Pub Date : 2024-03-07DOI: 10.1016/j.jhepr.2024.101055
Rudolf E. Stauber , Pierre-Emmanuel Rautou , Horia Stefanescu , Adelina Horhat , Maja Thiele , Carolin Lackner
Background & Aims
In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort.
Methods
Data from a large multinational cohort of 445 patients with alcohol-associated liver disease (ALD) that served to establish a novel grading and staging system of alcohol-associated liver disease were analyzed retrospectively. Diagnosis of ASH was based on presence of hepatocyte ballooning plus lobular neutrophil infiltration and established in virtual consensus meetings of multiple expert liver pathologists.
Results
Complete data including CRP values were available in 346 patients. Overall diagnostic accuracy for prediction of ASH was 73% for NIAAA criteria and 77% for NIAAAm-CRP criteria. In a subgroup with suspected severe AH (MELD >20, n = 123), overall diagnostic accuracy for prediction of ASH was 69% for NIAAA criteria and 74% for NIAAAm-CRP criteria.
Conclusion
Our findings confirm recent data on suboptimal diagnostic accuracy of original NIAAA criteria and validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for presence of ASH.
Impact and Implications
Alcohol-associated steatohepatitis (ASH) is diagnosed on liver histology but liver biopsy is not always feasible. Non-invasive diagnosis based on clinical findings has been proposed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria and recently improved using NIAAAm-CRP criteria. Our findings validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for the presence of histological ASH. Clinical trials of novel drugs should focus on histologically proven ASH.
{"title":"Validation of NIAAAm-CRP criteria to predict alcohol-associated steatohepatitis on liver histology","authors":"Rudolf E. Stauber , Pierre-Emmanuel Rautou , Horia Stefanescu , Adelina Horhat , Maja Thiele , Carolin Lackner","doi":"10.1016/j.jhepr.2024.101055","DOIUrl":"10.1016/j.jhepr.2024.101055","url":null,"abstract":"<div><h3>Background & Aims</h3><p>In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort.</p></div><div><h3>Methods</h3><p>Data from a large multinational cohort of 445 patients with alcohol-associated liver disease (ALD) that served to establish a novel grading and staging system of alcohol-associated liver disease were analyzed retrospectively. Diagnosis of ASH was based on presence of hepatocyte ballooning plus lobular neutrophil infiltration and established in virtual consensus meetings of multiple expert liver pathologists.</p></div><div><h3>Results</h3><p>Complete data including CRP values were available in 346 patients. Overall diagnostic accuracy for prediction of ASH was 73% for NIAAA criteria and 77% for NIAAAm-CRP criteria. In a subgroup with suspected severe AH (MELD >20, n = 123), overall diagnostic accuracy for prediction of ASH was 69% for NIAAA criteria and 74% for NIAAAm-CRP criteria.</p></div><div><h3>Conclusion</h3><p>Our findings confirm recent data on suboptimal diagnostic accuracy of original NIAAA criteria and validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for presence of ASH.</p></div><div><h3>Impact and Implications</h3><p>Alcohol-associated steatohepatitis (ASH) is diagnosed on liver histology but liver biopsy is not always feasible. Non-invasive diagnosis based on clinical findings has been proposed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria and recently improved using NIAAAm-CRP criteria. Our findings validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for the presence of histological ASH. Clinical trials of novel drugs should focus on histologically proven ASH.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000569/pdfft?md5=7cc2a363eb19bd0e9379846b875de3b4&pid=1-s2.0-S2589555924000569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140275852","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}
Pub Date : 2024-03-04DOI: 10.1016/j.jhepr.2024.101054
Sven H. Loosen , Fabian Benz , Raphael Mohr , Philipp A. Reuken , Theresa H. Wirtz , Lioba Junker , Christian Jansen , Carsten Meyer , Michael Praktiknjo , Alexander Wree , Johanna Reißing , Münevver Demir , Wenyi Gu , Mihael Vucur , Robert Schierwagen , Andreas Stallmach , Anselm Kunstein , Johannes Bode , Christian Trautwein , Frank Tacke , Christoph Roderburg
Background & Aims
Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion.
Methods
suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses.
Results
suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis.
Conclusion
suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion.
Impact and implications
Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.
