Hepatology International最新文献

{"title":"Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.","authors":"Pei-Xin Zhang, Qian-Qian Tang, Jie Zhu, Wan-Yu Deng, Zhen-Hua Zhang","doi":"10.1007/s12072-024-10666-6","DOIUrl":"10.1007/s12072-024-10666-6","url":null,"abstract":"<p><strong>Background and aims: </strong>The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis.</p><p><strong>Results: </strong>This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment.</p><p><strong>Conclusion: </strong>A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1110-1121"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylaxis of hepatic encephalopathy: current and future drug targets.","authors":"Sudhir Maharshi, Barjesh Chander Sharma","doi":"10.1007/s12072-024-10647-9","DOIUrl":"10.1007/s12072-024-10647-9","url":null,"abstract":"<p><p>Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1096-1109"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation of the liver, HCC development and HCC establishment.","authors":"Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai","doi":"10.1007/s12072-024-10707-0","DOIUrl":"10.1007/s12072-024-10707-0","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1090-1092"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep patterns, genetic susceptibility, and risk of cirrhosis among individuals with nonalcoholic fatty liver disease.","authors":"Shifan Qin, Xiang Cheng, Shanshan Zhang, Qian Shen, Rong Zhong, Xueqin Chen, Zhiqian Yi","doi":"10.1007/s12072-024-10665-7","DOIUrl":"10.1007/s12072-024-10665-7","url":null,"abstract":"<p><strong>Background: </strong>The associations between sleep patterns or behaviors and the risk of cirrhosis and the influence of genetic susceptibility on these associations among NAFLD participants remain inadequately elucidated.</p><p><strong>Methods: </strong>This study conducted a prospective follow-up of 112,196 NAFLD participants diagnosed at baseline from the UK Biobank cohort study. Five sleep behaviors were collected to measure a healthy sleep score. Five genetic variants were used to construct a polygenic risk score. We used Cox proportional hazard model to assess hazard ratios (HR) and 95% confidence intervals (CIs) for incidence of cirrhosis.</p><p><strong>Results: </strong>During the follow-up, 592 incident cirrhosis cases were documented. Healthy sleep pattern was associated with reduced risk of cirrhosis in a dose-response manner (p_trend < 0.001). Participants with favourable sleep score (versus unfavourable sleep score) had an HR of 0.55 for cirrhosis risk (95% CI 0.39-0.78). Multivariable-adjusted HRs (95% CIs) of cirrhosis incidence for NAFLDs with no frequent insomnia, sleeping for 7-8 h per day, and no excessive daytime dozing behaviors were 0.73 (0.61-0.87), 0.79 (0.66-0.93), and 0.69 (0.50-0.95), respectively. Compared with participants with favourable sleep pattern and low genetic risk, those with unfavourable sleep pattern and high genetic risk had higher risks of cirrhosis incidence (HR 3.16, 95% CI 1.88-5.33). In addition, a significant interaction between chronotype and genetic risk was detected for the incidence of cirrhosis (p for multiplicative interaction = 0.004).</p><p><strong>Conclusion: </strong>An association was observed between healthy sleep pattern and decreased risk of cirrhosis among NAFLD participants, regardless of low or high genetic risk.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1158-1167"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The upregulation of Annexin A2 by TLR4 pathway facilitates lipid accumulation and liver injury via blocking AMPK/mTOR-mediated autophagy flux during the development of non-alcoholic fatty liver disease.","authors":"Haifeng Wu, Meng Zhou, Qin Jin, Xun Wang, Yue Xu, Ming Li, Shuhui Chen, Qin Tang, Qi Wang, Baoying Hu, Hongpei Wu, Mingbing Xiao, Lishuai Qu, Qiong Zhang, Jinxia Liu","doi":"10.1007/s12072-023-10622-w","DOIUrl":"10.1007/s12072-023-10622-w","url":null,"abstract":"<p><strong>Background and aims: </strong>Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD.</p><p><strong>Methods: </strong>Histological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects. The role of ANXA2 was evaluated using high-fat diet (HFD)-fed mice via vein injection of adeno-associated viruses (AAV) knocking down ANXA2 or non-targeting control (NC) shRNAs. Moreover, HepG2 and LO2 cells were employed as in vitro hepatocyte models to investigate the expression and function of ANXA2.