Mei Chin Lim, Ethan Joo Wei Quek, Talia Yi Hui Chan, Margaret Teng, Cheng Han Ng, Mirudhula Gnanavelou, Vincent L. Chen, Jonathan A. Fallowfield, Huimiao Zhang, Mazen Noureddin, Donghyun Ko, Benjamin Nah, Hirokazu Takahashi, Mohammad Shadab Siddiqui, Jimmy Che-To Lai, Karn Wijarnpreecha, Minghua Zheng, Rahul Kumar, Chitchai Rattananukrom, Alfred Kow, Nicholas Syn, Yuan-Cheng Wang, Atsushi Nakajima, An Tang, Jeong Min Lee, Daniel Q. Huang, Mark Muthiah, Claude B. Sirlin
Cirrhosis is the irreversible architectural endpoint of chronic liver disease and is the greatest risk factor for hepatocellular carcinoma (HCC). Despite its centrality in HCC management algorithms, there are no standardised morphologic criteria for diagnosing cirrhosis on cross-sectional imaging. Criteria used in clinical studies and clinical practice guidelines have not been reviewed systematically. We aim to assess cross-sectional imaging criteria in clinical practice guidelines and clinical studies.
{"title":"Systematic Review: Imaging-Based Morphological Criteria for Liver Cirrhosis—A Call to Standardise","authors":"Mei Chin Lim, Ethan Joo Wei Quek, Talia Yi Hui Chan, Margaret Teng, Cheng Han Ng, Mirudhula Gnanavelou, Vincent L. Chen, Jonathan A. Fallowfield, Huimiao Zhang, Mazen Noureddin, Donghyun Ko, Benjamin Nah, Hirokazu Takahashi, Mohammad Shadab Siddiqui, Jimmy Che-To Lai, Karn Wijarnpreecha, Minghua Zheng, Rahul Kumar, Chitchai Rattananukrom, Alfred Kow, Nicholas Syn, Yuan-Cheng Wang, Atsushi Nakajima, An Tang, Jeong Min Lee, Daniel Q. Huang, Mark Muthiah, Claude B. Sirlin","doi":"10.1111/apt.70629","DOIUrl":"https://doi.org/10.1111/apt.70629","url":null,"abstract":"Cirrhosis is the irreversible architectural endpoint of chronic liver disease and is the greatest risk factor for hepatocellular carcinoma (HCC). Despite its centrality in HCC management algorithms, there are no standardised morphologic criteria for diagnosing cirrhosis on cross-sectional imaging. Criteria used in clinical studies and clinical practice guidelines have not been reviewed systematically. We aim to assess cross-sectional imaging criteria in clinical practice guidelines and clinical studies.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507613","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}
<p>We thank Professor Taha for the insightful Editorial on our study addressing hepatocellular carcinoma (HCC) risk prediction after hepatitis B surface antigen (HBsAg) seroclearance [<span>1, 2</span>]. His comments appropriately highlight emerging priorities in the future management of HCC, particularly the need for refined risk stratification and stage-shifting surveillance strategies [<span>3</span>]. We are encouraged that the clinical relevance of our model, particularly its capacity to identify early-stage HCC, has been recognized.</p> <p>Our study was designed to address a clinically under-recognized population, patients achieving HBsAg seroclearance, who retain a measurable but heterogeneous residual risk of HCC [<span>4</span>]. By focusing specifically on this population, our model integrates six routinely available clinical parameters to provide a simple and clinically implementable tool for risk stratification. We acknowledge that the CAMP-B model has also demonstrated robust performance in this setting [<span>5</span>]. Our model builds upon these prior efforts by further refining risk stratification in this population and offering complementary clinical value.</p> <p>Importantly, the limitations highlighted in the Editorial also point towards several directions for future research. The absence of detailed viral factors, performance status, and potentially protective exposures reflects inherent constraints of real-world retrospective datasets, but also underscores the need for prospective cohorts with more comprehensive phenotyping. In the context of HBsAg seroclearance, viral replication is typically minimal or undetectable, as serum HBsAg levels are thought to reflect intrahepatic cccDNA transcriptional activity and HBV DNA integration-derived transcripts [<span>6</span>]. However, this suggests that traditional virological markers may have limited ability to capture the underlying biological heterogeneity in this setting, thereby necessitating the exploration of alternative biomarkers. Importantly, HBV DNA integration can persist within the host genome even after effective viral suppression, and the burden of viral integration—particularly the number of integration breakpoints—has been shown to correlate with the likelihood of HBsAg loss [<span>7</span>]. These findings highlight that integration-related heterogeneity may contribute to differential clinical outcomes following seroclearance. In addition, performance status, such as Eastern Cooperative Oncology Group score, has been well established as a prognostic factor in oncology [<span>8</span>]. However, in real-world outpatient cohorts with regular follow-up, there may be an inherent selection towards patients with preserved functional status. Future studies are therefore warranted to clarify the role of functional status in both HBsAg seroclearance and subsequent HCC risk. Furthermore, metabolic comorbidities, including diabetes, metabolic associated fatty liver disease, an
