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Eslam M, Fan JG, Yu ML, Wong VWS, Cua IH, Liu CJ, Tanwandee T, Gani R, Seto WK, Alam S, Young DY, Hamid S, Zheng MH, Kawaguchi T, Chan WK, Payawal D, Tan SS, Goh GBB, Strasser SI, Viet HD, Kao JH, Kim W, Kim SU, Keating SE, Yilmaz Y, Kamani L, Wang CC, Fouad Y, Abbas Z, Treeprasertsuk S, Thanapirom K, Al Mahtab M, Lkhagvaa U, Baatarkhuu O, Choudhury AK, Stedman CAM, Chowdhury A, Dokmeci AK, Wang FS, Lin HC, Huang JF, Howell J, Jia J, Alboraie M, Roberts SK, Yoneda M, Ghazinian H, Mirijanyan A, Nan Y, Lesmana CRA, Adams LA, Shiha G, Kumar M, Örmeci N, Wei L, Lau G, Omata M, Sarin SK, George J. The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease. Hepatol Int 2025; 19:261-301. [PMID: 40016576 DOI: 10.1007/s12072-024-10774-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 12/28/2024] [Indexed: 03/01/2025]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal MedicineCollege of Medicine and Center for Liquid Biopsy and Cohort ResearchFaculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of MedicineSchool of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, Kaohsiung Medical University, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, China
| | - Ian Homer Cua
- Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Global City, Philippines
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal MedicineHepatitis Research CenterGraduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tawesak Tanwandee
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Rino Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Pangeran Diponegoro Road No. 71St, Central Jakarta, 10430, Indonesia
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Shahinul Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh
| | - Dan Yock Young
- Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Saeed Hamid
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Diana Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Philippines
| | - Soek-Siam Tan
- Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Medicine Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Hang Dao Viet
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
| | - Jia-Horng Kao
- Graduate Institute of Clinical MedicineDepartment of Internal MedicineHepatitis Research CenterDepartment of Medical Research, National Taiwan University College of Medicine, National Taiwan University, National Taiwan University Hospital, 1 Chang-Te Street, 10002, Taipei, Taiwan
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Shelley E Keating
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | | | - Chia-Chi Wang
- Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Taipei, Taiwan
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Cairo, Egypt
| | - Zaigham Abbas
- Department of Hepatogastroenterology, Dr.Ziauddin University Hospital, Clifton, Karachi, Pakistan
| | | | | | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Undram Lkhagvaa
- Department of Health Policy, School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Oidov Baatarkhuu
- Department of Infectious Diseases, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ashok Kumar Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - A Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, 100039, China
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Institute of Clinical Medicine, School of Medicine, Taipei Veterans General Hospital, National Yang-Ming Chiao Tung University, No. 201, Section 2, Shipai RdNo. 155, Section 2, Linong St, Beitou District, Taipei City, 112, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal MedicineCollege of Medicine and Center for Liquid Biopsy and Cohort ResearchFaculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jess Howell
- Burnet Institute, Melbourne, VIC, 3004, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Clayton, VIC, 3008, Australia
- Department of Medicine, The University of Melbourne, Parkville, VIC, 3050, Australia
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, VIC, 3165, Australia
| | - Jidong Jia
- Liver Research Center, Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, 11884, Egypt
| | - Stuart K Roberts
- Department of Gastroenterology and Hepatology, Central Clinical School, The Alfred, Monash University, Melbourne, Australia
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan
| | - Hasmik Ghazinian
- Gastroenterology and Hepatology Department, Yerevan Medical Scientific Center, Yerevan, Armenia
| | - Aram Mirijanyan
- Gastroenterology and Hepatology Department, Yerevan Medical Scientific Center, Yerevan, Armenia
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China
| | | | - Leon A Adams
- Medical School, Faculty of Medicine and Health Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Gamal Shiha
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Necati Örmeci
- Department of Gastroenterohepatology, Istanbul Health and Technology University, Istanbul, Turkey
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - George Lau
- Humanity and Health Medical Group, Humanity and Health Clinical Trial Center, Hong Kong SAR, China
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
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Schulz MS, Angeli P, Trebicka J. Acute and non-acute decompensation of liver cirrhosis (47/130). Liver Int 2025; 45:e15861. [PMID: 38426268 PMCID: PMC11815624 DOI: 10.1111/liv.15861] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 12/18/2023] [Accepted: 01/19/2024] [Indexed: 03/02/2024]
Abstract
In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.
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Affiliation(s)
- Martin S. Schulz
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
| | - Jonel Trebicka
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
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Wang X, Li J, Nong J, Deng X, Chen Y, Wu P, Huang X. Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats. Biochem Genet 2025; 63:281-297. [PMID: 38438779 DOI: 10.1007/s10528-024-10684-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 01/03/2024] [Indexed: 03/06/2024]
Abstract
Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.
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Affiliation(s)
- Xinyuan Wang
- Development of Planning Division, Guangxi University of Chinese Medicine, Nanning, 530000, China
| | - Juan Li
- Development of Pediatric, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530000, China
| | - Jiao Nong
- Development of Education, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530000, China
| | - Xin Deng
- Basic Medical College, Guangxi University of Chinese Medicine, Nanning, 530000, China
| | - Yiping Chen
- Development of Emergency, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No.28 Wangyuan Road, Qingxiu District, Nanning, 530000, China
| | - Peibin Wu
- Achievement Transformation and Social Service Office, Guangxi University of Chinese Medicine, Nanning, 530000, China
| | - Xiabing Huang
- Development of Emergency, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No.28 Wangyuan Road, Qingxiu District, Nanning, 530000, China.
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Wang T, Xiang Y, Wang J, Gu J, Yang L, Ma D, Zhu H, Liu T, Li C, Zhang Q, Han J, Ding D, Wang W, Li Q, Wan H, Qi X. A Multi-Scale Computational Model of the Hepatic Circulation Applied to Predict the Portal Pressure After Transjugular Intrahepatic Portosystemic Shunt (TIPS). INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING 2025; 41:e3908. [PMID: 39853965 DOI: 10.1002/cnm.3908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 12/17/2024] [Accepted: 12/29/2024] [Indexed: 01/26/2025]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertension. In clinical practice, the diameter of the stent forming a shunt is usually selected empirically, which will influence the postoperative portal pressure. Clinical studies found that inappropriate portal pressure after TIPS is responsible for poor prognosis; however, there is no scheme to predict postoperative portal pressure. Therefore, this study aims to develop a computational model applied to predict the portal pressure after TIPS ahead of the surgery. For this purpose, a patient-specific 0-3-D multi-scale computational model of the hepatic circulation was developed based on preoperative clinical data. The model was validated using the prospectively collected clinical data of 18 patients. Besides, the model of a representative patient was employed in the numerical experiment to further investigate the influences of multiple pathophysiological and surgical factors. Results showed that the difference between the simulated and in vivo measured portal pressures after TIPS was -1.37 ± 3.51 mmHg, and the simulated results were significantly correlated with the in vivo measured results (r = 0.93, p < 0.0001). Numerical experiment revealed that the estimated model parameters and the severity of possible inherent portosystemic collaterals slightly influenced the simulated results, while the shunt diameter considerably influenced the results. In particular, the existence of catheter for pressure measurement would markedly influence postoperative portal pressure. These findings demonstrated that this computational model is a promising tool for predicting postoperative portal pressure, which would guide the selection of stent diameter and promote individualization and precision of TIPS.
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Affiliation(s)
- Tianqi Wang
- School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai, China
- School of Mechanical Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Yi Xiang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Jitao Wang
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People's Hospital, Hebei Medical University, Xingtai, China
- School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Jiaqi Gu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Ling Yang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Deqiang Ma
- Department of Infectious Diseases, Hubei Provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - He Zhu
- First Department of Intervention, The Sixth People's Hospital of Shenyang, Shenyang, China
| | - Tianyu Liu
- Department of Gastroenterology, Suining Central Hospital, Suining, China
| | - Chunlong Li
- Department of Interventional Radiology, The Six Affiliated Hospital of Nantong University (Yancheng Third People's Hospital), Yancheng, China
| | - Qi Zhang
- Department of Interventional and Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jiahao Han
- Department of Ultrasound Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Deping Ding
- Department of Infectious Diseases, Hubei Provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Wei Wang
- First Department of Intervention, The Sixth People's Hospital of Shenyang, Shenyang, China
| | - Qianlong Li
- Department of Gastroenterology, Suining Central Hospital, Suining, China
| | - Haoguang Wan
- Department of Interventional Radiology, The Six Affiliated Hospital of Nantong University (Yancheng Third People's Hospital), Yancheng, China
| | - Xiaolong Qi
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, China; Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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Barr RG. Multiparametric Ultrasound for Chronic Liver Disease. Radiol Clin North Am 2025; 63:13-28. [PMID: 39510657 DOI: 10.1016/j.rcl.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Diffuse liver disease is a substantial world-wide problem. With the combination of conventional ultrasound of the abdomen, fat quantification and elastography, appropriate staging of the patient can be assessed. This information allows for the diagnosis of steatosis and detection of fibrosis as well as prognosis, surveillance, and prioritization for treatment. With the potential for reversibility with appropriate treatment accurate assessment for the stage of chronic liver disease is critical.
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Affiliation(s)
- Richard G Barr
- Northeastern Ohio Medical University, Southwoods Imaging, 7623 Market Street, Youngstown, OH 44512, USA.
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Yang L, Zhang Y, Wang T. Hemodynamic comparisons of different shunt positions and geometrical model simplification strategies in the simulation of transjugular intrahepatic portosystemic shunt (TIPS). Sci Rep 2024; 14:31486. [PMID: 39732832 PMCID: PMC11682052 DOI: 10.1038/s41598-024-82954-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 12/10/2024] [Indexed: 12/30/2024] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertensive patients, whose potential postoperative complications are closely related to the hemodynamic condition of the portal venous system. The selection of shunt position in the surgery may affect the postoperative hemodynamics; however, it is difficult for clinical studies to investigate the influence. Therefore, this study aims to employ the computational model simulating TIPS to compare the hemodynamic differences resulting from different shunt positions, and also to investigate the influences of different geometrical model simplification strategies used in the TIPS simulation. For this purpose, the clinical data of two representative patients were retrospectively collected, based on which, the computational hemodynamic models of the portal venous systems after TIPS were constructed, incorporating three typical shunt positions (i.e. shunt at the left/main/right portal vein) and three types of geometrical model simplification. Results showed that among the models with different shunt positions, the area-averaged flow velocity magnitudes in the shunts were very similar, while the model with shunt at the main portal vein showed the lowest postoperative portal pressure and the smallest area of high wall shear stress near the portal venous bifurcation. Among the models using different geometrical model simplification strategies, the simulated blood pressures at the main portal veins were very similar, but showed marked differences near the shunt inlets. Moreover, the area-averaged flow velocity magnitudes in the shunts were almost the same, while the velocity distributions differed a lot, leading to the different spatial distributions of wall shear stress near the portal venous bifurcations and shunt walls. These results on one hand suggested that placing the shunt at the main portal vein is more beneficial for the patient; on the other hand, they proved the feasibility of utilizing simplified model to save computational cost without losing the accuracy when the pressure at the main portal vein is mainly focused on. These findings would assist clinical decision-making and promote more accurate and efficient TIPS simulations.
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Affiliation(s)
- Liu Yang
- School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, No. 516 Jungong Road, Yangpu District, Shanghai, 200093, China
- School of Mechanical Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Yitao Zhang
- School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, No. 516 Jungong Road, Yangpu District, Shanghai, 200093, China
- School of Mechanical Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Tianqi Wang
- School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, No. 516 Jungong Road, Yangpu District, Shanghai, 200093, China.
