.2% and NPV of 95.2%. CBD diameter on MRCP (14.5±5.9 vs 11.3±2.7 mm, p=0.006), serum bilirubin (median 5.7 vs 1.2 mg/dL, p=0.006), and CA 19-9 (median 236.0 vs 34.0 U/mL, p=0.006) were significantly elevated in the malignant group. Multivariate analysis confirmed anorexia, weight loss, CA 19-9 elevation, jaundice, bilirubin, and CBD diameter as independent predictors of malignancy. CONCLUSIONS: Multidisciplinary treatment which combines clinical presentation, EUS, MRCP biliary measurements, serum biomarkers will greatly increase the prediction of malignancy in pancreaticobiliary lesions. These results help to develop a composite predictive scoring model that may be used in clinical practice.
Nelson M, Murthy S, Maddipatla S
… +6 more, Shenoy S, Ponder L, Chandrakasan S, Kugathasan S, Cutler D, Prahalad S
Lupus Sci Med
· 2026 Jun · PMID 42336467
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INTRODUCTION: Childhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. While numerous variants have been associated with adult-onset SLE, limited data exist on genetic v...INTRODUCTION: Childhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. While numerous variants have been associated with adult-onset SLE, limited data exist on genetic variation within cSLE. We aimed to investigate genetic factors of early-onset cSLE, defined as onset of cSLE prior to age 10. METHODS: Employing a case-only design, we performed whole genome sequencing analysis on 37 subjects with early onset cSLE. We hypothesised that rare, functional variants with large effects in genes associated with SLE contribute to the risk of early-onset cSLE and that the polygenic risk score (PRS) would be inversely associated with age of onset and presence of nephritis. A total of 153 linkage disequilibrium-independent variants were analysed and compared with previously reported SLE single-nucleotide polymorphisms. Rare (minor allele frequency (MAF) ≤1%), damaging protein-altering (Combined Annotation Dependent Depletion; CADD≥20) variants, including variants isolated to previously reported monogenic SLE genes (n=49), were prioritised for secondary analysis. RESULTS: 37.8% of our cSLE cohort carried at least one rare, pathogenic variant in monogenic SLE genes. We identified 31, 012 rare, damaging, pathogenic variants in our cSLE cohort, including two genes implicated in mitochondrial protein degradation () and several genes in the interferon pathway (). We found that higher PRS scores were associated with increased nephritis odds (p=0.0092) but not age of onset (p>0.05). Burden testing using the optimal sequence kernel association test (SKAT-O) revealed nominal enrichment of rare variants (MAF≤ 5%) in immune-related genes, including and , several of which are involved in type I interferon and antigen presentation pathways. CONCLUSION: These results have the potential to enhance our understanding of cSLE. Further studies must be conducted to expand our findings.
Ursodeoxycholic acid (UDCA) is a hydrophilic, non-toxic bile acid that represents the gold standard in the treatment of various cholestatic and hepatobiliary diseases. Its therapeutic benefit lies in its complex pleiotro...Ursodeoxycholic acid (UDCA) is a hydrophilic, non-toxic bile acid that represents the gold standard in the treatment of various cholestatic and hepatobiliary diseases. Its therapeutic benefit lies in its complex pleiotropic mechanism of action, including cytoprotection of hepatocytes and cholangiocytes, stimulation of hepatobiliary secretion, antiapoptotic effects, and immunomodulatory properties. This article comprehensively summarizes the pharmacological characteristics of UDCA and its rational clinical use in key indications such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), dissolution of cholesterol gallstones, reactive gastritis due to duodenogastric reflux, and intrahepatic cholestasis of pregnancy (ICP). Furthermore, it focuses on the safety profile of UDCA, including its excellent tolerability, dose-dependent diarrhea, and confirmed safety for use during pregnancy and lactation, making it a crucial drug in hepatology.
G A S, Maiya GA, Shetty S
… +4 more, Abrahamse H, Kadavigere R, Bhat N S, K N S
Lasers Med Sci
· 2026 Jun · PMID 42334638
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Fibromyalgia Syndrome (FMS) is a chronic pain disorder characterized by widespread pain and central sensitization that significantly impacts the quality of life (QoL). For management to be effective, a multidisciplinary...Fibromyalgia Syndrome (FMS) is a chronic pain disorder characterized by widespread pain and central sensitization that significantly impacts the quality of life (QoL). For management to be effective, a multidisciplinary approach to care is typically required. Photobiomodulation therapy (PBMT), a non-pharmacological treatment, has garnered attention lately, though its clinical relevance and applications are not well defined. The objective of this review was to assess the effectiveness of PBMT in reducing FMS symptoms. This systematic review was registered at PROSPERO (CRD420251084730) and conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines. A total of seven randomized controlled trials were identified following an extensive literature search across various databases, including PubMed, Scopus, Web of Science, the Cochrane Library, Embase, Ovid and ProQuest. To evaluate the methodological quality of these studies, the Cochrane Risk of Bias (RoB 2.0) tool was applied. PBMT demonstrated consistent short-term reductions in pain intensity and improvements in QoL. Additional positive effects on sleep quality and psychological well-being were observed, indicating that PBMT may provide additional therapeutic benefits beyond pain reduction, including improvements in sleep quality and psychological well-being. PBMT has shown promise as a safe, non-pharmacological adjunct therapy that may provide short-term improvements in pain levels and QoL, but substantial heterogeneity limits generalizability. Clinical trials with large samples and standardized methodologies should be conducted to better clarify the role of PBMT in multidisciplinary therapy for FMS.
