<p>The results of the large study of Tsai YN et al. [<span>1</span>] analysed the association of ALT elevation and HBsAg loss after cessation of Nucleos(t)ide analogue Nuc and concluded that ALT was not a factor for HBsAg loss. Several points in their discussion require clarification and further discussion:</p><p>First, it has already been well documented that “ALT elevation after Nuc cessation is not associated with higher HBsAg loss” [<span>2, 3</span>]. For example, a large study reported in 2018 [<span>2</span>] showed that the annual incidence of HBsAg loss was highest in those with normal ALT (sustained response 6.3%, virological relapse alone 2.4%), followed by clinical relapse (ALT> 2× ULN) without retreatment (1.7%) and lowest in those with relapse and retreatment (0.18%). Clearly, off-therapy HBsAg loss is highly associated with normal ALT.</p><p>Second, the cumulative HBsAg loss rate in the current study was 10-year 12.4%, which seems lower than 5-year 8.8% in their own previous prospective study [<span>4</span>] and apparently lower than 3-year 19% in a Caucasian cohort [<span>5</span>] and 13%–20.8% by year 6 in Asian cohorts [<span>2-4</span>]. One plausible explanation is that 17% of their patients were pretreatment HBeAg-positive, who are usually younger and likely have higher end-of-treatment (EOT) HBsAg levels, which were not reported in this study. The higher EOT HBsAg levels are only associated with a higher probability of relapse but not associated with relapse severity nor timing [<span>5</span>]. Naturally, higher EOT HBsAg levels would require a longer duration to achieve HBsAg seroclearance, thereby lowering the observed loss rate.</p><p>Third, our finding that off-therapy retreatment is inversely associated with HBsAg clearance [<span>2</span>] has been supported by other recent off-Nuc cohort studies [<span>3, 4, 6, 7</span>]. Importantly, the predictive value of combined HBsAg/ALT kinetics has been validated in a large study that no retreatment in patients with host-dominating flare is associated with a 3-yr HBsAg loss rate of 21%, in contrast to 0% in retreated counterparts [<span>8</span>]. With ‘safety first’ in mind, off-therapy monitoring of viral kinetics and tracking HBsAg levels throughout ALT elevations are vital for virus-dominating flare when prompt retreatment is necessary—especially for patients at risk of severe flare or hepatic decompensation [<span>9</span>].</p><p>Finally, the authors have misunderstood that selecting candidates for finite therapy relied on distinguishing ALT flares. The most important consideration in the strategy of finite Nuc therapy is a thorough discussion and evaluation right before the joint decision of the physician and patient. While accelerating HBsAg clearance—along with achieving optimal prognosis and reducing the risks of hepatocellular carcinoma or other adverse hepatic events [<span>10</span>]—is a shared ultimate therapeutic goal, vigilant follow-up and timely in
{"title":"Letter: No Biochemical Relapse Is Associated With the Highest Off-Therapy HBsAg Loss Rate","authors":"Wen-Juei Jeng, Yun-Fan Liaw","doi":"10.1111/apt.70061","DOIUrl":"https://doi.org/10.1111/apt.70061","url":null,"abstract":"<p>The results of the large study of Tsai YN et al. [<span>1</span>] analysed the association of ALT elevation and HBsAg loss after cessation of Nucleos(t)ide analogue Nuc and concluded that ALT was not a factor for HBsAg loss. Several points in their discussion require clarification and further discussion:</p>\u0000<p>First, it has already been well documented that “ALT elevation after Nuc cessation is not associated with higher HBsAg loss” [<span>2, 3</span>]. For example, a large study reported in 2018 [<span>2</span>] showed that the annual incidence of HBsAg loss was highest in those with normal ALT (sustained response 6.3%, virological relapse alone 2.4%), followed by clinical relapse (ALT> 2× ULN) without retreatment (1.7%) and lowest in those with relapse and retreatment (0.18%). Clearly, off-therapy HBsAg loss is highly associated with normal ALT.</p>\u0000<p>Second, the cumulative HBsAg loss rate in the current study was 10-year 12.4%, which seems lower than 5-year 8.8% in their own previous prospective study [<span>4</span>] and apparently lower than 3-year 19% in a Caucasian cohort [<span>5</span>] and 13%–20.8% by year 6 in Asian cohorts [<span>2-4</span>]. One plausible explanation is that 17% of their patients were pretreatment HBeAg-positive, who are usually younger and likely have higher end-of-treatment (EOT) HBsAg levels, which were not reported in this study. The higher EOT HBsAg levels are only associated with a higher probability of relapse but not associated with relapse severity nor timing [<span>5</span>]. Naturally, higher EOT HBsAg levels would require a longer duration to achieve HBsAg seroclearance, thereby lowering the observed loss rate.