{"title":"Editorial: Predicting Hepatocellular Cancer in Clinical Practice. Authors' Reply","authors":"Shuaibing Ying, Yunqing Qiu, Yan Lou","doi":"10.1111/apt.70647","DOIUrl":"https://doi.org/10.1111/apt.70647","url":null,"abstract":"<p>We thank Professor Taha for the insightful Editorial on our study addressing hepatocellular carcinoma (HCC) risk prediction after hepatitis B surface antigen (HBsAg) seroclearance [<span>1, 2</span>]. His comments appropriately highlight emerging priorities in the future management of HCC, particularly the need for refined risk stratification and stage-shifting surveillance strategies [<span>3</span>]. We are encouraged that the clinical relevance of our model, particularly its capacity to identify early-stage HCC, has been recognized.</p>\u0000<p>Our study was designed to address a clinically under-recognized population, patients achieving HBsAg seroclearance, who retain a measurable but heterogeneous residual risk of HCC [<span>4</span>]. By focusing specifically on this population, our model integrates six routinely available clinical parameters to provide a simple and clinically implementable tool for risk stratification. We acknowledge that the CAMP-B model has also demonstrated robust performance in this setting [<span>5</span>]. Our model builds upon these prior efforts by further refining risk stratification in this population and offering complementary clinical value.</p>\u0000<p>Importantly, the limitations highlighted in the Editorial also point towards several directions for future research. The absence of detailed viral factors, performance status, and potentially protective exposures reflects inherent constraints of real-world retrospective datasets, but also underscores the need for prospective cohorts with more comprehensive phenotyping. In the context of HBsAg seroclearance, viral replication is typically minimal or undetectable, as serum HBsAg levels are thought to reflect intrahepatic cccDNA transcriptional activity and HBV DNA integration-derived transcripts [<span>6</span>]. However, this suggests that traditional virological markers may have limited ability to capture the underlying biological heterogeneity in this setting, thereby necessitating the exploration of alternative biomarkers. Importantly, HBV DNA integration can persist within the host genome even after effective viral suppression, and the burden of viral integration—particularly the number of integration breakpoints—has been shown to correlate with the likelihood of HBsAg loss [<span>7</span>]. These findings highlight that integration-related heterogeneity may contribute to differential clinical outcomes following seroclearance. In addition, performance status, such as Eastern Cooperative Oncology Group score, has been well established as a prognostic factor in oncology [<span>8</span>]. However, in real-world outpatient cohorts with regular follow-up, there may be an inherent selection towards patients with preserved functional status. Future studies are therefore warranted to clarify the role of functional status in both HBsAg seroclearance and subsequent HCC risk. Furthermore, metabolic comorbidities, including diabetes, metabolic associated fatty liver disease, an","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"44 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507614","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}
<p>Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, with approximately 900,000 new cases and 830,000 deaths per year, making it the sixth most common cancer and the third most lethal cancer worldwide [<span>1, 2</span>]. Using both alpha-fetoprotein (AFP) measurement and ultrasound scans to screen patients in dedicated cirrhosis clinics has yielded a steady rise in the incidence of HCC but without necessarily improving the mortality outcomes [<span>3</span>]. Besides cirrhosis, other key risk factors for HCC include chronic viral hepatitis, haemochromatosis and, increasingly, metabolic dysfunction-associated steatotic liver disease, MASLD [<span>2, 3</span>].