[JOURNAL] HEPATOLOGY
Sun
200 papers
Clinical and physiological outcomes of peroral endoscopic myotomy in Thailand, with a comparative review of Southeast Asian cohorts.
Issariyakulkarn N, Bongkotvirawan P, Chonprasertsuk S … +6 more , Pornthisarn B, Siramolpiwat S, Bhanthumkomol P, Wongcha-Um A, Aumpan N, Vilaichone RK
Sci Rep · 2026 Jul · PMID 42393154 · Full text
Peroral endoscopic myotomy (POEM) is an established therapy for achalasia, but data from Southeast Asia remain limited. We evaluated the clinical and physiological outcomes of POEM in Thai patients and compared them with...
Peroral endoscopic myotomy (POEM) is an established therapy for achalasia, but data from Southeast Asia remain limited. We evaluated the clinical and physiological outcomes of POEM in Thai patients and compared them with regional cohorts from Singapore and Malaysia. We analyzed a pooled Thai cohort of 127 patients who underwent POEM between 2014 and 2024 and compared outcomes with published cohorts from Singapore (n = 58) and Malaysia (n = 65). Clinical success was defined as an Eckardt score ≤ 3 during the follow-up period. A total of 250 patients were included. Clinical success was achieved in 89.9%, 93.0%, and 93.4% of patients in Thailand, Singapore, and Malaysia, respectively. In the Thai cohort, significant improvements were observed in Eckardt scores, integrated relaxation pressure, and timed barium esophagogram parameters (p < 0.05). Post-POEM reflux occurred in 23.1% of Thai, 43.1% of Singaporean, and 37.0% of Malaysian patients. POEM is a safe and effective treatment for achalasia in Thailand, with clinical outcomes comparable to regional benchmarks. Differences in reflux rates suggest potential heterogeneity in practice and follow-up, highlighting the need for standardized regional protocols.
Small molecule-mediated activation of Notch signal transduction.
Dey S, Giaimo BD, Zöllner IK … +16 more , Yang Q, Zarrin H, Ballout J, Diener M, Friedrich T, Ferrante F, Dreute J, Schmitz ML, Weiss A, Polo P, Lauth M, Gahr B, Just S, Bartkuhn M, Oswald F, Borggrefe T
Cell Death Dis · 2026 Jul · PMID 42393021 · Publisher ↗
The Notch signaling pathway is pivotal in regulating cell differentiation, stem cell maintenance and oncogenesis. While several Notch inhibitors have been developed, effective small molecule activators are scarce. Here,...
The Notch signaling pathway is pivotal in regulating cell differentiation, stem cell maintenance and oncogenesis. While several Notch inhibitors have been developed, effective small molecule activators are scarce. Here, we identify a small molecule that robustly activates Notch signaling, leading to significant upregulation of Notch target genes in several human cell lines and in Danio rerio embryos. Mechanistically, this compound induces the expression of activated NOTCH3 protein via a cryptic internal promoter within the NOTCH3 locus. Notch induction is markedly diminished upon genetic depletion of NOTCH3 or the canonical Notch transcription factor RBPJ. Furthermore, we demonstrate that the compound inhibits complex I of the respiratory chain. This is accompanied by a raise of cytosolic Ca concentration, which is pivotal for the induction of NOTCH3. Functionally, the Notch inducer enforces cell-cycle arrest and promotes terminal differentiation in acute myeloid leukemia (AML) cells. These findings suggest that this small molecule serves as a potent tool for modulating Notch signaling and holds therapeutic potential for Notch-responsive malignancies.
Endoscopic-Assisted Division of Septal Formation After Duhamel Procedure for Hirschsprung Disease: Two Case Reports.
Takami S, Nonaka S, Yokokawa H … +5 more , Kitahara A, Yamamoto S, Obana K, Kanai Y, Fujishiro J
Asian J Endosc Surg · 2026 · PMID 42393001 · Full text
The management of septal formation after the Duhamel procedure in Hirschsprung disease remains unclear. We report two cases treated with an endoscopic-assisted approach. Case 1 is a 5-year-old girl with Hirschsprung dise...
The management of septal formation after the Duhamel procedure in Hirschsprung disease remains unclear. We report two cases treated with an endoscopic-assisted approach. Case 1 is a 5-year-old girl with Hirschsprung disease who underwent the Duhamel procedure. Persistent constipation led to a contrast enema, confirming septal formation. Transanal endoscopic-assisted division with an endoscopic linear stapler improved symptoms initially. However, constipation and enterocolitis with bleeding recurred 5 months later, requiring redo surgery. Case 2 is a 21-year-old female with a history of Hirschsprung disease, treated with the Duhamel procedure. She had three episodes of severe abdominal pain and enterocolitis in the past month. Colonoscopy revealed a septal formation with proximal intestinal dilatation. Endoscopic-assisted division resulted in complete resolution of symptoms. No complications occurred. Septal formation may cause an obstruction contributing to constipation and enterocolitis. Early recognition and division of the septum are recommended in patients with severe constipation or enterocolitis after the Duhamel procedure.