</p>\u0000<p>Third, our finding that off-therapy retreatment is inversely associated with HBsAg clearance [<span>2</span>] has been supported by other recent off-Nuc cohort studies [<span>3, 4, 6, 7</span>]. Importantly, the predictive value of combined HBsAg/ALT kinetics has been validated in a large study that no retreatment in patients with host-dominating flare is associated with a 3-yr HBsAg loss rate of 21%, in contrast to 0% in retreated counterparts [<span>8</span>]. With ‘safety first’ in mind, off-therapy monitoring of viral kinetics and tracking HBsAg levels throughout ALT elevations are vital for virus-dominating flare when prompt retreatment is necessary—especially for patients at risk of severe flare or hepatic decompensation [<span>9</span>].</p>\u0000<p>Finally, the authors have misunderstood that selecting candidates for finite therapy relied on distinguishing ALT flares. The most important consideration in the strategy of finite Nuc therapy is a thorough discussion and evaluation right before the joint decision of the physician and patient. While accelerating HBsAg clearance—along with achieving optimal prognosis and reducing the risks of hepatocellular carcinoma or other adverse hepatic events [<span>10</span>]—is a shared ultimate therapeutic goal, vigilant follow-up and timely in","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"89 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619028","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>Upadacitinib is an oral selective Janus kinase 1 (JAK 1) inhibitor, and its efficacy in inducing clinical and endoscopic remission has been demonstrated in randomised controlled trials in adult populations, both in Ulcerative colitis (UC) and Crohn's Disease (CD) [<span>1-3</span>]. Upadacitinib is currently used ‘off-label’ or without regulatory approval in children with refractory inflammatory bowel disease (IBD), exposing these patients to a medication without established safety, efficacy and dosing data.</p><p>To address this, Cohen et al. [<span>4</span>] conducted a retrospective multicentre cohort study, involving 30 international centres, to evaluate the effectiveness and safety of Upadacitinib as an induction therapy in 100 young patients with active CD. All of these patients had prior biologic exposure. At the end of the 8-week follow-up period, clinical response, clinical remission and corticosteroid/exclusive enteral nutrition-free clinical remission were achieved in 75%, 56% and 52% of patients, respectively. End of induction biomarkers including C-reactive protein normalised in 68% of patients, while faecal calprotectin normalised (< 150 μg/g) in 58% of patients. Drug durability was outlined, with 89% remaining on the medication over the induction period. Adverse events were reported in 24 patients, with 50% of them experiencing acne. Almost all patients (86%) received a dose of 45 mg/day over induction, the accepted dosing regimen in adult patients [<span>1-3</span>]. Importantly, early evidence of clinical response (at week 4) was a positive predictor for corticosteroid-free remission (CFR) at week 8 (odds ratio = 26 [95% confidence interval 5–139], <i>p</i> < 0.001). This rapid response may be a key attribute for paediatric patients as a steroid-sparing strategy.</p><p>A key limitation of the study is that this is an adolescent cohort, with a median (IQR) age of 15.8 (14.3–17.2) years. Younger children are often excluded from clinical trials in paediatrics; therefore, paediatric gastroenterologists depend on real-world evidence studies to generate efficacy data. The authors do make efforts to outline weight-based (mg/kg) and body surface area-based (mg/m<sup>2</sup>) dosing, but true pharmacokinetic (PK) and pharmacodynamic (PD) studies are needed to guide rational dosing regimens, especially in younger children. A further caveat is that steroid dosing/weaning plans were not standardised across the cohort, potentially influencing the reported outcomes at week 8. Lack of endoscopic outcome measures are recognised as a limitation by the authors. Whilst adverse events were relatively rare in this study, long-term prospective safety registries are required to identify incidence rates of rare and severe adverse events in children treated with Upadacitinib.</p><p>In conclusion, this real-world evidence study provides key insights into the clinical effectiveness of Upadacitinib for the induction of remission in paediatric CD
{"title":"Editorial: Upadacitinib—A Promising Induction Agent for Paediatric Crohn's Disease?","authors":"Vincenzo Stranges, Eileen Crowley","doi":"10.1111/apt.70076","DOIUrl":"https://doi.org/10.1111/apt.70076","url":null,"abstract":"<p>Upadacitinib is an oral selective Janus kinase 1 (JAK 1) inhibitor, and its efficacy in inducing clinical and endoscopic remission has been demonstrated in randomised controlled trials in adult populations, both in Ulcerative colitis (UC) and Crohn's Disease (CD) [<span>1-3</span>]. Upadacitinib is currently used ‘off-label’ or without regulatory approval in children with refractory inflammatory bowel disease (IBD), exposing these patients to a medication without established safety, efficacy and dosing data.