- School of Mechanical Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
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Itule PW, Mwanga A, Khamisi RH, Byomuganyizi M, Lutege W, Kagaruki TB. Clinical characteristics and management of patient with portal hypertension at tertial level hospital in Tanzania. BMC Cardiovasc Disord 2024; 24:428. [PMID: 39148048 PMCID: PMC11328360 DOI: 10.1186/s12872-024-04072-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 07/23/2024] [Indexed: 08/17/2024] Open
Abstract
BACKGROUND Portal hypertension is a common diagnosis in Sub-Saharan African countries, with the majority of patients presenting late. This study aimed to understand Clinical characteristics, aetiology, the treatment offered in our setting, and factors associated with portal hypertension at a tertiary-level hospital, in Tanzania. METHODOLOGY A prospective cross-sectional observational single hospital-based study was conducted at MNH, from May 2021 to April 2022. A minimum of 152 subjects were required with an error of less than 5% and a study power of 80% at a 95% confidence interval. A structured questionnaire was used to collect data. Ethical clearance was obtained from the MUHAS/MNH IRB. RESULTS A total of 154 eligible participants consented and participated in this study. The mean age of participants was 42 ± 15.8 years (range 2-87). Most of the study participants were males 64.9% with a male-to-female (M: F) ratio of 1.8:1. Vomiting blood was the common symptom among the study participants 51.3%. Schistosomiasis 53.9% and viral infection 26.6% were the common etiologies followed by alcohol abuse 7.8%. Most were medically treated at 89.61% followed by radiological treatment at 8.44% while only 1.95% of patients received surgical treatment. There was a significant association between the grade of oesophagal varices and bleeding consequences (p-value < 0.01). CONCLUSION The majority of patients were medically treated while patients who require surgical care are unable to assess it. We recommend the establishment of a transplant services program to counteract the unmet need and more retrospective research toward policy establishment.
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Affiliation(s)
| | - Ally Mwanga
- Muhimbili University of Health and Allied Sciences, P.O box 65001, Dar es Salaam, Tanzania
| | | | - Moses Byomuganyizi
- Muhimbili University of Health and Allied Sciences, P.O box 65001, Dar es Salaam, Tanzania
| | - William Lutege
- Muhimbili National Hospital, P.O box 65000, Dar es Salaam, Tanzania
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Owen N, Williams T, Maguire J, Kuc R, Davenport E, Davenport A. Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein. Biosci Rep 2024; 44:BSR20240528. [PMID: 38860875 PMCID: PMC12046063 DOI: 10.1042/bsr20240528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 05/28/2024] [Accepted: 06/11/2024] [Indexed: 06/12/2024] Open
Abstract
High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to β-adrenergic receptor blockade but approximately 40% of patients do not respond. Our aim was to use microarray to measure the expression of ∼20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n=12) versus healthy vessels (control, n=9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted P-value < 0.05, fold change > 1.5) identified 548 up-regulated genes and 1,996 down-regulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly up-regulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly down-regulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to β-blockers in patients with PH and cirrhosis.
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Affiliation(s)
- Nicola E. Owen
- Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, CB2 0QQ, U.K
| | - Thomas L. Williams
- Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, CB2 0QQ, U.K
| | - Janet J. Maguire
- Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, CB2 0QQ, U.K
| | - Rhoda E. Kuc
- Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, CB2 0QQ, U.K
| | - Emma E. Davenport
- Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, U.K
| | - Anthony P. Davenport
- Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, CB2 0QQ, U.K
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9
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Georgescu D, Lighezan DF, Lascu A, Buzas R, Faur A, Ionita I, Rosca CI, Suceava I, Calamar-Popovici D, Ionita M, Ancusa OE. Hepatic Veno-Occlusive Disease and Colorectal Cancer: Expect the Unexpected. Life (Basel) 2024; 14:845. [PMID: 39063599 PMCID: PMC11277572 DOI: 10.3390/life14070845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/15/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare liver vascular condition, potentially life-threatening, with clinical signs of portal hypertension, frequently reported in relation to bone marrow transplantation and possibly in non-transplantation-related chemotherapy. We report the case of a 65-year-old female patient who insidiously developed fatigue, mild tenderness of the right upper abdominal quadrant, hepato-splenomegaly and slight weight gain consecutive to ascites development, as well as persistent elevation of transaminases and mild thrombocytopenia. To note, she had a previous history of colorectal cancer (CRC) with liver metastases and several courses of chemotherapy. Abdominal duplex and elastography measurements made the diagnosis of cirrhosis improbable. A lot of lab work-ups were performed in order to rule out several diseases and conditions. Further, transjugular access was used to perform the measurement of the hepatic venous pressure gradient and liver biopsy that confirmed SOS/VOD. In late 2023, she was diagnosed with endometrial adenocarcinoma, requiring chemotherapy again. At present, the liver condition is stationary, but the prognosis is, however, uncertain. In conclusion, we presented the atypical case of a female patient who developed portal hypertension syndrome associated with the late onset of SOS/VOD, after 5-fluorouracil and oxaliplatin chemotherapy for CRC and liver metastases, subsequently diagnosed with endometrial adenocarcinoma, which posed many diagnostic and therapeutic challenges. Given the potentially bad outcome, an early diagnosis of SOS/VOD in patients receiving drugs of risk is important not only to stratify further risk, but also to initiate an appropriate therapy in order to improve the prognosis.
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Affiliation(s)
- Doina Georgescu
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Daniel Florin Lighezan
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ana Lascu
- Department of Functional Sciences, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Roxana Buzas
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Alexandra Faur
- Department of Anatomy and Embriology, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Ioana Ionita
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ciprian Ilie Rosca
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ioana Suceava
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Despina Calamar-Popovici
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Mihai Ionita
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Oana Elena Ancusa
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
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10
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Ahmed Z, Gangwani MK, Iqbal U, Kazi AI, Arif SF, Priyanka F, Lee-Smith W, Aziz M, Jaber F, Dahiya DS, Ali H, Inamdar S, Confer B. Role of Rifaximin in the Prevention of Variceal Bleeding: Systematic Review and Meta-Analysis. Am J Ther 2024; 31:e511-e514. [PMID: 38810173 DOI: 10.1097/mjt.0000000000001712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Affiliation(s)
- Zohaib Ahmed
- Department of Medicine, University of Toledo Medical Center, Toledo, OH
| | | | - Umair Iqbal
- Department of Gastroenterology and Hepatology, Geisenger Medical Center, Danville, PA
| | - Amal Iqbal Kazi
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Syeda Faiza Arif
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Fnu Priyanka
- Department of Medicine, University of Toledo Medical Center, Toledo, OH
| | - Wade Lee-Smith
- Depatment of Toledo Libraries, University of Toledo, Toledo, OH
| | - Muhammad Aziz
- Department of Medicine, University of Toledo Medical Center, Toledo, OH
| | - Fouad Jaber
- Department of Medicine, University of Missouri-Kansas City, Kansas, MO
| | | | - Hassam Ali
- Department of Gastroenterology and Hepatology, East Carolina University Health, Greenville, NC
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Texarkana, AR
| | - Bradley Confer
- Department of Gastroenterology and Hepatology, Geisenger Medical Center, Danville, PA
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11
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Ramakrishnan K, Vishwakarma R, Dev RR, Raju R, Rehman N. Etiologically Significant microRNAs in Hepatitis B Virus-Induced Hepatocellular Carcinoma. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2024; 28:280-290. [PMID: 38818956 DOI: 10.1089/omi.2024.0071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2024]
Abstract
Hepatitis B virus (HBV) infection has been causally linked to hepatocellular carcinoma (HCC) in more than 50% cases. MicroRNAs (miRNAs) play cross-cutting mechanistic roles in the complex interplay between viral pathogenesis, host survival, and clinical outcomes. The present study set out to identify etiologically significant human miRNAs associated with HBV infection in liver-related pathologies leading to HCC. In diverse tissue types, we assembled 573 miRNAs differentially expressed in HBV-associated liver pathologies, HBV infection, fibrosis, cirrhosis, acute on chronic liver failure, and HCC. Importantly, 43 human differentially expressed miRNAs (hDEmiRs) were regulated in serum/plasma and liver tissue of patients with HBV-positive conditions. However, only two hDEmiRs, hsa-miR-21-5p and hsa-miR-143-3p, were regulated across all disease conditions. To shortlist the functional miRNAs in HBV-induced HCC pathogenesis, a reverse bioinformatics analysis was performed using eight GEO datasets and the TCGA database containing the list of differentially regulated mRNAs in HCC. A comparative study using these data with the identified targets of hDEmiRs, a set of unidirectionally regulated hDEmiRs with the potential to modulate mRNAs in HCC, were found. Moreover, our study identified five miRNAs; hsa-miR-98-5p, hsa-miR-193b-3p, hsa-miR-142-5p, hsa-miR-522-5p, and hsa-miR-370-3p targeting PIGC, KNTC1, CSTF2, SLC41A2, and RAB17, respectively, in HCC. These hDEmiRs and their targets could be pivotal in HBV infection and subsequent liver pathologies modulating HCC clinical progression. HBV infection is the largest contributor to HCC, and the present study comprises the first of its kind compendium of hDEmiRs related to HBV-related pathologies.
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Affiliation(s)
| | - Riya Vishwakarma
- Centre for Integrative Omics Data Science, Yenepoya, Mangalore, India
| | - Radul R Dev
- Centre for Integrative Omics Data Science, Yenepoya, Mangalore, India
| | - Rajesh Raju
- Centre for Integrative Omics Data Science, Yenepoya, Mangalore, India
| | - Niyas Rehman
- Centre for Integrative Omics Data Science, Yenepoya, Mangalore, India
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12
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Peltec A, Sporea I. Multiparametric ultrasound as a new concept of assessment of liver tissue damage. World J Gastroenterol 2024; 30:1663-1669. [PMID: 38617743 PMCID: PMC11008374 DOI: 10.3748/wjg.v30.i12.1663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/05/2024] [Accepted: 03/12/2024] [Indexed: 03/28/2024] Open
Abstract
Liver disease accounts for approximately 2 million deaths per year worldwide. All chronic liver diseases (CLDs), whether of toxic, genetic, autoimmune, or infectious origin, undergo typical histological changes in the structure of the tissue. These changes may include the accumulation of extracellular matrix material, fats, triglycerides, or tissue scarring. Noninvasive methods for diagnosing CLD, such as conventional B-mode ultrasound (US), play a significant role in diagnosis. Doppler US, when coupled with B-mode US, can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation. US elastography can assess liver stiffness, serving as a surrogate marker for liver fibrosis. It is important to note that interpreting these values should not rely solely on a histological classification. Contrast-enhanced US (CEUS) provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions. Clinical evaluation, the etiology of liver disease, and the patient current comorbidities all influence the interpretation of liver stiffness measurements. These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD. B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis. The controlled attenuation parameter requires a dedicated device, and cutoff values are not clearly defined. Quan-titative US parameters for liver fat estimation include the attenuation coefficient, backscatter coefficient, and speed of sound. These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters. Multiparametric US (MPUS) of the liver introduces a new concept for complete noninvasive diagnosis. It encourages examiners to utilize the latest features of an US machine, including conventional B-mode, liver stiffness evaluation, fat quantification, dispersion imaging, Doppler US, and CEUS for focal liver lesion characterization. This comprehensive approach allows for diagnosis in a single examination, providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal. MPUS, in the hands of skilled clinicians, becomes an invaluable predictive tool for diagnosing, staging, and monitoring CLD.