Sacchaindols A-C, Dimeric Alkaloids with Anti-inflammatory Activity from Marine Sediment-Derived Mutant Strain SCSIO 07745/.
Li K, Luo X, Li P … +7 more , Sun C, Ma X, Shang Z, Liu D, Ma J, Zhu H, Ju J
Org Lett · 2026 Jul · PMID 42392986 · Publisher ↗
Two novel types of dimeric alkaloids were isolated from the marine sediment-derived mutant strain SCSIO 07745/. Among them, sacchaindol A () represents a previously unreported class of dimeric aminoquinolinone alkaloids...
Two novel types of dimeric alkaloids were isolated from the marine sediment-derived mutant strain SCSIO 07745/. Among them, sacchaindol A () represents a previously unreported class of dimeric aminoquinolinone alkaloids, whereas sacchaindols B () and C [(±)-] comprise a rare fused 6/6/5/5 tetracyclic indole alkaloid framework. Their structures were elucidated using a combination of spectroscopic analyses, single-crystal X-ray diffraction, and computational methods. Hypothetical biosynthetic pathways for - were proposed. Notably, sacchaindols C [(±)-] exhibited anti-inflammatory activity.
Liver Transplantation for Metastatic Neuroendocrine Tumors: A Single-Center Experience in a Brazilian Referral Center.
Pilz M, Almeida P, Fernandes G … +7 more , Souza A, Matielo C, Curvelo L, Felga G, Viveiros M, Calil I, Rezende M
Transplant Proc · 2026 Jul · PMID 42392955 · Publisher ↗
BACKGROUND: Liver transplantation (LT) has emerged as a potential therapeutic option for selected patients with unresectable liver-confined metastatic neuroendocrine tumors (NETs), although evidence remains limited, part...
BACKGROUND: Liver transplantation (LT) has emerged as a potential therapeutic option for selected patients with unresectable liver-confined metastatic neuroendocrine tumors (NETs), although evidence remains limited, particularly in low- and middle-income countries. OBJECTIVE: To describe the experience of a Brazilian referral center with orthotopic LT for metastatic NETs and to evaluate post-transplant outcomes. METHODS: A retrospective descriptive cohort study was conducted, including patients who underwent deceased-donor LT between 2002 and 2025 at a tertiary referral center in Brazil. Among 2312 liver transplants, six patients transplanted for unresectable hepatic metastases from well-differentiated NETs were identified. Demographic, clinical, oncological, and transplant-related variables were analyzed, with outcomes assessed over a 5-year follow-up period. RESULTS: The cohort consisted predominantly of middle-aged men, with a median age of 47.5 years. All patients had preserved liver function at transplantation, reflected by low MELD-Na scores. The median Ki-67 index was 10% (range: 1%-20%). Overall survival was 100%, and tumor recurrence occurred in two patients (33.3%). Acute rejection was infrequent and successfully managed, with no cases of chronic rejection. Post-transplant complications were limited, mainly involving biliary events. Immunosuppressive regimens were predominantly tacrolimus-based, with selective use of mycophenolate and everolimus. CONCLUSIONS: LT for metastatic NETs was associated with excellent survival and low morbidity in this highly selected cohort. Despite the small sample size, these findings support LT as a feasible therapeutic option in carefully selected patients treated at specialized referral centers.
Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study.
Zhuo S, Liu Y, Wei K … +2 more , Zheng J, Zhang L
Ann Coloproctol · 2026 Jun · PMID 42392857 · Full text
PURPOSE: For early colorectal cancer (CRC) following noncurative endoscopic resection, additional curative surgery is the standard of care, but the optimal timing remains unclear. This study investigated the effect of th...
