Pub Date : 2024-01-01DOI: 10.1136/egastro-2023-100042
S. Burgess, H. T. Cronjé
Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes. However, if performed without critical thought, we may simply have replaced one set of implausible assumptions (no unmeasured confounding or reverse causation) with another set of implausible assumptions (no pleiotropy or other instrument invalidity). The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables. Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy; in general, a biologically motivated strategy is preferred. In this review, we discuss various ways of implementing a biologically motivated selection strategy: using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels, using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy. In some cases, a genome-wide analysis can provide important complementary evidence, even when its reliability is questionable. In other cases, a biologically-motivated analysis may not be possible. The choice of genetic variants must be informed by biological and functional considerations where possible, requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.
{"title":"Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles","authors":"S. Burgess, H. T. Cronjé","doi":"10.1136/egastro-2023-100042","DOIUrl":"https://doi.org/10.1136/egastro-2023-100042","url":null,"abstract":"Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes. However, if performed without critical thought, we may simply have replaced one set of implausible assumptions (no unmeasured confounding or reverse causation) with another set of implausible assumptions (no pleiotropy or other instrument invalidity). The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables. Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy; in general, a biologically motivated strategy is preferred. In this review, we discuss various ways of implementing a biologically motivated selection strategy: using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels, using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy. In some cases, a genome-wide analysis can provide important complementary evidence, even when its reliability is questionable. In other cases, a biologically-motivated analysis may not be possible. The choice of genetic variants must be informed by biological and functional considerations where possible, requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"103 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139638552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1136/egastro-2023-100006
R. Little, Thisun Jayawardana, Sabrina Koentgen, Fan Zhang, Susan J Connor, Alex Boussioutas, M. Ward, Peter R. Gibson, Miles P Sparrow, Georgina L Hold
The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of ‘big data’ and machine learning in the path towards precision medicine.
{"title":"Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions","authors":"R. Little, Thisun Jayawardana, Sabrina Koentgen, Fan Zhang, Susan J Connor, Alex Boussioutas, M. Ward, Peter R. Gibson, Miles P Sparrow, Georgina L Hold","doi":"10.1136/egastro-2023-100006","DOIUrl":"https://doi.org/10.1136/egastro-2023-100006","url":null,"abstract":"The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of ‘big data’ and machine learning in the path towards precision medicine.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"23 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1136/egastro-2023-100036
B. Chang, Hui Tian, Ang Huang, Xingran Zhai, Qiaoling Wang, Lin Han, Xueyuan Jin, Li Gao, Qing-xiang Liang, Baosen Li, Yinying Lu, Huan Xie, Dong Ji, Zhengsheng Zou
To explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated liver disease (ALD)-related HCC risk.A database of 136 571 inpatients in the Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018 with chronic liver disease was established. Data were collected by medical records review. Multivariate logistic regression was used to identify the independent high-risk factors associated with HCC, and then were incorporated into a novel nomogram. Afterward, the new established model was validated using external cohort by receiver operating characteristic curves analysis. For external cohort, 1646 patients with ALD admitted to our hospital from 2019 to 2021 were included. ALD was diagnosed on the basis of a history of sustained heavy alcohol intake greater than 40 g/day for men and 20 g/day for women for >5 years, clinical evidence of liver disease and supporting laboratory abnormalities.Over the last 17 years, trends showed obviously increases in ALD. ALD-related HCC experienced a significant increase from 5.8% to 30.7%, whereas hepatitis B virus (HBV)-related HCC declined from 77.6% to 52.0%. In patients with ALD-related HCC (5119), 3816 (74.54%) cases had HBV infection, 493 (9.63%) cases had hepatitis C virus (HCV) infection, 71 (1.39%) cases were coinfected with both HBV and HCV, and 739 (14.44%) cases had neither HBV nor HCV infection. Drinking years (OR 1.009, 95% CI (1.000 to 1.017)), age (OR 1.060, 95% CI (1.051 to 1.069)), diabetes mellitus (OR 1.314, 95% CI (1.123 to 1.538)), HBV infection (OR 4.905, 95% CI (4.242 to 5.671)), liver cirrhosis (OR 4.922, 95% CI (3.887 to 6.232)) and male sex (OR 17.011, 95%CI (2.296 to 126.013)) were associated with increased risk of HCC in patients with ALD. A nomogram had a concordance index of 0.786 (95% CI 0.773 to 0.799) and had well-fitted calibration curves. These results were successfully validated both in the internal cohort and external cohort.The prevalence of ALD and ALD-related HCC has been increased dramatically. The nomogram model established here with its high accuracy and easy-to-use features achieved an optimal prediction of HCC development in patients with ALD, which can help clinicians to develop an individualised and precise treatment strategy.