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Affiliation(s)
- Angela Peltec
- Department of Internal Medicine, Discipline of Gastroenterology, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chishinev 2019, Moldova
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara 300736, Romania
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13
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Kotak PS, Kumar J, Kumar S, Varma A, Acharya S. Navigating Cirrhosis: A Comprehensive Review of Liver Scoring Systems for Diagnosis and Prognosis. Cureus 2024; 16:e57162. [PMID: 38681340 PMCID: PMC11056016 DOI: 10.7759/cureus.57162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 03/28/2024] [Indexed: 05/01/2024] Open
Abstract
This comprehensive review navigates the landscape of liver scoring systems for the diagnosis and prognosis of cirrhosis. Cirrhosis, a chronic and progressive liver disease, presents significant challenges in its diagnosis and management. The review begins by defining and providing an overview of cirrhosis, emphasizing its clinical implications. Highlighting the significance of liver scoring systems, including the Child-Pugh score, end-stage liver disease, albumin-bilirubin (ALBI) score, and fibrosis-4 (FIB-4) index, the study explores their role in assessing liver dysfunction severity and predicting outcomes. A meticulous analysis identifies the strengths and limitations of these scoring systems, offering valuable insights for clinicians. The recommendations emphasize incorporating these tools into routine clinical practice for early intervention and personalized treatment plans. Interdisciplinary collaboration is underscored as crucial for a holistic approach to cirrhosis management. The conclusion calls for future research to refine existing scoring systems, explore emerging biomarkers and imaging techniques, and conduct prospective studies to enhance precision. By embracing these recommendations, the medical community can advance the understanding and management of cirrhosis, ultimately improving patient outcomes and revolutionizing liver disease approaches.
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Affiliation(s)
- Palash S Kotak
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Jayanth Kumar
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sunil Kumar
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Anuj Varma
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sourya Acharya
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
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14
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Lesmana CRA, Kalista KF, Nababan SHH, Kurniawan J, Jasirwan COM, Sulaiman AS, Hasan I, Gani RA. Innovations in endoscopic ultrasound for portal hypertension and its role in managing complications in clinical practice: Lessons learned from a tertiary referral public hospital. PORTAL HYPERTENSION & CIRRHOSIS 2024; 3:31-35. [DOI: 10.1002/poh2.74] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 12/10/2023] [Indexed: 04/21/2025]
Abstract
AbstractPortal hypertension (PH) poses significant challenges. This paper presents an innovative study on the utilization of endoscopic ultrasound (EUS) for both the diagnosis and management of PH. Conducted at Dr. Cipto Mangunkusumo National General Hospital in Jakarta, this retrospective case series included patients diagnosed with PH through clinical examination, imaging evaluation, and esophagogastroduodenoscopy. Exclusion criteria comprised a history of reduced blood consumption within the last 5 days, hepatocellular carcinoma, massive ascites, or elevated international normalized ratio (>1.4). EUS‐guided portal pressure gradient (PPG) measurements were performed using an innovative standard manometer. The study involved 15 patients, with 14 having liver cirrhosis and 1 diagnosed with Budd–Chiari syndrome. Among them, nine patients experienced bleeding due to gastroesophageal varices. Small and large esophageal varices were identified in four and eight patients, respectively. Gastroesophageal varices type 1 were observed in two patients, and type 2 in four patients. Isolated gastric fundal varices type 1 were present in one patient. Based on EUS‐PPG measurements, 14 patients exhibited clinically significant portal hypertension. Seven patients underwent endoscopic band ligation and three underwent EUS‐guided cyanoacrylate injection during the same session as the EUS‐PPG measurement procedure. Notably, no adverse events, such as abdominal pain, perforation, or bleeding were observed during or after the procedure. EUS emerges as a promising and accurate tool for both diagnosis and management.
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Affiliation(s)
- Cosmas R. A. Lesmana
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital Jakarta Indonesia
- Gastrointestinal Cancer Center, MRCCC Siloam Semanggi Hospital Jakarta Indonesia
| | - Kemal F. Kalista
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
| | - Saut H. H. Nababan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
- Gastrointestinal Cancer Center, MRCCC Siloam Semanggi Hospital Jakarta Indonesia
| | - Juferdy Kurniawan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
| | - Chyntia O. M. Jasirwan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
| | - Andri S. Sulaiman
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
| | - Irsan Hasan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
| | - Rino A. Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital Medical Faculty Universitas Indonesia Jakarta Indonesia
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15
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Hizo GH, Rampelotto PH. The Role of Bifidobacterium in Liver Diseases: A Systematic Review of Next-Generation Sequencing Studies. Microorganisms 2023; 11:2999. [PMID: 38138143 PMCID: PMC10745637 DOI: 10.3390/microorganisms11122999] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 12/06/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023] Open
Abstract
The physiopathology of liver diseases is complex and can be caused by various factors. Bifidobacterium is a bacterial genus commonly found in the human gut microbiome and has been shown to influence the development of different stages of liver diseases significantly. This study investigated the relationship between the Bifidobacterium genus and liver injury. In this work, we performed a systematic review in major databases using the key terms "Bifidobacterium", "ALD", "NAFLD", "NASH", "cirrhosis", and "HCC" to achieve our purpose. In total, 31 articles were selected for analysis. In particular, we focused on studies that used next-generation sequencing (NGS) technologies. The studies focused on assessing Bifidobacterium levels in the diseases and interventional aimed at examining the therapeutic potential of Bifidobacterium in the mentioned conditions. Overall, the abundance of Bifidobacterium was reduced in hepatic pathologies. Low levels of Bifidobacterium were associated with harmful biochemical and physiological parameters, as well as an adverse clinical outcome. However, interventional studies using different drugs and treatments were able to increase the abundance of the genus and improve clinical outcomes. These results strongly support the hypothesis that changes in the abundance of Bifidobacterium significantly influence both the pathophysiology of hepatic diseases and the related clinical outcomes. In addition, our critical assessment of the NGS methods and related statistical analyses employed in each study highlights concerns with the methods used to define the differential abundance of Bifidobacterium, including potential biases and the omission of relevant information.
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Affiliation(s)
- Gabriel Henrique Hizo
- Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil
| | - Pabulo Henrique Rampelotto
- Bioinformatics and Biostatistics Core Facility, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-907, Brazil
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16
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Elbahrawy A, Atalla H, Mahmoud AA, Eliwa A, Alsawak A, Alboraie M, Madian A, Alashker A, Mostafa S, Alwassief A, Aly HH. Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents. FRONTIERS IN VIROLOGY 2023; 3. [DOI: 10.3389/fviro.2023.1227317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
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17
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Pratim Das P, Medhi S. Role of inflammasomes and cytokines in immune dysfunction of liver cirrhosis. Cytokine 2023; 170:156347. [PMID: 37639845 DOI: 10.1016/j.cyto.2023.156347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/28/2023] [Accepted: 08/21/2023] [Indexed: 08/31/2023]
Abstract
Liver cirrhosis develops as a result of persistent inflammation and liver injury. The prolonged inflammation triggers the buildup of fibrous tissue and regenerative nodules within the liver, leading to the distortion of the hepatic vascular structure and impaired liver function. Cirrhosis disrupts the ability of liver function to maintain homeostasis and hepatic immunosurveillance which causes immunological dysfunction in the body. In pathological conditions, the production of cytokines in the liver is carefully regulated by various cells in response to tissue stimulation. Cytokines and inflammasomes are the key regulators and systematically contribute to the development of cirrhosis which involves an inflammatory response. However, the crosstalk role of different cytokines in the cirrhosis progression is poorly understood. Tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), among others, are proinflammatory cytokines that contribute to liver cell necrosis, which in turn causes the development of fibrosis. While IL-10 exhibits a potent anti-inflammatory effect on the liver by inhibiting immune cell activation and neutralizing pro-inflammatory cytokine activity. Inflammasomes have also been implicated in the profibrotic processes of liver cirrhosis, as well as the production of chemokines such as CCL2/MCP-1. It is evident that inflammasomes have a role in the proinflammatory response seen in chronic liver illnesses. In conclusion, cirrhosis significantly impacts the immune system, leading to immunological dysfunction and alterations in both innate and acquired immunity. Proinflammatory cytokines like TNF-α, IL-1β, IL-6, and IFNγ are upregulated in cirrhosis, contributing to liver cell necrosis and fibrosis development. Managing cytokine-mediated inflammation and fibrosis is a key therapeutic approach to alleviate portal hypertension and its associated liver complications. This review attempted to focus largely on the role of immune dysfunction mediated by different cytokines and inflammasomes involved in the progression, regulation and development of liver cirrhosis.
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Affiliation(s)
- Partha Pratim Das
- Dept. of Bioengineering & Technology, Gauhati University, Assam 781014, India
| | - Subhash Medhi
- Dept. of Bioengineering & Technology, Gauhati University, Assam 781014, India.
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18
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Yoo JJ, Chang JI, Moon JE, Sinn DH, Kim SG, Kim YS. Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation. Liver Transpl 2023; 29:1029-1040. [PMID: 36929833 DOI: 10.1097/lvt.0000000000000126] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 03/07/2023] [Indexed: 03/18/2023]
Abstract
Recently, a new predictive model that jointly considers the Model of End-stage Liver Disease (MELD) 3.0 and albumin has been proposed. This study investigated the performance of the MELD 3.0 score in predicting the 3-month survival of East Asian patients with cirrhosis compared with the other MELD-based scores. Validation was performed with the retrospective data of 2153 patients in South Korea who were listed for liver transplantation (LT). Discrimination and calibration analyses were performed using the MELD-based scores as an independent variable. On average, patients had the original MELD score of 18.70 ± 9.65. Alcohol (39.99%) and chronic HBV (38.55%) were the 2 main etiologies. The MELD 3.0 with albumin showed slightly better discrimination [c-index = 0.738, incremental AUC (iAUC) = 0.719] compared with the MELD 3.0 without albumin (c-index = 0.737, iAUC = 0.715), MELD-Na (c-index = 0.730, iAUC = 0.707), or the original MELD (c-index = 0.718, iAUC = 0.687) for predicting 3-month survival but not significantly different compared with prior models. Likewise, in the stratified analysis according to the strata of MELD, although the performance of MELD 3.0 was better throughout all the MELD strata than MELD original, there was no statistical difference in performance. The MELD 3.0 with albumin reclassified 22.61% of cases classified by the original MELD to higher MELD score categories, and there was no significant difference in the reclassification rate between males and females. The predictive power of the MELD-based system is lower in Asian populations than in western countries. Nonetheless, the MELD 3.0 score with albumin was significantly better in predicting the short-term prognosis of East Asian patients on the LT waitlist than the current allocation system, original MELD.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Jong-In Chang
- Department of Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Ji Eun Moon
- Department of Statistics, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Young Seok Kim
- Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
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Dong B, Lyu G, Wang H, Chen Y, Wei K. Use of Sound Touch Elastography and Sound Touch Quantification for the Noninvasive Evaluation of Portal Hypertension in a Rat Model. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:1537-1547. [PMID: 36637111 DOI: 10.1002/jum.16172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/16/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVES In this study, we used the recently developed ultrasound elastography techniques sound touch elastography (STE) and sound touch quantification (STQ) to quantify portal hypertension (PHT) severity in a rat model of carbon tetrachloride (CCl4 )-induced cirrhotic PHT. METHODS In total, 60 rats were used. Various degrees of PHT were established. Liver and spleen stiffness were measured by STE (L-STE and S-STE, respectively) and STQ (L-STQ and S-STQ, respectively). We measured portal pressure (PP) after ultrasonographic examination. The performance of the STE and STQ parameters in the identification of PHT was evaluated using receiver operating characteristic (ROC) analyses. RESULTS Liver and spleen stiffness measurements obtained with STE and STQ correlated positively with the PP (r = 0.566-0.882, all P < .001). The areas under ROC curves for L-STE, S-STE, L-STQ, and S-STQ values were 0.931 (95% confidence interval [CI], 0.847-1.000), 0.982 (95% CI, 0.956-1.000), 0.796 (95% CI, 0.680-0.912), and 0.925 (95% CI, 0.858-0.993), respectively, for PP ≥5 mmHg; 0.937 (95% CI, 0.865-1.000), 0.938 (95% CI, 0.864-1.000), 0.967 (95% CI, 0.923-1.000), and 0.960 (95% CI, 0.897-1.000), respectively, for PP ≥10 mmHg; and 0.954 (95% CI, 0.897-1.000), 0.790 (95% CI, 0.652-0.928), 0.808 (95% CI, 0.680-0.935), and 0.740 (95% CI, 0.595-0.885), respectively, for PP ≥12 mmHg. CONCLUSIONS STE and STQ are reliable noninvasive tools for the assessment of PHT severity, especially for PP ≥10 mmHg, in a rat model of CCl4 -induced cirrhotic PHT.