PURPOSE: For early colorectal cancer (CRC) following noncurative endoscopic resection, additional curative surgery is the standard of care, but the optimal timing remains unclear. This study investigated the effect of the interval between procedures on surgical complexity, complications, and oncological outcomes. METHODS: This retrospective study included 112 patients with early CRC who underwent additional laparoscopic surgery after noncurative endoscopic resection between August 2019 and August 2024. Clinical and pathological data were collected, with primary endpoints focused on surgical difficulty (operative duration and intraoperative blood loss). Statistical analyses were performed using multivariate analysis of variance, logistic regression, and receiver operating characteristic curve analysis. RESULTS: The interval between procedures was not significantly associated with surgical difficulty or lymph node metastasis (P>0.05). Multivariate analysis did not identify an optimal timing point for surgery. However, a longer waiting time was independently associated with an increased risk of residual tumor (odds ratio, 1.09; 95% confidence interval, 1.03-1.16; P=0.004). Furthermore, lymphovascular invasion and elevated preoperative carcinoembryonic antigen levels were identified as independent predictors of lymph node metastasis. A higher preoperative lymphocyte ratio was associated with an increased risk of postoperative intra-abdominal infection (r=0.243, P=0.010). CONCLUSION: In the era of laparoscopic surgery, the timing of additional surgery does not appear to be the primary determinant of surgical difficulty in CRC. Clinical decision-making should prioritize high-risk pathological features, such as lymphovascular invasion, rather than rigid adherence to a predetermined waiting period. Strategically delaying surgery may facilitate the selection of patients without residual disease, thereby helping to avoid unnecessary procedures.
Isolated jejunal tuberculosis presenting as chronic intestinal obstruction.
Adiody S, T K J, Narayanan S V … +1 more , B V
BMJ Case Rep · 2026 Jul · PMID 42392676 · Publisher ↗
Intestinal tuberculosis (TB) most commonly involves the ileo-caecal region. Isolated involvement of the jejunum without concomitant ileo-caecal or colonic disease is exceptionally rare. We report the case of a woman in h...
Intestinal tuberculosis (TB) most commonly involves the ileo-caecal region. Isolated involvement of the jejunum without concomitant ileo-caecal or colonic disease is exceptionally rare. We report the case of a woman in her early 60s who presented with a 2-year history of postprandial abdominal pain, intermittent constipation, anorexia and weight loss, followed by acute-onset vomiting suggestive of small bowel obstruction. Contrast-enhanced CT demonstrated a short-segment jejunal stricture with proximal dilatation. Enteroscopy confirmed luminal narrowing. Ileo-colonoscopy showed no ileo-caecal involvement. The patient underwent laparoscopy-assisted segmental jejunal resection. Histopathology revealed necrotising epithelioid granulomatous inflammation consistent with TB. Cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF assay system, Cepheid, Sunnyvale, California, USA) was negative. She was commenced on standard antitubercular therapy with a good clinical response. This case highlights the importance of considering TB in isolated small bowel strictures in endemic regions, even in the absence of ileo-caecal disease or systemic features.
Liver fibrosis in metabolic dysfunction-associated steatotic liver disease: epidemiology, risk stratification and therapeutics.
Li F, Li H, Juramt D … +3 more , Kou K, Tacke F, Chen L
BMJ Open Gastroenterol · 2026 Jul · PMID 42392673 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide and is tightly linked to cardiometabolic comorbidities. A major clinical focus on MASLD is th...
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide and is tightly linked to cardiometabolic comorbidities. A major clinical focus on MASLD is the detection of hepatic fibrosis, which most strongly predicts liver-related events, hepatocellular carcinoma risk and mortality. While lifestyle modification and sustained weight loss remain foundational, therapeutic innovation has rapidly expanded, shifting the metabolic dysfunction-associated steatohepatitis (MASH) treatment landscape towards targeted pharmacotherapies that address metabolic stress, inflammation and fibrogenesis, particularly for moderate/advanced fibrosis (, F2/F3 fibrosis and cirrhosis). This review summarises the burden and systemic complications of MASLD, highlights endocrine influences that modulate hepatic steatosis and disease severity and emphasises the central role of fibrosis staging and non-invasive risk stratification in clinical decision-making. We then synthesise emerging pharmacotherapies across key mechanistic axes, including incretin-based agents (GLP-1 receptor agonists and dual/triple agonists), hepatocyte-directed metabolic modulators (thyroid hormone receptor-β agonists, fatty acid synthase inhibitors, acetyl-CoA carboxylase and other de novo lipogenesis inhibitors), bile acid pathway therapies (FXR agonists) and pleiotropic metabolic-fibrotic regulators (fibroblast growth factor 21 [FGF21] analogues and peroxisome proliferator-activated receptor [PPAR] agonists). We also discuss combination strategies, candidate agents with potential direct antifibrotic activity and the growing role of genetic risk stratification and hepatocyte-targeted oligonucleotide therapeutics. Finally, we outline current surrogate endpoints used in clinical trials and propose future directions towards stage-specific, mechanism-informed and combination regimens to achieve persistent MASH resolution and meaningful fibrosis regression.
Comment on "Development and Validation of the HLS-Q12-OA Health Literacy Instrument for Older Adults: A Multidimensional Rasch and Confirmatory Factor Analysis".
Zuo F, Yao Y, Liu L
Geriatr Gerontol Int · 2026 Jul · PMID 42392602 · Publisher ↗
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Resident doctor workforce wellbeing worldwide: lessons between the United Kingdom and Australia.
