Alimentary Pharmacology & Therapeutics最新文献

{"title":"Editorial: Cumulative Impact of Clinical Disease Activity, Biochemical Activity and Psychological Health on the Natural History of Inflammatory Bowel Disease During 8 Years of Longitudinal Follow-Up. Authors' Reply","authors":"Christy Riggott, Keeley M. Fairbrass, David J. Gracie, Alexander C. Ford","doi":"10.1111/apt.70100","DOIUrl":"https://doi.org/10.1111/apt.70100","url":null,"abstract":"<p>We would like to thank Drs Massouridis and Swaminathan for their editorial dealing with our article and welcome this opportunity for further discussion [<span>1, 2</span>]. Bi-directionality of gut–brain axis communications has been highlighted consistently in inflammatory bowel disease (IBD), with both a high prevalence of symptoms of common mental disorders (CMD) and an association between the presence of these symptoms and future adverse disease outcomes [<span>3</span>]. Although poor psychological health is most apparent during periods of disease activity, the prevalence of symptoms compatible with a CMD remains twice that of the general population even in quiescent disease, suggesting factors beyond inflammatory burden contribute to their development [<span>1, 3</span>]. Furthermore, a recently published longitudinal follow-up study examining trajectories of these symptoms in patients with IBD demonstrates that abnormal anxiety and depression scores persist in almost half of patients, suggesting poor psychological health is a constant for many patients [<span>4</span>]. Psychological health may, therefore, be an important therapeutic target in IBD.</p>\u0000<p>A biopsychosocial model of care is advocated for patients with irritable bowel syndrome (IBS), including access to brain–gut behavioural therapies and gut–brain neuromodulators to manage the associated symptoms [<span>5, 6</span>]. With the current lack of focus on psychological health in IBD management guidelines, holistic care models are yet to translate to routine IBD care. A substantial barrier to the implementation of such models is a lack of informative research. Few randomised controlled trials (RCTs) have assessed the effects of brain–gut behavioural therapies or gut–brain neuromodulators in patients with IBD with pre-existing psychological co-morbidity, who are the patient group most likely to benefit from the addition of such therapies [<span>7</span>]. In addition, identifying patients with symptoms of a CMD may be difficult given the time-sensitive nature of routine IBD care, where the focus is on managing inflammatory burden. Model-based clustering techniques incorporating measures of psychological and gastrointestinal symptom severity have identified clusters of patients with IBD and high psychological symptom burden, and could serve in clinical practice to identify subgroups of patients who may experience a benefit from brain–gut behavioural therapies or gut–brain neuromodulators [<span>8</span>]. Furthermore, one quarter of patients with IBD with endoscopically quiescent disease also report symptoms that are compatible with IBS [<span>9</span>]. Such patients, if identified in clinical practice, may also be best managed with brain–gut behavioural therapies or gut–brain neuromodulators, similar to the paradigm in IBS.</p>\u0000<p>Finally, as suggested, replication of this research is required in ethnically and socioeconomically diverse cohorts [<span>2</span>]. In fact, the un","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"2 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis: Pregnancies With Inflammatory Bowel Disease Complicated by Intrahepatic Cholestasis of Pregnancy","authors":"Shamim Joudaki, Olamide Oladipupo, Isabel Carbery, Marco Vincenzo Lenti, Christian P. Selinger","doi":"10.1111/apt.70096","DOIUrl":"https://doi.org/10.1111/apt.70096","url":null,"abstract":"Inflammatory Bowel Disease (IBD) requires maintenance of remission during pregnancy to avoid poor maternal and fetal outcomes. Intrahepatic cholestasis of pregnancy (ICP) could also increase these risks.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors for Liver Disease Cluster Geographically: A Precision Public Health Analysis of a UK City","authors":"R. Parker, A. Taylor, R. Dukes, B. Wilks, A. Hinkson, D. Burn, I. A. Rowe","doi":"10.1111/apt.70088","DOIUrl":"https://doi.org/10.1111/apt.70088","url":null,"abstract":"These data describe the distribution of risk factors for liver disease in Leeds, a large city in the UK. Anonymised, unlinked data were aggregated to lower super output areas by the Leeds GP data extraction programme for deprivation, obesity, diabetes and alcohol use. Incident liver disease was quantified from coding of hospital admissions. Alcohol use, deprivation and obesity were associated with LD. Risk factors clustered together geographically. Liver blood tests were more frequently done in areas of low-disease prevalence. These results illustrate health inequalities and support public health policies to reduce incident liver disease.