{"title":"Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases","authors":"B. Chang, Hui Tian, Ang Huang, Xingran Zhai, Qiaoling Wang, Lin Han, Xueyuan Jin, Li Gao, Qing-xiang Liang, Baosen Li, Yinying Lu, Huan Xie, Dong Ji, Zhengsheng Zou","doi":"10.1136/egastro-2023-100036","DOIUrl":"https://doi.org/10.1136/egastro-2023-100036","url":null,"abstract":"To explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated liver disease (ALD)-related HCC risk.A database of 136 571 inpatients in the Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018 with chronic liver disease was established. Data were collected by medical records review. Multivariate logistic regression was used to identify the independent high-risk factors associated with HCC, and then were incorporated into a novel nomogram. Afterward, the new established model was validated using external cohort by receiver operating characteristic curves analysis. For external cohort, 1646 patients with ALD admitted to our hospital from 2019 to 2021 were included. ALD was diagnosed on the basis of a history of sustained heavy alcohol intake greater than 40 g/day for men and 20 g/day for women for >5 years, clinical evidence of liver disease and supporting laboratory abnormalities.Over the last 17 years, trends showed obviously increases in ALD. ALD-related HCC experienced a significant increase from 5.8% to 30.7%, whereas hepatitis B virus (HBV)-related HCC declined from 77.6% to 52.0%. In patients with ALD-related HCC (5119), 3816 (74.54%) cases had HBV infection, 493 (9.63%) cases had hepatitis C virus (HCV) infection, 71 (1.39%) cases were coinfected with both HBV and HCV, and 739 (14.44%) cases had neither HBV nor HCV infection. Drinking years (OR 1.009, 95% CI (1.000 to 1.017)), age (OR 1.060, 95% CI (1.051 to 1.069)), diabetes mellitus (OR 1.314, 95% CI (1.123 to 1.538)), HBV infection (OR 4.905, 95% CI (4.242 to 5.671)), liver cirrhosis (OR 4.922, 95% CI (3.887 to 6.232)) and male sex (OR 17.011, 95%CI (2.296 to 126.013)) were associated with increased risk of HCC in patients with ALD. A nomogram had a concordance index of 0.786 (95% CI 0.773 to 0.799) and had well-fitted calibration curves. These results were successfully validated both in the internal cohort and external cohort.The prevalence of ALD and ALD-related HCC has been increased dramatically. The nomogram model established here with its high accuracy and easy-to-use features achieved an optimal prediction of HCC development in patients with ALD, which can help clinicians to develop an individualised and precise treatment strategy.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"262 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139636209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1136/egastro-2023-100035
F. Åberg, Mitja Lääperi, V. Männistö
Steatotic liver disease (SLD) is a growing global concern. The Chronic Liver Disease (CLivD) risk score predicts liver-related outcomes in the general population using easily accessible variables with or without laboratory tests (CLivDlaband CLivDnon-lab). We assessed CLivD’s associations with liver steatosis, fibrosis and its combined performance with fibrosis-4 (FIB-4) for advanced fibrosis detection.Using the National Health and Nutrition Examination Survey data (2017–2020), 3603 participants aged 40–70 years with valid liver stiffness measurements (LSMs) were included. Advanced fibrosis was defined as LSM ≥12 kPa, and SLD as controlled attenuation parameter ≥288 dB/m.Significant associations were found between CLivD and SLD and advanced fibrosis. CLivDlabhad an area under the curve (AUC) for advanced fibrosis of 0.72 (95% CI 0.68 to 0.77), while CLivDnon-labhad an AUC of 0.68 (95% CI 0.64 to 0.72), both slightly higher than FIB-4 (AUC 0.66, 95% CI 0.60 to 0.72). Among participants without obesity, AUC of CLivDlabwas 0.82 (95% CI 0.76 to 0.88) and AUC of CLivDnon-labwas 0.72 (95% CI 0.65 to 0.79). The CLivD score improved FIB-4’s AUC for advanced fibrosis detection from <0.5 at minimal CLivD scores to >0.8 at high CLivD scores. A sequential CLivD→FIB-4 strategy outperformed universal FIB-4 testing, enhancing specificity from 72% to 83%, with sensitivity at 51%–53%. This strategy identified a subgroup with a 55% prevalence of advanced fibrosis, while 47% had minimal-risk CLivD scores, eliminating the need for FIB-4 testing.The CLivD score, designed for predicting liver-related outcomes, effectively identifies liver steatosis and advanced fibrosis in the general population. Combining CLivD with FIB-4 enhances advanced fibrosis detection accuracy. The CLivD score could enhance population-based liver fibrosis screening, optimising resource allocation.
