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Xia Y, Tie J, Wang G, Wu H, Zhuge Y, Yuan X, Huang G, Li Z, Liu X, Chen A, Zhang L, Cai Z, Tang C, Zhang C. Benefits of TIPS for Patients With Large Ascites Preceding Recurrent or Refractory ascites: A Multicenter Cohort Study. J Gastroenterol Hepatol 2025. [PMID: 40135340 DOI: 10.1111/jgh.16948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 02/27/2025] [Accepted: 03/16/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND AND AIM Patients with recurrent or refractory ascites can benefit from transjugular intrahepatic portosystemic shunt (TIPS). However, the value of TIPS for patients with large ascites remains unclear. METHODS This retrospective multicenter study included patients who underwent TIPS or medicine plus large-volume paracentesis (medicine + LVP) for ascites between January 2014 and December 2022 at five centers. The primary endpoint was recurrence or worsening of ascites. The secondary endpoints were liver-related death, all-cause hemorrhage, overt hepatic encephalopathy (OHE), and shunt dysfunction. RESULTS Overall, 724 patients were evaluated, including 373 patients with large ascites preceding recurrent or refractory ascites received TIPS (the LA-TIPS group), 282 patients with recurrent and refractory ascites received TIPS (the RA-TIPS group), and 69 patients with large ascites preceding recurrent or refractory ascites received medicine + LVP (the LA-M group). Patients in the LA-TIPS group had significantly lower incidences of recurrence or worsening of ascites (37.4% vs. 45.3%, p < 0.001), liver-related death (44.8% vs. 62.0%, p < 0.001), and OHE (47.3% vs. 60.3%, p < 0.001) than those in the RA-TIPS group. Meanwhile, patients in the LA-TIPS group had significantly lower incidences of recurrence or worsening of ascites (37.4% vs. 44.6%, p = 0.006) and hemorrhage (38.3% vs. 47.2%, p = 0.042), but a higher incidence of OHE (34.2% vs. 4.5%, p < 0.001) than those in the LA-M group. CONCLUSIONS In terms of controlling ascites, the benefit of TIPS was greater in patients with large ascites preceding recurrent or refractory ascites, suggesting that TIPS might be considered in patients with large ascites before they progress to recurrent or refractory stages.
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Affiliation(s)
- Yifu Xia
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jun Tie
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xulong Yuan
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangjun Huang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Zhen Li
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xu Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Anbang Chen
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Linhao Zhang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zihao Cai
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Chengwei Tang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Bozon-Rivière P, Rudler M, Weiss N, Thabut D. TIPS and hepatic encephalopathy in patients with cirrhosis. Metab Brain Dis 2025; 40:117. [PMID: 39903376 DOI: 10.1007/s11011-025-01541-w] [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: 07/06/2024] [Accepted: 01/17/2025] [Indexed: 02/06/2025]
Abstract
Despite a better understanding in its prognosis and pathogenesis, hepatic encephalopathy (HE) remains one of the major complications of Transjugular Intrahepatic Portosystemic Shunt (TIPS) with a prevalence ranging from 35 to 50%. Its epidemiology differs according to the indication for TIPS (salvage/rescue TIPS, preemptive (pTIPS) or elective TIPS). In salvage/rescue TIPS, the prognosis is linked to that of bleeding, and HE should not be a contraindication to TIPS, especially as bleeding is a common precipitating factor of HE. In pTIPS, i.e. TIPS performed within the 72 h after stabilization of acute variceal bleeding in high-risk patients, the risk rebleeding and HE is reduced, when compared to endoscopic and drugs treatment. As a consequence, the Baveno VII recommendations state that HE at admission should not be considered as a contraindication to pTIPS placement. In elective situations, such as refractory (intractable ascites (intolerance to diuretics) or resistant ascites (i.e. despite optimal diuretic treatment (spironolactone 400 mg/d and Furosemide 160 mg/d combined with low-salt treatment (< 5.2 g/day) or recurrent ascites (the need for at least 3 paracenteses per year) and secondary prophylaxis of variceal bleeding, it is recommended to systematically look for risk factors for HE, and chronic or refractory HE remain not recommended to TIPS in most centers. Chronic HE involves persistent neurological symptoms with fluctuating acute episodes. Recurrent HE refers to repeated episodes occurring within 6 months, while refractory HE is resistant to standard treatments, often requiring more aggressive management (Vilstrup et al. 2014). A careful selection of patients is mandatory before elective TIPS decision. Risk factors must be identified and corrected if possible before any TIPS decision is made. Management of HE after TIPS is based on identification of precipitating factors, curative treatment with lactulose as first-line therapy and rifaximin as second-line therapy, and nutritional management. In elective TIPS, prophylactic administration of rifaximin is recommended in order to decrease the risk of further HE development in selected patients (not in everyone, at least according to Baveno VII). Liver transplantation (LT) should be discussed with a multidisciplinary team as an alternative option to TIPS in case of high-risk of post-TIPS HE, and in case of refractory HE after TIPS.
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Affiliation(s)
- Pauline Bozon-Rivière
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France
| | - Marika Rudler
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Nicolas Weiss
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Neurology Intensive Care Unit, Neurology Department, AP-HP, Sorbonne Université, La Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Dominique Thabut
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Wang G, Zhang F, Ojeda A, Shalaby S, Hernandez-Gea V, Garcia-Pagan JC. The evolution of the TIPS placement technique and its applications over four decades. Dig Liver Dis 2024; 56:1980-1988. [PMID: 38853090 DOI: 10.1016/j.dld.2024.05.018] [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: 03/14/2024] [Revised: 05/16/2024] [Accepted: 05/19/2024] [Indexed: 06/11/2024]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS), a highly effective procedure reducing portal hypertension, has been in use for over seven decades and is now a cornerstone in managing portal hypertension-related complications such as variceal bleeding and ascites. Historically, TIPS has dealt with two main challenges: ensuring stent patency and preventing post-TIPS hepatic encephalopathy. The introduction of PTFE-coated stents markedly reduced the risk of TIPS dysfunction and stent patency is no longer a major concern. However, despite improved patient selection criteria, hepatic encephalopathy continues to be a significant and persistent issue. In addition, the broader application of TIPS in recent decades has brought to light additional, albeit less common, complications, such as post-TIPS heart failure. This review offers a comprehensive overview of TIPS historical evolution, advancements in technique, and its application in the treatment of portal hypertension.
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Affiliation(s)
- Guangchuan Wang
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, PR China
| | - Feng Zhang
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, PR China
| | - Asuncion Ojeda
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Rare Liver)
| | - Sarah Shalaby
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Rare Liver)
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Rare Liver); Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Rare Liver); Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain.
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Wang X, Zeng X, Wang G. External treatment of refractory ascites induced by liver cirrhosis using traditional Chinese medicine. Asian J Surg 2024; 47:4429-4430. [PMID: 39069403 DOI: 10.1016/j.asjsur.2024.07.185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 07/21/2024] [Indexed: 07/30/2024] Open
Affiliation(s)
- Xuerong Wang
- Infectious Department, Zigong First People's Hospital, Zigong, PR China
| | - Xiaoqin Zeng
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, PR China
| | - Gang Wang
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, PR China.
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Lan T, Chen M, Tang C, Deltenre P. Recent developments in the management of ascites in cirrhosis. United European Gastroenterol J 2024; 12:261-272. [PMID: 38340308 PMCID: PMC10954428 DOI: 10.1002/ueg2.12539] [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: 07/24/2023] [Accepted: 12/05/2023] [Indexed: 02/12/2024] Open
Abstract
In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long-term albumin infusion may improve survival in patients with cirrhosis and ascites while beta-blockers may reduce ascites occurrence. Transjugular intrahepatic porto-systemic shunt (TIPS) placement may also improve survival in selected patients in addition to the control with ascites. Low-flow ascites pump insertion can be another option for some patients with intractable ascites. In this review, we summarize the latest data related to the management of ascites occurring in cirrhosis. There are still unanswered questions, such as the optimal use of albumin as a long-term therapy, the place of beta-blockers, and the best timing for TIPS placement to improve the natural history of ascites, as well as the optimal stent diameter to reduce the risk of shunt-related side-effects. These issued should be addressed in future studies.
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Affiliation(s)
- Tian Lan
- Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Chen
- Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Chengwei Tang
- Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
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Iannone G, Pompili E, De Venuto C, Pratelli D, Tedesco G, Baldassarre M, Caraceni P, Zaccherini G. The Role of Transjugular Intrahepatic Portosystemic Shunt for the Management of Ascites in Patients with Decompensated Cirrhosis. J Clin Med 2024; 13:1349. [PMID: 38592162 PMCID: PMC10932158 DOI: 10.3390/jcm13051349] [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: 01/17/2024] [Revised: 02/09/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
The development and progression of ascites represent a crucial event in the natural history of patients with cirrhosis, predisposing them to other complications and carrying a heavy impact on prognosis. The current standard of care for the management of ascites relies on various combinations of diuretics and large-volume paracenteses. Periodic long-term albumin infusions on top of diuretics have been recently shown to greatly facilitate the management of ascites. The insertion of a transjugular intrahepatic portosystemic shunt (TIPS), an artificial connection between the portal and caval systems, is indicated to treat patients with refractory ascites. TIPS acts to decrease portal hypertension, thus targeting an upstream event in the pathophysiological cascade of cirrhosis decompensation. Available evidence shows a significant benefit on ascites control/resolution, with less clear results on patient survival. Patient selection plays a crucial role in obtaining better clinical responses and avoiding TIPS-related adverse events, the most important of which are hepatic encephalopathy, cardiac overload and failure, and liver failure. At the same time, some recent technical evolutions of available stents appear promising but deserve further investigations. Future challenges and perspectives include (i) identifying the features for selecting the ideal candidate to TIPS; (ii) recognizing the better timing for TIPS placement; and (iii) understanding the most appropriate role of TIPS within the framework of all other available treatments for the management of patients with decompensated cirrhosis.