</p>\u0000<p>To address this, Cohen et al. [<span>4</span>] conducted a retrospective multicentre cohort study, involving 30 international centres, to evaluate the effectiveness and safety of Upadacitinib as an induction therapy in 100 young patients with active CD. All of these patients had prior biologic exposure. At the end of the 8-week follow-up period, clinical response, clinical remission and corticosteroid/exclusive enteral nutrition-free clinical remission were achieved in 75%, 56% and 52% of patients, respectively. End of induction biomarkers including C-reactive protein normalised in 68% of patients, while faecal calprotectin normalised (< 150 μg/g) in 58% of patients. Drug durability was outlined, with 89% remaining on the medication over the induction period. Adverse events were reported in 24 patients, with 50% of them experiencing acne. Almost all patients (86%) received a dose of 45 mg/day over induction, the accepted dosing regimen in adult patients [<span>1-3</span>]. Importantly, early evidence of clinical response (at week 4) was a positive predictor for corticosteroid-free remission (CFR) at week 8 (odds ratio = 26 [95% confidence interval 5–139], <i>p</i> < 0.001). This rapid response may be a key attribute for paediatric patients as a steroid-sparing strategy.</p>\u0000<p>A key limitation of the study is that this is an adolescent cohort, with a median (IQR) age of 15.8 (14.3–17.2) years. Younger children are often excluded from clinical trials in paediatrics; therefore, paediatric gastroenterologists depend on real-world evidence studies to generate efficacy data. The authors do make efforts to outline weight-based (mg/kg) and body surface area-based (mg/m<sup>2</sup>) dosing, but true pharmacokinetic (PK) and pharmacodynamic (PD) studies are needed to guide rational dosing regimens, especially in younger children. A further caveat is that steroid dosing/weaning plans were not standardised across the cohort, potentially influencing the reported outcomes at week 8. Lack of endoscopic outcome measures are recognised as a limitation by the authors. Whilst adverse events were relatively rare in this study, long-term prospective safety registries are required to identify incidence rates of rare and severe adverse events in children treated with Upadacitinib.</p>\u0000<p>In conclusion, this real-world evidence study provides key insights into the clinical effectiveness of Upadacitinib for the induction of remission in paediatric CD","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"22 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608378","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}
Syed Tawassul Hassan, Muhammad Shaheer Bin Faheem, Muhammad Rehan Zahid
{"title":"Letter on “Autoimmune Hepatitis and Vitamin D Deficiency: A Nationwide Perspective”","authors":"Syed Tawassul Hassan, Muhammad Shaheer Bin Faheem, Muhammad Rehan Zahid","doi":"10.1111/apt.70030","DOIUrl":"https://doi.org/10.1111/apt.70030","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"21 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599829","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}
Juan Macias, Mario Frias, Juan Antonio Pineda, Miguel García‐Deltoro, Luis Miguel Real
<p>We thank Ng et al. [<span>1</span>] for their interest and comments on our research article [<span>2</span>]. They rightly point out the role of liver stiffness measurement (LSM) in the predictive value of the FAST score. Indeed, we proposed the use of LSM instead of the FAST score to assess the prognosis of PLWH with or at risk of NAFLD or MASLD in clinical practice, as a simpler and more convenient index. Moreover, LSM can be measured using different ultrasound-based elastography techniques, with similar diagnostic performance, which could be more accessible in certain settings. As Ng et al. also correctly comment, a two-step approach using FIB-4 to select PLWH for LSM could improve cost-effectiveness. However, FIB-4 was not an independent predictor of death after adjustment for other risk factors (last paragraph in the Results section) [<span>2</span>]. Therefore, we did not further evaluate FIB-4 to select PLWH at risk of NAFLD or MASLD.</p><p>The definition of MASLD in our paper was ‘… steatotic liver disease with one or more … cardiometabolic risk factors, without other concomitant causes of steatotic liver disease: …’, which agrees with the definition commented by Ng et al. We included in our analyses a group of PLWH that could be considered ‘at risk of MASLD’, but without MASLD at the date of entry in the cohort. Those were PLWH with one or more of cardiometabolic risk factors at inclusion in the cohort, regardless of the CAP value.</p><p>Ng et al. make the interesting point of the influence of antiretroviral therapy, namely the effect of tenofovir alafenamide (TAF) and integrase inhibitors (INI), on weight gain and, consequently, on liver disease progression. We agree that the role of TAF or INI-induced weight gain on liver disease deserves further evaluation. However, previous attempts to identify an effect of INI on adverse clinical outcomes have failed. The influence on cardiovascular outcomes of INI has been evaluated in the HIV-CAUSAL collaboration. The use of INI compared with other drug classes did not result in a clinical impact on cardiovascular outcomes [<span>3</span>]. The sample size that allowed reaching this conclusion, nearly 20,000 drug-naïve individuals and more than 40,000 drug-experienced individuals, is many times greater than the sample size of our study. In addition, previous cross-sectional reports in PLWH did not find associations between steatotic liver disease and antiretroviral therapy [<span>4, 5</span>].