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"43 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Predictors of Corticosteroid Response in Alcohol-Related Hepatitis","authors":"Ewan Forrest, Richard Parker, Mark Thursz","doi":"10.1111/apt.70074","DOIUrl":"https://doi.org/10.1111/apt.70074","url":null,"abstract":"<p>We read with interest the observational study by Idalsoaga et al. [<span>1</span>], which analysed a group of 289 patients treated with corticosteroids for alcohol-related hepatitis (AH). Models to determine response to corticosteroid therapy were assessed. It found that the Lille-7 score was the best-performing model, although none of the tested models had a high degree of discrimination. Determining response to corticosteroids for AH is important in order to abbreviate treatment in those not deriving benefit and so avoid corticosteroid-related complications. A dynamic model is one which looks at a change in variables after exposure to corticosteroids to determine their effectiveness. This is certainly true of the Lille model, which includes change in bilirubin from baseline (pre-treatment) to either Day 4 or Day 7 of treatment. However, the authors have also tested the trajectory of serum bilirubin (TSB), the neutrophil-to-lymphocyte ratio (NLR) and the change in NLR (Delta NLR), none of which have been proposed as indicators of response to already initiated corticosteroid therapy.</p>\u0000<p>The TSB was originally described to categorise the trajectory of bilirubin before exposure to corticosteroids [<span>2</span>]. Therefore, it is a characteristic of a patient pre-treatment and not a dynamic model reflecting the response to already initiated corticosteroid treatment. If the authors wished to look at the change in bilirubin after exposure to corticosteroids, they should have used either ‘early change in bilirubin’ (ECBL) [<span>3</span>], or the percentage change in bilirubin over 1 week [<span>4</span>].</p>\u0000<p>Similarly, the NLR has only been described as a baseline characteristic to identify those likely to benefit from corticosteroid treatment compared with those not receiving such treatment. The NLR has never been advocated as a simple prognostic or dynamic model, but as a baseline variable with a narrow ‘window’ (between 5 and 8) to predict improved outcomes with corticosteroid treatment [<span>5</span>]. This was demonstrated in 789 patients enrolled in the STOPAH trial and validated in a separate group of 237 patients. As there is a ‘window’ of NLR which identifies those who may benefit from corticosteroids, it is to be expected that it would perform poorly when analysed as a linear prognostic score. Its value can only be determined by comparing treated with untreated patients, which the current study does not assess. Delta NLR has never previously been suggested as a model to assess corticosteroid treatment in AH, and the well-recognised effects of corticosteroids upon circulating leucocytes will make this difficult to interpret.</p>\u0000<p>In conclusion, Idalsoag and colleagues have identified the Lille score at Day 7 as the most useful model to determine response in those who have already started corticosteroids. However, their study has not been designed to investigate TSB or NLR as useful pre-treatment characteristics of patients. Th","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"91 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Predictors of Corticosteroid Response in Alcohol-Related Hepatitis—Authors' Reply","authors":"Francisco Idalsoaga, Luis Antonio Díaz, Ramon Bataller, Juan Pablo Arab","doi":"10.1111/apt.70095","DOIUrl":"https://doi.org/10.1111/apt.70095","url":null,"abstract":"<p>Severe alcohol-associated hepatitis (AH) is a condition that bears a high short-term mortality [<span>1</span>], and corticosteroids are currently the only available therapy for patients with this disease [<span>2</span>]. However, given the well-documented adverse effects associated with corticosteroid use, it is clinically relevant to identify patients who will benefit the most from this treatment [<span>3</span>]. In our recent study [<span>4</span>], through a multinational analysis, we evaluated the performance of different dynamic models (defined as those using laboratory data from at least two time-points) to predict 30- and 90-day mortality in patients with severe AH. Our results revealed that the Lille day 7 score (Lille-7) was the most accurate model for predicting both 30-day and 90-day mortality. The Lille day 4 score (Lille-4) and the Trajectory of serum bilirubin (TSB) also demonstrated moderate predictive value. Interestingly, no significant differences were found when comparing Lille-7, Lille-4 and TSB.