Alimentary Pharmacology & Therapeutics最新文献

{"title":"Association Between Elevation of Serum Alanine Aminotransferase and HBsAg Seroclearance After Nucleos(t)ide Analog Withdrawal","authors":"Ying-Nan Tsai, Jia-Ling Wu, Cheng-Hao Tseng, Shang-Chen Tseng, Chih-Lung Hung, Mindie H. Nguyen, Jaw-Town Lin, Yao-Chun Hsu","doi":"10.1111/apt.18515","DOIUrl":"https://doi.org/10.1111/apt.18515","url":null,"abstract":"Alanine aminotransferase (ALT) frequently elevates in chronic hepatitis B patients stopping nucleos(t)ide analogs (NAs).","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"19 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050833","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: Development and Validation of a Multimodal Machine Learning Model for Diagnosing and Assessing Risk of Crohn's Disease in Patients With Perianal Fistula","authors":"Alyssa M. Parian, David A. Schwartz","doi":"10.1111/apt.18490","DOIUrl":"10.1111/apt.18490","url":null,"abstract":"<p>Perianal fistulising Crohn's disease (PFCD) is found in up to 25% of patients with CD and is associated with decreased quality of life and increased healthcare expenditures. Approximately 11.5% of patients with CD present with perianal fistula (PAF) as their first symptom [<span>1</span>]. Furthermore, 4%–5% of patients have isolated PAF as their only manifestation [<span>2</span>]. Prolonged time to diagnosis of CD in patients with PAF may result in development of more complex fistula and progression of luminal disease. In one study, the median time to diagnosis of CD after PAF was 15 months with a range up to 4 years [<span>3</span>]. Earlier diagnosis and treatment is associated with higher rates of fistula closure and prevention of disease progression [<span>3, 4</span>]. However, differentiating PFCD from cryptoglandular fistula (CGF) can be challenging with two diverging treatment algorithms.</p><p>Xiang et al. [<span>5</span>] developed a web-based tool using the top five features in a machine learning model to predict the risk of CD in patients with PAF. Rectal wall ulceration, rectal wall thickening, submucosal fistula, T2 hyperintensity and age < 30 were independently associated with increased risk of CD and together achieved an AUROC of 0.94 (95% CI: 0.89–0.99). This is an excellent step towards risk-stratifying patients with PAF into those who require colonoscopic assessment for CD and those who likely have CGF unrelated to CD.</p><p>A major limitation of this study is the lack of endoscopic assessment in patients classified as having CGF to rule out subclinical CD. PAF can be challenging to treat, with a need for clinical decision tools and prediction models to determine which patients are more likely to have CD versus CGF. Xiang et al.'s model strongly focuses on rectal inflammation with two of the five features, including MRI findings seen in proctitis. Current MRI-based PFCD scoring systems all incorporate the items assessed in the model of Xiang et al. Important pieces of the history (chronic diarrhoea, abdominal pain, weight loss, rectal bleeding and family history of IBD), physical examination (irregular or hypertrophied anal skin tag) and laboratory testing (faecal calprotectin/lactoferrin), which are known predictors of CD could further improve the prediction model. Faecal calprotectin accurately distinguishes PFCD from CGF [<span>6</span>]. Furthermore, there is a strong correlation between fistula scraping calprotectin values and disease outcomes defined by the TOpCLASS classification system, suggesting a relationship with fistula prognosis [<span>6</span>]. Current ECCO guidelines recommend ileocolonoscopy in patients with an unexplained fistula and suspicion of CD [<span>7</span>]. In patients with negative ileocolonoscopy, capsule endoscopy can provide additional diagnostic yield [<span>7</span>].</p><p>Although an excellent start, further validation testing is needed in patients who have completed assessment to fo","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"903-904"},"PeriodicalIF":6.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026344","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}

