Alimentary Pharmacology & Therapeutics最新文献

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

{"title":"Editorial: Prevalence of Suspected Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents in the United States Using Updated Diagnostic Criteria","authors":"Julie Bonn, Stavra A. Xanthakos","doi":"10.1111/apt.70067","DOIUrl":"https://doi.org/10.1111/apt.70067","url":null,"abstract":"<p>In 2023, diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) were updated to require hepatic steatosis with one or more cardiometabolic risk factors, including overweight, obesity, dysglycaemia, dyslipidaemia or hypertension [<span>1</span>]. Prior diagnosis of nonalcoholic fatty liver disease (NAFLD) focused primarily on excluding other aetiologies and did not require cardiometabolic risk factors. Among US adolescents in the National Health Examination and Nutrition Surveys (NHANES) 2011–2018, an estimated 16.5% had NAFLD [<span>2</span>]; however, the prevalence of MASLD under the new diagnostic criteria remained uncertain.</p>\u0000<p>To estimate the prevalence of MASLD among US adolescents, Noon et al. [<span>3</span>] evaluated the association of elevated ALT level, a validated biomarker for hepatic steatosis [<span>4</span>], with cardiometabolic risk factors in a 2011–2020 NHANES sample of youth, ages 12–19 years. Among the 14.6% with elevated ALT (Figure 1), 77% met cardiometabolic criteria for MASLD (11% overall), defined as paediatric overweight/obesity, elevated waist circumference, triglyceride, fasting glucose, haemoglobin A1C levels and/or low high-density lipoprotein. Body mass index had the strongest association with elevated ALT. Among those without cardiometabolic risks, 0.7% had viral hepatitis, 1.9% had potential medication hepatotoxicity, and 20.2% had cryptogenic hepatitis.</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/e9850757-3fb3-4ce3-b6a4-6e6ba3361921/apt70067-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/e9850757-3fb3-4ce3-b6a4-6e6ba3361921/apt70067-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/7055a2b1-fa5d-4112-b398-ac676434153e/apt70067-fig-0001-m.png\" title=\"Details are in the caption following the image\"/></picture><figcaption>\u0000<div><strong>FIGURE 1<span style=\"font-weight:normal\"></span></strong><div>Open in figure viewer<i aria-hidden=\"true\"></i><span>PowerPoint</span></div>\u0000</div>\u0000<div>Prevalence of elevated ALT among US adolescents in NHANES, 2011–2020 and prevalence of suspected MASLD and other causes among those with elevated ALT.</div>\u0000</figcaption>\u0000</figure>\u0000<p>The 11% prevalence of MASLD was one third lower than the recent estimate of NAFLD in adolescents (16.5%) [<span>2</span>], although concordance could not be fully assessed without imaging or biopsy confirmation of hepatic steatosis. Notably, a substantial proportion with elevated ALT (23%) lacked any cardiometabolic risk factors, with 88% of these having cryptogenic elevation. Overall, 7% of adolescents with healthy weight and no other cardiometabolic risk factors had elevated ALT. Conversely, 50% of adolescents with normal ALT had at least one cardiometabolic risk factor. Without validated liver imaging (MRI proton-density fat fraction in children [<span>5</span>]), abnormal hepatic steatosis could not be assessed. One open questio","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"183 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635118","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: Coeliac Disease and Women's Reproductive Health: A Lifelong Challenge","authors":"C. Ciacci, A. Santonicola","doi":"10.1111/apt.70087","DOIUrl":"https://doi.org/10.1111/apt.70087","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"5 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627529","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: Linking Overt Hepatic Encephalopathy Post-TIPS to Mortality!","authors":"Anjan Kumar, Margaret L. P. Teng, Anand V. Kulkarni","doi":"10.1111/apt.70005","DOIUrl":"10.1111/apt.70005","url":null,"abstract":"<p>Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective therapy for portal hypertension-related complications and has significant survival benefits for patients with recurrent/refractory ascites and variceal bleeding [<span>1</span>]. Although procedure-related mortality is low (< 1%), common post-TIPS complications, which affect quality of life, include overt hepatic encephalopathy (OHE), decrease in liver function and cardiopulmonary dysfunction [<span>2</span>]. Around 30%–50% of patients develop an episode of HE post-TIPS, with 10% developing disabling HE requiring recurrent hospitalisations [<span>3, 4</span>]. However, the impact of post-TIPS OHE on mortality remains unclear.</p><p>Xiang et al. conducted a large multicentre retrospective cohort study comprising 3262 patients with cirrhosis underwent TIPS for variceal bleeding [<span>5</span>]. Post-TIPS OHE occurred in 33.2% of patients, of which 631 (19.3%) patients subsequently died. It was found that post-TIPS OHE independently predicted long-term mortality (beyond 24 months), but not short-term mortality within 6 months. Additionally, development of post-TIPS OHE within 1 month was associated with higher long-term mortality. The authors must be lauded for this exceptional long-term follow-up study, which provides invaluable insights into HE and mortality.