</p> <p>It is, therefore, understandable that attempts continue to be made to predict HCC and identify it in its early and potentially treatable stages. Predictions have involved the analysis of demographic, aetiological, laboratory and imaging findings. Machine Learning (AI) Models have been tested, such as the Convolutional Neural Networks (CNN) and Random Survival Forests (RSF), which are used to analyse electronic health records, focusing on age, gender and comorbidities, often without using laboratory results. Risk Scores and biomarkers were also used including the GALAD Score (combining Gender, Age and three biomarkers [AFP, AFP-L3, DCP] for high accuracy); aMAP Score (uses Age, Male gender, Albumin-bilirubin and Platelets); and AAAPD-C Score (focusing on patients with hepatitis C after treatment [Age, Albumin, AFP, Platelets, Diabetes status]) [<span>4-8</span>].</p> <p>Despite the existence of this multitude of scoring systems, in this issue of <i>AP&T</i>, Dr. Ying and colleagues shift the focus to the prediction of HCC after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B (CHB) [<span>9</span>]. This is justifiable by the ongoing common nature of hepatitis B, affecting 254 million people globally, and the still rising death rates from viral hepatitis despite recent advances in prevention and management [<span>10</span>]. Other risk models have already been proposed for the prediction of HCC development, including PAGE-B, modified PAGE-B (mPAGE-B) for CHB and Yang's model, CAMP-B model for HBsAg seroclearance patients; but as Dr. Ying and colleagues point out, most existing models were derived from cohorts of patients with ongoing CHB infection, and their applicability to patients who have achieved HBsAg seroclearance remains uncertain. The authors found six independent risk factors capable of predicting HCC occurrence, including age ≥ 50 years, male, platelet count ≤ 150 × 10<sup>9</sup>/L, albumin level ≤ 44 g/L, with cirrhosis at HBsAg seroclearance and AVT-induced HBsAg seroclearance. They concluded that their six-factor model enables risk stratification among patients achieving HBsAg seroclearance and may assist in informing surveillance strategies in clinical practice. Their data do not adjus
{"title":"Editorial: Predicting Hepatocellular Cancer in Clinical Practice","authors":"Ali S. Taha","doi":"10.1111/apt.70644","DOIUrl":"https://doi.org/10.1111/apt.70644","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, with approximately 900,000 new cases and 830,000 deaths per year, making it the sixth most common cancer and the third most lethal cancer worldwide [<span>1, 2</span>]. Using both alpha-fetoprotein (AFP) measurement and ultrasound scans to screen patients in dedicated cirrhosis clinics has yielded a steady rise in the incidence of HCC but without necessarily improving the mortality outcomes [<span>3</span>]. Besides cirrhosis, other key risk factors for HCC include chronic viral hepatitis, haemochromatosis and, increasingly, metabolic dysfunction-associated steatotic liver disease, MASLD [<span>2, 3</span>].</p>\u0000<p>It is, therefore, understandable that attempts continue to be made to predict HCC and identify it in its early and potentially treatable stages. Predictions have involved the analysis of demographic, aetiological, laboratory and imaging findings. Machine Learning (AI) Models have been tested, such as the Convolutional Neural Networks (CNN) and Random Survival Forests (RSF), which are used to analyse electronic health records, focusing on age, gender and comorbidities, often without using laboratory results. Risk Scores and biomarkers were also used including the GALAD Score (combining Gender, Age and three biomarkers [AFP, AFP-L3, DCP] for high accuracy); aMAP Score (uses Age, Male gender, Albumin-bilirubin and Platelets); and AAAPD-C Score (focusing on patients with hepatitis C after treatment [Age, Albumin, AFP, Platelets, Diabetes status]) [<span>4-8</span>].</p>\u0000<p>Despite the existence of this multitude of scoring systems, in this issue of <i>AP&T</i>, Dr. Ying and colleagues shift the focus to the prediction of HCC after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B (CHB) [<span>9</span>]. This is justifiable by the ongoing common nature of hepatitis B, affecting 254 million people globally, and the still rising death rates from viral hepatitis despite recent advances in prevention and management [<span>10</span>]. Other risk models have already been proposed for the prediction of HCC development, including PAGE-B, modified PAGE-B (mPAGE-B) for CHB and Yang's model, CAMP-B model for HBsAg seroclearance patients; but as Dr. Ying and colleagues point out, most existing models were derived from cohorts of patients with ongoing CHB infection, and their applicability to patients who have achieved HBsAg seroclearance remains uncertain. The authors found six independent risk factors capable of predicting HCC occurrence, including age ≥ 50 years, male, platelet count ≤ 150 × 10<sup>9</sup>/L, albumin level ≤ 44 g/L, with cirrhosis at HBsAg seroclearance and AVT-induced HBsAg seroclearance. They concluded that their six-factor model enables risk stratification among patients achieving HBsAg seroclearance and may assist in informing surveillance strategies in clinical practice. Their data do not adjus","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"43 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506732","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}