{"title":"Editorial: Development and Validation of a Multimodal Machine Learning Model for Diagnosing and Assessing Risk of Crohn's Disease in Patients With Perianal Fistulae: Authors' Reply","authors":"Lichao Qiao, Bolin Yang","doi":"10.1111/apt.18516","DOIUrl":"10.1111/apt.18516","url":null,"abstract":"<p>We thank Drs Parian and Schwartz for their insightful editorial on our study [<span>1</span>]. Patients presenting with perianal fistulae experience a significantly worse long-term prognosis when there is a delay in diagnosing Crohn's disease (CD) [<span>2</span>]. However, clinical decision-making tools for the early identification of patients with perianal fistulae at risk of CD are currently lacking in practice. The present model aims to facilitate the early diagnosis of CD in patients where perianal fistula is the primary manifestation, thereby enabling timely endoscopic evaluation [<span>3</span>].</p><p>The incidence of CD in China is increasing rapidly [<span>4</span>], but the training of colorectal specialists has not kept pace. This discrepancy poses challenges for surgeons in identifying perianal fistulising Crohn's disease (PFCD) and in implementing optimal management strategies. The surgical protocols and treatment objectives for PFCD differ substantially from those for cryptoglandular fistula (CGF); treating PFCD in the same way as CGF often has detrimental consequences. Magnetic resonance imaging (MRI) is widely regarded as the gold standard for evaluating perianal fistulae [<span>5</span>]. There is potential for developing a diagnostic prediction model based on MRI that offers a user-friendly tool for clinicians. We can use it to identify patients with PFCD at an early stage and provide appropriate recommendations for subsequent treatment.</p><p>We agree with the study's limitation of the absence of endoscopic assessment. As an invasive procedure, endoscopy is performed on all patients with fistula and may be considered excessive, particularly given the higher prevalence of CGF. Although the activity of perianal CD generally mirrors luminal disease activity, perianal symptoms may occasionally manifest independently [<span>6</span>]. The role of endoscopy in validating diagnostic models for CD is of paramount importance. While current models are largely based on MRI features, this is only the first stage of validation. We appreciate the suggestions regarding the expanded dimensions of the model. In the next phase, we plan to optimise the diagnostic process by combining the model results with current ECCO guideline recommendations and synthesising the MRI features with data from the medical history, physical examination, and laboratory investigations to form an integrated diagnostic process framework. We expect this approach to minimise diagnostic bias and enhance the accuracy of identifying subclinical CD. Prospective clinical trials involving multiple medical centres in China, including patients from different regions and covering more clinical features, are underway to further test the robustness and generalisability of the model. Meanwhile, the model will be integrated into an easy-to-use clinical decision support system (i.e., mobile application) to improve its usability and accessibility for clinicians.</p><p>Texture analy","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"905-906"},"PeriodicalIF":6.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026343","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}

{"title":"The Impact of Postoperative Prophylactic Medication on Long-Term Surgical, Severe Endoscopic and Endoscopic or Radiologic Recurrence Following Primary Ileocecal Resection in Patients With Crohn's Disease","authors":"Sebastiaan ten Bokkel Huinink, Michiel T. J. Bak, Evelien M. J. Beelen, Nicole S. Erler, Mark S. Silverberg, Matthieu Allez, Frank Hoentjen, Alexander G. L. Bodelier, Gerard Dijkstra, Marielle Romberg-Camps, Nanne K. H. de Boer, Laurents P. S. Stassen, Andrea E. van der Meulen – de Jong, Rachel L. West, C. Janneke van der Woude, Oddeke van Ruler, Annemarie C. de Vries, the Dutch Initiative on Crohn and Colitis (ICC)","doi":"10.1111/apt.18496","DOIUrl":"10.1111/apt.18496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of prophylactic medication following ileocecal resection (ICR) for Crohn's disease (CD) merits further elucidation. Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn’s disease (CD), particularly in patients at increased risk of recurrence, but the impact on long-term outcomes needs to be further elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effect of postoperative prophylactic medication on long-term prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study was performed in patients with CD who underwent primary ICR between 2000-2020 in the Netherlands. Patients were divided into two groups: postoperative prophylactic medication [< 12 weeks following ICR] versus no postoperative prophylactic medication. Outcomes were surgical recurrence [re-resection for CD], severe endoscopic recurrence [modified Rutgeerts score (mRS) ≥ i3] and endoscopic or radiologic recurrence [mRS ≥ i2b or radiologic recurrence]. Inverse probability of treatment weighting [IPTW] method was used to adjust for confounding and selection bias. Survival and association between postoperative prophylactic medication and outcomes were assessed with Kaplan-Meier analyses and Cox proportional hazard models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>807 patients underwent ICR (median follow-up 5.0 years); 36% received postoperative prophylactic medication. Surgical, severe endoscopic and endoscopic or radiologic recurrence rates were significantly lower in those who received prophylactic medication (<i>p</i> = 0.01; <i>p</i> < 0.01; <i>p</i> < 0.01). IPTW analysis showed a lower risk of severe endoscopic and endoscopic or radiologic recurrence in patients treated with postoperative prophylactic medication (aOR 0.64; 95% CI 0.43–0.97; aOR 0.65; 95% CI 0.47–0.91), which also was identified as a protective factor for severe endoscopic (aHR 0.5; 95% CI 0.4–0.6) and endoscopic or radiologic recurrence (aHR 0.6, 95% CI 0.5–0.7) in multivariable analysis after correction for confounding factors. A comparable protective effect of postoperative prophylactic medication was sustained in patients who underwent ileocolonoscopy <1 year postoperatively and who underwent surgery on or after 2010.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Prophylactic medication following primary ICR significantly reduces long-term recurrence rates ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1019-1031"},"PeriodicalIF":6.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031072","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}

{"title":"Letter: Toward Intra-Class Switching With JAK Inhibitors?","authors":"Mathieu Uzzan, David Laharie","doi":"10.1111/apt.18518","DOIUrl":"10.1111/apt.18518","url":null,"abstract":"<p>Akiyama et al. reported the real-world effectiveness of three JAK inhibitors in a Japanese multicentre cohort of 602 patients with ulcerative colitis (UC); 228, 215 and 159 patients, respectively, were treated with upadacitinib, filgotinib and tofacitinib [<span>1</span>]. Among these patients, 106 (46%) in the upadacitinib group, 30 (14%) in the filgotinib group and none in the tofacitinib group had prior exposure to another JAK inhibitor.</p><p>Using propensity score matching, they analysed 92 upadacitinib-treated patients previously exposed to other JAK inhibitors, including tofacitinib (<i>n</i> = 31), filgotinib (<i>n</i> = 54) or both (<i>n</i> = 7). Clinical remission was achieved by 57.3% (43/75) of these patients at 10 weeks and 82.9% (34/41) at 58 weeks. For filgotinib, 21 patients were treated after prior JAK inhibitor exposure: tofacitinib (<i>n</i> = 19), upadacitinib (<i>n</i> = 1) or both (<i>n</i> = 1). Clinical remission rates were 28.6% (4/14) at 10 weeks and 62.5% (5/8) at 58 weeks [<span>1</span>].</p><p>Other smaller observational studies have reported outcomes of JAK inhibitor use in patients previously exposed to another JAK inhibitor, almost exclusively focusing on upadacitinib in patients refractory to tofacitinib. For example, Levin et al. demonstrated that 36% of 16 tofacitinib-refractory patients achieved both clinical and steroid-free remission with upadacitinib [<span>2</span>]. Similarly, Gilmore et al. provided real-world evidence on upadacitinib in a multicentre Australian study. Of 152 patients, 42 were tofacitinib-experienced. Clinical remission rates were 24% (10/42) at baseline and 72% (30/42) at Week 8 for tofacitinib-experienced patients, compared to 19% (21/110) at baseline and 78% (86/110) at Week 8 for tofacitinib-naïve patients (<i>p</i> = 0.17) [<span>3</span>]. There are no controlled data on the effectiveness of switching from one JAK inhibitor to another.</p><p>While indirect and direct comparisons suggest that upadacitinib may be the best-in-class in terms of effectiveness [<span>4, 5</span>], this has yet to be specifically demonstrated in JAK inhibitor-refractory patients.