</p><p>A recent multicentre prospective study by Nardelli et al. reported that <i>episodic</i> post-TIPS OHE was not associated with higher mortality [<span>6</span>]. However, the percentage of patients with <i>persistent</i> post-TIPS OHE was significantly higher among patients who died. It is worth noting that median follow-up in this study was 30 months, slightly less than the 1077 days (~35 months) in Yi's study. A subsequent meta-analysis of seven cohort studies comprising 1712 patients showed that post-TIPS HE was associated with increased risk of mortality [<span>7</span>]. Yi's observation is hence in line with current literature, and the large cohort size adds credence to the link between post-TIPS HE and mortality. Additionally, Hartl et al. supported the observation that early onset of post-TIPS OHE within 1 month was linked with higher mortality [<span>8</span>].</p><p>Short-term mortality post-TIPS is predominantly driven by liver function, portal hypertension and stent-related complications, thereby suggesting a lack of association between post-TIPS OHE and short-term mortality. Only history of ascites and diameter of TIPS stent were significantly associated with mortality at 6 months, which suggests that these patients had an existing significant degree of portal hypertension not fully correctable by TIPS. Furthermore, 43.4% of patients who died within 12 months had stent dysfunction, which may exacerbate portal hypertension-related complications.</p><p>The study has numerous limitations. First, a higher proportion of patients with OHE had variceal bleeding, which may have been the trigger fo","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1238-1239"},"PeriodicalIF":6.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619029","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: No Biochemical Relapse Is Associated With the Highest Off-Therapy HBsAg Loss Rate—Authors' Reply","authors":"Ying-Nan Tsai, Yao-Chun Hsu","doi":"10.1111/apt.70083","DOIUrl":"https://doi.org/10.1111/apt.70083","url":null,"abstract":"<p>We thank Professors Jeng and Liaw for their interest in our study [<span>1, 2</span>]. We agree that ALT elevation following cessation of nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB) is not associated with higher HBsAg seroclearance rates. In our study, we found that elevated serum ALT analysed as a time-varying variable was not associated with HBsAg seroclearance regardless of whether the threshold was set at the upper limit of normal (ULN), two-time ULN (clinical relapse) or five-time ULN (acute flares). These findings further examine and validate the results reported in their study [<span>3</span>].</p>\u0000<p>They noted that the 10-year cumulative incidence of HBsAg seroclearance in the current study (12.4%) was lower than that in our previous research and other studies [<span>3, 4</span>]. We acknowledge that the incidence of HBsAg seroclearance could be underestimated in this real-world retrospective study because HBsAg was not regularly measured following a prespecified protocol in routine clinical practice, unlike in a prospective research setting with selected participants. Moreover, the apparent inconsistency might result from differences in analytical approaches. For instance, observation for HBsAg loss was censored on the resumption of antiviral treatment without considerations of competing risks in our prior study [<span>4</span>]. This approach would yield a significantly higher estimate of HBsAg loss rate as shown in the current study (figure S2). Since retreatment is unlikely independent of the probability of HBsAg seroclearance, analysing it as non-informative censoring may lead to an overestimation of HBsAg seroclearance incidence [<span>5</span>]. Regardless, our sensitivity analyses employing different approaches to estimate HBsAg seroclearance incidence consistently confirmed no association between ALT elevation and HBsAg loss.</p>\u0000<p>The current study did not specifically investigate the association between retreatment and subsequent HBsAg seroclearance. Nevertheless, a recent randomised study reported that delaying retreatment by adopting a higher threshold did not increase the chance of HBsAg seroclearance in HBeAg-negative patients who stopped NA therapy after a minimum 24 months of viral suppression. They found no patients with an end-of-treatment HBsAg level greater than 1000 IU/mL would clear HBsAg during follow-up, irrespective of the assignment to higher or lower retreatment thresholds [<span>6</span>]. Only patients with EOT HBsAg level below 1000 IU/mL had a chance of HBsAg seroclearance, suggesting that the likelihood of HBsAg seroclearance was already determined by the HBsAg level at treatment cessation, whether or not antiviral therapy was resumed for clinical relapses.</p>\u0000<p>We fully agree on the importance of rigorous monitoring and timely retreatment to ensure the safety of patients who stop NA therapy [<span>7</span>]. However, acute flare-ups induced by NA withdrawal can progress","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"6 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619027","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: 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}

{"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}

{"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}

{"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}

{"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}