脂肪肝（SLD）是全球日益关注的问题。慢性肝病（CLivD）风险评分利用易于获取的变量，通过或不通过实验室检测（CLivDlab 和 CLivDnon-lab）预测普通人群中与肝脏相关的结果。我们评估了CLivD与肝脏脂肪变性、肝纤维化的关联，以及其与纤维化-4（FIB-4）联合检测晚期肝纤维化的性能。利用美国国家健康与营养调查数据（2017-2020年），纳入了3603名年龄在40-70岁之间、具有有效肝脏硬度测量值（LSM）的参与者。晚期肝纤维化的定义为 LSM ≥12 kPa，SLD 为受控衰减参数 ≥288 dB/m.研究发现 CLivD 和 SLD 与晚期肝纤维化之间存在显著关联。CLivDlab的晚期纤维化曲线下面积（AUC）为0.72（95% CI 0.68至0.77），而CLivDnon-lab的AUC为0.68（95% CI 0.64至0.72），均略高于FIB-4（AUC 0.66，95% CI 0.60至0.72）。在无肥胖症的参与者中，CLivDlab的AUC为0.82（95% CI 0.76至0.88），CLivDnon-lab的AUC为0.72（95% CI 0.65至0.79）。CLivD评分提高了FIB-4的晚期纤维化检测AUC，CLivD高分时AUC为0.8。CLivD→FIB-4连续检测策略优于FIB-4全面检测，特异性从72%提高到83%，灵敏度为51%-53%。CLivD评分是为预测肝脏相关结果而设计的，能有效识别普通人群中的肝脏脂肪变性和晚期纤维化。将CLivD与FIB-4结合可提高晚期肝纤维化检测的准确性。CLivD评分可加强基于人群的肝纤维化筛查，优化资源分配。
{"title":"CLivD score modifies FIB-4 performance in liver fibrosis detection in the US general population","authors":"F. Åberg, Mitja Lääperi, V. Männistö","doi":"10.1136/egastro-2023-100035","DOIUrl":"https://doi.org/10.1136/egastro-2023-100035","url":null,"abstract":"Steatotic liver disease (SLD) is a growing global concern. The Chronic Liver Disease (CLivD) risk score predicts liver-related outcomes in the general population using easily accessible variables with or without laboratory tests (CLivDlaband CLivDnon-lab). We assessed CLivD’s associations with liver steatosis, fibrosis and its combined performance with fibrosis-4 (FIB-4) for advanced fibrosis detection.Using the National Health and Nutrition Examination Survey data (2017–2020), 3603 participants aged 40–70 years with valid liver stiffness measurements (LSMs) were included. Advanced fibrosis was defined as LSM ≥12 kPa, and SLD as controlled attenuation parameter ≥288 dB/m.Significant associations were found between CLivD and SLD and advanced fibrosis. CLivDlabhad an area under the curve (AUC) for advanced fibrosis of 0.72 (95% CI 0.68 to 0.77), while CLivDnon-labhad an AUC of 0.68 (95% CI 0.64 to 0.72), both slightly higher than FIB-4 (AUC 0.66, 95% CI 0.60 to 0.72). Among participants without obesity, AUC of CLivDlabwas 0.82 (95% CI 0.76 to 0.88) and AUC of CLivDnon-labwas 0.72 (95% CI 0.65 to 0.79). The CLivD score improved FIB-4’s AUC for advanced fibrosis detection from <0.5 at minimal CLivD scores to >0.8 at high CLivD scores. A sequential CLivD→FIB-4 strategy outperformed universal FIB-4 testing, enhancing specificity from 72% to 83%, with sensitivity at 51%–53%. This strategy identified a subgroup with a 55% prevalence of advanced fibrosis, while 47% had minimal-risk CLivD scores, eliminating the need for FIB-4 testing.The CLivD score, designed for predicting liver-related outcomes, effectively identifies liver steatosis and advanced fibrosis in the general population. Combining CLivD with FIB-4 enhances advanced fibrosis detection accuracy. The CLivD score could enhance population-based liver fibrosis screening, optimising resource allocation.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"333 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139016090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1136/egastro-2023-100017
F. Mokhtari-Esbuie, Bryan C Szeglin, Mohsen Rouhani Ravari, Mark Duncan, John W Harmon
Worldwide, gastric cancer results in significant morbidity and mortality. Ten per cent of patients with gastric cancer have a strong family history of the disease.CDH1(E-cadherin) has been identified as a key gene whose mutation leads to hereditary diffuse gastric cancer. We overviewed 33 articles with prophylactic total gastrectomy and assessed the outcomes and benefits. Families with mutations inCDH1may benefit from early prophylactic total gastrectomy. Dr Mark Duncan has applied his experience as a high-volume gastric cancer surgeon to treat not only individual patients, but several generations of patients within a family. This use of prophylactic total gastrectomy is well tolerated by patients and prevents the future development of gastric cancer.