{"title":"Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS","authors":"Sven H. Loosen , Fabian Benz , Raphael Mohr , Philipp A. Reuken , Theresa H. Wirtz , Lioba Junker , Christian Jansen , Carsten Meyer , Michael Praktiknjo , Alexander Wree , Johanna Reißing , Münevver Demir , Wenyi Gu , Mihael Vucur , Robert Schierwagen , Andreas Stallmach , Anselm Kunstein , Johannes Bode , Christian Trautwein , Frank Tacke , Christoph Roderburg","doi":"10.1016/j.jhepr.2024.101054","DOIUrl":"10.1016/j.jhepr.2024.101054","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion.</p></div><div><h3>Methods</h3><p>suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses.</p></div><div><h3>Results</h3><p>suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis.</p></div><div><h3>Conclusion</h3><p>suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion.</p></div><div><h3>Impact and implications</h3><p>Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000557/pdfft?md5=89e3d4ed48a048279553ab9ce9f68dce&pid=1-s2.0-S2589555924000557-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272629","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}
Pub Date : 2024-03-01DOI: 10.1016/S2589-5559(24)00049-1
{"title":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(24)00049-1","DOIUrl":"https://doi.org/10.1016/S2589-5559(24)00049-1","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000491/pdfft?md5=e4970b212d7ec370a3e6dacf81b9cb2a&pid=1-s2.0-S2589555924000491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052496","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}
Pub Date : 2024-03-01DOI: 10.1016/j.jhepr.2024.101022
Syed Hassan Bin Usman Shah , Maryam Alavi , Behzad Hajarizadeh , Gail V. Matthews , Marianne Martinello , Mark Danta , Janaki Amin , Matthew G. Law , Jacob George , Heather Valerio , Gregory J. Dore
{"title":"Corrigendum to “Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales” [JHEP Reports 4 (2022)]","authors":"Syed Hassan Bin Usman Shah , Maryam Alavi , Behzad Hajarizadeh , Gail V. Matthews , Marianne Martinello , Mark Danta , Janaki Amin , Matthew G. Law , Jacob George , Heather Valerio , Gregory J. Dore","doi":"10.1016/j.jhepr.2024.101022","DOIUrl":"10.1016/j.jhepr.2024.101022","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000235/pdfft?md5=6980a7fdbc86fac24ae82d64ecd8ebb3&pid=1-s2.0-S2589555924000235-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139818548","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}
Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis.
Methods
We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event.
Results
The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG <16 mmHg), high-risk (HVGP ≥16 mmHg), and very high-risk (HVPG ≥20 mmHg).
Conclusions
HVPG predicted major bleeding events in patients with cirrhosis undergoing OLT. Including HVPG as part of pre-transplant assessment might enable better anticipation of the intraoperative course.
Impact and implications
Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes but the proportion of this risk related to portal hypertension is unclear. Our work shows that hepatic venous pressure gradient (HVPG), the gold standard for estimating portal hypertension, is a strong predictor of major bleeding events and blood loss volume in patients with cirrhosis undergoing OLT. Three groups of patients can be identified according to their risk of major bleeding events: low-risk patients with HVPG <16 mmHg, high-risk patients with HVPG ≥16 mmHg, and very high-risk patients with HVPG ≥20 mmHg. HVPG could be systematically included in the pre-transplant assessment to anticipate intraoperative course and tailor patient management.
