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Fuest S, Fischer C, Alexander JT. Use of Intravenous Albumin. JAMA 2025:2833672. [PMID: 40332913 DOI: 10.1001/jama.2025.3792] [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: 05/08/2025]
Abstract
This JAMA Clinical Guidelines Synopsis summarizes the 2024 guidelines on use of intravenous albumin from the International Collaboration for Transfusion Medicine.
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Affiliation(s)
- Stephen Fuest
- Department of Medicine, University of Colorado School of Medicine, Aurora
| | - Cristina Fischer
- Department of Medicine, University of Colorado School of Medicine, Aurora
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Aramcharoen C, Praguylertluck W, Intarasak N, Yaowmaneerat T, Kaewdech A, Chamroonkul N, Sripongpun P. Serum sodium level is predictive for kidney injury or hyponatremia after modest-volume paracentesis (<5 L) in Asian patients with cirrhosis: A single-centered retrospective observational study. Medicine (Baltimore) 2025; 104:e41420. [PMID: 39928798 PMCID: PMC11813013 DOI: 10.1097/md.0000000000041420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 12/03/2024] [Accepted: 01/15/2025] [Indexed: 02/12/2025] Open
Abstract
Post-paracentesis circulatory dysfunction (PPCD) is a well-known complication in patients with decompensated cirrhosis undergoing large-volume paracentesis (>5 L ascites removal). PPCD can cause acute kidney injury (AKI) and hyponatremia. Given the generally smaller body size observed in patients of Asian descent, we hypothesized that the removal of <5 L of ascitic fluid (modest-volume paracentesis; MVP) might also contribute to the development of PPCD. We investigated whether MVP could lead to AKI/hyponatremia in Thai patients with cirrhosis and identified the factor(s) associated with these outcomes. This was a retrospective, single-center study that included all consecutive patients with cirrhosis who underwent MVP at our unit between 2020 and 2021. Baseline characteristics and laboratory results obtained within 3 days prior to and 7 to 28 days following paracentesis were collected. The occurrence of AKI or hyponatremia was recorded, and the characteristics and laboratory findings of patients who developed these complications were compared with those who did not. During the study period, 73 MVPs were performed in 39 patients. Eight patients (20.5%) developed AKI/hyponatremia within 7 to 28 days of the procedure. Baseline serum sodium level was significantly lower in patients who developed AKI/hyponatremia compared to those who did not (131.0 ± 5.9 vs 135.6 ± 3.0 mEq/L, P = .004). A serum sodium cutoff value of 132 mEq/L showed a specificity and sensitivity of 0.9 and 0.63, respectively, for predicting the development of AKI/hyponatremia, with an area under the curve of 0.81. These findings highlight that PPCD resulted in AKI/hyponatremia, which was previously not anticipated, can indeed occur after paracentesis of <5 L in Thai cirrhotic patients. These results may have significant implications for clinical decision-making regarding the administration of albumin replacement therapy in Asian patients with cirrhosis who are to undergo paracentesis in future clinical practice.
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Affiliation(s)
- Chayathorn Aramcharoen
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | | | - Naree Intarasak
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Thanapon Yaowmaneerat
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
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Khanna D, Kar P, Sahu P. Efficacy of long-term albumin therapy in the treatment of decompensated cirrhosis. Indian J Gastroenterol 2024; 43:494-504. [PMID: 38722510 DOI: 10.1007/s12664-024-01566-6] [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: 09/18/2023] [Accepted: 03/04/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND AIMS Decompensated liver cirrhosis has a poor prognosis, with a median overall survival of two to four years, which is worse than for many oncological disorders. These patients are highly susceptible to infections due to increased systemic inflammation leading to kidney failure and death. The aim was to study the efficacy of albumin in reducing episodes of decompensation, preventing bacterial infection, kidney dysfunction and mortality. METHOD Study involved patients with Child B or C cirrhosis with an albumin level below 3.0 g/dL, who were administered 20% human albumin weekly with standard medical treatment (SMT) for three months or till serum albumin levels were 4.0 g/dL (whichever is earlier) and compared with age and sex-matched controls who received only SMT. The primary end-point was six-month mortality and the secondary end-points were reduction in infections, kidney dysfunction, ascites recurrence, hepatic encephalopathy (HE), gastrointestinal (GI) bleed and complications of cirrhosis. RESULTS From September 2021 to January 2023, 88 cases and 86 controls were taken and followed up for six months. Overall, six-month survival was not statistically significant between groups (95.1% vs. 91.9%; p = 0·330). The incidence of recurrence of ascites (34.09% vs. 59.3%, p < 0.001), kidney dysfunction (6.8% vs. 24.4%, p < 0.001), HE (15.9% vs, 37.2%, p = 0.015), spontaneous bacterial peritonitis (SBP) (3.4% vs 17.4%, p = 0.002) and non-SBP infections (7.9% vs. 18.6%, p = 0.038) were significantly less in cases as compared with controls; however, GI bleed (14.8% vs. 17.4%, p = 0.632) was not statistically significant. CONCLUSION Long-term human albumin acts as a disease-modifying treatment in patients with decompensated cirrhosis.