在世界范围内，胃癌的发病率和死亡率都很高。10%的胃癌患者有强烈的胃癌家族史，cdh1 (e -钙粘蛋白)已被确定为一个关键基因，其突变导致遗传性弥漫性胃癌。我们回顾了33篇关于预防性全胃切除术的文章，并评估了结果和益处。有incdh1突变的家庭可能从早期预防性全胃切除术中获益。马克·邓肯医生运用他作为胃癌外科医生的经验，不仅治疗单个病人，而且治疗一个家庭中几代人的病人。这种预防性全胃切除术的使用被患者很好地耐受，并防止胃癌的未来发展。
{"title":"Pioneering use of genetic analysis forCDH1to identify candidates for prophylactic total gastrectomy to prevent hereditary diffuse gastric cancer","authors":"F. Mokhtari-Esbuie, Bryan C Szeglin, Mohsen Rouhani Ravari, Mark Duncan, John W Harmon","doi":"10.1136/egastro-2023-100017","DOIUrl":"https://doi.org/10.1136/egastro-2023-100017","url":null,"abstract":"Worldwide, gastric cancer results in significant morbidity and mortality. Ten per cent of patients with gastric cancer have a strong family history of the disease.CDH1(E-cadherin) has been identified as a key gene whose mutation leads to hereditary diffuse gastric cancer. We overviewed 33 articles with prophylactic total gastrectomy and assessed the outcomes and benefits. Families with mutations inCDH1may benefit from early prophylactic total gastrectomy. Dr Mark Duncan has applied his experience as a high-volume gastric cancer surgeon to treat not only individual patients, but several generations of patients within a family. This use of prophylactic total gastrectomy is well tolerated by patients and prevents the future development of gastric cancer.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":" 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1136/egastro-2023-100029
Lanlan Chen, Guoyue Lv
Recent studies have decoded the human Y chromosome sequencing with predominant precision and coverage, offering promising prospects in human genetics and clinical translation. Such an achievement is facilitated by third-generation sequencing technologies including Oxford Nanopore Technology and Pacific Biosciences, which can overcome the limitations of next-generation sequencing. In the context of digestive diseases, these advancements hold significant potential as they can help address the ‘missing heritability’ problem and detect various genomic variants in genetic association analyses, beyond single nucleotide polymorphisms, hoping to reveal ‘major’ genes for complex diseases. Besides, the completion of the Y chromosome enables research into sex-specific genetic effects on diseases and this knowledge can lead to sex-specific therapeutic targets and a better understanding of molecular mechanisms behind gender disparities. In summary, the recent decoding of the Y chromosome, coupled with third-generation sequencing, offers new opportunities to address heritability gaps, discover major disease genes and investigate sex-specific effects in digestive diseases, providing valuable insights for clinicians in delivering precise healthcare services.