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Affiliation(s)
- Bingtian Dong
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Guorong Lyu
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Huaming Wang
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yongjian Chen
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Kaipeng Wei
- Department of Pathology, The 910 Hospital, Quanzhou, China
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Lesmana CRA. Endoscopic ultrasound-guided portal pressure gradient measurement in managing portal hypertension. World J Gastrointest Surg 2023; 15:1033-1039. [PMID: 37405096 PMCID: PMC10315130 DOI: 10.4240/wjgs.v15.i6.1033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/30/2022] [Accepted: 04/24/2023] [Indexed: 06/15/2023] Open
Abstract
Portal hypertension (PH) is still a challenging clinical condition due to its silent manifestations in the early stage and needs to be measured accurately for early detection. Hepatic vein pressure gradient measurement has been considered as the gold standard measurement for PH; however, it needs special skill, experience, and high expertise. Recently, there has been an innovative development in using endoscopic ultrasound (EUS) for the diagnosis and management of liver diseases, including portal pressure measurement, which is commonly known as EUS-guided portal pressure gradient (EUS-PPG) measurement. EUS-PPG measurement can be performed concomitantly with EUS evaluation for deep esophageal varices, EUS-guided liver biopsy, and EUS-guided cyanoacrylate injection. However, there are still major issues, such as different etiologies of liver disease, procedural training, expertise, availability, and cost-effectiveness in several situations with regard to the standard management.
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Affiliation(s)
- Cosmas Rinaldi Adithya Lesmana
- Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta 10430, DKI, Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta 12950, DKI, Indonesia
- Gastrointestinal Cancer Center, MRCCC Siloam Semanggi Hospital, Jakarta 12930, DKI, Indonesia
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Fu C, Zhang Y, Xi WJ, Xu K, Meng F, Ma T, Li W, Wu L, Chen Z. Dahuang Zhechong pill attenuates hepatic sinusoidal capillarization in liver cirrhosis and hepatocellular carcinoma rat model via the MK/integrin signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116191. [PMID: 36731809 DOI: 10.1016/j.jep.2023.116191] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/08/2023] [Accepted: 01/17/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dahuang Zhechong pill (DHZCP), a traditional Chinese medicine, was derived from the famous book Unk "Synopsis of Prescriptions of the Golden Chamber" during the Han dynasty. Owing to its ability to invigorate the circulation of blood in Chinese medicine, DHZCP is usually used for treating liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Clinical application have shown that DHZCP exhibits satisfactory therapeutic effects in HCC adjuvant therapy; however, little is known about its underlying mechanisms. AIM OF THE STUDY We aimed to clarify the mechanism of DHZCP against hepatic sinusoidal capillarization in rats with LC and HCC by inhibiting the MK/integrin signaling pathway of liver sinusoidal endothelial cells (LSECs). MATERIALS AND METHODS The contents of 29 characteristic components in DHZCP were determined by ultraperformance liquid chromatography-tandem mass spectrometry. DEN (Diethylnitrosamine)-induced LC and HCC rat models were constructed, and DHZCP was administered when the disease entered the LC stage. After 4 or 12 weeks of administration, hematoxylin and eosin staining, Masson staining, Metavir score, and SSCP (Single strand conformation polymorphism) gene mutation detection were used to confirm tissue fibrosis and cancer. The levels of NO, ET-1 and TXA2, which can regulate vasomotor functions and activate the MK/Itgα6/Src signaling pathway were evaluated by using immunohistochemistry, chemiluminescence, immunofluorescence, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Similar methods were also used to evaluate the levels of VEGF, VEGFR, Ang-2 and Tie, which can promote pathological angiogenesis and activate the MK/Itgα4/NF-κB signaling pathway. In vitro cell experiments were performed using potential pharmacodynamic molecules targeting integrins in DHZCP were selected by molecular docking, and the effects of these molecules on the function of LSECs were studied by Itgα4+ and Itgα6+ cell models. RESULTS At the stage of LC, the animal experiments demonstrated that DHZCP mainly inhibited the MK/Itgα6 signaling pathway to increase the number and size of hepatic sinus fenestration, reversed the ET-1/NO and TXA2/NO ratios, regulated hepatic sinus relaxation and contraction balance, reduced the portal vein pressure, and inhibited cirrhotic carcinogenesis. At the HCC stage, DHZCP could also significantly inhibit the MK/Itgα4 signaling pathway, reduce pathological angiogenesis, and alleviate disease progression. The results of the cell experiments showed that Rhein, Naringenin, Liquiritin and Emodin-8-O-β-D-glucoside (PMEG) were involved in vascular regulation by affecting the MK/integrin signaling pathway. Liquiritin and PMEG mainly blocked the MK/α6 signal, which is important in regulating the vasomotor function of the liver sinus. Naringenin and Rhein mainly acted by blocked the signaling of MK/α4 action signal, which are potent molecules that inhibit pathological angiogenesis. CONCLUSIONS DHZCP could improve the hepatic sinusoidal capillarization of LC and HCC by inhibiting the MK/Itgα signaling pathway and inhibited disease progression. Rhein, Naringenin, Liquiritin and PMEG were the main active molecules that affected the MK/Itgα signaling pathway.
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Affiliation(s)
- Chuankui Fu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Yiheng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Wen Jie Xi
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Kejia Xu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Fansheng Meng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Tianle Ma
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Weidong Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Li Wu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Zhipeng Chen
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Bakhshipour A, Rafaiee R. Upper and Lower Gastrointestinal Bleeding: A Retrospective Study on 10 Years Experiences in Southeastern Iran. Middle East J Dig Dis 2023; 15:116-120. [PMID: 37546509 PMCID: PMC10404084 DOI: 10.34172/mejdd.2023.329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 02/18/2023] [Indexed: 08/08/2023] Open
Abstract
Background: Gastrointestinal bleeding (GIB) is an emergency medical situation that is very common, although often benign but can cause considerable morbidity and mortality and health care costs. The aim of this study was to analyze the endoscopic evaluation of upper GIB (UGIB) and lower GIB (LGIB) in Sistan and Balouchestan, southeast Iran. Methods: Data from patients with GIB in a referral university-affiliated hospital in Zahedan, Southeastern Iran during a 10-year period, were obtained. A total of 21884 reports of adult patients' endoscopy and colonoscopy from 2011 to 2020 who were admitted to Ali-Ibn-Abitaleb hospital were studied of which 5862 reports were related to GIB. Incomplete files were excluded. Information on age, sex, and endoscopic diagnosis of the 5053 reports was analyzed and compared using chi-square statistical test. Results: There were 3310 men (65.6%) and 1743 women (34.4%) with a mean (±SD) of age 48.4 (±19.83) years. 3079 patients had UGIB (60.8%) and 1974 patients had LGIB (39.2%). Peptic ulcer (72.8% duodenal ulcer and 27.2% gastric ulcer) was seen as the main reason for UGIB (29.7%) and hemorrhoids were the main reason for LGIB (44.2%). Mallory-Weiss syndrome was significantly common in the age<40 years old, and the incidence rate of malignancy was significantly higher in those aged>40 years old than in the younger age group (P<0.001). Conclusion: Peptic ulcer was the most common etiological factor and it was more common in men than in women. Gastroesophageal varices were the second most common cause of UGIB. Hemorrhoids and anal fissures were observed as the most common colonoscopic findings of LGIB. The prevalences of UGIB and LGIB are more common in men than women and increase with age. It is important for physicians to constantly update their information about the spectrum of diseases in their region and their changing over time to provide accurate diagnosis and management timely.
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Affiliation(s)
- Alireza Bakhshipour
- Professor, Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Raheleh Rafaiee
- Assistant Professor, Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Bai X, Ma P, Tan J, Li Y, He X, Huang J, An T, Wang C, Li J, Xu W. Double C-Arm Digital Subtraction Angiography Guidance During Transjugular Intrahepatic Portosystemic Shunt Placement. Med Sci Monit 2023; 29:e938912. [PMID: 36922715 PMCID: PMC10029320 DOI: 10.12659/msm.938912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND This study aimed to evaluate the safety and efficacy of portal vein puncture with a new guidance system using double C-arm digital subtraction angiography (DSA) during transjugular intrahepatic portosystemic shunt (TIPS) placement. MATERIAL AND METHODS The procedure details of TIPS placements performed on 39 patients in our center between January and December 2021 were retrospectively analyzed. The procedure was performed under double C-arm DSA guidance (study group) and C-arm DSA (control group) in 18 and 21 patients, respectively. We analyzed the procedure's technical success, duration of the overall procedure, portal vein puncture, fluoroscopy, radiation exposure, complications, and mortality and morbidity rates 30 days after the procedure. RESULTS TIPS placement was performed successfully in all patients. The mean portal vein puncture time in the study group (9±5.7 min) was significantly shorter than in the control group (33±14.9 min, p=0.02). The complete mean dose area product of the procedure showed no significant differences (study group, 126±53 Gy/cm²; control group. 142±66 Gy/cm²; p=0.42). The intraprocedural complication rates were 0% and 19% in the study and control groups, respectively (p=0.04). The 30-day post-procedural mortality rate in the control group was 4.8% (1/21), with no deaths from technical complications. CONCLUSIONS Double C-arm DSA guidance is a safe and effective method to assist TIPS placement. This approach may result in shorter portal vein puncture time and lower intraprocedural complication rates.
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Affiliation(s)
- Xiao Bai
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Ping Ma
- College of Intelligence and Information Engineering, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China (mainland)
| | - Junjie Tan
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Yong Li
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Xu He
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Jianwen Huang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Tao An
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Chunyan Wang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Jihua Li
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
| | - Weiguo Xu
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, China (mainland)
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Zeng HT, Zhang ZL, Lin XM, Peng MS, Wang LS, Xu ZL. Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy. World J Gastrointest Endosc 2023; 15:153-162. [PMID: 37034972 PMCID: PMC10080557 DOI: 10.4253/wjge.v15.i3.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/26/2022] [Accepted: 03/01/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Esophageal-gastro varices bleeding (EGVB) is the most widely known cause of mortality in individuals with cirrhosis, with an occurrence rate of 5% to 15%. Among them, gastric varices bleeding (GVB) is less frequent than esophageal varices bleeding (EVB), but the former is a more critical illness and has a higher mortality rate. At present, endoscopic variceal histoacryl injection therapy (EVHT) is safe and effective, and it has been recommended by relevant guidelines as the primary method for the treatment of GVB. However, gastric varices after endoscopic treatment still have a high rate of early rebleeding, which is mainly related to complications of its treatment, such as bleeding from drained ulcers, rebleeding of varices etc. Therefore, preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes. AIM To assess the efficacy of aluminium phosphate gel (APG) combined with proton pump inhibitor (PPI) in preventing early rebleeding after EVHT in individuals with GVB. METHODS Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021. Based on the selection criteria, 101 patients were sorted into the PPI alone treatment group, and 95 patients were sorted into the PPI combined with the APG treatment group. The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups. Statistical methods were performed by two-sample t-test, Wilcoxon rank sum test and χ 2 test. RESULTS No major variations were noted between the individuals of the two groups in terms of age, gender, Model for End-Stage Liver Disease score, coagulation function, serum albumin, hemoglobin, type of gastric varices, the dose of tissue glue injection and EV that needed to be treated simultaneously. The early rebleeding rate in PPI + APG group was 3.16% (3/95), which was much lower than that in the PPI group (12.87%, 13/101) (P = 0.013). Causes of early rebleeding: the incidence of gastric ulcer bleeding in the PPI + APG group was 2.11% (2/95), which was reduced in comparison to that in the PPI group (11.88%, 12/101) (P = 0.008); the incidence of venous bleeding in PPI + APG group and PPI group was 1. 05% (1/95) and 0.99% (1/101), respectively, and there was no significant difference between them (0.999). The early mortality rate was 0 in both groups within 6 wk after the operation, and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding. The overall incidence of complications in the PPI + APG group was 12.63% (12/95), which was not significantly different from 13.86% (14/101) in the PPI group (P = 0.800). of abdominal pain in the PPI + APG group was 3.16% (3/95), which was lower than that in the PPI group (11.88%, 12/101) (P = 0.022). However, due to aluminum phosphate gel usage, the incidence of constipation in the PPI + APG group was 9.47% (9/95), which was higher than that in the PPI group (1.98%, 2/101) (P = 0.023), but the health of the patients could be improved by increasing drinking water or oral lactulose. No patients in either group developed spontaneous peritonitis after taking PPI, and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment. CONCLUSION PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.