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Affiliation(s)
- Giulia Iannone
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Enrico Pompili
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Clara De Venuto
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Dario Pratelli
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Greta Tedesco
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
| | - Maurizio Baldassarre
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.I.); (E.P.); (C.D.V.); (D.P.); (G.T.); (P.C.)
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
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Di Cola S, Lapenna L, Gazda J, Fonte S, Cusi G, Esposito S, Mattana M, Merli M. Role of Transjugular Intrahepatic Portosystemic Shunt in the Liver Transplant Setting. J Clin Med 2024; 13:600. [PMID: 38276106 PMCID: PMC10816519 DOI: 10.3390/jcm13020600] [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: 10/10/2023] [Revised: 01/15/2024] [Accepted: 01/18/2024] [Indexed: 01/27/2024] Open
Abstract
Liver transplantation is currently the only curative therapy for patients with liver cirrhosis. Not all patients in the natural course of the disease will undergo transplantation, but the majority of them will experience portal hypertension and its complications. In addition to medical and endoscopic therapy, a key role in managing these complications is played by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Some indications for TIPS placement are well-established, and they are expanding and broadening over time. This review aims to describe the role of TIPS in managing patients with liver cirrhosis, in light of liver transplantation. As far as it is known, TIPS placement seems not to affect the surgical aspects of liver transplantation, in terms of intraoperative bleeding rates, postoperative complications, or length of stay in the Intensive Care Unit. However, the placement of a TIPS "towards transplant" can offer advantages in terms of ameliorating a patient's clinical condition at the time of transplantation and improving patient survival. Additionally, the TIPS procedure can help preserve the technical feasibility of the transplant itself. In this context, indications for TIPS placement at an earlier stage are drawing particular attention. However, TIPS insertion in decompensated patients can also lead to serious adverse events. For these reasons, further studies are needed to make reliable recommendations for TIPS in the pre-transplant setting.
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Affiliation(s)
- Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Jakub Gazda
- 2nd Department of Internal Medicine, PJ Safarik University and L. Pasteur University Hospital in Kosice, 040 11 Kosice, Slovakia;
| | - Stefano Fonte
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Giulia Cusi
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Samuele Esposito
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Marco Mattana
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (S.D.C.); (L.L.); (S.F.); (G.C.); (S.E.); (M.M.)
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Rajan A, Boike J. TIPS for Refractory Ascites and Hepatic Hydrothorax. CURRENT HEPATOLOGY REPORTS 2024; 23:45-53. [DOI: 10.1007/s11901-023-00625-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/09/2023] [Indexed: 01/04/2025]
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11
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Haskal ZJ, Mohammed X, Koppula R. Transjugular Intrahepatic Portosystemic Shunt (TIPS) and Portal Hypertension. IR PLAYBOOK 2024:515-523. [DOI: 10.1007/978-3-031-52546-9_42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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12
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Saltini D, Indulti F, Guasconi T, Bianchini M, Cuffari B, Caporali C, Casari F, Prampolini F, Senzolo M, Colecchia A, Schepis F. Transjugular Intrahepatic Portosystemic Shunt: Devices Evolution, Technical Tips and Future Perspectives. J Clin Med 2023; 12:6758. [PMID: 37959225 PMCID: PMC10650044 DOI: 10.3390/jcm12216758] [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: 09/30/2023] [Revised: 10/18/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis.
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Affiliation(s)
- Dario Saltini
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Federica Indulti
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Tomas Guasconi
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Marcello Bianchini
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Biagio Cuffari
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Cristian Caporali
- Division of Radiology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy; (C.C.)
| | - Federico Casari
- Division of Radiology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy; (C.C.)
| | - Francesco Prampolini
- Division of Radiology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy; (C.C.)
| | - Marco Senzolo
- Multivisceral Transplant Unit-Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy;
| | - Antonio Colecchia
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
| | - Filippo Schepis
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia, 41121 Modena, Italy (F.I.); (T.G.); (M.B.); (B.C.); (A.C.)
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13
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Carroll A, Boike JR. TIPS: indications, Contraindications, and Evaluation. Curr Gastroenterol Rep 2023; 25:232-241. [PMID: 37603109 DOI: 10.1007/s11894-023-00884-7] [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] [Accepted: 08/09/2023] [Indexed: 08/22/2023]
Abstract
PURPOSE OF REVIEW This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial changes and progress in this field, including the use of controlled-expansion, covered stents, which has broadened the clinical uses of TIPS. RECENT FINDINGS Recent findings have rapidly expanded the indications for TIPS, including emerging uses in hepatorenal syndrome, hepatopulmonary syndrome and before abdominal surgery. The widespread use of controlled-expansion, covered stents has decreased rates of post-TIPS hepatic encephalopathy, opening TIPS to a larger patient population. Overall, with newer stent technology and more research in this area, the clinical utility and potential of TIPS has rapidly expanded. Going forward, a renewed focus on randomized-control trials and long-term outcomes will be a crucial element to selecting appropriate TIPS recipients and recommending emerging indications for this procedure.
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Affiliation(s)
- Allison Carroll
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Suite 1900, Chicago, IL, 60611, USA
- Feinberg School of Medicine, Northwestern University, Chicago, USA
| | - Justin R Boike
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Suite 1900, Chicago, IL, 60611, USA.
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14
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Lapenna L, Di Cola S, Gazda J, De Felice I, Gioia S, Merli M. New Indications for TIPSs: What Do We Know So Far? J Clin Exp Hepatol 2023; 13:794-803. [PMID: 37693277 PMCID: PMC10483008 DOI: 10.1016/j.jceh.2023.01.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 01/29/2023] [Indexed: 09/12/2023] Open
Abstract
Since 1988, transjugular intrahepatic portosystemic shunt (TIPS) has been an effective therapy for portal hypertension in many settings. Thanks to continuous technical improvements and a wiser selection of patients, excellent results have been achieved with this therapeutic strategy. The historical indications for TIPS placement, in the context of liver cirrhosis, such as refractory ascites and variceal bleeding are now well established and known. However, in recent years, new indications are emerging. These have been investigated and approved in some studies but are not yet included in guidelines and clinical practice. This review aims to highlight what is new for the role of TIPS in portal vein thrombosis (especially in patients awaiting liver transplantation), in recurrent ascites and not only refractory ascites, as a neoadjuvant therapy before abdominal surgery and, finally, in the setting of noncirrhotic portal hypertension. All these new aspects are addressed in this review with a critical approach based on the literature revision and clinical practice. Future research is needed to explore and validate the new role of TIPS in these scenarios.
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Affiliation(s)
- Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Jakub Gazda
- 2nd Department of Internal Medicine, PJ Safarik University and L. Pasteur University Hospital in Kosice, Slovakia
| | - Ilaria De Felice
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
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15
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Ehrenbauer AF, Schneider H, Stockhoff L, Tiede A, Lorenz C, Dirks M, Witt J, Gabriel MM, Wedemeyer H, Hinrichs JB, Weissenborn K, Maasoumy B. Predicting overt hepatic encephalopathy after TIPS: Value of three minimal hepatic encephalopathy tests. JHEP Rep 2023; 5:100829. [PMID: 37600959 PMCID: PMC10432804 DOI: 10.1016/j.jhepr.2023.100829] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 05/19/2023] [Accepted: 06/12/2023] [Indexed: 08/22/2023] Open
Abstract
Background & Aims Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS. Methods We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion. Results The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion. Conclusions PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term. Impact and implications This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE. Clinical trial number ClinicalTrials.gov NCT04801290.
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Affiliation(s)
- Alena F. Ehrenbauer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Hannah Schneider
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Lena Stockhoff
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Charlotte Lorenz
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Meike Dirks
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Jennifer Witt
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Maria M. Gabriel
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Jan B. Hinrichs
- Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | | | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
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16
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Singh V, De A, Mehtani R, Angeli P, Maiwall R, Satapathy S, Singal AK, Saraya A, Sharma BC, Eapen CE, Rao PN, Shukla A, Shalimar, Choudhary NS, Alcantara-Payawal D, Arora V, Aithal G, Kulkarni A, Roy A, Shrestha A, Mamun Al Mahtab, Niriella MA, Siam TS, Zhang CQ, Huei LG, Yu ML, Roberts SK, Peng CY, Chen T, George J, Wong V, Yilmaz Y, Treeprasertsuk S, Kurniawan J, Kim SU, Younossi ZM, Sarin SK. Asia-Pacific association for study of liver guidelines on management of ascites in liver disease. Hepatol Int 2023; 17:792-826. [PMID: 37237088 DOI: 10.1007/s12072-023-10536-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 04/08/2023] [Indexed: 05/28/2023]
Affiliation(s)
- Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India.