{"title":"New horizons of human genetics in digestive diseases","authors":"Lanlan Chen, Guoyue Lv","doi":"10.1136/egastro-2023-100029","DOIUrl":"https://doi.org/10.1136/egastro-2023-100029","url":null,"abstract":"Recent studies have decoded the human Y chromosome sequencing with predominant precision and coverage, offering promising prospects in human genetics and clinical translation. Such an achievement is facilitated by third-generation sequencing technologies including Oxford Nanopore Technology and Pacific Biosciences, which can overcome the limitations of next-generation sequencing. In the context of digestive diseases, these advancements hold significant potential as they can help address the ‘missing heritability’ problem and detect various genomic variants in genetic association analyses, beyond single nucleotide polymorphisms, hoping to reveal ‘major’ genes for complex diseases. Besides, the completion of the Y chromosome enables research into sex-specific genetic effects on diseases and this knowledge can lead to sex-specific therapeutic targets and a better understanding of molecular mechanisms behind gender disparities. In summary, the recent decoding of the Y chromosome, coupled with third-generation sequencing, offers new opportunities to address heritability gaps, discover major disease genes and investigate sex-specific effects in digestive diseases, providing valuable insights for clinicians in delivering precise healthcare services.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"14 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135565753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1136/egastro-2023-100009
Jorge Arnold, Eduardo Avila, Francisco Idalsoaga, Luis Antonio Diaz, M. Ayala Valverde, Gustavo Ayares, Marco Arrese, Eric Roessler, Juan Pablo Huidobro, David Hudson, Mohammad Qasim Khan, J. Arab
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI—liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
在肝肾综合征-急性肾损伤（HRS-AKI）中，准确和早期诊断至关重要。肝肾综合征是晚期肝硬化的一种严重病症，需要及时识别和妥善处理，以提高患者的预后。与其他肝硬化 AKI 病例类似，HRS-AKI 的诊断依赖于血清肌酐升高。然而，在这些患者中将 HRS-AKI 与其他肾功能损害区分开来可能具有挑战性。生物标志物和临床标准有助于诊断和指导治疗。HRS-AKI 的治疗最初包括使用白蛋白和血管收缩剂（如特利加压素，一种合成的血管加压素类似物）改善血流动力学状况。尽管有报告称，与去甲肾上腺素相比，特利加压素会增加不良反应，但由于其反应更快、更强并能提高存活率，它仍是治疗 HRS-AKI 和急性-慢性肝衰竭的首选药物。其他疗法，如米多君（α-1肾上腺素能激动剂）、奥曲肽（体生长抑素类似物）和经颈静脉肝内门体分流术，被建议作为HRS-AKI的辅助疗法，旨在改善血管收缩和肾血流量。然而，这些辅助疗法不能取代 HRS-AKI 的最终治疗方法--肝移植（LT）。对于药物治疗无效的病例，肝移植是恢复肝功能和改善肾脏预后的唯一选择。目前的证据显示，在某些情况下，肝肾联合移植（CLKT）更受青睐。本综述旨在评估肝硬化患者 AKI 的现有证据和建议、HRS-AKI 的病理生理学、LT 和 CLKT 的不同治疗方法和适应症。了解处理 HRS-AKI 的复杂性对于优化患者护理和在这一具有挑战性的临床环境中取得更好的疗效至关重要。
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Pub Date : 2023-11-01DOI: 10.1136/egastro-2023-100004
Juan Gerardo Favela, Madison B. Argo, Sergio Huerta
In the absence of gallstones or any other form of mechanical obstruction, hypoperfusion to the gallbladder can lead to inflammation, ischaemia and perforation. This constellation of findings has historically been simply referred to as ‘acalculous cholecystitis’. However, this term makes no distinction between inflammation due to critical illness and poor perfusion, or what we will refer to as ischaemic cholecystitis, versus other non-obstructive aetiologies. Ischaemic cholecystitis presents diagnostic as well as treatment challenges that are unique to patients in the critical care setting. More importantly, the morbidity and mortality of this proposed subcategory of acute gallbladder inflammation is much higher compared with other forms of acute cholecystitis. In the present manuscript, we introduce the concept of ischaemic cholecystitis and the importance of differentiating this clinical diagnosis from other forms of acalculous cholecystitis. Additionally, we elaborate on the most recent diagnostic modalities and treatment options specific to this vulnerable patient population.