</p><p>We agree with the unmet needs in the field of steatotic liver disease in PLWH highlighted by Ng et al. First, there is a need for simple and cost-effective approaches to evaluate and manage liver health in PLWH. Second, while the role of antiretroviral therapy in steatotic liver disease needs elucidation, those with metabolic risk factors clearly should be evaluated and treated. Finally, PLWH without control of metabolic factors and increased LSM should be a priority for coming MASLD clinical tri
{"title":"Letter: Impact of Nonalcoholic Fatty Liver Disease on the Survival of People Living With HIV—Authors' Reply","authors":"Juan Macias, Mario Frias, Juan Antonio Pineda, Miguel García‐Deltoro, Luis Miguel Real","doi":"10.1111/apt.70082","DOIUrl":"https://doi.org/10.1111/apt.70082","url":null,"abstract":"<p>We thank Ng et al. [<span>1</span>] for their interest and comments on our research article [<span>2</span>]. They rightly point out the role of liver stiffness measurement (LSM) in the predictive value of the FAST score. Indeed, we proposed the use of LSM instead of the FAST score to assess the prognosis of PLWH with or at risk of NAFLD or MASLD in clinical practice, as a simpler and more convenient index. Moreover, LSM can be measured using different ultrasound-based elastography techniques, with similar diagnostic performance, which could be more accessible in certain settings. As Ng et al. also correctly comment, a two-step approach using FIB-4 to select PLWH for LSM could improve cost-effectiveness. However, FIB-4 was not an independent predictor of death after adjustment for other risk factors (last paragraph in the Results section) [<span>2</span>]. Therefore, we did not further evaluate FIB-4 to select PLWH at risk of NAFLD or MASLD.</p>\u0000<p>The definition of MASLD in our paper was ‘… steatotic liver disease with one or more … cardiometabolic risk factors, without other concomitant causes of steatotic liver disease: …’, which agrees with the definition commented by Ng et al. We included in our analyses a group of PLWH that could be considered ‘at risk of MASLD’, but without MASLD at the date of entry in the cohort. Those were PLWH with one or more of cardiometabolic risk factors at inclusion in the cohort, regardless of the CAP value.</p>\u0000<p>Ng et al. make the interesting point of the influence of antiretroviral therapy, namely the effect of tenofovir alafenamide (TAF) and integrase inhibitors (INI), on weight gain and, consequently, on liver disease progression. We agree that the role of TAF or INI-induced weight gain on liver disease deserves further evaluation. However, previous attempts to identify an effect of INI on adverse clinical outcomes have failed. The influence on cardiovascular outcomes of INI has been evaluated in the HIV-CAUSAL collaboration. The use of INI compared with other drug classes did not result in a clinical impact on cardiovascular outcomes [<span>3</span>]. The sample size that allowed reaching this conclusion, nearly 20,000 drug-naïve individuals and more than 40,000 drug-experienced individuals, is many times greater than the sample size of our study. In addition, previous cross-sectional reports in PLWH did not find associations between steatotic liver disease and antiretroviral therapy [<span>4, 5</span>].</p>\u0000<p>We agree with the unmet needs in the field of steatotic liver disease in PLWH highlighted by Ng et al. First, there is a need for simple and cost-effective approaches to evaluate and manage liver health in PLWH. Second, while the role of antiretroviral therapy in steatotic liver disease needs elucidation, those with metabolic risk factors clearly should be evaluated and treated. Finally, PLWH without control of metabolic factors and increased LSM should be a priority for coming MASLD clinical tri","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"3 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599374","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}
Rong-Xiang Ng, Raja Iskandar Shah Raja Azwa, Wah-Kheong Chan