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Affiliation(s)
- Hao-Tian Zeng
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zhu-Liang Zhang
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Xi-Min Lin
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Min-Si Peng
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zheng-Lei Xu
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
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Segna D, Mendoza YP, Lange NF, Rodrigues SG, Berzigotti A. Non-invasive tools for compensated advanced chronic liver disease and portal hypertension after Baveno VII - an update. Dig Liver Dis 2023; 55:326-335. [PMID: 36369196 DOI: 10.1016/j.dld.2022.10.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/10/2022]
Abstract
Non-invasive tests (NITs) and liver stiffness measurement (LSM) in particular, have entered clinical practice over 20 years ago as point-of-care tests to diagnose liver fibrosis in patients with compensated chronic liver disease. Since then, NITs use has evolved thanks to a large number of studies in all major etiologies of liver disease, and they have become important tools to stratify the risk of portal hypertension and liver-related events. The Baveno VII consensus workshop provided several novel recommendations regarding the use of well-established and novel NITs in the specific setting of portal hypertension screening, diagnosis and follow-up. The Baveno VII expert panels paid special attention to summarizing the existing data into simple clinical rules able to guide clinicians in their practice. The "rule of five" for LSM is a tool to stratify the risk of liver-related events, and LSM alone or in combination with platelet count, can be used now to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension, as well as to rule-out high-risk varices. Use of NITs in obese subjects with non-alcoholic fatty liver disease (NAFLD) and patients with viral hepatitis C that has been successfully treated, require specific knowledge. This review will update the reader on these aspects.
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Affiliation(s)
- Daniel Segna
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Bern 3010, Switzerland
| | - Yuly P Mendoza
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Bern 3010, Switzerland
| | - Naomi F Lange
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Bern 3010, Switzerland; Graduate School for Health Sciences (GHS), University of Bern, Switzerland
| | - Susana G Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Bern 3010, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Bern 3010, Switzerland.
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Zhu M, Li H, Yin Y, Ding M, Philips CA, Romeiro FG, Qi X. U-shaped relationship between subcutaneous adipose tissue index and mortality in liver cirrhosis. J Cachexia Sarcopenia Muscle 2023; 14:508-516. [PMID: 36577511 PMCID: PMC9891908 DOI: 10.1002/jcsm.13154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/03/2022] [Accepted: 11/29/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence. METHODS We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score. RESULTS Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8 cm2 /m2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7 cm2 /m2 ), moderate (19.7-51.8 cm2 /m2 ), and high (>51.8 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992-2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059-3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1-2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195-3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2 cm2 /m2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8 cm2 /m2 ), moderate (9.8-40.2 cm2 /m2 ), and high (>40.2 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599-2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539-1.34, P = 0.48) was an independent predictor of death compared with moderate VATI. CONCLUSIONS Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients.
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Affiliation(s)
- Menghua Zhu
- Department of GastroenterologyGeneral Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)ShenyangChina
- Postgraduate CollegeJinzhou Medical UniversityJinzhouChina
| | - Hongyu Li
- Department of GastroenterologyGeneral Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)ShenyangChina
- Postgraduate CollegeJinzhou Medical UniversityJinzhouChina
- Postgraduate CollegeChina Medical UniversityShenyangChina
| | - Yue Yin
- Department of GastroenterologyGeneral Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)ShenyangChina
- Postgraduate CollegeChina Medical UniversityShenyangChina
| | - Min Ding
- Department of GastroenterologyGeneral Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)ShenyangChina
- Postgraduate CollegeChina Medical UniversityShenyangChina
| | - Cyriac Abby Philips
- Department of Clinical and Translational HepatologyThe Liver Institute, Center of Excellence in GI Sciences, Rajagiri HospitalAluvaKeralaIndia
| | | | - Xingshun Qi
- Department of GastroenterologyGeneral Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)ShenyangChina
- Postgraduate CollegeJinzhou Medical UniversityJinzhouChina
- Postgraduate CollegeChina Medical UniversityShenyangChina
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Lee S, Saffo S. Evolution of care in cirrhosis: Preventing hepatic decompensation through pharmacotherapy. World J Gastroenterol 2023; 29:61-74. [PMID: 36683719 PMCID: PMC9850948 DOI: 10.3748/wjg.v29.i1.61] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/22/2022] [Accepted: 12/14/2022] [Indexed: 01/04/2023] Open
Abstract
Cirrhosis is a leading cause of morbidity and mortality, impacting more than 120 million people worldwide. Although geographic differences exist, etiologic factors such as alcohol use disorder, chronic viral hepatitis infections, and non-alcoholic fatty liver disease are prevalent in nearly every region. Historically, significant effort has been devoted to modifying these risks to prevent disease progression. Nevertheless, more than 11% of patients with compensated cirrhosis experience hepatic decompensation each year. This transition signifies the most important prognostic factor in the natural history of the disease, corresponding to a decline in median survival to below 2 years. Over the past decade, the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized, and non-selective beta-blockers have emerged as the most effective option to date. However, a critical therapeutic gap still exists, and additional therapies have been proposed, including statins, rifaximin, and sodium-glucose cotransporter-2 inhibitors. Based on the results of innovative retrospective analyses and small-scale prospective trials, these pharmacotherapies represent promising options, but further studies, including randomized controlled trials, are necessary before they can be incorporated into clinical use. This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.
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Affiliation(s)
- Seohyuk Lee
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520-8019, United States
| | - Saad Saffo
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520-8019, United States
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Huang S, Liu J, Cai J, Zhou C, Wang Y, Yang C, Li T, Chen Y, Ju S, Wang C, Yao W, Bai Y, Xiong B. Predictors of Improvement of Sarcopenia after Transjugular Intrahepatic Portosystemic Shunt Creation in Cirrhotic Patients. J Vasc Interv Radiol 2022; 34:639-644. [PMID: 36586464 DOI: 10.1016/j.jvir.2022.12.474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 12/16/2022] [Accepted: 12/21/2022] [Indexed: 12/29/2022] Open
Abstract
To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who underwent TIPS creation. Computed tomography-based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months after TIPS creation. Multivariate logistic regression analysis was used to identify independent risk factors, which showed a significant increase in 6-month post-TIPS SMI compared with that at baseline in both men and women (for both, P < .001). Pre-TIPS SMI (odds ratio [OR], 0.93; 95% CI, 0.87-0.99; P = .031) and change in portal pressure gradient (OR, 1.13; 95% CI, 1.03-1.24; P = .009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.
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Affiliation(s)
- Songjiang Huang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Jinzhong Cai
- Interventional Section, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
| | - Chen Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yingliang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chongtu Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Tongqiang Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yang Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Shuguang Ju
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chaoyang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wei Yao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yaowei Bai
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China; Department of Interventional Radiology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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Ma WL, Chang DY, Lin CH, Liu KL, Liang PC, Lien HC, Hu CC, Huang LY, Yeh YC, Lu YS. Clinical Outcomes of Metastatic Breast Cancer in Patients Having Imaging Liver Pseudocirrhosis with or without Evident Varices. Oncologist 2022; 27:1008-1015. [PMID: 36215276 DOI: 10.1093/oncolo/oyac199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 08/16/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis-related portal hypertension (pHTN). This study defined evident pHTN by the presence of esophageal or gastric varices and compared patients' outcomes of metastatic breast cancer with imaging-diagnosed pseudocirrhosis with or without varices. METHODS The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Survival outcomes were compared based on endoscopic evidence of esophageal or gastric varices. RESULTS Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Eighty-one (76%) had initial metastases in both hepatic lobes, and 32 (30%) had esophageal or gastric varices. The median overall survival (OS) was 5 and 13 months in patients with and without varices (P = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative subtype was 16, 9, and 2 months, respectively (P = .001). Patients with varices usually had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with varices had OS exceeding 1 year. In multivariate analysis, evident varices (P = .007) and triple-negative subtype (P = .013) were associated with poor OS. CONCLUSIONS Patients with pseudocirrhosis and evident varices had a significantly shorter median OS, and were usually associated with clinical cirrhosis-related complications. To maximize OS, early identification and meticulous supportive care are warranted.
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Affiliation(s)
- Wei-Li Ma
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Dwan-Ying Chang
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Hung Lin
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, Taiwan
| | - Kao-Lang Liu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Huang-Chun Lien
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chan-Chuan Hu
- Department of Medical Research and Education, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Ling-Yun Huang
- Clinical Trial Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Chun Yeh
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Shen Lu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
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Comorbid Chronic Diseases and Survival in Compensated and Decompensated Cirrhosis: A Population-Based Study. Am J Gastroenterol 2022; 117:2009-2016. [PMID: 35849622 DOI: 10.14309/ajg.0000000000001909] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 07/11/2022] [Indexed: 01/30/2023]
Abstract
INTRODUCTION The burden of liver disease is substantial and increasing; the impact of comorbid chronic diseases on the clinical course of patients with compensated and decompensated cirrhosis is not well-defined. The aim of this study was to examine the individual and additive impact of comorbid chronic diseases on mortality in patients with cirrhosis. METHODS In this population-based study, we used Cox proportional hazards modeling with time-dependent covariates to assess the impact of comorbid chronic diseases (diabetes mellitus, chronic kidney disease, and cardiovascular disease [CVD]) on mortality in patients with cirrhosis in a large, diverse Metroplex. RESULTS There were 35,361 patients with cirrhosis (mean age 59.5 years, 41.8% females, 29.7% non-White, and 17.5% Hispanic ethnicity). Overall, the presence of chronic comorbidities was 1 disease (28.9%), 2 diseases (17.5%), and 3 diseases (12.6%) with a majority having CVD (45%). Adjusted risk of mortality progressively increased with an increase in chronic diseases from 1 (hazard ratio [HR] 2.5, 95% confidence interval [CI] 2.23-2.8) to 2 (HR 3.27.95% CI 2.9-3.69) to 3 (HR 4.52, 95% CI 3.99-5.12) diseases. Survival of patients with compensated cirrhosis and 3 chronic diseases was similar to subsets of decompensated cirrhosis (67.7% as compared with decompensated cirrhosis with 1-3 conditions, 61.9%-63.9%). DISCUSSION In patients with cirrhosis, a focus on comorbid chronic disease(s) as potential management targets may help avoid premature mortality, regardless of etiology. Multidisciplinary care early in the clinical course of cirrhosis is needed in addition to the current focus on management of complications of portal hypertension.