<p>Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction featuring recurrent abdominal pain or discomfort in conjunction with altered bowel habit [<span>1</span>]. Diet is a mainstay of IBS management, with first-line dietary advice being the NICE diet that recommends regular meal size and frequency; maintaining hydration; restricting fatty, spicy and processed foods; and limiting caffeine and alcohol.</p> <p>Second line dietary advice is for the low FODMAP diet (LFD), the most extensively researched whole diet intervention in IBS. FODMAPs are fermentable oligosaccharides, disaccharides, monosaccharides and polyols, some of which increase small intestinal luminal water and some of which undergo colonic fermentation to produce gas that can contribute to IBS symptoms in those with visceral hypersensitivity [<span>2</span>].</p> <p>The LFD has numerous limitations, including being restrictive for patients, risking excessive or prolonged restriction in some, and can impact the gut microbiome [<span>3</span>]. The LFD therefore requires expert advice and management from a dietitian, which can be challenging in some healthcare settings for a prevalent disorder commonly managed in the community [<span>3</span>].</p> <p>In this issue of <i>Alimentary Pharmacology & Therapeutics</i>, Garcia-Cedillo and colleagues [<span>4</span>] present data from a randomised clinical trial of a personalised-LFD. The personalised-LFD differed from the full LFD in two ways: first, it only restricted FODMAPs that appeared to result in symptom exacerbation from prospective recording, and second, only major sources of the relevant FODMAPs were reduced and even then only by approximately 50%. The goal of the personalised-LFD was to achieve the therapeutic benefits of the full LFD while maintaining dietary diversity [<span>4</span>].</p> <p>In this randomised clinical trial, there was no difference in the numbers experiencing adequate relief between the personalised-LFD (54.5%) and NICE diet (41.2%, <i>p</i> = 0.33) [<span>4</span>]. Response rates to the personalised-LFD (54.5%) were in keeping with some trials of the full LFD that report responses including 52% [<span>5</span>], 55% [<span>6</span>] and 57% [<span>7</span>]. Large reductions in energy intake (circa −750 kcal/d) were identified in both groups that do not reflect evidence from other studies, at least some of which may represent under-reporting due to social desirability bias [<span>8</span>].</p> <p>This is not the first study to investigate modification to the LFD. In a small feeding study, blanket restriction only of oligosaccharides (fructans and galacto-oligosaccharides, termed ‘FODMAP simple’) led to no difference in symptom response compared with the full LFD [<span>9</span>].</p> <p>In the current study [<span>4</span>], two active dietary interventions are shown to be no different, which is different from proving they are the same (which would require an equivalence trial) or no wor
{"title":"Editorial: Personalising the Low FODMAP Diet to Achieve Therapeutic Benefit Whilst Reducing Burden and Maintaining Dietary Diversity in Irritable Bowel Syndrome","authors":"Kevin Whelan","doi":"10.1111/apt.70626","DOIUrl":"https://doi.org/10.1111/apt.70626","url":null,"abstract":"<p>Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction featuring recurrent abdominal pain or discomfort in conjunction with altered bowel habit [<span>1</span>]. Diet is a mainstay of IBS management, with first-line dietary advice being the NICE diet that recommends regular meal size and frequency; maintaining hydration; restricting fatty, spicy and processed foods; and limiting caffeine and alcohol.</p>\u0000<p>Second line dietary advice is for the low FODMAP diet (LFD), the most extensively researched whole diet intervention in IBS. FODMAPs are fermentable oligosaccharides, disaccharides, monosaccharides and polyols, some of which increase small intestinal luminal water and some of which undergo colonic fermentation to produce gas that can contribute to IBS symptoms in those with visceral hypersensitivity [<span>2</span>].