<p>We read with great interest the cohort study by Macias and colleagues [<span>1</span>] demonstrating that liver stiffness measurement (LSM) and the FAST score independently predicted mortality in people living with HIV (PLWH). Nonalcoholic fatty liver disease (NAFLD) is an emerging concern in PLWH, with a prevalence ranging from 13% to 72%, associated with accelerated liver fibrosis and increased mortality, driven by metabolic risk factors like obesity, diabetes and antiretroviral therapy (ART)-related side effects like weight gain and insulin resistance [<span>1-3</span>]. Despite its clinical significance, PLWH are often excluded from NAFLD research or clinical trials, leading to gaps in understanding its natural history and optimal management [<span>4</span>].</p><p>From a methodological perspective, the predictive capability of the FAST score (calculated using CAP, AST and LSM) observed in this study likely stemmed primarily from its liver stiffness measurement component. Liver fibrosis has long been recognised as an important predictor of liver-related and all-cause mortality in patients with NAFLD [<span>5</span>]. The finding from this study highlighted the importance of assessment of liver fibrosis in PLHIV. On this note, we wonder if the author had looked at a two-step approach (i.e., liver stiffness measurement in persons with elevated fibrosis-4 score) for prognostication in their cohort of PLHIV, which could improve the cost-effectiveness of liver health screening in this population [<span>6</span>]. The authors have made a commendable effort presenting the findings of their study in line with the recent nomenclature change [<span>7</span>]. However, an analysis on PLHIV with steatotic liver disease based on CAP, following the exclusion of other causes of chronic liver disease and in the presence of at least one cardiometabolic criterion would be most consistent with the current definition of MASLD. Studies have shown that a significant proportion of people with at least one cardiometabolic criterion (used to define those with potential MASLD in this study) do not have steatotic liver disease [<span>8</span>].</p><p>From a clinical point of view, most PLHIV had suppressed HIV viral load in this cohort. At baseline, participants received integrase inhibitors (InI) (24%), protease inhibitors (PI) (39%) and non-nucleoside reverse transcriptase inhibitors (NNRTI) (32%). Notably, 78% transitioned to InI-based therapy during follow-up.</p><p>InI and tenofovir alafenamide (TAF), although improving HIV outcomes, are associated with weight gain and metabolic disturbances that can potentially contribute to liver disease progression [<span>9</span>]. Continuation of PI- and NNRTI-based regimens may also impact liver health [<span>10</span>]. On this note, the influence of ART regimen changes on liver disease trajectories deserves further exploration.</p><p>In conclusion, while the study by Macias and colleagues provided crucial insights i
{"title":"Letter: Impact of Nonalcoholic Fatty Liver Disease on the Survival of People Living With HIV","authors":"Rong-Xiang Ng, Raja Iskandar Shah Raja Azwa, Wah-Kheong Chan","doi":"10.1111/apt.70021","DOIUrl":"https://doi.org/10.1111/apt.70021","url":null,"abstract":"<p>We read with great interest the cohort study by Macias and colleagues [<span>1</span>] demonstrating that liver stiffness measurement (LSM) and the FAST score independently predicted mortality in people living with HIV (PLWH). Nonalcoholic fatty liver disease (NAFLD) is an emerging concern in PLWH, with a prevalence ranging from 13% to 72%, associated with accelerated liver fibrosis and increased mortality, driven by metabolic risk factors like obesity, diabetes and antiretroviral therapy (ART)-related side effects like weight gain and insulin resistance [<span>1-3</span>]. Despite its clinical significance, PLWH are often excluded from NAFLD research or clinical trials, leading to gaps in understanding its natural history and optimal management [<span>4</span>].</p>\u0000<p>From a methodological perspective, the predictive capability of the FAST score (calculated using CAP, AST and LSM) observed in this study likely stemmed primarily from its liver stiffness measurement component. Liver fibrosis has long been recognised as an important predictor of liver-related and all-cause mortality in patients with NAFLD [<span>5</span>]. The finding from this study highlighted the importance of assessment of liver fibrosis in PLHIV. On this note, we wonder if the author had looked at a two-step approach (i.e., liver stiffness measurement in persons with elevated fibrosis-4 score) for prognostication in their cohort of PLHIV, which could improve the cost-effectiveness of liver health screening in this population [<span>6</span>]. The authors have made a commendable effort presenting the findings of their study in line with the recent nomenclature change [<span>7</span>]. However, an analysis on PLHIV with steatotic liver disease based on CAP, following the exclusion of other causes of chronic liver disease and in the presence of at least one cardiometabolic criterion would be most consistent with the current definition of MASLD. Studies have shown that a significant proportion of people with at least one cardiometabolic criterion (used to define those with potential MASLD in this study) do not have steatotic liver disease [<span>8</span>].</p>\u0000<p>From a clinical point of view, most PLHIV had suppressed HIV viral load in this cohort. At baseline, participants received integrase inhibitors (InI) (24%), protease inhibitors (PI) (39%) and non-nucleoside reverse transcriptase inhibitors (NNRTI) (32%). Notably, 78% transitioned to InI-based therapy during follow-up.