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, India
| | - Paolo Angeli
- Department of Internal Medicine and Hepatology, University of Padova, Padua, Italy
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sanjaya Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY, USA
| | - Ashwini K Singal
- University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, Delhi, India
| | - C E Eapen
- Department of Hepatology, Christian Medical College, Vellore, India
| | - P N Rao
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Akash Shukla
- Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guru Aithal
- Biomedical Research Unit, NIHR Nottingham Digestive Diseases, Nottingham, UK
| | - Anand Kulkarni
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, India
| | - Ananta Shrestha
- Department of Hepatology, The Liver Clinic, Liver Foundation, Kathmandu, Nepal
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Madunil A Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Tan Soek Siam
- Department of Hepatology, Hospital Selayang, Selangor Darul Ehsan, Malaysia
| | - Chun-Qing Zhang
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Lee Guan Huei
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Ming-Lung Yu
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | | | - Cheng-Yuan Peng
- Centre for Digestive Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Tao Chen
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jacob George
- University of Sydney School of Medicine, Sydney, Australia
| | - Vincent Wong
- Mok Hing Yiu Professor of Medicine, Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Yusuf Yilmaz
- Liver Research Unit, Institute of Gastroenterology, Marmara University, Istanbul, Turkey
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | | | - Juferdy Kurniawan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital Jakarta, Jakarta, Indonesia
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | | | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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17
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Ferral H, Schepis F, Gaba RC, Garcia-Tsao G, Zanetto A, Perez-Campuzano V, Haskal ZJ, Garcia-Pagan JC. Endovascular Assessment of Liver Hemodynamics in Patients with Cirrhosis Complicated by Portal Hypertension. J Vasc Interv Radiol 2023; 34:327-336. [PMID: 36516940 DOI: 10.1016/j.jvir.2022.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/02/2022] [Accepted: 12/04/2022] [Indexed: 12/14/2022] Open
Abstract
The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.
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Affiliation(s)
- Hector Ferral
- Section of Interventional Radiology, Department of Radiology, Louisiana State University, New Orleans, Louisiana
| | - Filippo Schepis
- Hepatic Hemodynamic Laboratory, Division of Gastroenterology, AOU of Modena and University of Modena and Reggio Emilia, Modena, Italy
| | - Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois at Chicago, Chicago, Illinois
| | - Guadalupe Garcia-Tsao
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, Connecticut; VA-Connecticut Healthcare System, West Haven, Connecticut
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Italy
| | - Valeria Perez-Campuzano
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Madrid, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders, Hamburg, Germany
| | - Ziv J Haskal
- Department of Radiology and Medical Imaging/Interventional Radiology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Madrid, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders, Hamburg, Germany.
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18
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Deltenre P, Zanetto A, Saltini D, Moreno C, Schepis F. The role of transjugular intrahepatic portosystemic shunt in patients with cirrhosis and ascites: Recent evolution and open questions. Hepatology 2023; 77:640-658. [PMID: 35665949 DOI: 10.1002/hep.32596] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 01/28/2023]
Abstract
In selected patients with cirrhosis and ascites, transjugular intrahepatic portosystemic shunt (TIPS) placement improves control of ascites and may reduce mortality. In this review, we summarize the current knowledge concerning the use of TIPS for the treatment of ascites in patients with cirrhosis, from pathophysiology of ascites formation to hemodynamic consequences, patient selection, and technical issues of TIPS insertion. The combination of these factors is important to guide clinical decision-making and identify the best strategy for each individual patient. There is still a need to identify the best timing for TIPS placement in the natural history of ascites (recurrent vs. refractory) as well as which type and level of renal dysfunction is acceptable when TIPS is proposed for the treatment of ascites in cirrhosis. Future studies are needed to define the optimal stent diameter according to patient characteristics and individual risk of shunt-related side effects, particularly hepatic encephalopathy and insufficient cardiac response to hemodynamic consequences of TIPS insertion.
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Affiliation(s)
- Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology , CUB Hôpital Erasme, Université Libre de Bruxelles , Brussels , Belgium.,Department of Gastroenterology and Hepatology , CHU UCL Namur, Université Catholique de Louvain , Yvoir , Belgium.,Department of Gastroenterology and Hepatology , Clinique St Luc , Bouge , Belgium
| | - Alberto Zanetto
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy.,Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology , Padova University Hospital , Padova , Italy
| | - Dario Saltini
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology , CUB Hôpital Erasme, Université Libre de Bruxelles , Brussels , Belgium.,Laboratory of Experimental Gastroenterology , Université Libre de Bruxelles , Brussels , Belgium
| | - Filippo Schepis
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy
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19
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Abstract
The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.
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Affiliation(s)
- Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada,Corresponding author : Florence Wong Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto Ontario M5G2C4, Canada Tel: +1-416-3403834, Fax: +1-416-3405019, E-mail:
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20
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Ahmed Z, Farooq U, Faiza Arif S, Aziz M, Iqbal U, Nawaz A, Lee-Smith W, Badal J, Mahmood A, Kobeissy A, Nawras A, Hassan M, Saab S. Transjugular Intrahepatic Portosystemic Shunt Outcomes in the Elderly Population: A Systematic Review and Meta-Analysis. Gastroenterology Res 2022; 15:325-333. [PMID: 36660467 PMCID: PMC9822662 DOI: 10.14740/gr1571] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/10/2022] [Indexed: 12/23/2022] Open
Abstract
Background Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure typically utilized to treat refractory ascites and variceal bleeding. However, TIPS can lead to significant complications, most commonly hepatic encephalopathy (HE). Advanced age has been described as a risk factor for HE, as the elderly population tends to have decreased cognitive reserve and increased sarcopenia. We conducted a systematic review and meta-analysis of the available literature to summarize the association between advanced age and risk of adverse events after undergoing TIPS. Methods A comprehensive search strategy to identify reports of specific outcomes (HE, 30-day and 90-day mortality, and 30-day readmission due to HE) in elderly patients after undergoing TIPS was developed in Embase (Embase.com, Elsevier). We compared outcomes and performed separate data analyses for patients aged < 70 vs. > 70 years and patients aged < 65 vs. > 65 years. Results Six studies with a total of 1,591 patients met our inclusion criteria and were included in the final meta-analysis. Three studies divided patients by age < 65 vs. > 65 years, with a total of 816 patients who were 54% male. The remaining three studies divided patients by age < 70 vs. > 70 years, with a total of 775 patients who were 63% male. Results demonstrated a significantly lower risk of post-TIPS HE (risk ratio (RR): 0.42, confidence interval (CI): 0.185 - 0.953, P = 0.03, I2 = 49%), 30-day mortality (RR: 0.37, CI: 0.188 - 0.74, P = 0.005, I2 = 0%), and 90-day mortality (RR: 0.35, CI: 0.24 - 0.49, P = 0.001, I2 = 0%) in patients aged > 70 vs. < 70 years, as well as a trend towards lower risk of 30-day readmission due to HE. There was no significant difference in post-TIPS HE, 30-day or 90-day mortality, or 30-day readmission due to HE between patients aged < 65 vs. > 65 years. Conclusion Age > 70 years is associated with significantly higher rates of HE and 30-day and 90-day mortality rates in patients after undergoing TIPS, as well as a trend towards higher 30-day readmission due to HE.
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Affiliation(s)
- Zohaib Ahmed
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | - Umer Farooq
- Department of Internal Medicine, Loyola Medicine/MacNeal Hospital, Chicago, IL, USA
| | | | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA
| | - Umair Iqbal
- Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA, USA
| | - Ahmad Nawaz
- Division of Internal Medicine, Yale-New Haven Hospital, New Haven, CT, USA
| | - Wade Lee-Smith
- University of Toledo Libraries, University of Toledo, Toledo, OH, USA
| | - Joyce Badal
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Asif Mahmood
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | - Abdallah Kobeissy
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA
| | - Ali Nawras
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA
| | - Mona Hassan
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA
| | - Sammy Saab
- Department of Medicine and Surgery at the David Geffen School of Medicine at UCLA (University of California Los Angeles), Los Angeles, CA, USA
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21
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Nardelli S, Bellafante D, Ridola L, Faccioli J, Riggio O, Gioia S. Prevention of post-tips hepatic encephalopathy: The search of the ideal candidate. Metab Brain Dis 2022; 38:1729-1736. [PMID: 36445629 DOI: 10.1007/s11011-022-01131-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 11/22/2022] [Indexed: 11/30/2022]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) has been used since more than 25 years to treat some of the complications of portal hypertension, especially variceal bleeding and ascites refractory to conventional therapy. TIPS establishes a communication between the portal and hepatic veins, inducing the blood to shift from the splanchnic circulation into the systemic vascular bed with the aim of decompressing the portal venous system, and avoids the major complications of portal hypertension. However, the shunt of the portal blood into the systemic circulation is the cause of one of the major complications of the procedure: the post-TIPS hepatic encephalopathy (HE). To date, few pharmacological treatment has been proven effective to prevent this complication and thus, the identification of patients at high risk of post-TIPS hepatic encephalopathy and the patients' carefully selection is the only way to prevent this frequent complication.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy.
| | - Daniele Bellafante
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, Rome, Italy
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22
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Philipp M, Blattmann T, Bienert J, Fischer K, Hausberg L, Kröger JC, Heller T, Weber MA, Lamprecht G. Transjugular intrahepatic portosystemic shunt vs conservative treatment for recurrent ascites: A propensity score matched comparison. World J Gastroenterol 2022; 28:5944-5956. [PMID: 36405105 PMCID: PMC9669826 DOI: 10.3748/wjg.v28.i41.5944] [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: 07/09/2022] [Revised: 09/15/2022] [Accepted: 10/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective intervention for recurrent tense ascites. Some studies show an increased risk of acute on chronic liver failure (ACLF) associated with TIPS placement. It is not clear whether ACLF in this context is a consequence of TIPS or of the pre-existing liver disease.
AIM To better understand the risks of TIPS in this challenging setting and to compare them with those of conservative therapy.
METHODS Two hundred and fourteen patients undergoing their first TIPS placement for recurrent tense ascites at our tertiary-care center between 2007 and 2017 were identified (TIPS group). Three hundred and ninety-eight patients of the same time interval with liver cirrhosis and recurrent tense ascites not undergoing TIPS placement (No TIPS group) were analyzed as a control group. TIPS indication, diagnosis of recurrent ascites, further diagnoses and clinical findings were obtained from a database search and patient records. The in-hospital mortality and ACLF incidence of both groups were compared using 1:1 propensity score matching and multivariate logistic regressions.