</p>\u0000<p>We appreciate the letter from Forrest et al. regarding our paper and their comments on the prognostic utility of the delta neutrophil-to-lymphocyte ratio (NLR) in patients with AH [<span>5</span>]. Although the original study by Forrest et al. [<span>6</span>], on the neutrophil-to-lymphocyte ratio (NLR) was primarily designed to identify patients who were likely to benefit from corticosteroid treatment, the use of delta NLR has been explored in multiple disease scenarios with significant inflammatory components, such as AH [<span>7</span>]. In fact, its utility has been assessed in various contexts, including living donor liver transplantation and graft survival [<span>8</span>], as well as its association with increased mortality in patients with hepatocellular carcinoma [<span>9</span>]. Furthermore, a study conducted in France that included 116 patients with cirrhosis admitted to the ICU found that the use of delta NLR was also an independent predictor of mortality at 28 days [<span>10</span>]. However, when specifically evaluated in AH in our study, this score did not demonstrate predictive power for mortality at 30 or 90 days, particularly in patients receiving corticosteroids.</p>\u0000<p>The use of TSB as a predictor of mortality had been validated in AH, specifically in patients before corticosteroid treatment [<span>11</span>]. In our study, when using this model as a dynamic score during the use of steroids, it was useful to predict mortality at 30 and 90 days. Interestingly, no significant differences were observed when comparing TSB to Lille-7, and it also demonstrated comparable performance to Lille-4. Both TSB and Lille-4 are valuable tools for risk stratification in patients with severe AH. Thus, although Lille-7 remains the most validated dynamic score, shortening the assessment period to 4 days may have a good discriminatory ability, reducing unnecessary exposure to corticosteroids. Finally, there is a clear ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"183 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Setons on Perianal Fistula Outcomes in Patients With Crohn's Disease Treated With Anti-TNF Therapy: A Multicentre Study","authors":"Jeffrey McCurdy, Javeria Munir, Simon Parlow, Gagan Sambhi, Jacqueline Reid, Russell Yanofsky, Talal Alenezi, Joseph Meserve, Kuan-Hung Yeh, Brenda Becker, Zubin Lahijanian, Anas Hussam Eddin, Ranjeeta Mallick, Tim Ramsay, Greg Rosenfeld, Ali Bessissow, Talat Bessissow, Vipul Jairath, David H. Bruining, Blair Macdonald, Siddharth Singh","doi":"10.1111/apt.70081","DOIUrl":"https://doi.org/10.1111/apt.70081","url":null,"abstract":"We aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti-TNF therapy.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"72 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Can We Prevent Inflammatory Bowel Disease? Authors' Reply","authors":"Fai Fai Ho, Irene Xin-Yin Wu, Vincent Chi Ho Chung","doi":"10.1111/apt.70093","DOIUrl":"https://doi.org/10.1111/apt.70093","url":null,"abstract":"<p>We sincerely appreciate the insightful comments from Ho and Mak regarding our recent study [<span>1</span>], which highlights the potential of lifestyle modification as a primary preventive strategy for inflammatory bowel disease (IBD) [<span>2</span>]. Utilising data from 105,715 participants aged 40–70 years in the UK Biobank Study, our analysis demonstrated a significant association between adherence to a combination of healthy lifestyle behaviours—never smoking, optimal sleep duration, high levels of vigorous physical activity, high dietary quality and moderate alcohol intake—and a reduced risk of incident IBD, including both Crohn's disease and ulcerative colitis [<span>2</span>]. Even after adjusting for potential confounders, participants adhering to one, two or three to five healthy lifestyle behaviours exhibited adjusted hazard ratios (95% confidence intervals) of 0.75 (0.59–0.97), 0.72 (0.56–0.92) and 0.50 (0.37–0.68), respectively (<i>p</i> for trend < 0.001), compared with those who engaged in none of these behaviours [<span>2</span>].