</p>\u0000<p>InI and tenofovir alafenamide (TAF), although improving HIV outcomes, are associated with weight gain and metabolic disturbances that can potentially contribute to liver disease progression [<span>9</span>]. Continuation of PI- and NNRTI-based regimens may also impact liver health [<span>10</span>]. On this note, the influence of ART regimen changes on liver disease trajectories deserves further exploration.</p>\u0000<p>In conclusion, while the study by Macias and colleagues provided crucial insights i","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"213 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599779","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}
Vilhelm Hjälte, Pär Myrelid, Henrik Hjortswang, Martin Rejler, Jonas F Ludvigsson, Anders Forss, Marcus Bendtsen, Ola Olén, Åsa H Everhov, Michael Eberhardson
Background: The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort.
Aim: To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease.
Methods: Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019. We stratified patients according to mean annual systemic corticosteroid (prednisolone equivalents) use in the last 5 years before surgery and compared Crohn's disease treatment after surgery.
Results: Some 19% (290/1565) of the patients had a mean annual corticosteroid use of ≥ 1000 mg up to 5 years pre-operatively, of whom 33% (97/290) had ≥ 2000 mg. Mean annual pre-operative CS use did not decrease during the study period (p = 0.35). Compared with patients with < 1000 mg/year pre-operative steroid use, patients with ≥ 1000 mg/year had more frequent previous bowel surgery (10% vs. 16%), exposure to biologics (29% vs. 38%), and immunomodulators (56% vs. 83%). Patients with a pre-operative mean annual corticosteroid use of ≥ 1000 mg had a mean annual reduction in corticosteroid use of 1354 mg after ileocaecal resection (1847 mg pre-operative versus 493 mg post-operative). During follow-up (median 6.8 years), exposure to biologics was similar among patients with different levels of pre-operative corticosteroid use.
Conclusion: Our results suggest a significant corticosteroid-sparing effect of ileocaecal resection in Crohn's disease patients with high pre-operative use, indicating a beneficial outcome of earlier surgical intervention. Despite increasing use of biologics, pre-operative corticosteroid use was consistent over the study period.
{"title":"Substantial Reduction of Systemic Corticosteroid Use After Primary Ileocaecal Resection in Swedish Patients With Crohn's Disease: A Population-Based Cohort Study.","authors":"Vilhelm Hjälte, Pär Myrelid, Henrik Hjortswang, Martin Rejler, Jonas F Ludvigsson, Anders Forss, Marcus Bendtsen, Ola Olén, Åsa H Everhov, Michael Eberhardson","doi":"10.1111/apt.70069","DOIUrl":"https://doi.org/10.1111/apt.70069","url":null,"abstract":"<p><strong>Background: </strong>The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort.</p><p><strong>Aim: </strong>To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease.</p><p><strong>Methods: </strong>Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019. We stratified patients according to mean annual systemic corticosteroid (prednisolone equivalents) use in the last 5 years before surgery and compared Crohn's disease treatment after surgery.</p><p><strong>Results: </strong>Some 19% (290/1565) of the patients had a mean annual corticosteroid use of ≥ 1000 mg up to 5 years pre-operatively, of whom 33% (97/290) had ≥ 2000 mg. Mean annual pre-operative CS use did not decrease during the study period (p = 0.35). Compared with patients with < 1000 mg/year pre-operative steroid use, patients with ≥ 1000 mg/year had more frequent previous bowel surgery (10% vs. 16%), exposure to biologics (29% vs. 38%), and immunomodulators (56% vs. 83%). Patients with a pre-operative mean annual corticosteroid use of ≥ 1000 mg had a mean annual reduction in corticosteroid use of 1354 mg after ileocaecal resection (1847 mg pre-operative versus 493 mg post-operative). During follow-up (median 6.8 years), exposure to biologics was similar among patients with different levels of pre-operative corticosteroid use.</p><p><strong>Conclusion: </strong>Our results suggest a significant corticosteroid-sparing effect of ileocaecal resection in Crohn's disease patients with high pre-operative use, indicating a beneficial outcome of earlier surgical intervention. Despite increasing use of biologics, pre-operative corticosteroid use was consistent over the study period.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595931","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}
Christy Riggott, Keeley M. Fairbrass, David J. Gracie, Alexander C. Ford
Common mental disorders, including anxiety and depression, are prevalent in patients with inflammatory bowel disease (IBD) and may be associated with adverse outcomes. However, whether increasing psychological co-morbidity, in combination with disease activity, exerts a cumulative effect on prognosis is uncertain.