Bhala NB, Taylor EC, Goddard AF … +1 more , Verma AM
Clin Med (Lond) · 2026 Jul · PMID 42392509 · Publisher ↗
Healthcare systems fundamentally depend on the wellbeing and sustainability of their workforce. Physician burnout, workload strain and declining professional fulfilment are widely documented across high-income health sys...
Healthcare systems fundamentally depend on the wellbeing and sustainability of their workforce. Physician burnout, workload strain and declining professional fulfilment are widely documented across high-income health systems. The United Kingdom and Australia share similar professional cultures and training pathways but operate within distinct health system structures. Comparing these systems provides insight into the structural determinants of resident doctor wellbeing. Both countries face common challenges including rising demand for care, domestic workforce shortages, and changing expectations of work-life balance. Data from both countries demonstrate persistently high levels of moral distress and intention to leave practice, alongside structural pressures including industrial action, training bottlenecks and changing workforce composition. Evidence on suicide risk further underscores the seriousness of workforce wellbeing as a public health issue. These shared outcomes highlight that structural differences do not protect resident doctors from distress. System-level reform and cultural change are essential to safeguard workforce wellbeing and health system sustainability.
Changes in alcohol use following a diagnosis of alcohol-related liver disease: a clinical cohort study.
Kann AE, Madsen LG, Rønn JH … +5 more , Shawcross DL, Kalk N, Bergmann ML, Jepsen P, Askgaard G
JHEP Rep · 2026 Jul · PMID 42392507 · Publisher ↗
BACKGROUND AND AIMS: Alcohol use is the key driver of progression in alcohol-related liver disease (ALD). We aimed to describe changes in alcohol use following a diagnosis of ALD. METHODS: From 2021-2025, we screened 299...
BACKGROUND AND AIMS: Alcohol use is the key driver of progression in alcohol-related liver disease (ALD). We aimed to describe changes in alcohol use following a diagnosis of ALD. METHODS: From 2021-2025, we screened 299 consecutive patients newly diagnosed with ALD at Zealand University Hospital, Denmark. At baseline, we interviewed patients about their current and lifetime alcohol use and motivation to reduce it, and we measured the alcohol biomarker phosphatidylethanol (PEth). We followed patients' alcohol use for 90 days and assessed predictors of abstinence after 90 days. 1 drink equalled 12 grams of alcohol. RESULTS: Of 104 newly diagnosed patients with ALD, 30% had decompensated cirrhosis, the median age was 64 years, and 76% were men. Patients reported escalating use of alcohol in the 30 years leading up to diagnosis of ALD, with 76% drinking ≥20 drinks/week the last five years before diagnosis. Shortly after the ALD diagnosis, only 24% reported drinking ≥20 drinks/week, and 56% reported abstinence, whereas abstinence occurred for 37% based on the alcohol biomarker. About 60% of patients expressed high motivation for and high confidence in obtaining abstinence at diagnosis. The risk of relapse after 90 days of follow-up was 37% (95%CI, 26-52) in patients abstaining at baseline. Predictors of abstinence at 90 days were motivation to change, confidence in change, and low PEth value at baseline, whereas severity of liver disease and AUDIT were not significantly associated. CONCLUSIONS: A diagnosis of ALD leads to a profound change in alcohol use, with around half of patients reporting abstinence after years of escalating use. Unfortunately, early relapse is common. IMPACT AND IMPLICATIONS: Our study demonstrated a window for behavioural change shortly after a diagnosis of ALD, during which many patients reduced alcohol use or achieved abstinence. These findings highlighted early change but also a considerable risk of relapse after diagnosis. The results supported integrating structured alcohol use disorder treatment into liver clinics, although the observational design, self-reported alcohol use, and small sample size should be considered.
Gastrointestinal Cryptococcosis in immunosuppressed patients.
Albayeh A, Khoury A, Katrib M … +7 more , Omar MA, El Halabi L, Alchaer A, Nasr J, Al-Obaidi A, Salyers WJ, Tofteland N
Infect Dis Now · 2026 Jul · PMID 42392450 · Publisher ↗
Cryptococcus neoformans is a yeast-like fungus found in soil contaminated with avian droppings. It most often produces disseminated disease in immunocompromised hosts, particularly individuals with impaired T-cell mediat...