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Interventional Management of Portal Hypertension in Cancer Patients. Curr Oncol Rep 2022; 24:1461-1475. [PMID: 35953600 DOI: 10.1007/s11912-022-01319-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2022] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW To provide an overview of the classifications and clinical hallmarks of common cancer-related conditions that contribute to the high incidence of portal hypertension in this population and provide an update on currently available interventional radiology therapeutic approaches. RECENT FINDINGS In the last few decades, there have been significant advancements in understanding the pathophysiology of portal hypertension. This knowledge has led to the development of safer and more effective minimally invasive approaches. The main objective is to provide alternatives to prevent life-threatening complications from clinically significant portal hypertension and to allow the continuation of cancer treatment interventions that would otherwise be stopped. Clinicians involved in cancer care should be aware of risk factors, associated complications, and management of portal hypertension in cancer patients. Interventional radiology offers minimally invasive alternatives that play a central role in improving clinical outcomes and survival of these patients, allowing the continuation of cancer treatments.
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He J, Liu X, Duan S, Ye R, Yang Y, Wang J, He N. Untargeted Plasma Metabolomics Reveals Extensive Metabolic Alterations Among Treatment-Naive Human Immunodeficiency Virus/Hepatitis C Virus Co-Infected Patients with Liver Disease Progression. AIDS Res Hum Retroviruses 2022; 38:378-393. [PMID: 35383478 DOI: 10.1089/aid.2021.0123] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may induce metabolic disorders and cause liver complications. Therefore, we aim to analyze the metabolite differences among treatment-naive HIV/HCV co-infected patients with versus without liver disease progression (LDP) and HIV mono-infected patients. A cross-sectional study was conducted in 65 HIV/HCV co-infected patients (22 with LDP and 43 without) and 65 HIV mono-infected patients in Dehong prefecture of Yunnan province, China. Plasma metabolomics were measured by gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Discrimination analysis, pathway enrichment analysis, generalized linear model with binomial distribution, and area under the receiver-operating characteristic curve (AUC) were conducted to identify bilateral differences in metabolites and pathways in different comparison groups. A total of 10,831 with 673 named and 10,158 unnamed metabolites were detected. Compared with HIV/HCV co-infected patients without LDP, phenylalanine, tyrosine, and tryptophan biosynthesis pathway with the increased level of tyrosine were significantly altered among HIV/HCV co-infected patients with LDP. Compared with HIV mono-infected patients, the decreased level of glutamine and increased levels of glutamic acid, arachidonic acid, and its derivatives were identified among HIV/HCV co-infected patients. Metabolite panels adjusted for baseline information had a higher accuracy than baseline model (without metabolite information) in distinguishing HIV/HCV co-infected patients with versus without LDP (AUC 0.951 vs. 0.849, p = .027) and HIV/HCV co-infected patients from HIV mono-infected patients (AUC 0.889 vs. 0.766, p < .001). A novel set of metabolites were found to discriminate HIV/HCV co-infected patients with versus without LDP, and from HIV mono-infected patients, which may have mechanistic and interventional implications.
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Affiliation(s)
- Jiayu He
- Department of Epidemiology, School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Xing Liu
- Department of Epidemiology, School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Song Duan
- Dehong Prefecture Center for Disease Control and Prevention, Mangshi, China
| | - Runhua Ye
- Dehong Prefecture Center for Disease Control and Prevention, Mangshi, China
| | - Yuecheng Yang
- Dehong Prefecture Center for Disease Control and Prevention, Mangshi, China
| | - Jibao Wang
- Dehong Prefecture Center for Disease Control and Prevention, Mangshi, China
| | - Na He
- Department of Epidemiology, School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
- Key Laboratory of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China
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Asesio N, Pollo-Flores P, Caliez O, Munteanu M, Ngo A, Ngo Y, Poynard T, Thabut D, Rudler M. Baveno VI criteria as a prognostic factor for clinical complications in patients with compensated cirrhosis. Dig Liver Dis 2022; 54:645-653. [PMID: 34583904 DOI: 10.1016/j.dld.2021.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/16/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Combination of liver stiffness measurement and platelets count is a tool to safely rule out varices needing treatment (VNT) in patients with compensated advanced chronic liver disease (cACLD). AIMS to evaluate 4-year liver-related complications and survival in low-risk patients according to Baveno VI criteria. METHODS we conducted a monocentric retrospective analysis of prospectively collected data of all consecutive patients, with cirrhosis (LSM≥12.5 kPa) and without previous complication, evaluated between 2012 and 2015. Liver-related complications and survival were compared between 2 groups of patients: favourable (LSM< 20 kPa and platelet count>150.000/mm3) and unfavourable Baveno VI status patients (LSM ≥ 20 kPa or platelet count ≤150.000/mm3). RESULTS 455 patients with cACLD were analysed. Two hundred patients had favourable Baveno VI criteria, 3.6% with VNT. The 4-year probability of being free of acute decompensation was higher in low-risk patients (94.4 ± 1.8% vs. 85.7%±2.6%, p = 0.018). Unfavourable Baveno status was independently associated with acute decompensation. The probability of being free of HCC was significantly higher in low-risk patients (94.2 ± 1.8% vs. 87.6 ± 2.4%, p = 0.048). Liver-related mortality was not different between the 2 groups (p = 0.56). CONCLUSION The Baveno VI criteria could predict clinical outcome in cACLD.
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Affiliation(s)
- Nicolas Asesio
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Priscila Pollo-Flores
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; CAPES (coordenação de aperfeiçoamento de pessoal de nível superior), Fluminense's Federal University (UFF), Rio de Janeiro, Brasil
| | - Olivier Caliez
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | | | - An Ngo
- BioPredictive, Paris, France
| | - Yen Ngo
- BioPredictive, Paris, France
| | - Thierry Poynard
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; BioPredictive, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Thabut
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Marika Rudler
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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Lee H, Jang S, Ahn SH, Kim BK. Cost-effectiveness of antiviral therapy in untreated compensated cirrhosis patient with serum HBV-DNA level < 2000 IU/mL. Hepatol Int 2022; 16:294-305. [PMID: 35322374 DOI: 10.1007/s12072-022-10310-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 01/28/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Due to stringent reimbursement criteria, significant numbers of patients with compensated cirrhosis (CC) and low-level viremia [LLV; serum hepatitis B virus (HBV)-DNA levels of 20-2000 IU/mL] remain untreated especially in the East Asian countries, despite potential risk of disease progression. We analyzed cost-effectiveness to assess rationales for antiviral therapy (AVT) for this population. METHODS We compared cost and effectiveness (quality-adjusted life years, QALYs) in a virtual cohort including 10,000 54-year-old CC-LLV patients receiving AVT (Scenario I) versus no treatment (Scenario II). A Markov model, including seven HBV-related conditions, was used. Values for transition probabilities and costs were mostly obtained from recent real-world South Korean data. RESULTS As per a simulation of a base-case analysis, AVT reduced costs by $639 USD and yielded 0.108 QALYs per patient for 5 years among CC-LLV patients compared to no treatment. Thus, AVT is a cost-saving option with lower costs and better effectiveness than no treatment. If 10,000 patients received AVT, 815 incident cases of hepatocellular carcinoma (HCC) and 630 HBV-related deaths could be averted in 5 years compared to no treatment. In case of 10-year observation, AVT was consistently dominant. Even when the transition probabilities from CC-LLV vs. maintained virological response to HCC were same, fluctuation of results also lied within willingness-to-pay in South Korea. In the probabilistic sensitivity analysis with the willingness-to-pay threshold, the probability of AVT cost-effectiveness was 100%. CONCLUSION The extended application of AVT in CC-LLV patients may contribute positively to individual clinical benefits and national healthcare budgets.
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Affiliation(s)
- Hankil Lee
- College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, Republic of Korea
| | - Sungin Jang
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
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A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes. Int J Mol Sci 2022; 23:ijms23063131. [PMID: 35328564 PMCID: PMC8948922 DOI: 10.3390/ijms23063131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 12/12/2022] Open
Abstract
Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the ‘thin-film hydration’ method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.
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Diagnostic and prognostic significance of cell death markers in patients with cirrhosis and acute decompensation. PLoS One 2022; 17:e0263989. [PMID: 35176084 PMCID: PMC8853504 DOI: 10.1371/journal.pone.0263989] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/31/2022] [Indexed: 12/13/2022] Open
Abstract
Background The transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, however, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. Here, we characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation. Methods A post-hoc analysis was based on prospectively collected clinical data from 160 patients with chronic liver disease, stably compensated or decompensated at baseline or during follow-up, over a median period of 721 days. Serum levels of damage-associated molecular patterns (DAMPs) and routine biochemistry are quantified at baseline (for all patients) and during follow-up (for patients with acute decompensation). The panel of DAMPs assessed in this study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 (CK18-M65) and its caspase‐cleaved fragment CK18-M30. Results In this cohort study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed decompensated liver disease and another 28 patients (17.5%) developed acute decompensation during follow-up (within 24 months). One hundred fifteen patients showed stable liver disease (71.9%). We found DAMPs significantly elevated in patients with decompensated liver disease versus compensated liver disease. Patients with acute decompensation during follow-up showed higher baseline levels of IL-6, sFasL, CK18-M65 and–M30 (P<0.01) compared to patients with stably compensated liver disease. In multivariate analyses, we found an independent association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. Accuracy of the marker combination for predicting acute decompensation was high (AUC = 0.79). Elevated aminotransferase levels did not correlate with decompensated liver disease and acute decompensation. Conclusions DAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation. The prognostic value of a marker combination with soluble Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.
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Nazir N, Abbas S, Nasir H, Hussain I. Electrochemical sensing of limonene using thiol capped gold nanoparticles and its detection in the real breath sample of a cirrhotic patient. J Electroanal Chem (Lausanne) 2022. [DOI: 10.1016/j.jelechem.2021.115977] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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El Shazli LB, Ragab DA, Abdelhady KA, Abdelaziz AW. Role of plasma von Willebrand factor antigen in prediction of esophageal varices in pediatric and adolescent patients with portal hypertension. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00159-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Ruptured esophageal varices (EVs) are a leading cause of death in Portal hypertension (PHT), it has been a big concern of research to screen EVs through non-invasive approaches. This study aimed to evaluate the role of plasma von Willebrand factor antigen (VWF-Ag) assay for early detection of EVs in patients with portal hypertension. This was a cross-sectional study, done on 47 portal hypertensive children and adolescents who were collected from the Pediatrics Hepatology Clinic, Children Hospital, Ain Shams University. All patients were subjected to comprehensive history taking, thorough clinical examination, routine investigations, abdominal ultrasound, upper GI endoscopy, and measurement of plasma VWF-Ag level. The patients were divided based on their endoscopic findings into two groups; a varices group which included 37 patients, and a non-varices group which included 10 patients.
Results
VWF-Ag rise significantly in patients with EVs, revealing a direct positive association with the degree of EVs.
Conclusion
The plasma VWF-Ag can be applied as a non-invasive evidence of the presence and grading of EVs.