{"title":"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":"Christy Riggott, Keeley M. Fairbrass, David J. Gracie, Alexander C. Ford","doi":"10.1111/apt.70068","DOIUrl":"https://doi.org/10.1111/apt.70068","url":null,"abstract":"Common mental disorders, including anxiety and depression, are prevalent in patients with inflammatory bowel disease (IBD) and may be associated with adverse outcomes. However, whether increasing psychological co-morbidity, in combination with disease activity, exerts a cumulative effect on prognosis is uncertain.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576381","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}
Cécile Cussac, Pauline Rivière, Romain Altwegg, Ludovic Caillo, Florian Poullenot, David Laharie, Cyrielle Gilletta, Guillaume Le Cosquer
This multicenter retrospective study examines 18 patients with difficult-to-treat inflammatory bowel diseases who received advanced combination treatment (ACT) with selective JAK1 inhibitors and biologics, totaling 11.8 patient-years of exposure. Treatment was discontinued in three patients due to adverse events. At 3 months, 77.8% achieved steroid-free clinical remission. The infection incidence rate was 25.4 per 100 person-years (95% CI: 6.47–69.19), though the wide confidence interval limits conclusions on safety differences with monotherapy. These findings highlight the importance of preventive measures, careful patient selection, and rigorous monitoring to mitigate infection risks associated with ACT.
{"title":"Safety of Advanced Combination Treatment With Selective JAK1 Inhibitors and Biological Therapies in Inflammatory Bowel Diseases: A Real World Experience","authors":"Cécile Cussac, Pauline Rivière, Romain Altwegg, Ludovic Caillo, Florian Poullenot, David Laharie, Cyrielle Gilletta, Guillaume Le Cosquer","doi":"10.1111/apt.70077","DOIUrl":"https://doi.org/10.1111/apt.70077","url":null,"abstract":"This multicenter retrospective study examines 18 patients with difficult-to-treat inflammatory bowel diseases who received advanced combination treatment (ACT) with selective JAK1 inhibitors and biologics, totaling 11.8 patient-years of exposure. Treatment was discontinued in three patients due to adverse events. At 3 months, 77.8% achieved steroid-free clinical remission. The infection incidence rate was 25.4 per 100 person-years (95% CI: 6.47–69.19), though the wide confidence interval limits conclusions on safety differences with monotherapy. These findings highlight the importance of preventive measures, careful patient selection, and rigorous monitoring to mitigate infection risks associated with ACT.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"2 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560787","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 appreciate the thoughtful comments on our letter discussing the role of iron metabolism in steatotic liver disease (SLD) [<span>1</span>]. We acknowledge their concerns regarding ferritin's role as an acute-phase reactant and the potential confounding effect of inflammation. While serum ferritin is influenced by systemic inflammation, it also reflects hepatic iron stores and metabolic stress, both of which may contribute to liver disease progression [<span>2</span>]. To further clarify this issue, we conducted an additional analysis incorporating C-reactive protein (CRP), an inflammatory marker that was available for 16,966 individuals in our cohort. When CRP was included as a covariate in our fully adjusted Cox proportional hazards model, the association between high ferritin and liver-related events (LREs) remained significant (HR 3.53, 95% CI: 2.10–5.91, <i>p</i> < 0.001). These findings suggest that ferritin is not merely an inflammatory marker but may independently reflect hepatic metabolic dysfunction or subclinical iron overload, contributing to an increased risk of LRE.</p><p>Regarding the use of gender-specific ferritin thresholds, we acknowledge the potential influence of racial and genetic differences in ferritin levels [<span>3</span>]. The cut-offs we applied (≥ 300 μg/L for men and ≥ 200 μg/L for women) are widely used in clinical practice and prior research evaluating hyperferritinemia in metabolic-associated liver disease [<span>4, 5</span>]. However, we recognise that dietary habits, genetic predispositions, and ethnic variability could significantly influence ferritin levels and their association with liver-related outcomes [<span>6</span>]. Future research should aim to refine ethnicity-specific thresholds and investigate the role of dietary patterns and genetic variations in modifying ferritin's impact on liver disease progression.