RESULTS After propensity score matching, the TIPS and No TIPS groups were comparable in terms of laboratory values and ACLF incidence at hospital admission. There was no detectable difference in mortality (TIPS: 11/214, No TIPS 13/214). During the hospital stay, ACLF occurred more frequently in the TIPS group than in the No TIPS group (TIPS: 70/214, No TIPS: 57/214, P = 0.04). This effect was confined to patients with severely impaired liver function at hospital admission as indicated by a significant interaction term of Child score and TIPS placement in multivariate logistic regression. The TIPS group had a lower ACLF incidence at Child scores < 8 points and a higher ACLF incidence at ≥ 11 points. No significant difference was found between groups in patients with Child scores of 8 to 10 points.
CONCLUSION TIPS placement for recurrent tense ascites is associated with an increased rate of ACLF in patients with severely impaired liver function but does not result in higher in-hospital mortality.
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Affiliation(s)
- Martin Philipp
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
| | - Theresia Blattmann
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
| | - Jörn Bienert
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
| | - Kristian Fischer
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
| | - Luisa Hausberg
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
| | - Jens-Christian Kröger
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Centre, Rostock 18057, Germany
| | - Thomas Heller
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Centre, Rostock 18057, Germany
| | - Marc-André Weber
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Centre, Rostock 18057, Germany
| | - Georg Lamprecht
- Department of Medicine, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock 18057, Germany
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23
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Osman KT, Abdelfattah AM, Mahmood SK, Elkhabiry L, Gordon FD, Qamar AA. Refractory Hepatic Hydrothorax Is an Independent Predictor of Mortality When Compared to Refractory Ascites. Dig Dis Sci 2022; 67:4929-4938. [PMID: 35534742 DOI: 10.1007/s10620-022-07522-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 02/14/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatic hydrothorax (HHT) is an uncommon but significant complication of cirrhosis and portal hypertension, associated with a worse prognosis and mortality. Nearly 25% of patients with HHT will have refractory pleural effusion. It is unclear if refractory HHT has a different prognosis compared to refractory ascites. AIMS We aim to evaluate the prognostic significance of refractory HHT when compared to refractory ascites. METHODS Forty-seven patients who had refractory HHT in a tertiary care center were identified, and matched, retrospectively, one-to-one by age, gender and MELD-Na with 47 patients with refractory ascites. One-year mortality rate was compared between both groups. Cox proportional hazard regression was used to identify the association between different covariates and primary endpoint. RESULTS The 1-year mortality was 51.06% in the HHT group compared to 19.15% in the refractory ascites group. The median survival for patients with refractory hepatic hydrothorax was 4.87 months while the median survival for patients with refractory ascites exceeded 1 year. The presence of HHT was statistically significant in predicting the development of 1-year mortality [Hazard Ratio (HR) 4.45, 95% Confidence Interval (CI) 2.25-8.82; P value < 0.001]. Furthermore, refractory HHT remained associated with one-year mortality after adjusting for all other covariates. In a subgroup of patients with MELD-Na ≤ 20, HHT continued to be a significant predictor of one-year mortality (HR 3.30, 95% CI 1.47-7.40; P value 0.004). CONCLUSIONS Refractory HHT is a significant independent predictor of mortality and offers additional prognostic value.
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Affiliation(s)
- Karim T Osman
- Department of Internal Medicine, Lahey Hospital and Medical Center, 41 Mall Rd, Burlington, MA, 01805, USA.
| | - Ahmed M Abdelfattah
- Department of Gastroenterology, Lahey Hospital and Medical Center, 41 Mall Rd, Burlington, MA, 01805, USA
| | - Syed K Mahmood
- Department of Gastroenterology, Lahey Hospital and Medical Center, 41 Mall Rd, Burlington, MA, 01805, USA
| | - Lina Elkhabiry
- Department of Internal Medicine, University of Alexandria, Alexandria, Egypt
| | - Fredric D Gordon
- Department of Transplant and Hepatobiliary Diseases, Lahey Hospital and Medical Center, 41 Mall Rd, Burlington, MA, 01805, USA.,Tufts University School of Medicine, Boston, MA, USA
| | - Amir A Qamar
- Department of Transplant and Hepatobiliary Diseases, Lahey Hospital and Medical Center, 41 Mall Rd, Burlington, MA, 01805, USA.,Tufts University School of Medicine, Boston, MA, USA
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24
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Gluud LL, Kimer N, Møller S. Editorial: Percutaneous placement of a permanent tunnelled catheter for patients with non-malignant ascites-Is it safe? Aliment Pharmacol Ther 2022; 56:909-910. [PMID: 35934857 DOI: 10.1111/apt.17099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Lise Lotte Gluud
- Gastro Unit, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Copenhagen University Hospital, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark
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25
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Boike JR, Thornburg BG, Asrani SK, Fallon MB, Fortune BE, Izzy MJ, Verna EC, Abraldes JG, Allegretti AS, Bajaj JS, Biggins SW, Darcy MD, Farr MA, Farsad K, Garcia-Tsao G, Hall SA, Jadlowiec CC, Krowka MJ, Laberge J, Lee EW, Mulligan DC, Nadim MK, Northup PG, Salem R, Shatzel JJ, Shaw CJ, Simonetto DA, Susman J, Kolli KP, VanWagner LB. North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension. Clin Gastroenterol Hepatol 2022; 20:1636-1662.e36. [PMID: 34274511 PMCID: PMC8760361 DOI: 10.1016/j.cgh.2021.07.018] [Citation(s) in RCA: 134] [Impact Index Per Article: 44.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/01/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023]
Abstract
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
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Affiliation(s)
- Justin R. Boike
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bartley G. Thornburg
- Department of Radiology, Division of Vascular and Interventional Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Michael B. Fallon
- Department of Medicine, Division of Gastroenterology and Hepatology, Banner - University Medical Center Phoenix, Phoenix, AZ, USA
| | - Brett E. Fortune
- Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA
| | - Manhal J. Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Elizabeth C. Verna
- Department of Medicine, Division of Digestive and Liver Diseases, Columbia University College of Physicians & Surgeons, New York, NY, USA
| | - Juan G. Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Andrew S. Allegretti
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA
| | - Jasmohan S. Bajaj
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, VA, USA
| | - Scott W. Biggins
- Department of Medicine, Division of Gastroenterology & Hepatology, University of Washington Medical Center, Seattle, WA, USA
| | - Michael D. Darcy
- Department of Radiology, Division of Interventional Radiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Maryjane A. Farr
- Department of Medicine, Division of Cardiology, Columbia University College of Physicians & Surgeons, New York, NY, USA
| | - Khashayar Farsad
- Dotter Department of Interventional Radiology, Oregon Health and Science University, Portland, OR, USA
| | - Guadalupe Garcia-Tsao
- Department of Digestive Diseases, Yale University, Yale University School of Medicine, and VA-CT Healthcare System, CT, USA
| | - Shelley A. Hall
- Department of Internal Medicine, Division of Cardiology, Baylor University Medical Center, Dallas, TX, USA
| | - Caroline C. Jadlowiec
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | - Michael J. Krowka
- Department of Pulmonary and Critical Care Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jeanne Laberge
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, University of California San Francisco, San Francisco, CA, USA
| | - Edward W. Lee
- Department of Radiology, Division of Interventional Radiology, University of California-Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA
| | - David C. Mulligan
- Department of Surgery, Division of Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Mitra K. Nadim
- Department of Medicine, Division of Nephrology and Hypertension, University of Southern California, Los Angeles, California, USA
| | - Patrick G. Northup
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
| | - Riad Salem
- Department of Radiology, Division of Vascular and Interventional Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Joseph J. Shatzel
- Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA
| | - Cathryn J. Shaw
- Department of Radiology, Division of Interventional Radiology, Baylor University Medical Center, Dallas, TX, USA
| | - Douglas A. Simonetto
- Department of Physiology, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jonathan Susman
- Department of Radiology, Division of Interventional Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - K. Pallav Kolli
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, University of California San Francisco, San Francisco, CA, USA
| | - Lisa B. VanWagner
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,Address for correspondence: Lisa B. VanWagner MD MSc FAST FAHA, Assistant Professor of Medicine and Preventive Medicine, Divisions of Gastroenterology & Hepatology and Epidemiology, Northwestern University Feinberg School of Medicine, 676 N. St Clair St - Suite 1400, Chicago, Illinois 60611 USA, Phone: 312 695 1632, Fax: 312 695 0036,
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26
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Will V, Rodrigues SG, Berzigotti A. Current treatment options of refractory ascites in liver cirrhosis - A systematic review and meta-analysis. Dig Liver Dis 2022; 54:1007-1014. [PMID: 35016859 DOI: 10.1016/j.dld.2021.12.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 10/24/2021] [Accepted: 12/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Refractory ascites is a severe complication of liver cirrhosis and treatment options consist in large volume paracentesis, transjugular intrahepatic portosystemic shunt, alfapump®, peritoneovenous shunt and permanent indwelling peritoneal catheter. AIM Our aim was to assess the efficacy, mortality and complications of each treatment. METHODS We performed a systematic review using Pubmed and Embase. Frequencies were summarized with Comprehensive Meta-Analysis Software. RESULTS Seventy-seven studies were included. In patients with transjugular intrahepatic portosystemic shunt, 1-year mortality was 33% (95% CI 0.29-0.39, I2=82.1; τ2 = 0.37; p<0.001) with lower mortality in newer studies (26% vs. 44%). At 6 months, mortality in patients with alfapump® was 24% (95% CI 0.16-0.33, I2=0.00; τ2 = 0.00; p = 0.83), 31% developed acute kidney injury (95% CI 0.18-0.48, I2=44.0; τ2 = 0.22; p = 0.15). Mortality at 12 months was 44% (95% CI 32%-58%, I2=76.7, τ2 = 0.44, p<0.001) in peritoneovenous shunts and 45% (95% CI 38%-53%, I2=61.4, τ2 = 0.18, p = 0.003) in large volume paracentesis, respectively. Overall mortality in patients with permanent indwelling catheters was 66% (95% CI 33%-89%, I2=82.5, τ2 = 1.57, p = 0.001). DISCUSSION Mortality in patients with transjugular intrahepatic portosystemic shunt was lower in newer studies, probably due to a better patient selection. Acute kidney injury was frequent in patients with alfapump®. Permanent indwelling catheters seemed to be a good option in a palliative setting.