{"title":"Predictive role of hepatic venous pressure gradient in bleeding events among patients with cirrhosis undergoing orthotopic liver transplantation","authors":"Mikhael Giabicani , Pauline Joly , Stéphanie Sigaut , Clara Timsit , Pauline Devauchelle , Fédérica Dondero , François Durand , Pierre Antoine Froissant , Myriam Lamamri , Audrey Payancé , Aymeric Restoux , Olivier Roux , Tristan Thibault-Sogorb , Shantha Ram Valainathan , Mickaël Lesurtel , Pierre-Emmanuel Rautou , Emmanuel Weiss","doi":"10.1016/j.jhepr.2024.101051","DOIUrl":"10.1016/j.jhepr.2024.101051","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis.</p></div><div><h3>Methods</h3><p>We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event.</p></div><div><h3>Results</h3><p>The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG <16 mmHg), high-risk (HVGP ≥16 mmHg), and very high-risk (HVPG ≥20 mmHg).</p></div><div><h3>Conclusions</h3><p>HVPG predicted major bleeding events in patients with cirrhosis undergoing OLT. Including HVPG as part of pre-transplant assessment might enable better anticipation of the intraoperative course.</p></div><div><h3>Impact and implications</h3><p>Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes but the proportion of this risk related to portal hypertension is unclear. Our work shows that hepatic venous pressure gradient (HVPG), the gold standard for estimating portal hypertension, is a strong predictor of major bleeding events and blood loss volume in patients with cirrhosis undergoing OLT. Three groups of patients can be identified according to their risk of major bleeding events: low-risk patients with HVPG <16 mmHg, high-risk patients with HVPG ≥16 mmHg, and very high-risk patients with HVPG ≥20 mmHg. HVPG could be systematically included in the pre-transplant assessment to anticipate intraoperative course and tailor patient management.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000521/pdfft?md5=f8e70d7bfcc17e1b76098bcbe70de7c2&pid=1-s2.0-S2589555924000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140464493","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}
Pub Date : 2024-02-28DOI: 10.1016/j.jhepr.2024.101050
Yu Chen , Lung-Yi Mak , Mary H.Y. Tang , Jingyi Yang , Chun Bong Chow , Ai-Ming Tan , Tao Lyu , Juan Wu , Qingjuan Huang , Hai-Bo Huang , Ka-Shing Cheung , Man-Fung Yuen , Wai-Kay Seto
Background & Aims
Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants.
Methods
In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24–28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6–8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7–12 months of age.
Results
Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity.
Conclusions
PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment.
Impact and Implications
In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.
背景& 目的富马酸替诺福韦二吡呋酯（TDF）产前预防（PP）是预防高病毒血症母亲感染慢性乙型肝炎（CHB）后母婴传播的标准治疗方法。在这项前瞻性研究中，未经治疗的慢性乙型肝炎高病毒血症（HBV DNA ≥200,000 IU/ml）但无肝硬化的母亲在怀孕 24-28 周时接受了 TDF 治疗。根据中国慢性阻塞性肺病指南，TDF在分娩时或产后≥4周时停用。每6-8周监测一次血清HBV DNA和丙氨酸氨基转移酶，以确定病毒学复发（VR）。结果在招募的 330 名参与者中（中位年龄 30 岁，82.7% HBeAg+，中位 HBV DNA 7.82 log IU/ml），66.4% 在分娩时停用了 TDF，33.6% 在≥4 周时停用了 TDF。98.3%的患者出现了 VR，其中 11.6%的患者再次接受了 TDF 治疗。停用 TDF 的时间并不会改变 VR（99.0% vs. 96.9%）、临床复发（19.5% vs. 14.3%）或再治疗（12.6% vs. 10.1%）的风险（所有 p > 0.05）。在早期停药组和晚期停药组中，分别有相似比例的患者丙氨酸氨基转移酶超过正常值上限（ULN）5 倍（1.1% 对 2.1%；P = 0.464）和 10 倍（0.5% 对 0%；P = 0.669）。结论 PP-TDF和新生儿免疫接种对预防高病毒血症母亲的HBV母婴传播非常有效。停用 PP-TDF 的时机并不影响 VR 或再治疗的风险。影响和意义在为预防母婴传播（MTCT）而开始使用围产期替诺福韦酯的慢性乙型肝炎感染孕产妇中，产后停用抗病毒药物的最佳时机仍然未知。这项前瞻性研究表明，与延长替诺福韦的治疗时间相比，分娩时立即停用替诺福韦不会导致病毒复发、再治疗或将病毒传播给婴儿的风险增加。可以考虑将围产期抗病毒预防治疗的持续时间从 12 周缩短至分娩后立即停药。立即停用围产期替诺福韦，并结合标准的新生儿免疫计划，对预防高病毒血症合并慢性乙型肝炎孕产妇的母婴传播有效率达 100%，婴儿的疫苗应答率也很高。
{"title":"Immediate postpartum cessation of tenofovir did not increase risk of virological or clinical relapse in highly viremic pregnant mothers with chronic hepatitis B infection","authors":"Yu Chen , Lung-Yi Mak , Mary H.Y. Tang , Jingyi Yang , Chun Bong Chow , Ai-Ming Tan , Tao Lyu , Juan Wu , Qingjuan Huang , Hai-Bo Huang , Ka-Shing Cheung , Man-Fung Yuen , Wai-Kay Seto","doi":"10.1016/j.jhepr.2024.101050","DOIUrl":"10.1016/j.jhepr.2024.101050","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants.</p></div><div><h3>Methods</h3><p>In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24–28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6–8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7–12 months of age.