</p>\u0000<p>The LFD has numerous limitations, including being restrictive for patients, risking excessive or prolonged restriction in some, and can impact the gut microbiome [<span>3</span>]. The LFD therefore requires expert advice and management from a dietitian, which can be challenging in some healthcare settings for a prevalent disorder commonly managed in the community [<span>3</span>].</p>\u0000<p>In this issue of <i>Alimentary Pharmacology & Therapeutics</i>, Garcia-Cedillo and colleagues [<span>4</span>] present data from a randomised clinical trial of a personalised-LFD. The personalised-LFD differed from the full LFD in two ways: first, it only restricted FODMAPs that appeared to result in symptom exacerbation from prospective recording, and second, only major sources of the relevant FODMAPs were reduced and even then only by approximately 50%. The goal of the personalised-LFD was to achieve the therapeutic benefits of the full LFD while maintaining dietary diversity [<span>4</span>].</p>\u0000<p>In this randomised clinical trial, there was no difference in the numbers experiencing adequate relief between the personalised-LFD (54.5%) and NICE diet (41.2%, <i>p</i> = 0.33) [<span>4</span>]. Response rates to the personalised-LFD (54.5%) were in keeping with some trials of the full LFD that report responses including 52% [<span>5</span>], 55% [<span>6</span>] and 57% [<span>7</span>]. Large reductions in energy intake (circa −750 kcal/d) were identified in both groups that do not reflect evidence from other studies, at least some of which may represent under-reporting due to social desirability bias [<span>8</span>].</p>\u0000<p>This is not the first study to investigate modification to the LFD. In a small feeding study, blanket restriction only of oligosaccharides (fructans and galacto-oligosaccharides, termed ‘FODMAP simple’) led to no difference in symptom response compared with the full LFD [<span>9</span>].</p>\u0000<p>In the current study [<span>4</span>], two active dietary interventions are shown to be no different, which is different from proving they are the same (which would require an equivalence trial) or no wor","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"17 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507612","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}
Sydney Pomenti,Annabel Gerber,David Katzka,Michael Camilleri,Chin Hur
{"title":"Letter: From Safety to Precision-Optimising the Use of GLP-1 Receptor Agonists in Gastroenterology: Authors' Reply.","authors":"Sydney Pomenti,Annabel Gerber,David Katzka,Michael Camilleri,Chin Hur","doi":"10.1111/apt.70547","DOIUrl":"https://doi.org/10.1111/apt.70547","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"08 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502500","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}
Luke D Tyson,Stephen Atkinson,Benjamin H Mullish,Alexandros Pechlivanis,Michael Allison,Andrew Austin,Katie Chappell,Stuart J Forbes,Ewan H Forrest,Alastair M Kilpatrick,Tong Liu,Laura Martinez-Gili,Steven Masson,Mark J W McPhail,Joao Nunes,Paul Richardson,Daniel Rodrigo-Torres,Stephen D Ryder,Mark Wright,Vishal C Patel,Nikhil Vergis,Elaine Holmes,Mark R Thursz
BACKGROUNDAlcohol-related hepatitis (AH) is characterised by acute cholestasis and liver dysfunction in patients consuming alcohol.AIMSTo define the bile acid (BA) profile in AH compared to decompensated alcohol-related cirrhosis (DC) and healthy controls (HC).METHODSSerum and faecal BAs were measured by UHPLC-MS; FGF19 by ELISA; RNA-sequencing data obtained from liver biopsies; serum cytokines and growth factors quantified by multiplex immunoassay. Hepatocyte growth factor (HGF) was applied to primary human hepatocytes (PHH) and BA transporter expression was assessed by RT-qPCR.RESULTSIn two cohorts (Cohort 1: 164 AH, 63 DC, 36 HC; Cohort 2: 94 AH, 175 DC, 72 HC), total serum BAs were highest in AH (median concentration 186.0 μM vs. 64.5 DC vs. 5.0 HC), driven by elevated conjugated primary BAs (182.0 μM vs. 54.0 vs. 2.2). Unconjugated primary BAs were highest in DC. Serum BAs distinguished AH from DC (Cohort 1 AUROC 0.964; Cohort 2 0.922; p < 0.001). Faecal BAs were reduced in AH (0.47 mg/g vs. 1.11 DC vs. 2.64 HC); serum FGF19 elevated (5835 pg/mL AH vs. 865 jaundiced DC [bilirubin > 80 μmol/L]). Serum conjugated BAs correlated negatively with NTCP expression (n = 25, Spearman's rho -0.432, p = 0.031). CYP7A1 was below the limit of detection. HGF was elevated in AH (7899 pg/mL vs. 2607 DC, p < 0.001). HGF treatment reduced PHH BSEP expression.CONCLUSIONSerum conjugated primary BAs accumulate in AH. Elevated HGF may detrimentally affect the hepatoprotective adaptive reduction in NTCP/increase in BSEP seen in cholestasis, contributing to the AH BA profile.