</p>\u0000<p>Given the increasing incidence of IBD worldwide, particularly in newly industrialised nations [<span>3</span>], Ho and Mak aptly underscore the urgent need for effective preventive strategies to mitigate disease burden and reduce healthcare system pressures [<span>1</span>]. Despite the growing recognition of lifestyle factors in disease prevention, current consensus guidelines predominantly emphasise diagnosis and treatment for IBD rather than comprehensive prevention strategies [<span>6, 4</span>]. IBD is a multifactorial disease influenced by genetic predisposition, environmental exposures and gut microbiota composition [<span>7</span>]. Our findings highlight the collective benefits of multiple healthy lifestyle behaviours in lowering IBD risk and suggest that lifestyle modification may attenuate the impact of etiological factors on disease development.</p>\u0000<p>To effectively implement IBD prevention, primary healthcare providers must play a pivotal role in facilitating health behaviour change during routine consultations, as they often serve as the first point of contact within the healthcare system [<span>8, 9</span>]. The World Health Organisation advocates for the use of the ‘5As’ framework (Ask, Advise, Assess, Assist and Arrange), which can be seamlessly integrated into healthcare delivery at all levels, to guide primary care practitioners in delivering brief, structured counselling on health risk factors [<span>10</span>]. Beyond individual clinical efforts, fostering a supportive macro-environment is essential to encourage the adoption and maintenance of healthy behaviours. This necessitates coordinated action from national and local authorities. In the UK, national guidelines on behaviour change urge policymakers and healthcare commissioners to contribute actively to the design and implementation of evidence-based, sustainable interventions [<span>5</span>]. These efforts should","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Can We Prevent Inflammatory Bowel Disease?","authors":"Agnes Hiu Yan Ho, Joyce Wing Yan Mak","doi":"10.1111/apt.70071","DOIUrl":"https://doi.org/10.1111/apt.70071","url":null,"abstract":"<p>Inflammatory Bowel Disease (IBD), characterised by chronic inflammation of the gastrointestinal tract, can lead to a range of disabling symptoms and complications that impact both young and elderly individuals. It was observed that not only is the prevalence of IBD increasing in urbanised regions across the globe, but the incidence of IBD in newly industrialised regions has been rising as well [<span>1</span>]. The increasing burden of this chronic disease poses significant challenges to our healthcare systems. The exact causes of IBD remain unclear, but recent studies have identified several modifiable environmental risk factors that contribute to its development [<span>2</span>]. One approach to mitigating these risks is through the adoption of a healthy lifestyle.</p>\u0000<p>In the present study, Ho et al. studied the association of healthy lifestyle behaviours and risks of IBD development using the data from more than 100,000 individuals aged 40–70 from the UK Biobank [<span>3</span>]. The authors identified five lifestyle behaviours, including never smoking, optimal sleep, high levels of vigorous physical activity, high dietary quality, and moderate alcohol intake, as critical factors in mitigating IBD development. The most fascinating finding was that adopting a combination of healthy lifestyle behaviours, but not a single individual healthy behaviour, was associated with a greater reduction in the risk of developing both CD and UC. Although IBD mainly affects the young population, there is a bimodal pattern of disease onset, with another peak occurring between 60 and 70 years of age. With the increasing prevalence of elderly-onset IBD, which has been shown to exhibit disease activity at least as complex as that of adult-onset IBD [<span>4</span>], this study could still provide important insights on important preventive strategies against IBD.