{"title":"Aetiology, diagnosis and management for ischaemic cholecystitis: current perspectives","authors":"Juan Gerardo Favela, Madison B. Argo, Sergio Huerta","doi":"10.1136/egastro-2023-100004","DOIUrl":"https://doi.org/10.1136/egastro-2023-100004","url":null,"abstract":"In the absence of gallstones or any other form of mechanical obstruction, hypoperfusion to the gallbladder can lead to inflammation, ischaemia and perforation. This constellation of findings has historically been simply referred to as ‘acalculous cholecystitis’. However, this term makes no distinction between inflammation due to critical illness and poor perfusion, or what we will refer to as ischaemic cholecystitis, versus other non-obstructive aetiologies. Ischaemic cholecystitis presents diagnostic as well as treatment challenges that are unique to patients in the critical care setting. More importantly, the morbidity and mortality of this proposed subcategory of acute gallbladder inflammation is much higher compared with other forms of acute cholecystitis. In the present manuscript, we introduce the concept of ischaemic cholecystitis and the importance of differentiating this clinical diagnosis from other forms of acalculous cholecystitis. Additionally, we elaborate on the most recent diagnostic modalities and treatment options specific to this vulnerable patient population.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139303408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1136/egastro-2023-100043
Lanlan Chen, Stephen Burgess, Shan Luo, Guoyue Lv
We are delighted to announce the release of the first Chinese book on Mendelian randomisation, translated from Mendelian Randomization: Methods for Causal Inference Using Genetic Variants (Second Edition) by Dr Stephen Burgess and Professor Simon G Thompson, on 25 September 2023. The original
我们很高兴地宣布，第一本关于孟德尔随机化的中文书将于2023年9月25日出版，该书翻译自Stephen Burgess博士和Simon G Thompson教授的《孟德尔随机化:使用遗传变异进行因果推理的方法(第二版)》。最初的
{"title":"First release of Mendelian randomisation book in Chinese","authors":"Lanlan Chen, Stephen Burgess, Shan Luo, Guoyue Lv","doi":"10.1136/egastro-2023-100043","DOIUrl":"https://doi.org/10.1136/egastro-2023-100043","url":null,"abstract":"We are delighted to announce the release of the first Chinese book on Mendelian randomisation, translated from Mendelian Randomization: Methods for Causal Inference Using Genetic Variants (Second Edition) by Dr Stephen Burgess and Professor Simon G Thompson, on 25 September 2023. The original","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"11 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135565481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1136/egastro-2023-100012
Aditi Kumar, Philip J Smith
The current mainstay treatment modalities for inflammatory bowel disease (IBD) include immunomodulators (methotrexate and thiopurines), biologics (antitumour necrosis factor alpha (TNF-α) being the most commonly used) and other monoclonal antibodies such as the anti-integrins and anti-interleukins (IL-12/23). While ideally treatment should be initiated early in the disease process to avoid relapses and complications, the major recurring issue continues to be primary and secondary loss of response, with often ‘diminishing returns’ in terms of efficacy for the next line of therapies prescribed for patients with IBD. Additional concerns include the long-term risk factors such as malignancy and susceptibility to infections. Recently, there has been an influx of new and emerging medications entering the market that are showing promising efficacy results in patients with moderate-to-severe disease who have previously failed to respond to multiple drugs. This review will focus on these novel and emerging therapies—in essence, ‘horizon scanning’—which includes the antiadhesion agents, cytokine inhibitors, Janus kinase inhibitors, phosphodiesterase inhibitors, sphingosine-1 phosphate receptor modulators and MicroRNA-124 (miR-124) upregulators.
{"title":"Horizon scanning: new and future therapies in the management of inflammatory bowel disease","authors":"Aditi Kumar, Philip J Smith","doi":"10.1136/egastro-2023-100012","DOIUrl":"https://doi.org/10.1136/egastro-2023-100012","url":null,"abstract":"The current mainstay treatment modalities for inflammatory bowel disease (IBD) include immunomodulators (methotrexate and thiopurines), biologics (antitumour necrosis factor alpha (TNF-α) being the most commonly used) and other monoclonal antibodies such as the anti-integrins and anti-interleukins (IL-12/23). While ideally treatment should be initiated early in the disease process to avoid relapses and complications, the major recurring issue continues to be primary and secondary loss of response, with often ‘diminishing returns’ in terms of efficacy for the next line of therapies prescribed for patients with IBD. Additional concerns include the long-term risk factors such as malignancy and susceptibility to infections. Recently, there has been an influx of new and emerging medications entering the market that are showing promising efficacy results in patients with moderate-to-severe disease who have previously failed to respond to multiple drugs. This review will focus on these novel and emerging therapies—in essence, ‘horizon scanning’—which includes the antiadhesion agents, cytokine inhibitors, Janus kinase inhibitors, phosphodiesterase inhibitors, sphingosine-1 phosphate receptor modulators and MicroRNA-124 (miR-124) upregulators.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136094236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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