背景：酒精相关性肝炎（AH）以急性胆汁淤积和肝功能障碍为特征。目的：与失代偿性酒精相关性肝硬化（DC）和健康对照组（HC）比较，确定AH患者的胆汁酸（BA）谱。方法采用高效液相色谱-质谱法测定血清和粪便中的BAs；ELISA检测FGF19；肝活检获得的rna测序数据；多重免疫分析法定量测定血清细胞因子和生长因子。将肝细胞生长因子（HGF）应用于原代人肝细胞（PHH）， RT-qPCR检测BA转运蛋白的表达。结果在两个队列（队列1:164 AH， 63 DC, 36 HC；队列2:94 AH， 175 DC, 72 HC）中，AH患者的血清总BAs最高（中位浓度186.0 μM vs. 64.5 DC vs. 5.0 HC），这是由升高的共轭初级BAs （182.0 μM vs. 54.0 vs. 2.2）驱动的。未结合的初级BAs在DC中含量最高。血清BAs可区分AH和DC（队列1 AUROC 0.964；队列2 0.922;p 80 μmol/L）。血清共轭BAs与NTCP表达呈负相关（n = 25, Spearman’s ρ -0.432, p = 0.031）。CYP7A1低于检出限。HGF在AH组升高（7899 pg/mL vs. 2607 DC, p < 0.001）。HGF处理降低了PHH BSEP的表达。结论血清结合原发性BAs在AH中蓄积。升高的HGF可能会对肝保护性的NTCP适应性降低/胆汁淤滞中BSEP的增加产生不利影响，从而导致AH - BA。
{"title":"Disordered Bile Acid Metabolism in Alcohol-Related Hepatitis.","authors":"Luke D Tyson,Stephen Atkinson,Benjamin H Mullish,Alexandros Pechlivanis,Michael Allison,Andrew Austin,Katie Chappell,Stuart J Forbes,Ewan H Forrest,Alastair M Kilpatrick,Tong Liu,Laura Martinez-Gili,Steven Masson,Mark J W McPhail,Joao Nunes,Paul Richardson,Daniel Rodrigo-Torres,Stephen D Ryder,Mark Wright,Vishal C Patel,Nikhil Vergis,Elaine Holmes,Mark R Thursz","doi":"10.1111/apt.70616","DOIUrl":"https://doi.org/10.1111/apt.70616","url":null,"abstract":"BACKGROUNDAlcohol-related hepatitis (AH) is characterised by acute cholestasis and liver dysfunction in patients consuming alcohol.AIMSTo define the bile acid (BA) profile in AH compared to decompensated alcohol-related cirrhosis (DC) and healthy controls (HC).METHODSSerum and faecal BAs were measured by UHPLC-MS; FGF19 by ELISA; RNA-sequencing data obtained from liver biopsies; serum cytokines and growth factors quantified by multiplex immunoassay. Hepatocyte growth factor (HGF) was applied to primary human hepatocytes (PHH) and BA transporter expression was assessed by RT-qPCR.RESULTSIn two cohorts (Cohort 1: 164 AH, 63 DC, 36 HC; Cohort 2: 94 AH, 175 DC, 72 HC), total serum BAs were highest in AH (median concentration 186.0 μM vs. 64.5 DC vs. 5.0 HC), driven by elevated conjugated primary BAs (182.0 μM vs. 54.0 vs. 2.2). Unconjugated primary BAs were highest in DC. Serum BAs distinguished AH from DC (Cohort 1 AUROC 0.964; Cohort 2 0.922; p < 0.001). Faecal BAs were reduced in AH (0.47 mg/g vs. 1.11 DC vs. 2.64 HC); serum FGF19 elevated (5835 pg/mL AH vs. 865 jaundiced DC [bilirubin > 80 μmol/L]). Serum conjugated BAs correlated negatively with NTCP expression (n = 25, Spearman's rho -0.432, p = 0.031). CYP7A1 was below the limit of detection. HGF was elevated in AH (7899 pg/mL vs. 2607 DC, p < 0.001). HGF treatment reduced PHH BSEP expression.CONCLUSIONSerum conjugated primary BAs accumulate in AH. Elevated HGF may detrimentally affect the hepatoprotective adaptive reduction in NTCP/increase in BSEP seen in cholestasis, contributing to the AH BA profile.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495170","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}
Adrielly Martins,Nidah S Khakoo,Christophe Corpechot,Alexandra Rousseau,John M Reynolds,Andreas E Kremer,M Hassan Murad,Shahnaz Sultan,Cynthia Levy
BACKGROUND AND AIMSPruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator-activated receptor (PPAR) agonists are promising second-line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta-analysis to evaluate the efficacy of PPAR agonists on pruritus and health-related quality of life (HRQoL) in PBC.METHODSWe systematically searched for randomised placebo-controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC-40 total score. Pooled estimates were calculated using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CI).RESULTSFive RCTs evaluating bezafibrate, elafibranor and seladelpar (n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate-to-severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, -1.38; 95% CI, -2.62 to -0.14), 6 months (MD, -1.13; 95% CI, -1.98 to -0.27) and 12 months (MD, -1.73; 95% CI, -3.00 to -0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at one or more time points. While improvements were also noted in PBC-40 itch-domain and 5D-itch score, an impact on overall HRQoL as reflected by PBC-40 total score could not be demonstrated, with a lower level of certainty.CONCLUSIONSPPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate-to-severe symptoms and consistently improve itch-specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom-focused endpoints in future PBC trials.
{"title":"Meta-Analysis: PPAR Agonists for Pruritus and Quality of Life in Primary Biliary Cholangitis.","authors":"Adrielly Martins,Nidah S Khakoo,Christophe Corpechot,Alexandra Rousseau,John M Reynolds,Andreas E Kremer,M Hassan Murad,Shahnaz Sultan,Cynthia Levy","doi":"10.1111/apt.70634","DOIUrl":"https://doi.org/10.1111/apt.70634","url":null,"abstract":"BACKGROUND AND AIMSPruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator-activated receptor (PPAR) agonists are promising second-line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta-analysis to evaluate the efficacy of PPAR agonists on pruritus and health-related quality of life (HRQoL) in PBC.METHODSWe systematically searched for randomised placebo-controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC-40 total score. Pooled estimates were calculated using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CI).RESULTSFive RCTs evaluating bezafibrate, elafibranor and seladelpar (n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate-to-severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, -1.38; 95% CI, -2.62 to -0.14), 6 months (MD, -1.13; 95% CI, -1.98 to -0.27) and 12 months (MD, -1.73; 95% CI, -3.00 to -0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at one or more time points. While improvements were also noted in PBC-40 itch-domain and 5D-itch score, an impact on overall HRQoL as reflected by PBC-40 total score could not be demonstrated, with a lower level of certainty.CONCLUSIONSPPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate-to-severe symptoms and consistently improve itch-specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom-focused endpoints in future PBC trials.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495186","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}
BACKGROUNDPrediction of hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) after hepatitis B surface antigen (HBsAg) seroclearance is important for optimizing surveillance strategies.AIMThis study aimed to identify independent risk factors of HCC after HBsAg seroclearance and to develop and validate a risk prediction model.METHODSA total of 6536 CHB patients who achieved HBsAg seroclearance between January 2006 and June 2025 were retrospectively screened, with 3852 patients meeting the criteria for final analysis. A predictive model was developed via multivariate Cox proportional hazards regression analysis, with discrimination assessed using Harrell's C-index and time-dependent receiver operating characteristic curve area under the curve (AUC). Internal validation of the model was conducted through bootstrap resampling analysis.RESULTSDuring 21,711 person-years of follow-up, 128 patients (3.3%) developed HCC (incidence rate: 0.59% per year). Multivariable analysis identified age, male sex, cirrhosis, antiviral therapy (AVT)-induced seroclearance and lower levels of platelets and