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Affiliation(s)
- Valerie Will
- Department for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, University of Bern, BHH D115, Freiburgstrasse 10, CH-3008 Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Susana G Rodrigues
- Department for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, University of Bern, BHH D115, Freiburgstrasse 10, CH-3008 Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Annalisa Berzigotti
- Department for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, University of Bern, BHH D115, Freiburgstrasse 10, CH-3008 Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland.
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27
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Bettinger D, Thimme R, Schultheiß M. Implantation of transjugular intrahepatic portosystemic shunt (TIPS): indication and patient selection. Curr Opin Gastroenterol 2022; 38:221-229. [PMID: 35471813 DOI: 10.1097/mog.0000000000000831] [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] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW This review summarizes indications and contraindications for implantation of transjugular intrahepatic portosystemic shunt (TIPS). Further, patient selection strategies are discussed. RECENT FINDINGS TIPS implantation is a highly effective treatment for portal hypertension. Main indications are ascites and variceal bleeding in patients with liver cirrhosis. There is growing evidence that early TIPS implantation after variceal bleeding is associated with an improved survival (preemptive TIPS).Preliminary data also suggest that an analogous concept of early TIPS implantation may be beneficial for patients with ascites. Further, well-selected patients with acute or chronic nonmalignant portal vein thrombosis can be effectively treated with TIPS implantation. In contrast, there is generally no recommendation for TIPS implantation in patients with hepatic veno-occlusive disease, noncirrhotic portal hypertension or prior before surgery to avoid complications of portal hypertension. Apart from evidence-based patient selection, the newly developed FIPS score can be an objective component in decision-making. SUMMARY Consideration of well-established indications and contraindications for TIPS implantation as well as concise patient selection criteria are essential for an optimal outcome after TIPS implantation.
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Affiliation(s)
- Dominik Bettinger
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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28
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Artru F, Moschouri E, Denys A. Direct intrahepatic portocaval shunt (DIPS) or transjugular transcaval intrahepatic portosystemic shunt (TTIPS) to treat complications of portal hypertension: Indications, technique, and outcomes beyond Budd-Chiari syndrome. Clin Res Hepatol Gastroenterol 2022; 46:101858. [PMID: 34999250 DOI: 10.1016/j.clinre.2022.101858] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/04/2023]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is nowadays the benchmark treatment of severe portal hypertension complications. However, besides usual contraindication to the procedure (namely recurrent hepatic encephalopathy, severe liver dysfunction, right heart failure and/or pulmonary hypertension), TIPS appears regularly unfeasible due to abnormal and/or distorted anatomy. In this situation, the only non-surgical approaches to treat severe portal hypertension consist in the creation of an intrahepatic portocaval shunt from percutaneous (direct intrahepatic portocaval shunt - DIPS) or transjugular route (transjugular transcaval intrahepatic portosystemic shunt - TTIPS). These procedures have been rapidly adopted in patients with Budd-Chiari syndrome but are only poorly reported in patients with cirrhosis and without BCS. Considering the broadening landscape of TIPS indication in patients with cirrhosis within the last ten years, we aimed to describe the techniques, safety and efficacy of DIPS and TTIPS procedures as an alternative to TIPS in case of unfavourable anatomy.
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Affiliation(s)
- Florent Artru
- Service de gastroentérologie et d'hépatologie du Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland; Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Eleni Moschouri
- Service de gastroentérologie et d'hépatologie du Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland
| | - Alban Denys
- Service radiodiagnostic et de radiologie interventionnelle du Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland.
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29
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Helzberg JH, Parish A, Niedzwiecki D, Kim CY, Patel YA, Wilder JM, Muir AJ. Racial disparities in transjugular intrahepatic portosystemic shunt procedure outcomes. BMJ Open Gastroenterol 2022; 9:bmjgast-2021-000747. [PMID: 35086849 PMCID: PMC8796249 DOI: 10.1136/bmjgast-2021-000747] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022] Open
Abstract
Objective The transjugular intrahepatic portosystemic shunt (TIPS) procedure is an important intervention for management of complications of portal hypertension. The objective of this study was to identify predictors of mortality from the TIPS procedure with a focus on race and ethnicity. Design TIPS procedures from 2012 to 2014 in the National Inpatient Sample were identified. Weighting was applied to generate nationally representative results. In-hospital mortality was the primary outcome of interest. χ2 and Student’s t-tests were performed for categorical and continuous variables, respectively. Predictors of mortality following TIPS were assessed by survey-weighted logistic regression. Results 17 175 (95% CI 16 254 to 18 096) TIPS cases were identified. Approximately 71% were non-Hispanic (NH) white, 6% were NH black, 16% were Hispanic and 7% were other. NH black patients undergoing TIPS had an in-hospital mortality rate of 20.1%, nearly double the in-hospital mortality of any other racial or ethnic group. NH black patients also had significantly longer median postprocedure and total lengths of stay (p=0.03 and p<0.001, respectively). The interaction of race by clinical indication was a significant predictor of in-hospital mortality (p<0.001). NH black patients had increased mortality compared with other racial/ethnic groups when presenting with bleeding oesophageal varices (OR 3.85, 95% CI 2.14 to 6.95). Conclusion This cohort study presents important findings in end-stage liver disease care, with clear racial disparities in in-hospital outcomes following the TIPS procedure. Specifically, black patients had significantly higher in-hospital mortality and longer lengths of stay. Further research is needed to understand how we can better care for black patients with liver disease.
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Affiliation(s)
- James H Helzberg
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Alice Parish
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA
| | - Donna Niedzwiecki
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA
| | - Charles Y Kim
- Department of Radiology, Division of Interventional Radiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Yuval A Patel
- Department of Medicine, Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Julius M Wilder
- Department of Medicine, Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina, USA.,Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Andrew J Muir
- Department of Medicine, Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina, USA .,Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
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A simple nomogram identifies patients with refractory ascites with worse outcome after transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 2021; 33:e587-e593. [PMID: 35048651 DOI: 10.1097/meg.0000000000002179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly used in the management of refractory ascites. Controversy exists regarding the predictive factors of unfavorable outcomes, useful for patient selection. The primary aim was to identify predictive factors of 1-year survival or recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. The secondary aim was overall survival. METHODS Observational, retrospective, multicentric study, that included all cirrhotic patients treated with covered-TIPS for refractory ascites since 2001. Demographic, clinical, laboratory and hemodynamic data were collected at baseline and consecutively until dead, liver transplant or end of follow-up. The Cox model was used to identify predictive factors of overall survival. A Fine-Gray competing risk regression model was used to identify predictive factors of 1-year mortality or recurrent hepatic encephalopathy. A predictive nomogram was created based on those factors. RESULTS In total 159 patients were included. Predictive factors of survival or recurrent severe encephalopathy were renal dysfunction [hazard ratio, 2.12 (95% CI, 1.11-4.04); P = 0.022], albumin [hazard ratio, 0.58 (95% CI, 0.34-0.97); P = 0.036], serum sodium [hazard ratio, 0.94 (95% CI, 0.89-0.98); P = 0.008] and international normalized ratio [hazard ratio 4.27 (95% CI, 1.41-12.88); P = 0.010]. In the competing risk analysis, predictive factors of 1-year mortality/recurrent severe encephalopathy in multivariate analysis were age [sub-distribution hazard ratio (sHR) 1.05 (95% CI, 1.02-1.09); P = 0.001], creatinine [sHR 1.55 (95% CI, 1.23-1.96); P = 0.001] and serum sodium [sHR 0.94 (95% CI, 0.90-0.99); P = 0.011] at baseline. CONCLUSIONS Age, creatinine and sodium baseline levels strongly influence 1-year survival/recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. A simple nomogram accurately and easily identifies those patients with worse prognosis.
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Long-term survival prediction for transjugular intrahepatic portosystemic shunt in severe cirrhotic ascites: assessment of ten prognostic models. Eur J Gastroenterol Hepatol 2021; 33:1547-1555. [PMID: 32868654 DOI: 10.1097/meg.0000000000001890] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Patients with severe cirrhotic ascites have poor prognosis, yet individual patient survival varies greatly. Therefore, suitable prognostic models can be helpful in clinical decision making. The aim of this study was to evaluate and compare the performance of 10 scores in predicting transplant-free survival (TFS) after transjugular intrahepatic portosystemic shunt (TIPS) in severe cirrhotic ascites. METHODS Two hundred eighty consecutive cirrhotic patients with severe ascites undergoing TIPS between March 2006 and December 2017 were retrospectively screened and included from nine tertiary Chinese centers, consisting of 123 patients with refractory ascites and 157 with recurrent ascites. Discriminatory ability of these models was further assessed in the whole cohort and subgroups. RESULTS TFS rates of all 280 patients were 75.4, 65.7, and 53.6% at 6-month, 1-year, and 2-year follow-up, respectively. Compared with other prognostic systems, the integrated model for end-stage liver disease (iMELD, incorporating serum sodium and age) showed optimal performance in predicting 6-month, 1-year, and 2-year TFS. Cutoffs were determined according to c-index and were used to stratify patients into three strata presenting significantly different TFS for short-term and long-term: iMELD < 32, ≥32 but <38 and ≥38 (log-rank P < 0.001). CONCLUSIONS The iMELD score proved to be the best prognostic model in predicting TFS in patients with severe cirrhotic ascites receiving TIPS. Meanwhile, the model could stratify patients in three strata to help guiding clinical practice.