</p><p>As the number of patients refractory to multiple treatment lines, including different mechanisms of action, continues to rise—along with the proportion of patients exposed to at least one JAK inhibitor—it is crucial to generate data to refine treatment strategies. Switching within the same class of drugs is an established practice with anti-TNF agents [<span>6, 7</span>]. However, this is relatively new for JAK inhibitors including three FDA- and EMA-approved drugs with distinct JAK selectivity profiles [<span>8</span>].</p><p>Notably, it is unknown whether tofacitinib may be beneficial after the use of a JAK1 inhibitor, or what is the best cycling strategy among JAK inhibitors.</p><p>Consequently, further studies are needed to evaluate intra-class switching between JAK inhibitors on a larger scale and to guide clinical","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"919-920"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020909","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}

{"title":"Letter: Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Liver Cancer—Results From the Global Burden of Disease Study 2021","authors":"Chunlong Liu, Ziqiang He, Jiangtao Yu, Rui Yang","doi":"10.1111/apt.18510","DOIUrl":"10.1111/apt.18510","url":null,"abstract":"<p>We read with great interest the study by Danpanichkul et al. [<span>1</span>], which conducted an in-depth analysis of the burden of primary liver cancer (PLC) in the United States from 2000 to 2021. The results revealed that PLC incidences increased by 141% and deaths by 136%. The age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) for PLC also rose, primarily driven by alcohol-related liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). Additionally, with the rising prevalence of obesity and metabolic syndrome, the prevalence of MASLD has risen substantially, fuelling a rise in MASLD-related liver cancer [<span>2, 3</span>]. These findings highlight the necessity for further in-depth research into the global burden of MASLD-related liver cancer.</p><p>Using the Global Burden of Disease Study 2021 database, we analysed incident cases, deaths, ASIR and ASDR for MASLD-related liver cancer globally from 1990 to 2021. We assessed these by country, region, year, age and sex and measured trends using the average annual percentage change (AAPC). Additionally, we employed the Bayesian age-period-cohort (BAPC) model to forecast the disease burden from 2022 to 2045.</p><p>In 2021, global incident cases and deaths of MASLD-related liver cancer were 42,291 (95% uncertainty interval [UI] 34,032.6–51,129.5) and 40,925 (95% UI: 32,961–49,610), respectively. From 1990 to 2021, ASIR and ASDR increased, with AAPCs of 0.99 (95% confidence interval [CI] 0.95–1.03) and 0.82 (95% CI: 0.72–0.92). East Asia recorded the highest incident cases and deaths, while Australasia showed the most significant increases in ASIR and ASDR (Figure 1A,B). Nationally, China, Japan and the United States had the highest burdens, with over 60% of countries showing rising ASIR and ASDR trends (Figure 1C,D). The 65–74 age group had the highest cases and deaths, while ASIR and ASDR peaked in the 85–89 and 90–94 age groups, respectively (Figure 1E,F). BAPC modelling predicts rising incident cases and deaths in both sexes (Figure 1G,H), though ASIR and ASDR are projected to decline in females and stabilise in males over the next 24 years.</p><p>In conclusion, the burden of MASLD-related liver cancer varies significantly across regions, underlining the need for region-specific strategies to address the growing problem. While the age-standardised burden is expected to stabilise over the next 24 years, the global incidence and prevalence of MASLD will continue to increase, exacerbated by metabolic factors [<span>4</span>]. In addition, our previous studies have shown that ageing as a major factor in the increasing burden of MASLD-related liver cancer [<span>5</span>]. Notably, according to the world population ageing report released by the United Nations in 2019, the size of the elderly population (≥ 65 years) will increase in all regions of the world over the next three decades, and the number of elderly people worldwide is expected to","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1077-1079"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026346","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}