</p><p><strong>Results: </strong>ANXA2 was confirmed to be one of three hub genes in liver injury, and its expression was positively correlated with NAFLD activity score (NAS) and macrophage infiltration in NAFLD. Moreover, ANXA2 was significantly upregulated in NAFLD patients and HFD-fed mice. LPS/TLR4 pathway strongly upregulated ANXA2 expression, which is mediated by direct ANXA2 promoter binding by TLR4 downstream NF-κB p65 and c-Jun transcription factors. Increased ANXA2 expression was correlated with decreased autophagy flux and autophagy was activated by the depletion of ANXA2 in the models of NAFLD. Furthermore, ANXA2 interference led to the activation of AMPK/mTOR signaling axis, which may play a causal role in autophagy flux and the amelioration of steatosis.</p><p><strong>Conclusions: </strong>ANXA2 is a pathological predictor and promising therapeutic target for NAFLD. ANXA2 plays a crucial role in linking inflammation to hepatic metabolic disorder and injury, mainly through the blockage of AMPK/mTOR-mediated lipophagy.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1144-1157"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to the letter of HEPI-D-24-00252.","authors":"Shang-Chin Huang, Tung-Hung Su, Jia-Horng Kao","doi":"10.1007/s12072-024-10681-7","DOIUrl":"10.1007/s12072-024-10681-7","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1340-1341"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic-associated vascular morphological assessment to predict overt hepatic encephalopathy before TIPS: a multicenter study.","authors":"Xiaoqiong Chen, Mingsheng Huang, Xiangrong Yu, Jinqiang Chen, Chunchun Xu, Yunzheng Jiang, Yiting Li, Yujie Zhao, Chongyang Duan, Yixin Luo, Jiawei Zhang, Weifu Lv, Qiyang Li, Junyang Luo, Dandan Dong, Taixue An, Ligong Lu, Sirui Fu","doi":"10.1007/s12072-024-10686-2","DOIUrl":"10.1007/s12072-024-10686-2","url":null,"abstract":"<p><strong>Background: </strong>To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks.</p><p><strong>Methods: </strong>In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of Model^C-V, we compared it with four previous models, both in discrimination and calibration.</p><p><strong>Results: </strong>The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, Model^C-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups.</p><p><strong>Conclusion: </strong>Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1238-1248"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis.","authors":"Bastian Engel, Jana Diestelhorst, Katharina Luise Hupa-Breier, Theresa Kirchner, Nicole Henjes, Stephanie Loges, Muhammed Yuksel, Wojciech Janczyk, Claudine Lalanne, Kalliopi Zachou, Ye H Oo, Jérôme Gournay, Simon Pape, Joost P H Drenth, Amédée Renand, George N Dalekos, Luigi Muratori, Piotr Socha, Yun Ma, Cigdem Arikan, Ulrich Baumann, Michael P Manns, Heiner Wedemeyer, Norman Junge, Elmar Jaeckel, Richard Taubert","doi":"10.1007/s12072-024-10695-1","DOIUrl":"10.1007/s12072-024-10695-1","url":null,"abstract":"<p><strong>Objective: </strong>The detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH.</p><p><strong>Design: </strong>pIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285).</p><p><strong>Results: </strong>IgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31-73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6-20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21-34% higher accuracy than conventional autoantibodies, was positive in 43-75% of children with AIH and normal IgG and independent from treatment response.</p><p><strong>Conclusion: </strong>Detecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1214-1226"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is TACE plus tyrosine kinase inhibitors and immune checkpoint inhibitors superior to TACE plus tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: the debate continues.","authors":"Shiye Yang, Huoqi Liang, Xing Li, Jiayi Qian, Zhibing Ming","doi":"10.1007/s12072-024-10651-z","DOIUrl":"10.1007/s12072-024-10651-z","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1336-1337"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.","authors":"Wenchen Gong, Su Zhang, Xiangdong Tian, Wenshuai Chen, Yuchao He, Liwei Chen, Tingting Ding, Peiqi Ren, Lin Shi, Qiang Wu, Yan Sun, Lu Chen, Hua Guo","doi":"10.1007/s12072-024-10694-2","DOIUrl":"10.1007/s12072-024-10694-2","url":null,"abstract":"<p><strong>Background: </strong>Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation.</p><p><strong>Methods: </strong>The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry.</p><p><strong>Results: </strong>A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence.</p><p><strong>Conclusion: </strong>The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1310-1325"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}