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Zaccherini G, Tufoni M, Iannone G, Caraceni P. Management of Ascites in Patients with Cirrhosis: An Update. J Clin Med 2021; 10:5226. [PMID: 34830508 PMCID: PMC8621554 DOI: 10.3390/jcm10225226] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/03/2021] [Accepted: 11/06/2021] [Indexed: 12/16/2022] Open
Abstract
Ascites represents a critical event in the natural history of liver cirrhosis. From a prognostic perspective, its occurrence marks the transition from the compensated to the decompensated stage of the disease, leading to an abrupt worsening of patients' life expectancy. Moreover, ascites heralds a turbulent clinical course, characterized by acute events and further complications, frequent hospitalizations, and eventually death. The pathophysiology of ascites classically relies on hemodynamic mechanisms, with effective hypovolemia as the pivotal event. Recent discoveries, however, integrated this hypothesis, proposing systemic inflammation and immune system dysregulation as key mechanisms. The mainstays of ascites treatment are represented by anti-mineralocorticoids and loop diuretics, and large volume paracentesis. When ascites reaches the stage of refractoriness, however, diuretics administration should be cautious due to the high risk of adverse events, and patients should be treated with periodic execution of paracentesis or with the placement of a trans-jugular intra-hepatic portosystemic shunt (TIPS). TIPS reduces portal hypertension, eases ascites control, and potentially modify the clinical course of the disease. Further studies are required to expand its indications and improve the management of complications. Long-term human albumin administration has been studied in two RCTs, with contradictory results, and remains a debated issue worldwide, despite a potential effectiveness both in ascites control and long-term survival. Other treatments (vaptans, vasoconstrictors, or implantable drainage systems) present some promising aspects but cannot be currently recommended outside clinical protocols or a case-by-case evaluation.
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Affiliation(s)
- Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (G.I.)
| | - Manuel Tufoni
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
| | - Giulia Iannone
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (G.I.)
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (G.I.)
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
- Center for Biomedical Applied Research, University of Bologna, 40126 Bologna, Italy
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Zaccherini G, Tufoni M, Bernardi M, Caraceni P. Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents. J Clin Med 2021; 10:4590. [PMID: 34640608 PMCID: PMC8509683 DOI: 10.3390/jcm10194590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/29/2021] [Accepted: 10/04/2021] [Indexed: 02/07/2023] Open
Abstract
The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment.
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Affiliation(s)
- Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
| | - Manuel Tufoni
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
- Center for Biomedical Applied Research, University of Bologna, 40138 Bologna, Italy
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Lee HL, Lee SW. The role of transjugular intrahepatic portosystemic shunt in patients with portal hypertension: advantages and pitfalls. Clin Mol Hepatol 2021; 28:121-134. [PMID: 34571587 PMCID: PMC9013617 DOI: 10.3350/cmh.2021.0239] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/25/2021] [Indexed: 12/31/2022] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is an effective interventional procedure to relieve portal hypertension, which is a main mechanism for the development of complications of liver cirrhosis (LC), such as variceal hemorrhage, ascites, and hepatorenal syndrome. However, the high incidence of adverse events after TIPS implementation limits its application in clinical practice. Esophageal variceal hemorrhage is one of the major indications for TIPS. Recently, preemptively performed TIPS has been recommended, as several studies have shown that TIPS significantly reduced mortality as well as rebleeding or failure to control bleeding in patients who are at high risk of treatment failure for bleeding control with endoscopic variceal ligation and vasoactive drugs. Meanwhile, recurrent ascites is another indication for TIPS with a proven survival benefit. TIPS may also be considered as an effective treatment for other LC complications, usually as an alternative therapy. Although there are concerns about the development of hepatic encephalopathy and hepatic dysfunction after TIPS implementation, careful patient selection using prognostic scores can lead to excellent outcomes. Assessments of cardiac and renal function prior to TIPS may also be considered to improve patient prognosis.
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Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Bruno R, Cammà C, Caraceni P, D'Amico G, Grattagliano I, La Mura V, Riggio O, Schepis F, Senzolo M, Angeli P, de Franchis R. Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF). Dig Liver Dis 2021; 53:1089-1104. [PMID: 34321192 DOI: 10.1016/j.dld.2021.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/30/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023]
Abstract
Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to national regulations and resources, local circumstances and settings, infrastructure, and cost/benefit strategies to avoid duplication of efforts and optimize resource utilization. The committee defined the objectives, the key issues and retrieved the relevant evidence by performing a systematic review of the literature. Finally, the committee members (chosen on the basis of their specific expertise) identified the guidelines' key questions and developed them following the PICO format (Population, Intervention, Comparison, Outcomes). For each of the PICO questions, the systematic review of the literature was made on the most important scientific databases (Pubmed, Scopus, Embase).
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Bakhtiar M, Forde KA, Nadolski GJ, Soulen MC, Weinberg EM. Radiologically Placed Peritoneovenous Shunt is an Acceptable Treatment Alternative for Refractory Ascites Due to End-Stage Liver Disease. J Vasc Interv Radiol 2021; 32:1606-1614. [PMID: 34416366 DOI: 10.1016/j.jvir.2021.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 08/03/2021] [Accepted: 08/09/2021] [Indexed: 11/15/2022] Open
Abstract
PURPOSE To compare patients treated with large-volume paracentesis (LVP), transjugular intrahepatic portosystemic shunt (TIPS), and peritoneovenous shunt (PVS) for ascites. MATERIALS AND METHODS A retrospective study of 192 patients treated with LVP (94), TIPS (75), or PVS (23) was performed. Records were reviewed for patient characteristics and outcomes. The patients' age differed (LVP, 59.5 years; TIPS, 58.8 years; and PVS, 65.6 years; P = .003). Nonalcoholic steatohepatitis was the most common etiology in the PVS cohort (11/23, 47%), and hepatitis C in the TIPS (27/75, 36%), and LVP cohorts (43/94, 46%) (P = .032). The model for end-stage liver disease score was significantly different (LVP, 14; TIPS, 13; and PVS, 8; P = .035). Hepatocellular carcinoma was higher in the PVS cohort (6/23 patients, 25%) than in the TIPS (4/75, 5%), and LVP (12/94, 12%) cohorts (P = .03). RESULTS Emergency department visits and hospital readmissions were the highest in the LVP cohort (40%, ≥2 readmissions, P < .001). Patients required fewer LVPs after TIPS (1.5 to 0.14, P < .001) or PVS (2.1 to 0.5, P = .019). In an unadjusted Cox model, patients in the TIPS cohort were found to have a 58% reduction in the risk of death compared with patients in the LVP cohort (P = .003). Transplant-free survival (PVS, 44 days; TIPS, 155 days; and LVP, 213 days) differed (log rank = 0.001). CONCLUSIONS The survival in the PVS and TIPS cohorts was similar, with less healthcare utilization than the LVP cohort. PVS is a satisfactory alternative to LVP.
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Affiliation(s)
- Mina Bakhtiar
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kimberly A Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Gregory J Nadolski
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael C Soulen
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ethan M Weinberg
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Caraceni P, Abraldes JG, Ginès P, Newsome PN, Sarin SK. The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery. J Hepatol 2021; 75 Suppl 1:S118-S134. [PMID: 34039483 DOI: 10.1016/j.jhep.2021.01.024] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 02/06/2023]
Abstract
Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing.
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Affiliation(s)
- Paolo Caraceni
- Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences and Center for Biomedical Applied Research, Alma Mater Studiorum University of Bologna, Italy.
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Canada
| | - Pere Ginès
- Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBEReHD, Barcelona, Catalonia, Spain
| | - Phil N Newsome
- National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, UK; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shiv K Sarin
- Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
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Bagheri Lankarani K, Honarvar B, Rouhezamin MR, Raeisi Shahraki H, Seifi V, Geramizadeh B, Salahi H, Nikeghbalian S, Shamsaeefar A, Keshani P, Malekhosseini SA. Mortality and Its Determinants in Adult Patients with End-stage Liver Disease on Waiting List for Liver Transplantation: A Preliminary Report on Baseline Data. SHIRAZ E-MEDICAL JOURNAL 2021; 22. [DOI: 10.5812/semj.110254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background: Prevention of death in patients on the waiting list for liver transplantation (LT) is a major concern to prioritize organ allocation. Since the model for the end-stage liver disease (MELD) and its modifications have many shortages, there is a need for further refinement of the allocation strategy. Objectives: The current study aimed at assessing the predictors of mortality in LT candidates in a more comprehensive manner with the possible implications to improve the care of such patients and assist in developing better strategies for organ allocation. Methods: In the current cohort study, 544 adult LT candidates with end-stage liver disease were followed up for a mean of 12 months in three-month intervals. Data analysis was performed in Nutritionist, SPSS, and R software, using Kaplan-Meier, Cox proportional hazard (HRC), and LASSO Cox regression hazard (HRL) tests. Results: The mean age of the patients was 46.7 ± 13.7 years; the majority were male (n = 336, 61.7%). At the end of the study, 414 (76.1%) subjects were still alive and 130 (23.9%) dead. The cumulative percentages of death were 33.1%, 57.7%, and 79.2% after 3, 6, and 12 months of waiting for a donor, respectively. Although there was a strong association between having hepatopulmonary syndrome (HPS) (HRC = 4.7, HRL = 1.8), a history of myocardial infarction (MI) (HRC = 3.3, HRL = 1.6), low-carbohydrate (CHO) diet (HRC = 2.7, HRL = 1.5), and mortality, it was weak for MELD score. Moreover, a serum level of CA 125, high polymorphonuclear (PMN) count, weight loss, a high level of alanine aminotransferase (ALT), positive hepatitis B virus (HBV) markers, high mean corpuscular volume (MCV) of red blood cells, ascites, and edema of gallbladder wall had association with mortality in LT patients. Conclusions: In addition to MELD score, HPS, a history of MI, low CHO intake, weight loss, ascites, PMN, CA 125, ALT, hepatitis B surface antigen, MCV, blood urea nitrogen, and gallbladder wall thickness are predictors of mortality in LT candidates and need to be considered in the LT allocation system.