Cryptococcus neoformans is a yeast-like fungus found in soil contaminated with avian droppings. It most often produces disseminated disease in immunocompromised hosts, particularly individuals with impaired T-cell mediated immunity such as those with HIV infection, patients receiving corticosteroids or other immunosuppressive therapy, and solid organ transplant recipients. The usual clinical manifestations are meningoencephalitis and pulmonary involvement, and it remains the most common systemic mycosis in patients with acquired immunodeficiency syndrome. Although the organism can involve nearly any organ, gastrointestinal cryptococcosis is exceedingly rare and has been described only in isolated case reports. Gastric and intestinal disease may present with acute abdominal symptoms or with more indolent features such as dyspepsia, nausea, vomiting, diarrhea, or melena. Diagnosis depends on endoscopic evaluation with histopathological confirmation, yet the condition is frequently unrecognized during life and is often identified primarily at postmortem examination. Reported endoscopic findings include ulcers, nodular lesions, and whitish petechiae. Prognosis is often poor, which highlights the need for early consideration of this entity in immunocompromised patients and prompt diagnostic evaluation given the absence of specific presenting features. This review summarizes susceptible host categories, the clinical spectrum of gastrointestinal cryptococcosis, diagnostic approaches, treatment considerations, and reported outcomes.
Formulation-dependent differences in systemic glutathione availability: Comparative pharmacokinetics of orally dissolving film and tablet formulations in healthy adults.
Jung ES, Jang HY, Jung SJ … +5 more , Kim BH, Kim YJ, Moon JH, Chae SW, Lee SO
Eur J Pharm Biopharm · 2026 Jul · PMID 42392376 · Publisher ↗
BACKGROUND: Glutathione is a tripeptide involved in antioxidant defense; however, its systemic availability following oral administration remains controversial, and pharmacokinetic differences between formulations in hum...
BACKGROUND: Glutathione is a tripeptide involved in antioxidant defense; however, its systemic availability following oral administration remains controversial, and pharmacokinetic differences between formulations in humans are not well characterized. OBJECTIVE: This study compared the pharmacokinetics and short-term supplementation effects of an orally dissolving film (ODF) and a conventional tablet formulation of glutathione in healthy adults. METHODS: In Study I, a randomized open-label crossover trial evaluated single-dose (300 mg) pharmacokinetics following administration of ODF or tablets. In Study II, participants consumed ODF (100 mg/day) or tablets (100 mg/day) for 4 weeks. RESULTS: Plasma glutathione concentrations were higher in the ODF group, with significant differences at 4 and 6 h. The ODF formulation showed a longer T and tended toward higher C and systemic exposure (iAUC). During 4-week supplementation, both formulations increased circulating glutathione levels, with no significant changes in oxidative stress-related biomarkers. No adverse events were reported. CONCLUSIONS: The ODF formulation exhibited a distinct pharmacokinetic profile and showed a trend toward greater systemic glutathione exposure compared with the tablet formulation. These findings suggest that formulation characteristics may contribute to differences in the bioavailability and pharmacokinetic behavior of orally administered glutathione. CLINICAL TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0011710.
Hierarchical analysis of metabolic phenotype reveals distinct microbiota and circulatory transcriptome in metabolic dysfunction-associated steatotic liver disease.
Tung CY, Lin YH, Chang YY … +10 more , Ruan JW, Chen PC, Chen CF, Yeh HY, Shen HC, Tsai HC, Li TH, Su CW, Yang YY, Hou MC
Gene · 2026 Jul · PMID 42392328 · Publisher ↗
AIM: To investigate how visceral adiposity and insulin resistance, defined respectively by visceral adiposity index (VAI) and triglyceride-glucose (TyG) index, jointly influence gut microbiota composition and immune tran...
AIM: To investigate how visceral adiposity and insulin resistance, defined respectively by visceral adiposity index (VAI) and triglyceride-glucose (TyG) index, jointly influence gut microbiota composition and immune transcriptomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and to explore potential mechanistic pathways. METHODS: We enrolled 169 adults stratified by VAI, controlled attenuation parameter (CAP), TyG index, and physical activity. Gut microbiota and immune transcriptomes were profiled using 16S rRNA and RNA sequencing, respectively. Differentially expressed genes (DEGs) were identified across subgroups. Functional annotation and upstream regulatory networks were analyzed using DAVID and Ingenuity Pathway Analysis (IPA). RESULTS: Higher VAI correlated with obesity, inflammation, and steatosis, while the TyG index independently predicted fibrosis risk. Specific taxa, includingTM7x,Acidaminococcus, andDielma, were consistently enriched in adverse metabolic phenotypes. Transcriptomic analysis of circulating immune cells identified 348 TyG-associated DEGs significantly enriched in mitochondrial and cytokine signaling pathways. IPA highlighted IL6, SREBF1, PTGS1 and SNCA as central regulators linking metabolic stress to mitochondrial dysfunction. CONCLUSIONS: Gut microbiota shifts and immune transcriptome alterations jointly mediate the interplay between insulin resistance and visceral adiposity in MASLD. The identified insulin resistance-associated genes suggest that mitochondrial dysfunction and cytokine dysregulation contribute to obesity-related hepatic pathology, supporting precision strategies targeting VAI and metabolic dysregulation.