</p></div><div><h3>Results</h3><p>Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 <em>vs</em>. 96.9%), clinical relapse (19.5 <em>vs</em>. 14.3%), or retreatment (12.6 <em>vs</em>. 10.1%) (all <em>p</em> > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 <em>vs</em>. 2.1%; <em>p</em> = 0.464) and 10 times (0.5 <em>vs</em>. 0%; <em>p</em> = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity.</p></div><div><h3>Conclusions</h3><p>PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment.</p></div><div><h3>Impact and Implications</h3><p>In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258955592400051X/pdfft?md5=7c823a326115936fcf170ca16dbfa557&pid=1-s2.0-S258955592400051X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140470198","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}
Pub Date : 2024-02-23DOI: 10.1016/j.jhepr.2024.101033
Young Mi Jung , Seung Mi Lee , Wonyoung Wi , Min-Jeong Oh , Joong Shin Park , Geum Joon Cho , Won Kim
Background & Aims
Adverse pregnancy outcomes (APOs) can worsen cardiometabolic risk factors in women, raising their likelihood of developing cardiometabolic diseases at a young age after their initial pregnancy. Nevertheless, there are limited data on the risk of newly developing metabolic dysfunction-associated steatotic liver disease (MASLD) in women who have had APOs. This study aimed to evaluate the risk of new-onset MASLD after experiencing APOs.
Methods
Singleton pregnant women who underwent national health screenings 1 year before pregnancy and 1 year after delivery were included in this study. APOs were defined as the presence of at least one of the followings: hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth, low birth weight, and placental abruption. The primary outcome was new-onset MASLD based on the presence of APOs.
Results
Among 80,037 study participants, 9,320 (11.6%) experienced APOs during pregnancy. Women who experienced APOs had an increased risk of developing new-onset MASLD after delivery even after adjustments for various covariates (adjusted odds ratio [OR] 1.58, 95% CI 1.45–1.72). In particular, women who experienced either HDP or GDM showed a significantly increased risk of developing new-onset MASLD (adjusted OR 2.20, 95% CI 1.81–2.67, for HDP and adjusted OR 1.83, 95% CI 1.65–2.03, for GDM). Moreover, there was a tendency toward an increased risk of new-onset MASLD according to the number of APOs (p <0.001 for trend of odds).
Conclusions
APOs were associated with the risk of new-onset MASLD after delivery. Specifically, only HDP or GDM were identified as risk factors for new-onset MASLD.
Impact and implications
This nationwide cohort study confirms that postpartum women with a history of adverse pregnancy outcomes (APOs) are at an increased risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). These findings may bring us one step closer to understanding the exact mechanisms underlying such an important association between prior APOs and cardiovascular disease (CVD) risk among postpartum women. This bidirectional association between APOs and MASLD highlights the importance of considering pregnancy history in assessing CVD risk in women. It suggests a need for closer monitoring and lifestyle interventions for women with a history of APOs to reduce the risk of MASLD and subsequent CVD complications.
背景& 目的不良妊娠结局（APO）会使妇女的心脏代谢风险因素恶化，增加她们在初次怀孕后年轻时罹患心脏代谢疾病的可能性。然而，关于曾有过妊娠结局的妇女新近罹患代谢功能障碍相关性脂肪性肝病（MASLD）风险的数据却很有限。本研究旨在评估经历过 APOs 后新发 MASLD 的风险。方法本研究纳入了在孕前 1 年和产后 1 年接受国民健康检查的中产孕妇。妊娠高血压疾病（HDP）、妊娠糖尿病（GDM）、早产、低出生体重和胎盘早剥是指至少出现以下一种情况。结果在 80,037 名研究参与者中，有 9,320 人（11.6%）在怀孕期间出现过 APO。即使在对各种协变量进行调整后，经历过 APOs 的妇女在产后罹患新发 MASLD 的风险也会增加（调整后的几率比 [OR] 1.58，95% CI 1.45-1.72）。特别是，经历过 HDP 或 GDM 的妇女患上新发 MASLD 的风险显著增加（HDP 的调整 OR 为 2.20，95% CI 为 1.81-2.67；GDM 的调整 OR 为 1.83，95% CI 为 1.65-2.03）。结论 APOs 与产后新发 MASLD 的风险有关。影响和意义这项全国性队列研究证实，有不良妊娠结局（APOs）史的产后妇女患代谢功能障碍相关性脂肪肝（MASLD）的风险增加。这些发现可能会让我们更进一步了解产后妇女的不良妊娠结局与心血管疾病（CVD）风险之间存在如此重要关联的确切机制。APOs与MASLD之间的这种双向关联凸显了在评估妇女心血管疾病风险时考虑妊娠史的重要性。这表明有必要对有APOs病史的妇女进行更密切的监测和生活方式干预，以降低MASLD和随后的心血管疾病并发症的风险。