</p><p>Shen and Xu also raised concerns about the exclusion of patients with iron deficiency. In our sensitivity analysis, we excluded individuals with a diagnosis of iron deficiency anaemia (IDA) and those who had received iron supplementation, as their ferritin levels could be influenced by factors unrelated to hepatic iron stores [<span>7</span>]. In our primary analysis, we did not exclude these individuals, but in our sensitivity analysis, we specifically excluded those diagnosed with IDA and those who had received iron supplementation to assess the independent impact of hyperferritinemia. A separate investigation into the impact of iron deficiency on LREs, particularly in patients with SLD, could be an important area for future research, as exploring the potential risks in this subgroup may provide further insights into iron metabolism and liver disease progression.</p><p>Lastly, we appreciate the suggestion to consider the impact of antidiabetic medications on iron metabolism. While metformin and other agents may influence hepcidin regulation [<span>8</span>], our study adjusted for d
{"title":"Letter: Iron Metabolism in SLD—A Complex Puzzle Yet to be Explored. Authors' Reply","authors":"Byeong Geun Song, Dong Hyun Sinn","doi":"10.1111/apt.70055","DOIUrl":"10.1111/apt.70055","url":null,"abstract":"<p>We appreciate the thoughtful comments on our letter discussing the role of iron metabolism in steatotic liver disease (SLD) [<span>1</span>]. We acknowledge their concerns regarding ferritin's role as an acute-phase reactant and the potential confounding effect of inflammation. While serum ferritin is influenced by systemic inflammation, it also reflects hepatic iron stores and metabolic stress, both of which may contribute to liver disease progression [<span>2</span>]. To further clarify this issue, we conducted an additional analysis incorporating C-reactive protein (CRP), an inflammatory marker that was available for 16,966 individuals in our cohort. When CRP was included as a covariate in our fully adjusted Cox proportional hazards model, the association between high ferritin and liver-related events (LREs) remained significant (HR 3.53, 95% CI: 2.10–5.91, <i>p</i> < 0.001). These findings suggest that ferritin is not merely an inflammatory marker but may independently reflect hepatic metabolic dysfunction or subclinical iron overload, contributing to an increased risk of LRE.</p><p>Regarding the use of gender-specific ferritin thresholds, we acknowledge the potential influence of racial and genetic differences in ferritin levels [<span>3</span>]. The cut-offs we applied (≥ 300 μg/L for men and ≥ 200 μg/L for women) are widely used in clinical practice and prior research evaluating hyperferritinemia in metabolic-associated liver disease [<span>4, 5</span>]. However, we recognise that dietary habits, genetic predispositions, and ethnic variability could significantly influence ferritin levels and their association with liver-related outcomes [<span>6</span>]. Future research should aim to refine ethnicity-specific thresholds and investigate the role of dietary patterns and genetic variations in modifying ferritin's impact on liver disease progression.</p><p>Shen and Xu also raised concerns about the exclusion of patients with iron deficiency. In our sensitivity analysis, we excluded individuals with a diagnosis of iron deficiency anaemia (IDA) and those who had received iron supplementation, as their ferritin levels could be influenced by factors unrelated to hepatic iron stores [<span>7</span>]. In our primary analysis, we did not exclude these individuals, but in our sensitivity analysis, we specifically excluded those diagnosed with IDA and those who had received iron supplementation to assess the independent impact of hyperferritinemia. A separate investigation into the impact of iron deficiency on LREs, particularly in patients with SLD, could be an important area for future research, as exploring the potential risks in this subgroup may provide further insights into iron metabolism and liver disease progression.</p><p>Lastly, we appreciate the suggestion to consider the impact of antidiabetic medications on iron metabolism. While metformin and other agents may influence hepcidin regulation [<span>8</span>], our study adjusted for d","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1270-1271"},"PeriodicalIF":6.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：