Ahtola K, Ulander M, Agholme J
… +11 more, Amiri F, Henriksson P, Leinhard OD, Lundberg P, Dahlström N, Carlhäll CJ, Kechagias S, Nasr P, Forsgren M, Ekstedt M, Iredahl F
Obstructive Sleep Apnea (OSA) affects 1 billion people globally, with a male-to-female ratio of 2:1. While obesity is a major risk factor, sex differences in fat distribution may influence OSA risk. This study examined t...Obstructive Sleep Apnea (OSA) affects 1 billion people globally, with a male-to-female ratio of 2:1. While obesity is a major risk factor, sex differences in fat distribution may influence OSA risk. This study examined the relationship between visceral (VAT), subcutaneous (ASAT), and total abdominal fat (TAAT) and OSA severity in patients with type 2 diabetes (T2DM). We enrolled 164 T2DM patients (97 males, 67 females) from the EPSONIP-Sleep study; 151 had complete MRI and polygraphy data. OSA severity was evaluated by home respiratory polygraphy. Linear regression assessed AHI, logistic regression assessed moderate-to-severe OSA, and the Kruskal-Wallis test compared AHI across VAT-z/ASAT-z strata. In males, VAT, ASAT, and TAAT were associated with AHI in unadjusted analyses (β = 1.3, p = 0.009; β = 1.5, p = 0.010; β = 0.85, p = 0.009, respectively). ASAT (OR = 1.23/L, 95% CI 1.01-1.49, p = 0.049) and TAAT (OR = 1.10/L, 95% CI 1.00-1.22, p = 0.02), but not VAT, were associated with moderate-to-severe OSA. No statistically significant associations were detected in females. Associations were attenuated after BMI adjustment. AHI did not differ across VAT-z/ASAT-z strata (p = 0.430). Sex differences influenced the relationship between fat and OSA severity. In males, abdominal fat volumes were associated with higher OSA severity in unadjusted analyses, but not after BMI adjustment. No statistically significant associations were detected in females. These findings should be interpreted cautiously given the modest sample size.
Zhonghua Yu Fang Yi Xue Za Zhi
· 2026 Jun · PMID 42331538
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To assess the disease burden of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis in China from 1990 to 2021. Data were obtained from the Global Burden of Disease (GBD) 2021 study. The age-standardized rate wa...To assess the disease burden of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis in China from 1990 to 2021. Data were obtained from the Global Burden of Disease (GBD) 2021 study. The age-standardized rate was calculated using the direct standardization method with the GBD world standard population as the reference. The Joinpoint model was used to calculate the change of NAFLD-related cirrhosis in China, and the age-period-cohort analysis was used to estimate the independent effects of age, period, and cohort. In 2021, the age-standardized incidence rate (ASIR) of NAFLD-related cirrhosis in China was 621/100 000, with the age-standardized prevalence rate (ASPR) of 15 606/100 000 and the age-standardized mortality rate (ASMR) of 0.31/100 000. The average annual percentage change (AAPC) of ASIR of the whole population from 1990 to 2021 was 0.74% (95: 0.69%, 0.78%). There was a decreasing trend in the ASMR of the whole population with an AAPC of -1.73% (95:-2.06%, -1.40%). The age effect showed a fluctuating downward trend in the overall incidence rate with age. The overall mortality rate showed an increasing trend. The period effect showed that the period rate ratios (RR) first decreased and then increased, with the highest incidence risk in 2017-2021. The period RR of incidence rate was 1.16 (95: 1.11, 1.21). The trend of change in mortality rate showed a decreasing tendency, with the highest mortality risk in 1992-1996. The of mortality risk was 1.50 (95: 1.43, 1.58). The cohort effect showed a significant increase in incidence risk and a decreasing trend in mortality risk from 1977 to 2002. The overall disease burden of NAFLD-related cirrhosis in China has shown a continuous upward trend from 1990 to 2021, and there are significant gender and age differences.