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Pinchot JW, Kalva SP, Majdalany BS, Kim CY, Ahmed O, Asrani SK, Cash BD, Eldrup-Jorgensen J, Kendi AT, Scheidt MJ, Sella DM, Dill KE, Hohenwalter EJ. ACR Appropriateness Criteria® Radiologic Management of Portal Hypertension. J Am Coll Radiol 2021; 18:S153-S173. [PMID: 33958110 DOI: 10.1016/j.jacr.2021.02.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 02/10/2021] [Indexed: 12/17/2022]
Abstract
Cirrhosis is a heterogeneous disease that cannot be studied as a single entity and is classified in two main prognostic stages: compensated and decompensated cirrhosis. Portal hypertension, characterized by a pathological increase of the portal pressure and by the formation of portal-systemic collaterals that bypass the liver, is the initial and main consequence of cirrhosis and is responsible for the majority of its complications. A myriad of treatment options exists for appropriately managing the most common complications of portal hypertension, including acute variceal bleeding and refractory ascites. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Affiliation(s)
| | - Sanjeeva P Kalva
- Panel Chair, Massachusetts General Hospital, Boston, Massachusetts, Chief, Division of Interventional Radiology, Massachusetts General Hospital
| | | | - Charles Y Kim
- Panel Vice-Chair, Duke University Medical Center, Durham, North Carolina, Chief, Division of Interventional Radiology, Duke University Medical Center
| | | | - Sumeet K Asrani
- Baylor University Medical Center, Dallas, Texas, American Association for the Study of Liver Diseases
| | - Brooks D Cash
- University of Texas Health Science Center at Houston and McGovern Medical School, Houston, Texas, American Gastroenterological Association
| | - Jens Eldrup-Jorgensen
- Tufts University School of Medicine, Boston, Massachusetts, Society for Vascular Surgery
| | - A Tuba Kendi
- Mayo Clinic, Rochester, Minnesota, Director of Nuclear Medicine Therapy at Mayo Clinic Rochester
| | | | | | - Karin E Dill
- Specialty Chair, Emory University Hospital, Atlanta, Georgia
| | - Eric J Hohenwalter
- Specialty Chair, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin, Chair, FMLH credentials committee, Division chief of IR at Medical College of Wisconsin
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40
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Larrue H, Vinel JP, Bureau C. Management of Severe and Refractory Ascites. Clin Liver Dis 2021; 25:431-440. [PMID: 33838859 DOI: 10.1016/j.cld.2021.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Considering the poor prognosis, severe and refractory ascites is a milestone in cirrhotic patients. Liver transplantation must be considered first. In the case of contraindication to liver transplantation or when the waiting period is estimated to be more than 6 months, transjugular intrahepatic portosystemic shunt should be discussed in eligible patients. Regardless of the type of treatment, a careful selection of patients is crucial to avoid further decompensation and specific complications of each treatment.
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Affiliation(s)
- Hélène Larrue
- Service d'Hépatologie Hôpital Rangueil 1, Avenue Jean Poulhès CHU Toulouse France and Université Toulouse III-Paul Sabatier, France 31400
| | - Jean Pierre Vinel
- Service d'Hépatologie Hôpital Rangueil 1, Avenue Jean Poulhès CHU Toulouse France and Université Toulouse III-Paul Sabatier, France 31400
| | - Christophe Bureau
- Service d'Hépatologie Hôpital Rangueil 1, Avenue Jean Poulhès CHU Toulouse France and Université Toulouse III-Paul Sabatier, France 31400.
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Horhat A, Bureau C, Thabut D, Rudler M. Transjugular intrahepatic portosystemic shunt in patients with cirrhosis: Indications and posttransjugular intrahepatic portosystemic shunt complications in 2020. United European Gastroenterol J 2021; 9:203-208. [PMID: 32819214 PMCID: PMC8259430 DOI: 10.1177/2050640620952637] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 07/27/2020] [Indexed: 02/06/2023] Open
Abstract
Transjugular intrahepatic portosystemic shunt is a percutaneous radiologic-guided procedure that aims to reduce portal hypertension by creating a shunt between the portal venous system and the hepatic venous system. The most common cause of portal hypertension is liver cirrhosis in Western countries. Two main indications of transjugular intrahepatic portosystemic shunt are validated by randomised controlled studies in patients with cirrhosis and variceal bleeding (salvage transjugular intrahepatic portosystemic shunt, early transjugular intrahepatic portosystemic shunt or rebleeding despite an optimal secondary prophylaxis) or refractory ascites. Careful selection of the patients is crucial in order to prevent posttransjugular intrahepatic portosystemic shunt complications, including liver failure, posttransjugular intrahepatic portosystemic shunt encephalopathy occurrence and cardiac decompensation, for a better long-term outcome. In this review, we will discuss transjugular intrahepatic portosystemic shunt indications in 2020 in patients with cirrhosis and portal hypertension, with a special focus on variceal bleeding and refractory ascites. Then, we will describe transjugular intrahepatic portosystemic shunt-related complications, the contraindications and the current knowledge on patient's selection.
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Affiliation(s)
- Adelina Horhat
- Hepato-Gastroenterology Regional Institute, Cluj-Napoca, Romania
| | - Christophe Bureau
- Hepatology Department, Toulouse University Hospital, Toulouse, France
| | - Dominique Thabut
- Hepatology Intensive Care Unit, Pitie-Salpêtrière Hospital, Paris, France.,Hepatogastroenterology Intensive Care Unit, Hepatogastroenterology Department, APHP Sorbonne University, Paris, France
| | - Marika Rudler
- Hepatology Intensive Care Unit, Pitie-Salpêtrière Hospital, Paris, France
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Tonon M, Piano S, Gambino CG, Romano A, Pilutti C, Incicco S, Brocca A, Sticca A, Bolognesi M, Angeli P. Outcomes and Mortality of Grade 1 Ascites and Recurrent Ascites in Patients With Cirrhosis. Clin Gastroenterol Hepatol 2021; 19:358-366.e8. [PMID: 32272250 DOI: 10.1016/j.cgh.2020.03.065] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 03/05/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Ascites has been classified according to quantity and response to medical therapy. Despite its precise definitions, little is known about the effects of grade 1 ascites or recurrent ascites (i.e. ascites that recurs at least on 3 occasions within a 12-month period despite dietary sodium restriction and adequate diuretic dosage) on patient outcome. We studied progression of grade 1 ascites and recurrent ascites in a large cohort of outpatients with cirrhosis. METHODS We performed a post-hoc analysis of data from 547 outpatients with cirrhosis (259 without ascites, 54 patients with grade 1 ascites, 234 with grade 2 or 3 ascites) who participated a care management program study in Italy from March 2003 through September 2017. We collected demographic, clinical, and laboratory data and patients were evaluated at least every 6 months. Patients received abdominal ultrasound analysis at study inclusion and at least twice a year. Number and volume of paracentesis were collected, when available. Patients were followed until death, liver transplantation, or March 2018. The median follow-up time was 29 months. Primary outcomes were mortality and development of complications of cirrhosis. RESULTS There was no significant difference in 60-month transplant-free survival between patients with grade 1 vs grade 2 or 3 ascites (36% vs 43%) but survival was significantly lower when both groups were compared with patients without ascites (68%; P < .001 for both comparisons). However, the grade of systemic inflammation and the rate of complications were significantly greater in patients with grade 1 ascites than in patients without ascites, but significantly lower than in patients with grade 2 or 3 ascites. Development of grade 2 or 3 ascites did not differ significantly between patients with no ascites vs grade 1 ascites (10% vs 14%). There was no significant difference in 36-month transplant-free survival between patients with ascites responsive to medical treatment vs recurrent ascites (78% vs 62%), whereas patients with refractory ascites had significantly lower survival than patients with responsive or recurrent ascites (23%; responsive vs refractory ascites P<.001; recurrent vs refractory ascites P = .022). CONCLUSIONS In an analysis of data from a large cohort of outpatients with cirrhosis, we found that grade 1 ascites is associated with systemic inflammation, more complications, and increased mortality compared with no ascites. Mortality does not differ significantly between patients with recurrent ascites vs ascites responsive to medical treatment.
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Affiliation(s)
- Marta Tonon
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Carmine G Gambino
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Antonietta Romano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Chiara Pilutti
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Alessandra Brocca
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Antonietta Sticca
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Massimo Bolognesi
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Padova, Italy.