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Virseda-Berdices A, Brochado-Kith O, Díez C, Hontañon V, Berenguer J, González-García J, Rojo D, Fernández-Rodríguez A, Ibañez-Samaniego L, Llop-Herrera E, Olveira A, Perez-Latorre L, Barbas C, Rava M, Resino S, Jiménez-Sousa MA. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis. J Antimicrob Chemother 2021; 77:719-726. [PMID: 34888660 DOI: 10.1093/jac/dkab444] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/08/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Patients with a significant decrease in hepatic venous pressure gradient (HVPG) have a considerable reduction of liver complications and higher survival after HCV eradication. OBJECTIVES To evaluate the association between the baseline blood microbiome and the changes in HVPG after successful direct-acting antiviral (DAA) therapy in patients with HCV-related cirrhosis. METHODS We performed a prospective study in 32 cirrhotic patients (21 HIV positive) with clinically significant portal hypertension (HVPG ≥10 mmHg). Patients were assessed at baseline and 48 weeks after HCV treatment completion. The clinical endpoint was a decrease in HVPG of ≥20% or HVPG <12 mmHg at the end of follow-up. Bacterial 16S ribosomal DNA was sequenced using MiSeq Illumina technology, inflammatory plasma biomarkers were investigated using ProcartaPlex immunoassays and the metabolome was investigated using GC-MS. RESULTS During the follow-up, 47% of patients reached the clinical endpoint. At baseline, those patients had a higher relative abundance of Corynebacteriales and Diplorickettsiales order, Diplorickettsiaceae family, Corynebacterium and Aquicella genus and Undibacterium parvum species organisms and a lower relative abundance of Oceanospirillales and Rhodospirillales order, Halomonadaceae family and Massilia genus organisms compared with those who did not achieve the clinical endpoint according to the LEfSe algorithm. Corynebacteriales and Massilia were consistently found within the 10 bacterial taxa with the highest differential abundance between groups. Additionally, the relative abundance of the Corynebacteriales order was inversely correlated with IFN-γ, IL-17A and TNF-α levels and the Massilia genus with glycerol and lauric acid. CONCLUSIONS Baseline-specific bacterial taxa are related to an HVPG decrease in patients with HCV-related cirrhosis after successful DAA therapy.
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Affiliation(s)
- Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain
| | - Oscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - David Rojo
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Luis Ibañez-Samaniego
- Servicio de Aparato Digestivo, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain
| | - Elba Llop-Herrera
- Departamento de Gastroenterología, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain
| | - Antonio Olveira
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
| | - Leire Perez-Latorre
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Coral Barbas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Marta Rava
- Unidad de la Cohorte de la Red de Investigación en Sida (CoRIS), Centro Nacional de Epidemiologia (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Angeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Getachew A, Hussain M, Huang X, Li Y. Toll-like receptor 2 signaling in liver pathophysiology. Life Sci 2021; 284:119941. [PMID: 34508761 DOI: 10.1016/j.lfs.2021.119941] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/19/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022]
Abstract
Chronic liver diseases (CLD) are among the major cause of mortality and morbidity worldwide. Despite current achievements in the area of hepatitis virus, chronic alcohol abuse and high-fat diet are still fueling an epidemic of severe liver disease, for which, an effective therapy has yet not been discovered. In particular, the therapeutic regimens that could prevent the progression of fibrosis and, in turn, aid cirrhotic liver to develop a robust regenerative capability are intensively needed. To this context, a better understanding of the signaling pathways regulating hepatic disease development may be of critical value. In general, the liver responds to various insults with an orchestrated healing process involving variety of signaling pathways. One such pathway is the TLR2 signaling pathway, which essentially regulates adult liver pathogenesis and thus has emerged as an attractive target to treat liver disease. TLR2 is expressed by different liver cells, including Kupffer cells (KCs), hepatocytes, and hepatic stellate cells (HSCs). From a pathologic perspective, the crosstalk between antigens and TLR2 may preferentially trigger a distinctive set of signaling mechanisms in these liver cells and, thereby, induce the production of inflammatory and fibrogenic cytokines that can initiate and prolong liver inflammation, ultimately leading to fibrosis. In this review, we summarize the currently available evidence regarding the role of TLR2 signaling in hepatic disease progression. We first elaborate its pathological involvement in liver-disease states, such as inflammation, fibrosis, and cirrhosis. We then discuss how therapeutic targeting of this pathway may help to alleviate its disease-related functioning.
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Affiliation(s)
- Anteneh Getachew
- Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Muzammal Hussain
- Center for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Xinping Huang
- Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Yinxiong Li
- Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China.
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Lee DU, Fan GH, Hastie DJ, Addonizio EA, Prakasam VN, Ahern RR, Suh J, Seog KJ, Karagozian R. The clinical impact of cirrhosis on the postoperative outcomes of patients undergoing bariatric surgery: propensity score-matched analysis of 2011-2017 US hospitals. Expert Rev Gastroenterol Hepatol 2021; 15:1191-1200. [PMID: 33706616 DOI: 10.1080/17474124.2021.1902803] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Objectives: Since there is increasing number of patients with cirrhosis who require the bariatric procedure due to obesity and obesity-related nonalcoholic steatohepatitis fibrosis, we evaluate the effect of cirrhosis on post-bariatric surgery outcomes.Methods: 2011-2017 National Inpatient Sample was used to isolate bariatric cases, which were stratified by cirrhosis; controls were propensity-score matched to cases and compared to endpoints: mortality, length of stay (LOS), costs, and postoperative complications.Results: From 190,753 patients undergoing bariatric surgery, there were 957 with cirrhosis and 957 matched controls. There was no difference in mortality (0.94 vs 0.52% p = 0.42, OR 1.81 95%CI 0.60-5.41); however, cirrhosis patients had higher LOS (3.36 vs 2.89d p = 0.002), costs ($68,671 vs $61,301 p < 0.001), and bleeding (2.09 vs 0.72% p < 0.001, OR 2.95 95%CI 1.89-4.61). In multivariate, there was no difference in mortality (p = 0.330, aOR 1.73 95%CI 0.58-5.19). In subgroup comparison of cirrhosis patients, those with decompensated cirrhosis had higher mortality (7.69 vs 0.94% p < 0.001, OR 8.78 95%CI 3.41-22.59).Conclusion: The results of this study show compensated cirrhosis does not pose an increased risk toward post-bariatric surgery mortality; however, hepatic decompensation increases the postsurgical risks.
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Affiliation(s)
- David Uihwan Lee
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Gregory Hongyuan Fan
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - David Jeffrey Hastie
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Elyse Ann Addonizio
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | | | - Ryan Richard Ahern
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Julie Suh
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Kristen Jin Seog
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Raffi Karagozian
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
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Ballester MP, Lluch P, Gómez C, Capilla M, Tosca J, Martí-Aguado D, Guijarro J, Mínguez M. Transjugular intrahepatic portosystemic shunt reduces hospital care burden in patients with decompensated cirrhosis. Intern Emerg Med 2021; 16:1519-1527. [PMID: 33400160 DOI: 10.1007/s11739-020-02602-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 12/07/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND AIMS Patients with decompensated cirrhosis frequently require hospital admissions, which are associated with worse prognosis. The aim of this study was to analyze the effect of TIPS on the need for hospital care. Secondary objectives were to assess the clinical and biological impact of TIPS and to identify predictors of post-TIPS hospital care. METHODS An observational, retrospective study of patients with decompensated cirrhosis treated with TIPS from January 2008 until March 2019. Exclusion criteria were TIPS placed for non-cirrhotic portal hypertension (PH) and patients referred from another hospital without prior or subsequent follow-up at our Unit. Hospital care, PH-related complications, and laboratory data were compared before and after TIPS. RESULTS The final cohort comprised 104 patients (72% male) with a mean age of 60 (± 10) years. Follow-up from first decompensation until TIPS and that from procedure to study completion were 7 (4.2-9.8) and 20 (4.6-35.4) months, respectively. TIPS was indicated mainly for refractory ascites (50%) and variceal bleeding (39%). Hemodynamic and clinical success rates were 97% and 92%, respectively. The number of emergency department visits and hospital admissions decreased after the procedure (p < 0.001). Improvement was seen in MELD and Child-Pugh scores, renal function, hyponatremia, and anemia after TIPS. Variceal bleeding as the indication for TIPS (OR 0.047; 95 CI 0.006-0,39; p < 0.05) together with early creation of the shunt (stage 3 vs 5; p < 0.05) were associated with a reduction in risk of post-TIPS hospital care. CONCLUSION TIPS is a safe and effective procedure that reduces hospital care burden by improving PH-related complications, hepatic, renal function, hyponatremia, and anemia. Variceal bleeding as the indication and early placement of the device were associated with a reduction in post-TIPS hospital care. These findings support a role for this treatment, predominantly in the early stages of cirrhosis.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain.
- Neurological Impairment Research Unit, INCLIVA Biomedical Research Institute of Clinic University Hospital of Valencia, Valencia, Spain.
| | - Paloma Lluch
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
- Department of Medicine. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Concepción Gómez
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
| | - Maria Capilla
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
| | - Joan Tosca
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
| | - David Martí-Aguado
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia, Spain
| | - Jorge Guijarro
- Interventional Radiology Department, Clinic University Hospital of Valencia, Valencia, Spain
| | - Miguel Mínguez
- Digestive Disease Department, Clinic University Hospital of Valencia, Blasco Ibañez 17, 46010, Valencia, Spain
- Department of Medicine. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
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Rajesh S, Philips CA, Betgeri SS, George T, Ahamed R, Mohanan M, Augustine P. Transjugular intrahepatic portosystemic shunt (TIPS) placement at index portal hypertensive decompensation (anticipant TIPS) in cirrhosis and the role of early intervention in variceal bleeding and ascites. Indian J Gastroenterol 2021; 40:361-372. [PMID: 34324168 DOI: 10.1007/s12664-021-01179-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 04/01/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) placement improves survival in patients with refractory/recurrent acute variceal bleeding (RAVB) and refractory ascites/hydrothorax. Recently, early TIPS was shown to reduce rebleeding and improve survival compared to the conventional TIPS. We aimed to study outcomes in patients with cirrhosis undergoing TIPS at first significant portal hypertensive (PHT) decompensation (termed anticipant TIPS) compared to those undergoing TIPS for recurrent or persistent PHT complications (conventional) and compared the former to matched controls on standard medical management (SMT). METHODS We retrospectively analyzed the clinical, biochemical, and liver disease severity parameters and survival at baseline and post-intervention in cirrhosis patients at two major hepatobiliary intervention centers undergoing anticipant (n = 27) or conventional TIPS (n = 30) and compared the former group to matched historical controls on SMT (n = 35). RESULTS Baseline parameters were comparable between both the groups, including the Child-Pugh class and model for end-stage liver disease (MELD) scores. Length of stay in the intensive care unit, post-procedure admission rates, and sepsis events were higher among patients undergoing conventional TIPS (p < 0.05). Post-TIPS, at 1 year, overall and sub-grouped survivals were better in patients undergoing anticipant TIPS. On further sub-group analysis, based on the PHT events and stratified based on Child-Pugh and MELD scores, a higher proportion of patients survived after anticipant TIPS at 1 year. Compared to SMT, patients undergoing anticipant TIPS had significantly lesser hospitalizations, recurrence of varices, and ascites at 1 year, reducing hospital visits and financial burden. CONCLUSIONS Anticipant TIPS at the first significant PHT event could improve liver-related events and survival compared to standard medical management and conventional TIPS, respectively.
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Affiliation(s)
- Sasidharan Rajesh
- Interventional Radiology, Ernakulam Medical Center, Kochi 682 028, India
| | - Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Ernakulam Medical Center, Kochi 682 028, India.
- Philip Augustine Associates, Symphony, AMRA-15, Automobile Road, Palarivattom, Kochi, 682 025, India.
| | | | - Tom George
- Interventional Radiology, Ernakulam Medical Center, Kochi 682 028, India
| | - Rizwan Ahamed
- Gastroenterology and Advanced G.I. Endoscopy, Ernakulam Medical Center, Kochi 682 028, India
| | - Meera Mohanan
- Department of Anaesthesia and Critical Care, Ernakulam Medical Center, Kochi 682 028, India
| | - Philip Augustine
- Gastroenterology and Advanced G.I. Endoscopy, Ernakulam Medical Center, Kochi 682 028, India
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Yu S, Sun L, Wang H, Jiang J, Zhou Q. Autonomic regulation of imbalance-induced myocardial fibrosis and its mechanism in rats with cirrhosis. Exp Ther Med 2021; 22:1040. [PMID: 34373726 PMCID: PMC8343770 DOI: 10.3892/etm.2021.10472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 06/10/2021] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.