{"title":"Editorial: Steatotic Liver Diseases Emerge as Rapidly Growing Drivers of Primary Liver Cancer in the United States—Author's Reply","authors":"Pojsakorn Danpanichkul, Donghee Kim, Chun Wei Pan, Amit G. Singal, Ju Dong Yang, Karn Wijarnpreecha","doi":"10.1111/apt.18511","DOIUrl":"10.1111/apt.18511","url":null,"abstract":"<p>We extend our sincere gratitude for the recent editorial highlighting our manuscript [<span>1</span>]. In our study titled ‘Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States’, we analysed the prevalence, incidence and mortality trends of primary liver cancer (PLC) in the United States using data from the Global Burden of Disease (GBD) 2021 database [<span>2</span>]. Our findings emphasise the increasing contribution of steatotic liver disease–related PLC to the overall burden of PLC in the United States, although chronic hepatitis C virus (HCV) infection remains the leading contributor of PLC. We also acknowledge the limitations raised by Torosian et al. [<span>1</span>], particularly the inability of the GBD database to evaluate trends based on race, ethnicity, histological subtypes or distinctions between metabolic dysfunction–associated and alcohol-associated liver disease (MetALD) [<span>3</span>]. Future iterations of the GBD should strive to incorporate these subgroups to provide a more nuanced understanding.</p><p>Despite recent advancements in PLC management, progress in identifying at-risk individuals and achieving early detection of HCC in these populations has not kept pace with treatment innovations, particularly for PLC associated with steatotic liver disease (SLD) [<span>4, 5</span>]. For instance, prior meta-analyses demonstrated that SLD-associated hepatocellular carcinoma is significantly less likely to be detected by screening and is often diagnosed at a more advanced stage compared to other etiologies [<span>6, 7</span>]. Beyond improving screening, policy measures such as alcohol taxation, pricing strategies and reducing alcohol availability could play a pivotal role in alleviating the burden of alcohol-associated PLC [<span>8</span>].</p><p>For metabolic dysfunction-associated steatohepatitis (MASH), it is essential to implement strategies that include screening, intensive lifestyle interventions, and pharmacological treatments to slow or prevent the progression of liver fibrosis [<span>9</span>]. Supporting patients with MASH requires a multidisciplinary approach, including expanded involvement of nutritionists, social prescribing initiatives and acknowledgement of the critical role of social nutrition. These steps are essential for addressing the public health challenges posed by MASLD, MASH and MASH-associated PLC [<span>10</span>]. The elimination of HCV requires sustained momentum as it continues to contribute significantly to the global disease burden. However, elimination is attainable due to HCV's distinct characteristics, reliable diagnostic tests and the availability of cost-effective or cost-saving interventions. Key measures include screening blood donors for HCV, promoting safe injection practices, enforcing robust infection-control programmes to minimise HCV transmission ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1059-1060"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021096","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}

{"title":"Letter: Toward Intra-Class Switching With JAK Inhibitors? Authors' Reply","authors":"Shintaro Akiyama, Toshimitsu Fujii","doi":"10.1111/apt.18521","DOIUrl":"10.1111/apt.18521","url":null,"abstract":"<p>We thank Dr. Uzzan et al. [<span>1</span>] for their comments on our publication [<span>2</span>]. We have clarified the data availability regarding intra-class switching with Janus kinase (JAK) inhibitors in our study (Figure 1). We demonstrated the efficacy of upadacitinib in ulcerative colitis (UC) after the use of tofacitinib and filgotinib [<span>2</span>]. As a result, upadacitinib-treated patients showed a clinical remission rate of 71.9% (64/89) at the most recent follow-up (median 53 weeks). This suggests that upadacitinib can be considered after the use of tofacitinib or filgotinib. Given the highest efficacy of upadacitinib among the three JAK inhibitors in UC [<span>2</span>], opposite approaches may not be reasonable. We also assessed the efficacy of filgotinib after the use of other JAK inhibitors, predominantly tofacitinib [<span>2, 3</span>]; filgotinib-treated patients showed a clinical remission rate of 50% (10/20) at the most recent follow-up (median 52 weeks) [<span>2</span>]. Our results also indicate that filgotinib could offer a chance to achieve remission in patients previously exposed to tofacitinib.