Rousian M, Alessandris R, Schleimer L
… +33 more, Kalvin H, Zaki O, Connell L, Harding J, O'Reilly E, Abou-Alfa G, Vachharajani N, Doyle M, Tan B, Khan A, Fields R, Franssen S, Filipe W, Buisman F, Mostert B, Homs M, Doukas M, Haaft BT, Swijnenburg RJ, Klümpen HJ, Hagendoorn J, Mohammad NH, D'Amico FE, Soares K, Kingham P, Wei A, D'Angelica M, Gönen M, Chapman W, Kemeny N, Cercek A, Jarnagin W, Koerkamp BG
BACKGROUND & AIMS: Systemic therapy is the standard of care for unresectable intrahepatic cholangiocarcinoma (iCCA), but overall survival (OS) remains poor. Hepatic artery infusion pump (HAIP) chemotherapy with floxuridi...BACKGROUND & AIMS: Systemic therapy is the standard of care for unresectable intrahepatic cholangiocarcinoma (iCCA), but overall survival (OS) remains poor. Hepatic artery infusion pump (HAIP) chemotherapy with floxuridine (FUDR) has shown prolonged survival but is limited to expert centers. We assessed long-term OS among patients with unresectable, liver-confined iCCA treated with HAIP chemotherapy. METHODS: Individual patient data from four phase II trials were pooled, including 142 patients with unresectable, liver-confined iCCA, with or without resectable regional lymph node metastases. Patients received HAIP chemotherapy with FUDR, with or without systemic therapy. The primary outcome was OS. Cox models examined associations between preselected covariates and OS. RESULTS: Multifocal disease was found in 92 patients (65%) and 58 (41%) had tumors larger than 10 cm. Twenty-five patients (18%) received prior systemic treatment. Partial response on imaging was achieved in 73/139 patients (53%), with a disease control rate of 96%. Thirteen patients (9%) underwent resection; 4 achieved complete pathological response. The pooled median OS was 26 months (95% CI: 22-30), 3-year OS rate was 28% (95% CI: 22%-37%), and 5-year OS rate was 15% (95% CI: 10%-23%). OS was similar across trials (p=0.95). The intention to treat 3-year and 5-year OS rates were 26% and 14%, respectively, which included 12 patients (7.8%) who did not undergo HAIP chemotherapy due to peritoneal disease. Hepatic disease progression was independently associated with worse OS (HR: 4.46, 95% CI: 2.69-7.40; p<0.001). CONCLUSIONS: Patients with unresectable, liver-confined iCCA who underwent HAIP with systemic chemotherapy had a 3-year OS rate of 28% and 5-year OS rate of 15% across four phase II trials. These results provide long-term benchmark results for a selected patient population. IMPACT AND IMPLICATIONS: Unresectable, locally advanced intrahepatic cholangiocarcinoma remains a disease with poor long-term survival, and evidence supporting liver-directed strategies is limited to small, heterogeneous single-arm studies. By pooling individual patient data from all prospective phase II trials of hepatic artery infusion pump chemotherapy with extended follow-up, this study provides the most comprehensive and mature long-term survival benchmarks. These findings inform multidisciplinary decision-making at specialized centers and support further prospective evaluation of hepatic artery infusion pump chemotherapy within modern multimodality treatment strategies.
Martín-Grau M, Kamstra JH, Hyötyläinen T
… +10 more, Orešič M, Song Y, Veličković N, Djordjevic A, Vojnović Milutinović D, Jackson RF, van Vorstenbosch R, Massart J, Vidal-Puig A, Carobbio S
Metabolically dysfunction-associated steatotic liver disease (MASLD) is rising worldwide at a pace that cannot be fully explained by obesity, diet, or genetics alone. Emerging evidence supports a mechanistic dissection o...Metabolically dysfunction-associated steatotic liver disease (MASLD) is rising worldwide at a pace that cannot be fully explained by obesity, diet, or genetics alone. Emerging evidence supports a mechanistic dissection of how defined endocrine-disrupting chemicals (EDCs) rewire hepatic transcriptional and metabolic networks relevant to MASLD. This review focuses on the molecular interfaces through which major EDC families intersect with hepatic metabolic regulation. We propose the "hepato-exposome axis" as a receptor-centric framework that maps specific EDC classes to nuclear receptors (NRs) and key metabolic pathways that regulate lipid metabolism, glucose homeostasis, mitochondrial dysfunction and inflammatory signalling implicated in MASLD progression. We summarise key EDC groups linked to liver disease, including organochlorine pesticides, pyrethroids, bisphenols, phthalates, organophosphate esters, and per- and polyfluoroalkyl substances (PFAS). We then integrate current understanding of hepatic metabolic and xenobiotic pathways in homeostasis and MASLD, emphasising xenobiotic-sensing and metabolic NRs (AhR, PXR, CAR, PPARs, FXR, LXRs, RXR) as convergence points for EDC action. Drawing on in vivo and in vitro studies, we show that distinct EDC families imprint overlapping molecular signatures onto pathways that control de novo lipogenesis, β-oxidation, glucose handling, antioxidant defences, and inflammatory/immune signalling, collectively fostering a pro-steatotic and pro-inflammatory hepatic milieu. We further discuss vulnerable populations, critical windows of exposure, mixture effects, and sex-specific responses, positioning EDCs as environmental modifiers of the MASLD trajectory across the life course. Finally, we outline priorities for mechanistic and translational research, including mixture toxicology, multi-omics exposome profiling, and biomarker discovery, to better quantify and mitigate endocrine disruptors' contribution to the global MASLD burden.