Evaluating Performance of Non-Invasive Tests for Fibrosis Detection in MASLD with Type 2 Diabetes Mellitus: Insights from VCTE-Based Assessment.
Kagzi Y, Asif A, Wang Y … +2 more , Fischer J, Dhillon S
Clin Res Hepatol Gastroenterol · 2026 Jul · PMID 42392311 · Publisher ↗
INTRODUCTION: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) affects over half of patients with type 2 diabetes (T2DM), and advanced fibrosis is the strongest predictor of liver-related mortality. Altho...
INTRODUCTION: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) affects over half of patients with type 2 diabetes (T2DM), and advanced fibrosis is the strongest predictor of liver-related mortality. Although liver biopsy is the diagnostic gold standard, its invasiveness limits routine use. The accuracy of serum-based non-invasive tests (NITs) compared with liver stiffness measurement (LSM) in T2DM remains uncertain. The Universal Index for Cirrhosis (UIC index) is a newer fibrosis score with strong performance across mixed liver disease etiologies and has not been evaluated in MASLD in T2DM. This study assessed the diagnostic accuracy of the UIC index compared with established NITs using vibration-controlled transient elastography (VCTE) as the comparator for clinically significant and advanced fibrosis in a referral-based T2DM outpatient population. METHODS: In this retrospective study, adults with T2DM evaluated across outpatient clinics between 2013 and 2024 were included. Demographic, clinical, and laboratory data were collected within 30 days of VCTE. Clinically significant fibrosis and advanced fibrosis/cirrhosis were defined as LSM >8 kPa and >12 kPa, respectively. Diagnostic performance was assessed, and the area under the receiver operating curve (AUROC) was calculated. Logistic regression identified predictors of fibrosis presence and severity. RESULTS: A total of 199 patients were analyzed (mean age 58.8 years; mean BMI 35 kg/m²). Fibrosis prevalence was 97.5% for LSM >8 kPa and 44% for LSM >12 kPa. Non-Caucasian race and higher serum albumin were independently associated with lower fibrosis risk, while increasing AST and declining platelet counts were associated with greater fibrosis severity. For LSM >8 kPa, FIB-4 ≥1.3, and UIC index ≥4.5, the diagnostic performance was similar (AUROC 0.69 vs. 0.68). For LSM >12 kPa, FIB-4 >2.67 demonstrated the highest AUROC (0.72), while UIC index ≥8 showed balanced sensitivity (66%) and specificity (57%). The AUROC differences between FIB-4 and UIC were not statistically significant. CONCLUSIONS: FIB-4 and the UIC index demonstrated comparable diagnostic performance, each with distinct strengths and limitations.
The Disease Burden of Gastric Cancer in China, 1990-2023: A Comprehensive Analysis and Projections to 2035.
Yu Z, Jiao J, Liang C … +3 more , Hou S, Li L, Xu M
Clin Res Hepatol Gastroenterol · 2026 Jul · PMID 42392310 · Publisher ↗
BACKGROUND & AIMS: The disease burden of gastric cancer (GC) in China remains heavy. This study analyzed GC disease burden trends in China over recent years and projected future epidemiological patterns to inform targete...
BACKGROUND & AIMS: The disease burden of gastric cancer (GC) in China remains heavy. This study analyzed GC disease burden trends in China over recent years and projected future epidemiological patterns to inform targeted national public health prevention strategies. METHODS: The prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of GC in China were extracted from the Global Burden of Disease (GBD) 2023 database. The epidemiological characteristics and temporal trends were described and analyzed. The main risk factors associated with GC were analyzed, and the ARIMA model was used to predict the changing trends from 2024 to 2035. RESULTS: The above epidemiological indicators of GC decreased from 1990 to 2023, and exhibited a modest rebound between 2020 and 2023. The prevalence showed a downward trend in most age groups, but there was a significant upward trend in the 15-19 and 85-89 age groups. Moreover, the burden on males was significantly higher than females. The main modifiable risk factors included smoking, excessive alcohol consumption, and a high-sodium diet. Projections indicate a continued overall decline in GC burden from 2024 to 2035. CONCLUSIONS: Precise prevention and control measures should be implemented according to gender and age groups, and screening should be strengthened to improve the early diagnosis rate, ultimately alleviating the burden of GC in China.
The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study.
Staller K, Goodory VC, Khasawneh M … +2 more , Black CJ, Ford AC
Lancet Gastroenterol Hepatol · 2026 Jul · PMID 42392123 · Publisher ↗
BACKGROUND: The Rome V criteria for irritable bowel syndrome (IBS) were proposed in May, 2026. Their performance for the diagnosis of IBS in clinical practice is as yet unknown. We aimed to conduct a diagnostic accuracy...