</p>\u0000<p>While previous studies mainly focus on the effect of individual environmental factors in IBD development [<span>5</span>], this study provides a new insight: no single lifestyle factor holds a magic bullet. Instead, the combined impact of healthy lifestyle choices creates a powerful protective effect. IBD is a complex, multi-factorial disease where dysbiosis of the gut microbiome, environmental factors, and host genetics are implicated in disease development. Diet and host immune responses determine gut microbial composition and function. Excessive intake of specific macronutrients enriched in a Western diet promotes experimental gut inflammation by perturbation of host–microbe commensalism [<span>6</span>]. Physical activity, on the contrary, influences the composition and diversity of the microbiome, reducing inflammation and intestinal permeability [<span>7</span>]. Sleep, often overlooked, also plays a critical role, as disruptions to the sleep–wake cycle can significantly alter the gut microbiome's function and resilience [<span>8</span>]. The gut microbiome, in turn, produces metabolites ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"183 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma","authors":"Subin Heo, Jiwon Yang, Jeayeon Park, Rex Wan-Hin Hui, Byeong Geun Song, In-Hye Song, Young-In Yoon, Tan-To Cheung, Sung Won Chung, Jonggi Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Wai-Kay Seto, Jeong-Hoon Lee, Won-Mook Choi","doi":"10.1111/apt.70085","DOIUrl":"https://doi.org/10.1111/apt.70085","url":null,"abstract":"Baseline viral replication activity influences the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B virus (HBV) infection.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"16 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Prevalence of Suspected Metabolic Dysfunction-Associated Liver Disease in Adolescents in the United States Using Updated Diagnostic Criteria—Authors' Reply","authors":"Sheila L. Noon, Tin Bo Nicholas Lam, Jeffrey B. Schwimmer","doi":"10.1111/apt.70092","DOIUrl":"https://doi.org/10.1111/apt.70092","url":null,"abstract":"<p>We appreciate the editorial by Bonn and Xanthakos [<span>1</span>] discussing our recent study on the prevalence and predictors of suspected MASLD in US adolescents [<span>2</span>]. Their commentary highlights the importance of MASLD in paediatrics and reinforces the key questions that remain about its clinical and research application. While the transition in nomenclature from NAFLD to MASLD provides a more structured definition, its implementation in children requires further investigation.</p>\u0000<p>A challenge in paediatric MASLD is misdiagnosis, especially in children with obesity whose liver disease is unrelated to steatosis. Hildreth et al. showed how autoimmune hepatitis can present with obesity, elevated ALT, and imaging findings that mimic steatosis, resulting in an erroneous MASLD diagnosis [<span>3</span>]. Conversely, our study found that 20.2% of adolescents with elevated ALT had no cardiometabolic risk factors, raising concerns that some children with liver disease may remain undetected under the updated criteria. Further complicating diagnosis, paediatric MASLD exhibits distinct histologic features, with a greater tendency for periportal inflammation and fibrosis than the pericentral pattern seen in adults [<span>4</span>]. These differences suggest MASLD in children involves unique developmental and metabolic pathways, reinforcing the need for paediatric-specific research rather than assuming direct parallels with adult disease.</p>\u0000<p>Distinguishing association from causation is another key challenge in MASLD. While the definition links hepatic steatosis to metabolic dysfunction, it is unclear whether one drives the other. Hepatic fat accumulation in preschool-aged children, as described by Goyal et al., challenges the assumption that metabolic dysfunction is always the initiating factor [<span>5</span>]. If it were, it should precede hepatic steatosis. However, steatosis can appear before insulin resistance, dyslipidemia, or hypertension, suggesting it may contribute to metabolic dysfunction. Alternatively, both may share early-life determinants, such as prenatal exposures, epigenetic modifications, or perinatal nutrition patterns. Resolving these uncertainties requires longitudinal studies tracking hepatic steatosis from early childhood and would rely on repeated measures of hepatic steatosis. Currently, the only validated non-invasive tool for measuring hepatic steatosis in children is MRI-PDFF [<span>6, 7</span>]. Integrating this technology would allow us to determine whether steatosis precedes, predicts, or parallels metabolic dysfunction and help identify windows for intervention and stratify risk.</p>\u0000<p>The inclusion of waist circumference in MASLD criteria aims to improve specificity by capturing central adiposity [<span>8</span>]. Malki et al. demonstrated that visceral adiposity is the strongest predictor of hepatic steatosis, supporting waist circumference as a potential surrogate [<span>9</span>]. However, our stu","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"90 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}