albumin as independent predictors of HCC. The six independent variables were used for constructing the novel prediction model. Harrell's C-index of the model was 0.766. The novel model has a good predictive ability for HCC risk in the 3-year (AUC = 0.785), 5-year (AUC = 0.775) and 10-year (AUC = 0.830) with similar discriminative performance observed in internal validation.CONCLUSIONSThe independent risk factors of HCC occurrence are age ≥ 50 years, male, platelet count≤ 150 × 109/L, albumin level ≤ 44 g/L, with cirrhosis at HBsAg seroclearance and AVT-induced HBsAg seroclearance. Our six-factor model enables risk stratification among patients achieving HBsAg seroclearance and may assist in informing surveillance strategies in clinical practice.
{"title":"Risk Prediction of Hepatocellular Carcinoma After Hepatitis B Surface Antigen Seroclearance in Patients With Chronic Hepatitis B.","authors":"Shuaibing Ying,Jinyao Dai,Qiudan Zhang,Yujing Wang,Yina Yu,Zhijuan Zhang,Shaohua Dong,Yichun Zhang,Haoyang Hu,Yuqi Hong,Yi Liu,Yuqi Guo,Haomin Yan,Yunqing Qiu,Yan Lou","doi":"10.1111/apt.70637","DOIUrl":"https://doi.org/10.1111/apt.70637","url":null,"abstract":"BACKGROUNDPrediction of hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) after hepatitis B surface antigen (HBsAg) seroclearance is important for optimizing surveillance strategies.AIMThis study aimed to identify independent risk factors of HCC after HBsAg seroclearance and to develop and validate a risk prediction model.METHODSA total of 6536 CHB patients who achieved HBsAg seroclearance between January 2006 and June 2025 were retrospectively screened, with 3852 patients meeting the criteria for final analysis. A predictive model was developed via multivariate Cox proportional hazards regression analysis, with discrimination assessed using Harrell's C-index and time-dependent receiver operating characteristic curve area under the curve (AUC). Internal validation of the model was conducted through bootstrap resampling analysis.RESULTSDuring 21,711 person-years of follow-up, 128 patients (3.3%) developed HCC (incidence rate: 0.59% per year). Multivariable analysis identified age, male sex, cirrhosis, antiviral therapy (AVT)-induced seroclearance and lower levels of platelets and albumin as independent predictors of HCC. The six independent variables were used for constructing the novel prediction model. Harrell's C-index of the model was 0.766. The novel model has a good predictive ability for HCC risk in the 3-year (AUC = 0.785), 5-year (AUC = 0.775) and 10-year (AUC = 0.830) with similar discriminative performance observed in internal validation.CONCLUSIONSThe independent risk factors of HCC occurrence are age ≥ 50 years, male, platelet count≤ 150 × 109/L, albumin level ≤ 44 g/L, with cirrhosis at HBsAg seroclearance and AVT-induced HBsAg seroclearance. Our six-factor model enables risk stratification among patients achieving HBsAg seroclearance and may assist in informing surveillance strategies in clinical practice.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"92 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502507","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: Thiopurines the Silent Workhorse for Many Patients After a Flare of Ulcerative Colitis. Authors' Reply","authors":"Ankit Kumar, Amol Patil, Vishal Sharma","doi":"10.1111/apt.70624","DOIUrl":"https://doi.org/10.1111/apt.70624","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"231 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478122","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}
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