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Madoff DC, Cornman-Homonoff J, Fortune BE, Gaba RC, Lipnik AJ, Yarmohammadi H, Ray CE. Management of Refractory Ascites Due to Portal Hypertension: Current Status. Radiology 2021; 298:493-504. [PMID: 33497318 DOI: 10.1148/radiol.2021201960] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Refractory ascites is a costly and debilitating condition that occurs most frequently in the setting of substantial cirrhotic portal hypertension, where it portends a poor prognosis. Many treatment options are available, among them medical management, serial large volume paracenteses, transjugular intrahepatic portosystemic shunts, and implanted drainage devices. Although the availability of multiple therapies ensures that most patients will achieve satisfactory results, it can be challenging for the provider to select the appropriate treatment for each specific patient. This article reviews the available therapeutic options for refractory ascites and incorporates available data and clinical experience to suggest a linear stepwise management approach to enhance patient outcomes.
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Affiliation(s)
- David C Madoff
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Joshua Cornman-Homonoff
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Brett E Fortune
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Ron C Gaba
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Andrew J Lipnik
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Hooman Yarmohammadi
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
| | - Charles E Ray
- From the Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, 330 Cedar St, TE-2, New Haven, CT 06520-8055 (D.C.M., J.C.); Department of Medicine, Division of Hepatology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY (B.E.F.); Department of Radiology, Division of Interventional Radiology, University of Illinois at Chicago, Chicago, Ill (R.C.G., A.J.L., C.E.R.); and Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (H.Y.)
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Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium. J Hepatol 2021; 74:200-219. [PMID: 32896580 DOI: 10.1016/j.jhep.2020.08.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 07/09/2020] [Accepted: 08/02/2020] [Indexed: 12/15/2022]
Abstract
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
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Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O'Brien AJ, Verma S. Guidelines on the management of ascites in cirrhosis. Gut 2021; 70:9-29. [PMID: 33067334 PMCID: PMC7788190 DOI: 10.1136/gutjnl-2020-321790] [Citation(s) in RCA: 225] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/27/2020] [Accepted: 09/04/2020] [Indexed: 12/15/2022]
Abstract
The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.
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Affiliation(s)
- Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Louise China
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Suvi Härmälä
- Institute of Health Informatics, University College London, London, UK
| | - Lucia Macken
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | - Jennifer M Ryan
- Institute of Liver Disease and Digestive Health, University College London, London, UK
- Royal Free London NHS Foundation Trust, London, UK
| | - Emilie A Wilkes
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Kevin Moore
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Joanna A Leithead
- Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Peter C Hayes
- Hepatology Department, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Alastair J O'Brien
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Sumita Verma
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
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Gallo A, Dedionigi C, Civitelli C, Panzeri A, Corradi C, Squizzato A. Optimal Management of Cirrhotic Ascites: A Review for Internal Medicine Physicians. J Transl Int Med 2020; 8:220-236. [PMID: 33511049 PMCID: PMC7805288 DOI: 10.2478/jtim-2020-0035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Clinical history of liver cirrhosis is characterised by two phases: the asymptomatic phase, also termed 'compensated cirrhosis', and the phase of complications due to the development of portal hypertension and liver dysfunction, also termed 'decompensated cirrhosis', in which patients may develop ascites, the most frequent and clinically relevant complication of liver cirrhosis. Ascites can be classified into uncomplicated and complicated according to the development of refractoriness, spontaneous bacterial peritonitis (SBP) or the association with hepatorenal syndrome (HRS). In this narrative review, we will extensively discuss the optimal pharmacological and non-pharmacological management of cirrhotic ascites with the aim to offer an updated practical guide to Internal Medicine physicians. According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients. The occurrence of renal impairment, especially HRS, worsens the prognosis of patients with cirrhotic ascites and deserves a specific treatment. Also, the management of SBP faces the rising and alarming spread of antibiotic resistance. Hepatic hydrothorax may even complicate the course of the disease and its management is a challenge. Last but not least, liver transplantation (LT) is the ultimate and more effective measure to offer to patients with cirrhotic ascites, particularly when complications occur.
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Affiliation(s)
- Andrea Gallo
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Cristina Dedionigi
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Chiara Civitelli
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Anna Panzeri
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
- Hepatology Center, Ospedale Sant’Anna, Como, Italy
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Mah JM, Djerboua M, Groome PA, Booth CM, Flemming JA. Transjugular intrahepatic portosystemic shunt for the treatment of refractory ascites: A population-based cohort study. CANADIAN LIVER JOURNAL 2020; 3:334-347. [PMID: 35990506 PMCID: PMC9202739 DOI: 10.3138/canlivj-2020-0002] [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: 01/07/2020] [Accepted: 02/22/2020] [Indexed: 01/04/2025]
Abstract
BACKGROUND Randomized trials have shown that transjugular intrahepatic portosystemic shunt (TIPS) improves control of ascites compared with serial large volume paracentesis (LVP) in patients with refractory ascites. However, the effect of TIPS on liver transplant-free (LTF) survival is controversial. Our objective was to compare TIPS versus serial LVP on LTF survival in the general population of patients with refractory ascites. METHODS This is a retrospective, population-based cohort study using linked administrative health data from Ontario, Canada. Adult patients identified with refractory ascites from January 1, 2008 to December 31, 2016 were included and followed until December 31, 2017. A propensity score was used to match patients treated with serial LVP to those who received TIPS in a 2:1 ratio. LTF survival was evaluated using Kaplan-Meier analysis and Cox proportional hazards regression with TIPS treated as a time-varying exposure. RESULTS Overall, 4,935 patients with refractory ascites were identified and 488 patients were matched (325 serial LVP, 163 TIPS). The mean age was 58 years, 70% were male, 50% had viral hepatitis, the median model for end-stage liver disease (MELD) score was 12, 13% received liver transplant and the 1-year LTF survival was 72%. After TIPS, 80 patients (49%) had no further requirement for LVP by 6 months and 61 patients (37%) never required a repeat paracentesis. In survival analysis, there was marginally worse LTF survival in patients receiving TIPS (TIPS HR 1.29, 95% CI 1.00-1.67; p = .052). CONCLUSION In this population-based study of patients with refractory ascites, TIPS was associated with improved control of ascites but not improved LTF survival.
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Affiliation(s)
- Jeffrey M Mah
- Department of Medicine, Queen’s University, Kingston, Ontario, Canada
| | | | - Patti A Groome
- ICES, Queen’s University, Kingston, Ontario, Canada
- Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
| | - Christopher M Booth
- ICES, Queen’s University, Kingston, Ontario, Canada
- Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
| | - Jennifer A Flemming
- Department of Medicine, Queen’s University, Kingston, Ontario, Canada
- ICES, Queen’s University, Kingston, Ontario, Canada
- Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
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Rajesh S, George T, Philips CA, Ahamed R, Kumbar S, Mohan N, Mohanan M, Augustine P. Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update. World J Gastroenterol 2020; 26:5561-5596. [PMID: 33088154 PMCID: PMC7545393 DOI: 10.3748/wjg.v26.i37.5561] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/31/2020] [Accepted: 08/29/2020] [Indexed: 02/06/2023] Open
Abstract
More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt (TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.
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Affiliation(s)
- Sasidharan Rajesh
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Tom George
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Rizwan Ahamed
- Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Sandeep Kumbar
- Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Narain Mohan
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Meera Mohanan
- Anesthesia and Critical Care, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Philip Augustine
- Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
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Schultheiß M, Bettinger D, Thimme R, Rössle M. 30 Jahre transjugulärer intrahepatischer portosystemischer Shunt (TIPS) – Rückblick und Perspektive. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:877-889. [PMID: 32947633 DOI: 10.1055/a-1217-7866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
ZusammenfassungDer transjuguläre intrahepatische portosystemische Shunt (TIPS) wird seit 30 Jahren in der Therapie der portalen Hypertonie erfolgreich eingesetzt. In nationalen und internationalen Leitlinien ist die Indikation zur TIPS-Anlage bei Varizenblutung und refraktärem Aszites wissenschaftlich gut belegt und klar definiert. Bei seltenen Indikationen wie dem hepatorenalen Syndrom, der Pfortaderthrombose oder dem neoadjuvanten Einsatz fehlt derzeit noch eine eindeutige Studienlage. Eine wichtige Kontraindikation und klinisch bedeutendste Komplikation nach TIPS ist die hepatische Enzephalopathie (HE). Es wird versucht, die Post-TIPS HE mit technischen Weiterentwicklungen der Stents zu reduzieren.
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Affiliation(s)
- Michael Schultheiß
- Department Innere Medizin, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Dominik Bettinger
- Department Innere Medizin, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Robert Thimme
- Department Innere Medizin, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Martin Rössle
- Department Innere Medizin, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
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50
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Boike JR, Flamm SL. Transjugular Intrahepatic Portosystemic Shunts: Advances and New Uses in Patients with Chronic Liver Disease. Clin Liver Dis 2020; 24:373-388. [PMID: 32620278 DOI: 10.1016/j.cld.2020.04.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Transjugular intrahepatic portosystemic shunts is an established treatment for portal hypertensive complications. Advancements in technology and technique have led to novel indications, including treatment of chronic portal vein thrombosis and use before abdominal surgery to alleviate portal hypertensive complications. Use of TIPS can facilitate the embolization of large portal-systemic shunts to alleviate refractory hepatic encephalopathy owing to excessive portal shunting. Despite these advances, transjugular intrahepatic portosystemic shunts is an invasive procedure with risk for complications and should be performed at a center with expertise to ensure a successful patient outcome.
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Affiliation(s)
- Justin R Boike
- Department of Medicine, Northwestern Feinberg School of Medicine, 676 North St. Clair Street, Suite 1400, Chicago, IL 60611, USA.
| | - Steven L Flamm
- Hepatology Program, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, IL, USA
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