BACKGROUND: The Rome V criteria for irritable bowel syndrome (IBS) were proposed in May, 2026. Their performance for the diagnosis of IBS in clinical practice is as yet unknown. We aimed to conduct a diagnostic accuracy study to examine this issue. METHODS: This diagnostic accuracy study was conducted in the specialist IBS clinic in Leeds Teaching Hospitals National Health Service Trust, Leeds, UK. Consecutive adults aged 16 years and older who were referred with suspected IBS between Sept 22, 2016, and June 18, 2024, provided complete symptom data. We applied standardised investigations (including full blood count, C-reactive protein, and coeliac serology), with assessors masked to symptom status. We assessed performance of the Rome V criteria, compared with the previous iterations, Rome IV and Rome III. The reference standard used to confirm IBS was the presence of lower abdominal pain or discomfort in association with altered stool form or frequency combined with no evidence of organic gastrointestinal disease after standardised investigations. Sensitivity, specificity, and positive and negative likelihood ratios were calculated for each of the diagnostic criteria, with 95% CIs. FINDINGS: Of the 745 eligible patients recruited, 726 patients had complete Rome V symptom data (546 [75%] were female, 180 [25%] were male, and mean age was 36·9 years [SD 14·0]). 417 (57%) patients met Rome V criteria for IBS. The level of agreement between the Rome V and either the Rome III or Rome IV criteria was fair to moderate (κ=0·36-0·55). Of patients with complete Rome V symptom data, 590 had IBS according to the reference standard, of whom 390 met Rome V criteria for IBS. Sensitivity of the Rome V criteria was therefore 66·1% (95% CI 62·1-69·9) and specificity was 80·1% (72·4-86·5). Positive likelihood ratio for the Rome V criteria was 3·33 (95% CI 2·40-4·74) and negative likelihood ratio was 0·42 (0·37-0·49). The Rome III and Rome IV criteria for IBS performed differently, with sensitivities of 87·5% (95% CI 84·4-90·3) and 78·9% (75·4-82·1) and specificities of 75·0% (66·3-82·4) and 81·0% (73·4-87·2). Positive and negative likelihood ratios for the Rome III criteria were 3·50 (2·61-4·84) and 0·17 (0·13-0·21) and for the Rome IV criteria were 4·16 (2·98-5·95) and 0·26 (0·22-0·31). INTERPRETATION: The Rome V criteria for IBS identified a different group of patients, with lower sensitivity than either Rome III or IV criteria in this single centre secondary care study. The clinical relevance of this is uncertain. FUNDING: None.
[Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial.
Walter T, Jann H, Ansquer C … +27 more , Deshayes E, Garcia-Carbonero R, Teulé A, Baum RP, Verberne HJ, Ćwikła JB, Srirajaskanthan R, de Mestier L, Grana CM, Buck A, Hörsch D, Pavel M, Dierickx LO, Michael M, Strosberg J, Kollár A, Jimenez-Fonseca P, Rinke A, Del Olmo-García M, Flaus A, Hernando J, Kluge A, Breuninger M, Melnyk S, Zhernosekov K, Capdevila J, COMPETE Investigator Team
Lancet · 2026 Jul · PMID 42392118 · Publisher ↗
BACKGROUND: Peptide receptor radionuclide and targeted therapy are both approved treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs), but clinical evidence for preferre...