</p><p>As Dr. Uzzan et al. [<span>1</span>] pointed out, we did not evaluate the efficacy of tofacitinib in patients who had previously been treated with other JAK inhibitors as we primarily collected data from patients who started JAK inhibitors within the first 18 months following the approval of each drug in Japan. Tofacitinib was approved in 2018 as the first JAK inhibitor for UC; therefore, there were no data on its efficacy following upadacitinib or filgotinib, which were approved in 2022. To the best of our knowledge, there have been no real-world data specifically addressing this issue, and the number of comparative studies between tofacitinib and filgotinib is also limited.</p><p>Our comparative analysis using propensity score matching showed that some clinical outcomes (e.g., clinical response at 10 and 26 weeks, as well as endoscopic improvement) appeared to be better with tofacitinib than with filgotinib, although the differences were not statistically significant. In addition, Yagi et al. [<span>4</span>] showed that tofacitinib was more effective than filgotinib at 8 weeks for patients with UC who did not respond to therapy within the first 4 weeks. These findings suggest that tofacitinib may be more effective than filgotinib for UC and could be considered an option for patients previously treated with filgotinib. We agree that more data are needed to better understand the cycling strategy within JAK inhibitors in UC, and we look forward to seeing the data from the European Crohn's and Colitis Organisation [<span>1</span>].</p><p>The authors' declarations of personal and financial interests are unchanged from those in the original article [<span>2</span>].</p><p><b>Shintaro Akiyama:</b> writing – original draft, writing – review and editing. <b>Toshimitsu Fujii:</b> writing – review and editing.</p><p>This art","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"921-922"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020908","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}

{"title":"Letter: Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Liver Cancer—Results From the Global Burden of Disease Study 2021. Authors' Reply","authors":"Pojsakorn Danpanichkul, Donghee Kim, Markos Kalligeros, Amit G. Singal, Ju Dong Yang, Karn Wijarnpreecha","doi":"10.1111/apt.18520","DOIUrl":"10.1111/apt.18520","url":null,"abstract":"<p>We deeply appreciate the insightful letter from Liu and He et al., which highlights their analysis of the global burden of metabolic dysfunction-associated steatotic liver disease (MASLD)-related liver cancer using the Global Burden of Disease Study (GBD) 2021 database [<span>1</span>]. The similarities between their findings and our observations on the rising burden of MASLD-related liver cancer in the United States underscore the global importance of this issue [<span>2</span>].</p><p>The data on global trends in MASLD-related liver cancer, particularly the notable increases in incidence and mortality, are highly significant. Prior studies using the same database also emphasised the rising burden of steatotic liver disease-related liver cancer, with increasing age-standardised incidence rates for both alcohol-associated liver disease (ALD) (APC: 0.26%, 95% CI 0.22%–0.30%) and MASLD (APC: 0.62%, 95% CI 0.58%–0.67%) [<span>3, 4</span>]. The non-overlapping confidence intervals support the assertion, as noted by Liu and He et al., that MASLD is a primary driver of the global burden of steatotic liver disease, as evidenced by projections through 2050 [<span>1</span>]. However, several limitations to the GBD methodology warrant consideration [<span>5</span>]. For example, alcohol use is frequently underreported, which could result in some MASLD cases being reclassified as metabolic dysfunction and alcohol-associated liver disease (MetALD) or ALD [<span>6, 7</span>]. A comprehensive alcohol history, including recent and lifetime intake, is essential to ensure accurate prognosis and management. Consideration of alcohol's impact on metabolic syndrome criteria, reassessing alcohol use and metabolic dysfunction over time, and addressing challenges with underreporting through biomarkers, validated questionnaires and collateral information are essential [<span>6</span>]. Furthermore, since 2024, Resmetirom has received conditional approval for treating MASH, while treatment advancements for ALD have lagged behind, suggesting the future burden of ALD may increase more than MASLD [<span>8, 9</span>].