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Affiliation(s)
- Shanshan Yu
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Lei Sun
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Hua Wang
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Jue Jiang
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Qi Zhou
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
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Lamanna A, Mitreski G, Maingard J, Owen A, Schelleman T, Goodwin M, Ranatunga D. Ultrasound-guided portal vein puncture during Transjugular Intrahepatic Portosystemic Shunt: Technique and experience of a quaternary liver transplant hospital. J Med Imaging Radiat Oncol 2021; 66:60-67. [PMID: 34278730 DOI: 10.1111/1754-9485.13288] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/24/2021] [Accepted: 07/02/2021] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Portal hypertension (PH) is associated with complications including refractory ascites and variceal haemorrhage and can be treated endovascularly with a Transjugular Intrahepatic Portosystemic Shunt (TIPS). Portal vein puncture during TIPS using real-time transabdominal ultrasound guidance is one of many portal vein puncture techniques and is seldom used compared with other methods. The purpose of this manuscript is to describe this technique and its associated procedural outcomes at a quaternary liver transplant hospital. METHODS Clinical data of all patients who underwent ultrasound-guided TIPS at our institution between 1 January 2009 and 1 January 2019 were retrospectively obtained from electronic medical records and reviewed. Patient demographics, indications, procedural outcomes and complications were recorded. RESULTS Forty-four ultrasound-guided TIPS procedures were performed during the study period. The most common indication for TIPS was refractory ascites (n = 26; 57%) and variceal haemorrhage (n = 12; 26%). Technical success rate was 100%. No intraprocedural complications occurred. Periprocedural complication rate was 35% (n = 16) with encephalopathy (n = 8; 17%) and sepsis (n = 5; 11%) the most common. One patient with sepsis died. No other TIPS-related deaths occurred. Median fluoroscopy time, contrast volume, air kerma and dose area product values for all procedures were 35 minutes (IQR 24-51), 100 ml (IQR 70-160), 0.95 Gy (IQR 0.50-1.53) and 127 Gycm2 (IQR 68.75-206), respectively. CONCLUSION Transabdominal ultrasound-guided portal vein puncture during TIPS is safe and technically feasible. When compared to fluoroscopically guided methods, it is associated with lower intraprocedural complication rates, fluoroscopy times, contrast volumes and radiation doses in our experience. Radiation doses, FTs and contrast volumes were also considerably lower than recommended limits.
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Affiliation(s)
- Anthony Lamanna
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Goran Mitreski
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Julian Maingard
- Department of Imaging, Monash Health, Melbourne, Victoria, Australia.,School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Andrew Owen
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia.,Interventional Radiology Service - Department of Radiology, Barwon Health, Geelong, Victoria, Australia
| | - Tony Schelleman
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Mark Goodwin
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Dinesh Ranatunga
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
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Engelmann C, Clària J, Szabo G, Bosch J, Bernardi M. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction. J Hepatol 2021; 75 Suppl 1:S49-S66. [PMID: 34039492 PMCID: PMC9272511 DOI: 10.1016/j.jhep.2021.01.002] [Citation(s) in RCA: 209] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/31/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.
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Affiliation(s)
- Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany; Institute for Liver and Digestive Health, University College London, London, United Kingdom; Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
| | - Joan Clària
- European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain,Biochemistry and Molecular Genetics Service, Hospital ClínicIDIBAPS and CIBERehd, Spain,Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain
| | - Gyongyi Szabo
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Jaume Bosch
- IDIBAPS and CIBERehd, University of Barcelona, Barcelona, Spain,Department for Biomedical Research (DBMR), Bern University, Bern, Switzerland
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences; Alma Mater Studiorum – University of Bologna; Italy
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Lee H, Kim BK, Jang S, Ahn SH. Cost-Effectiveness Analysis of Antiviral Therapy for Untreated Minimally Active Chronic Hepatitis B to Prevent Liver Disease Progression. Clin Transl Gastroenterol 2021; 12:e00299. [PMID: 33600103 PMCID: PMC7889372 DOI: 10.14309/ctg.0000000000000299] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 12/07/2020] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Antiviral therapy (AVT) for chronic hepatitis B (CHB) can prevent liver disease progression. Because of its stringent reimbursement criteria, significant numbers of patients with untreated minimally active (UMA)-CHB exist, although they are still subject to disease progression. We thus performed a cost-effectiveness analysis to assess the rationale for AVT for UMA-CHB. METHODS We compared cost and effectiveness (quality-adjusted life years, QALYs) in virtual UMA-CHB cohorts of 10,000 50-year-olds receiving AVT (scenario 1) vs no treatment (scenario 2) for 10 years. A Markov model, including 7 health states of CHB-related disease progression, was used. Values for transition probabilities and costs were mostly obtained from recent South Korean data. RESULTS The simulation of AVT vs no treatment predicted $2,201 incremental costs and 0.175 incremental QALYs per patient for 10 years, with an incremental cost-effectiveness ratio (ICER) of $12,607/QALY, suggesting cost-effectiveness of AVT. In sum, if 10,000 patients received AVT, 720 incident hepatocellular carcinoma and 465 CHB-related more deaths could be averted in 10 years relative to no treatment. When the simulated analysis period was extended to 20 years, AVT was also highly cost-effective with an ICER of $2,036/QALY. Although hepatocellular carcinoma-related mortality was a major factor influencing ICER, its fluctuation can be accepted within willingness to pay of $33,000 in South Korea. According to probabilistic sensitivity analysis with the threshold of willingness to pay, the probability of AVT cost-effectiveness was 83.3%. DISCUSSION Long-term AVT for patients with UMA-CHB may contribute positively toward individual clinical benefit and national health care budget.
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Affiliation(s)
- Hankil Lee
- Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Sungin Jang
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
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Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options. J Clin Med 2021; 10:jcm10040702. [PMID: 33670126 PMCID: PMC7916881 DOI: 10.3390/jcm10040702] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/29/2021] [Accepted: 02/06/2021] [Indexed: 02/07/2023] Open
Abstract
There is considerable experimental evidence that the renin angiotensin system (RAS) plays a central role in both hepatic fibrogenesis and portal hypertension. Angiotensin converting enzyme (ACE), a key enzyme of the classical RAS, converts angiotensin I (Ang I) to angiotensin II (Ang II), which acts via the Ang II type 1 receptor (AT1R) to stimulate hepatic fibrosis and increase intrahepatic vascular tone and portal pressure. Inhibitors of the classical RAS, drugs which are widely used in clinical practice in patients with hypertension, have been shown to inhibit liver fibrosis in animal models but their efficacy in human liver disease is yet to be tested in adequately powered clinical trials. Small trials in cirrhotic patients have demonstrated that these drugs may lower portal pressure but produce off-target complications such as systemic hypotension and renal failure. More recently, the alternate RAS, comprising its key enzyme, ACE2, the effector peptide angiotensin-(1–7) (Ang-(1–7)) which mediates its effects via the putative receptor Mas (MasR), has also been implicated in the pathogenesis of liver fibrosis and portal hypertension. This system is activated in both preclinical animal models and human chronic liver disease and it is now well established that the alternate RAS counter-regulates many of the deleterious effects of the ACE-dependent classical RAS. Work from our laboratory has demonstrated that liver-specific ACE2 overexpression reduces hepatic fibrosis and liver perfusion pressure without producing off-target effects. In addition, recent studies suggest that the blockers of the receptors of alternate RAS, such as the MasR and Mas related G protein-coupled receptor type-D (MrgD), increase splanchnic vascular resistance in cirrhotic animals, and thus drugs targeting the alternate RAS may be useful in the treatment of portal hypertension. This review outlines the role of the RAS in liver fibrosis and portal hypertension with a special emphasis on the possible new therapeutic approaches targeting the ACE2-driven alternate RAS.
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Accuracy of liver and spleen stiffness on magnetic resonance elastography for detecting portal hypertension: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2021; 32:237-245. [PMID: 32282542 DOI: 10.1097/meg.0000000000001724] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The purpose of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of liver and spleen stiffness on magnetic resonance elastography (MRE) for detecting clinically significant portal hypertension. METHODS A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Grey Literature through to 15 August 2019 was performed. Original articles with >10 patients evaluating liver and/or spleen stiffness on MRE using a reference standard of portal hypertension defined as intractable ascites, esophageal varices, encephalopathy and/or death were included in analysis. Patient, clinical, MRI, and diagnostic performance was independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. RESULTS Fourteen studies were included with 12 studies evaluating liver stiffness and eight studies evaluating spleen stiffness. The pooled and weighted sensitivity, specificity, and area under the curve (AUC) values for liver stiffness on MRE were 83% [95% confidence interval (CI) 72-90%], 80% (95% CI 70-88%), and 88% (95% CI 85-91%), respectively. The pooled and weighted sensitivity, specificity, and AUC values for spleen stiffness on MRE were 79% (95% CI 61-90%), 90% (95% CI 80-95%), and 92% (95% CI 89-94%), respectively. The liver and spleen stiffness sensitivity and specificity values were comparable when evaluating for esophageal varices only at of 80% (95% CI 66-89%) and 76% (95% CI 62-86%) for liver stiffness, and 75% (95% CI 52-90%) and 89% (95% CI 70-96%) for spleen stiffness. DISCUSSION Liver and spleen stiffness on MRE can serve as a supplemental noninvasive assessment tools for detecting clinically significant portal hypertension. Spleen stiffness may be more specific and accurate than liver stiffness for detecting portal hypertension.
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Zhang H, Zhang S, Zhang J, Zhou R, Nie Y, Ren S, Li J, Feng K, Ji F, Kong G, Li Z. Improvement of human platelet aggregation post-splenectomy with paraesophagogastric devascularization in chronic hepatitis B patients with cirrhotic hypersplenism. Platelets 2020; 31:1019-1027. [PMID: 31851564 DOI: 10.1080/09537104.2019.1704715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 12/05/2019] [Accepted: 12/09/2019] [Indexed: 12/13/2022]
Abstract
Thrombocytopenia is a common hematological abnormality in patients with cirrhotic hypersplenism. Splenectomy with paraesophagogastric devascularization (SPD) is a conventional surgical therapy which can reverse pancytopenia in these patients. Platelets are traditionally recognized for their central role in hemostasis. However, the status of platelet aggregation in chronic hepatitis B patients with cirrhotic hypersplenism before and after SPD has not been reported yet. A total of 41 cirrhotic patients and 31 healthy controls were included in this study. Platelet aggregation was detected by AggRAM® Advanced Modular System (Helena Laboratories, USA). ELISA was used to detect the cytokines closely related to platelet aggregation. Expressions of platelet membrane glycoproteins (GPs) were evaluated by flow cytometric analysis. Platelet aggregation was found to be decreased distinctly in the cirrhotic patients, and to be restored to normal level after SPD. The cirrhotic patients showed higher plasma levels of the cytokines HMGB1, PEDF, vWF, cAMP and cGMP, which also improved partially after SPD. Moreover, the cirrhotic patients had much lower expression of GPIIb/IIIa, GPIbα and P-selectin than either the healthy controls or SPD patients at basal or activated level. Generally, SPD benefits cirrhotic patients with bleeding tendencies by improving platelet counts and aggregation. GPIIb/IIIa may be the key membrane protein responsible for the change in platelet aggregation before and after SPD.
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Affiliation(s)
- Hui Zhang
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Shaoying Zhang
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Jian Zhang
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Rui Zhou
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an, Shaanxi Province, People's Republic of China
| | - Song Ren
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Jun Li
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Keping Feng
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Fanpu Ji
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
| | - Guangyao Kong
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
| | - Zongfang Li
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
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