BACKGROUND: Peptide receptor radionuclide and targeted therapy are both approved treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs), but clinical evidence for preferred sequencing is scarce. The COMPETE trial evaluated the efficacy and harms of peptide receptor radionuclide therapy ([Lu]Lu-edotreotide) versus targeted molecular therapy (everolimus) in patients with advanced, progressive, somatostatin receptor-positive GEP NETs. METHODS: This phase 3, open-label, superiority trial included patients aged 18 years or older with treatment-naive or previously treated unresectable or metastatic (or both) grade 1-2 GEP NETs. Patients were enrolled from 49 specialist neuroendocrine tumour treatment centres across 14 countries in Africa, Europe, North America, and Oceania and randomised (2:1) to intravenous [Lu]Lu-edotreotide (7·5 ± 0·7 GBq every 3 months, maximum four cycles) or oral everolimus (10 mg/day) for up to 30 months. Random assignment was via a central, web-based randomisation system (block size of 6) and stratified by primary tumour origin and previous therapy. The primary endpoint was progression-free survival, assessed via blinded independent central review in all randomly assigned patients at 30 months. Harms were assessed in all enrolled patients who received at least one dose of a study drug. This study was registered with ClinicalTrials.gov (NCT03049189) and is no longer recruiting. FINDINGS: Between April 13, 2017, and June 20, 2022, 324 patients were enrolled and 309 patients (including 168 [54%] male patients and 141 [46%] female patients) were randomly assigned to treatment: 207 to the [Lu]Lu-edotreotide group and 102 to the everolimus group. The median follow-up for progression-free survival was 27·5 months (IQR 19·6-30·4) for the [Lu]Lu-edotreotide group and 21·2 months (8·9-29·4) for the everolimus group. Median progression-free survival was significantly longer with [Lu]Lu-edotreotide versus everolimus (23·9 months [95% CI 18·7-30·0] vs 14·1 months [9·2-20·9]; stratified hazard ratio 0·67 [95% CI 0·48-0·95]; p=0·022). Treatment-related adverse events occurred in 178 (82%) of 217 patients in the [Lu]Lu-edotreotide group and 96 (97%) of 99 patients in the everolimus group. 40 (18%) patients in the [Lu]Lu-edotreotide group and 40 (40%) in the everolimus group had at least one treatment-related grade 3-4 adverse event. The most common treatment-related adverse events in the [Lu]Lu-edotreotide group were diarrhoea and nausea (both 79 [36%] patients) and asthenia (66 [33%] patients), whereas those in the everolimus group were diarrhoea (45 [45%] patients), asthenia (36 [36%] patients), and anaemia (27 [27%] patients). No treatment-related deaths occurred in either study group. INTERPRETATION: [Lu]Lu-edotreotide led to statistically significant and clinically meaningful improvements in progression-free survival. Efficacy and harms results support the use of [Lu]Lu-edotreotide in early lines of therapy in patients with advanced, progressive GEP NETs. FUNDING: ITM Solucin.
Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.
Wright SJ, Kang S, An M … +14 more , Heo YJ, Parikh M, Bi L, Lee H, Moorhead G, Haradhvala N, Lim SH, Kim ST, Getz G, Hacohen N, Lee J, Mehta A, Klempner SJ, Park RJ
Cell Rep Med · 2026 Jul · PMID 42392078 · Publisher ↗
The addition of anti-programmed cell death protein 1 (aPD-1) to 5-fluorouracil (5-FU)/platinum in advanced gastric cancer (GC) yields variable responses. To understand chemotherapy-immunotherapy cooperativity, we previou...
The addition of anti-programmed cell death protein 1 (aPD-1) to 5-fluorouracil (5-FU)/platinum in advanced gastric cancer (GC) yields variable responses. To understand chemotherapy-immunotherapy cooperativity, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA sequencing and T cell receptor (TCR) sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients. We observe greater abundance, persistence, and recruitment of T cells with transcriptionally predicted tumor-reactivity in patients with prolonged progression-free survival (slow progressors). Increased B cell abundance and predicted B cell to T cell interactions support T cell memory and co-stimulation, providing a mechanism for increased abundance and persistence of progenitor-exhausted and tumor-reactive T cells in slow progressors. T cell clones emerging in the tumor after immunotherapy are present in the blood before treatment only in slow progressors. We thus highlight mechanisms that may drive durable responses to chemoimmunotherapy in GC.
B cell-derived type I interferon sustains T cell functionality upon strong TCR stimulation during chronic infection.
Gago da Graça C, Cao Y, Li S … +20 more , Lindemann AF, Heyden L, Wijesinghe SKM, Poch A, Nguyen MT, Huynh-Anh NT, Daum E, Chen D, Tsui C, Rupasinghe E, Gantier MP, Roers A, Thimme R, Hofmann M, Bedoui S, Abdullah Z, Schröder J, Kallies A, Alexandre YO, Utzschneider DT
Immunity · 2026 Jul · PMID 42392074 · Publisher ↗
B cells are highly abundant lymphocytes and central players in humoral immunity. Although T cells are well known to support humoral responses, how B cells influence T cell responses is less understood. Here, we show that...
B cells are highly abundant lymphocytes and central players in humoral immunity. Although T cells are well known to support humoral responses, how B cells influence T cell responses is less understood. Here, we show that B cells are critical for CD8 T cell responses to chronic, but not acute, viral infections. In the absence of B cells, T cells responding to chronic infection exhibited severely impaired effector differentiation. This dependency on B cell help was dictated by high antigen loads and strong T cell receptor (TCR) stimulation. Loss of either B cells or interferon-I (IFN-I) signaling led to severe functional deficits in exhausted T cells, implicating B cells as key producers of IFN-I. The IFN-I-dependent T cell response to strong TCR stimulation is mediated, in part, by the transcription factor IRF1. Therefore, during chronic infection, we uncover an important role for B cell-derived IFN-I in modulating T cell responses to strong TCR stimulation.
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