</p><p>The letter further underscores the critical need to incorporate demographic factors, particularly population aging, into strategies for preventing and managing MASLD-related liver cancer. This consideration extends to ALD-associated liver cancer, as alcohol use disorder shows similar age-standardised prevalence rates as the general population [<span>10</span>]. Such demographic insights can guide the development of tailored public health strategies and resource allocation to effectively address these populations' unique needs, which will translate into primary prevention of ALD-associated liver cancer.</p><p>Further refinement of large-scale databases to accurately quantify aetiology-specific contributions, both in the United States and globally, is essential for informing prevention efforts, including target populations, to effectively reduce liver can","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1080-1081"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026345","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}

{"title":"Editorial: Steatotic Liver Diseases Emerge as Rapidly Growing Drivers of Primary Liver Cancer in the United States","authors":"Kelly Torosian, Veeral Ajmera","doi":"10.1111/apt.18508","DOIUrl":"10.1111/apt.18508","url":null,"abstract":"<p>With the advent of direct-acting antiviral agents for hepatitis C (HCV) in 2013 and increased uptake of vaccines for hepatitis B, the burden of viral-related chronic liver disease has significantly decreased [<span>1, 2</span>]. It was predicted that this would lead to a plateau or even decrease in the incidence of primary liver cancer (PLC) especially in younger cohorts and specific ethnic groups [<span>3-5</span>]. However, the concurrent rise in metabolic syndrome and alcohol use disorder has led to the emergence of steatotic liver disease as the most common cause of chronic liver disease [<span>6-8</span>]. It was previously unknown how this shift in the aetiology of liver disease affected recent trends in PLC incidence, prevalence and mortality.</p><p>Utilising the Global Burden of Disease (GBD) Study 2021, Danpanichkul et al. demonstrated that PLC cases and deaths in the United States have steadily increased from 2000 to 2021, mostly due to the increased burden of alcohol-associated liver disease (ALD) and metabolic dysfunction associated liver disease (MASLD) [<span>9</span>]. They found ALD to be the fastest growing aetiology of PLC, which contrasts prior data from GBD 2019, which identified MASLD as the fastest growing aetiology of PLC. The authors astutely point out the increased harmful alcohol use in the context of the COVID-19 pandemic and the rise of cardio metabolic disease in the United States, which are likely driving the rapid rise of both ALD and MASLD. Despite this, HCV is still the leading cause of PLC in the United States and contributed the highest prevalence, incidence and deaths by aetiology of liver disease in 2021, albeit with slower growth in the most recently evaluated era from 2015 to 2021.</p><p>The paper aligns with prior studies that have shown an increased frequency of PLC in males and older adults, but due to constraints of the GBD data, was unable to evaluate trends in race/ethnicity or distinguish between the specific type of PLC, i.e., hepatocellular carcinoma or cholangiocarcinoma [<span>3, 10</span>]. The authors work highlights the importance of continuing to bolster HCV screening and treatment programs not only to reduce the burden of HCV but also to prevent morbidity and mortality from PLC, as we have not yet seen the peak of HCV-related PLC. With PLC projected to be the third leading cause of cancer deaths by 2040, further study will be required to address many unanswered questions including the incidence of PLC in metabolic dysfunction and ALD, MetALD, and how best to refine screening to identify PLC in patients without cirrhosis, particularly the large non-cirrhotic MASLD population. Still, this important work advances our knowledge of the evolving etiologic drivers of PLC and their large impact on cancer-related death and disability-adjusted life years. Public health policies focused on curbing the drivers of SLD, like the efforts made to eradicate HCV, will be required to meaningfully decrease th","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1057-1058"},"PeriodicalIF":6.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020894","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}