{"title":"Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study","authors":"Young Mi Jung , Seung Mi Lee , Wonyoung Wi , Min-Jeong Oh , Joong Shin Park , Geum Joon Cho , Won Kim","doi":"10.1016/j.jhepr.2024.101033","DOIUrl":"https://doi.org/10.1016/j.jhepr.2024.101033","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Adverse pregnancy outcomes (APOs) can worsen cardiometabolic risk factors in women, raising their likelihood of developing cardiometabolic diseases at a young age after their initial pregnancy. Nevertheless, there are limited data on the risk of newly developing metabolic dysfunction-associated steatotic liver disease (MASLD) in women who have had APOs. This study aimed to evaluate the risk of new-onset MASLD after experiencing APOs.</p></div><div><h3>Methods</h3><p>Singleton pregnant women who underwent national health screenings 1 year before pregnancy and 1 year after delivery were included in this study. APOs were defined as the presence of at least one of the followings: hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth, low birth weight, and placental abruption. The primary outcome was new-onset MASLD based on the presence of APOs.</p></div><div><h3>Results</h3><p>Among 80,037 study participants, 9,320 (11.6%) experienced APOs during pregnancy. Women who experienced APOs had an increased risk of developing new-onset MASLD after delivery even after adjustments for various covariates (adjusted odds ratio [OR] 1.58, 95% CI 1.45–1.72). In particular, women who experienced either HDP or GDM showed a significantly increased risk of developing new-onset MASLD (adjusted OR 2.20, 95% CI 1.81–2.67, for HDP and adjusted OR 1.83, 95% CI 1.65–2.03, for GDM). Moreover, there was a tendency toward an increased risk of new-onset MASLD according to the number of APOs (<em>p</em> <0.001 for trend of odds).</p></div><div><h3>Conclusions</h3><p>APOs were associated with the risk of new-onset MASLD after delivery. Specifically, only HDP or GDM were identified as risk factors for new-onset MASLD.</p></div><div><h3>Impact and implications</h3><p>This nationwide cohort study confirms that postpartum women with a history of adverse pregnancy outcomes (APOs) are at an increased risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). These findings may bring us one step closer to understanding the exact mechanisms underlying such an important association between prior APOs and cardiovascular disease (CVD) risk among postpartum women. This bidirectional association between APOs and MASLD highlights the importance of considering pregnancy history in assessing CVD risk in women. It suggests a need for closer monitoring and lifestyle interventions for women with a history of APOs to reduce the risk of MASLD and subsequent CVD complications.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258955592400034X/pdfft?md5=34f9f1f8228a5c3dd628e5a52d8739fe&pid=1-s2.0-S258955592400034X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163567","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}
The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).
Methods
A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).
Results
Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.
Conclusions
GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.
Impact and implications
Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.
{"title":"Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study","authors":"Federica D’Amico , Matteo Rinaldi , Renato Pascale , Marco Fabbrini , Maria Cristina Morelli , Antonio Siniscalchi , Cristiana Laici , Simona Coladonato , Matteo Ravaioli , Matteo Cescon , Simone Ambretti , Pierluigi Viale , Patrizia Brigidi , Silvia Turroni , Maddalena Giannella","doi":"10.1016/j.jhepr.2024.101039","DOIUrl":"10.1016/j.jhepr.2024.101039","url":null,"abstract":"<div><h3>Background & Aims</h3><p>The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).</p></div><div><h3>Methods</h3><p>A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).</p></div><div><h3>Results</h3><p>Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of <em>Klebsiella</em> and <em>Enterococcus</em>. The proportions of <em>Klebsiella</em> were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.</p></div><div><h3>Conclusions</h3><p>GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.</p></div><div><h3>Impact and implications</h3><p>Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000405/pdfft?md5=3b165275703f2183e963fb5c2db0507e&pid=1-s2.0-S2589555924000405-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139828955","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}
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