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Affiliation(s)
- Deepanshu Khanna
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India
| | - Premashis Kar
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India.
| | - Pabitra Sahu
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India
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Sujith Reddy JSN, Jagtap N, Kalpala R, Kulkarni A, Gupta R, Nagaraja Rao P, Iyengar S, Alla M, Nageshwar Reddy D, Sharma M. Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic-a Randomized Controlled Trial. J Clin Exp Hepatol 2023; 13:576-585. [PMID: 37440947 PMCID: PMC10333951 DOI: 10.1016/j.jceh.2023.01.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/20/2023] [Indexed: 07/15/2023] Open
Abstract
Background Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). Methods This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. Results 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. Conclusions Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.
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Affiliation(s)
| | - Nitin Jagtap
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rakesh Kalpala
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rajesh Gupta
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Sowmya Iyengar
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Manasa Alla
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
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Bai Z, Wang L, Wang R, Zou M, Méndez-Sánchez N, Romeiro FG, Cheng G, Qi X. Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials. Hepatol Int 2022; 16:1468-1483. [PMID: 36048318 DOI: 10.1007/s12072-022-10374-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/04/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial. METHODS EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding. CONCLUSIONS Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.
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Affiliation(s)
- Zhaohui Bai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Postgraduate College, China Medical University, Shenyang, Liaoning, China
| | - Ran Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Meijuan Zou
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Nahum Méndez-Sánchez
- Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
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Bai Z, Wang L, Lin H, Tacke F, Cheng G, Qi X. Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:5928. [PMID: 36233795 PMCID: PMC9572637 DOI: 10.3390/jcm11195928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/15/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Hyponatremia is a common complication of liver cirrhosis and aggravates patients' outcomes. It may be corrected by human albumin (HA) infusion. Herein, we have conducted a systematic review and meta-analysis to evaluate the efficacy of intravenous HA administration for the prevention and treatment of hyponatremia in liver cirrhosis. METHODS Literature was searched in the PubMed, EMBASE, and Cochrane Library databases. If possible, a meta-analysis would be conducted. Incidence of hyponatremia, rate of resolution of hyponatremia, and serum sodium level were compared between cirrhotic patients who received and did not receive HA infusion. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS Initially, 3231 papers were identified. Among them, 30 studies, including 25 randomized controlled trials (RCTs) and 5 cohort studies, were eligible. Among cirrhotic patients without hyponatremia, the HA infusion group had significantly lower incidence of hyponatremia (OR = 0.55, 95%CI = 0.38-0.80, p = 0.001) and higher serum sodium level (MD = 0.95, 95%CI = 0.47-1.43, p = 0.0001) as compared to the control group. Among cirrhotic patients with hyponatremia, the HA infusion group had a significantly higher rate of resolution of hyponatremia (OR = 1.50, 95%CI = 1.17-1.92, p = 0.001) as compared to the control group. Generally, the quality of available evidence is low. CONCLUSIONS Based on the current evidence, HA may be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. Well-designed studies are required to clarify the effects of HA infusion on hyponatremia in liver cirrhosis.
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Affiliation(s)
- Zhaohui Bai
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Hanyang Lin
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité University Medical Center, 10117 Berlin, Germany
| | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xingshun Qi
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
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de Mattos ÂZ, Simonetto DA, Terra C, Farias AQ, Bittencourt PL, Pase THS, Toazza MR, de Mattos AA. Albumin administration in patients with cirrhosis: Current role and novel perspectives. World J Gastroenterol 2022; 28:4773-4786. [PMID: 36156923 PMCID: PMC9476855 DOI: 10.3748/wjg.v28.i33.4773] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/05/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
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Affiliation(s)
- Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Douglas Alano Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, United States
| | - Carlos Terra
- Department of Gastroenterology, State University of Rio de Janeiro, Rio de Janeiro 20550-170, Brazil
| | | | | | - Tales Henrique Soares Pase
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Marlon Rubini Toazza
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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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: 127] [Impact Index Per Article: 42.3] [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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Safety and efficacy of human serum albumin treatment in patients with cirrhotic ascites undergoing paracentesis: A systematic review and meta-analysis. Ann Hepatol 2021; 26:100547. [PMID: 34626828 DOI: 10.1016/j.aohep.2021.100547] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 06/02/2021] [Accepted: 06/10/2021] [Indexed: 02/04/2023]
Abstract
Ascites is the most common presentation of decompensated liver cirrhosis. It is treated with therapeutic paracentesis which is associated with several complications. The role of human albumin in patients with cirrhotic ascites remains elusive and has been extensively studied with conflicting results. Thus, in order to fully appraise the available data we sought to perform this systematic review and meta-analysis. Herein we included studies comparing the efficacy and safety of human albumin comparing with other volume expanders and vasoactive agents in patients undergoing paracentesis in cirrhotic ascites. Odds ratio (OR) and mean difference (MD) were used to estimate the outcome with a 95% confidence interval (CI). Albumin use reduced the odds of paracentesis induced circulatory dysfunction (PICD) by 60% (OR 0.40, 95% CI 0.27-0.58). While performing subgroup analysis, albumin use lowered the odds of PICD significantly (OR 0.34, 95% CI 0.22-0.52) in comparison to other colloid volume expanders, but did not lower the odds of PICD in comparison to vasoconstrictor therapy (OR 0.93, 95% CI 0.35-2.45). Albumin was associated with a statistically significant lower incidence of hyponatremia (OR 0.59, 95% CI 0.39-0.88). Albumin did not reduce the overall mortality, readmission rate, recurrence of ascites, mean arterial pressure, incidence of renal impairment, hepatic encephalopathy, and gastrointestinal (GI) bleeding. Thus, treatment with albumin in cirrhotic ascites reduced PICD and hyponatremia although there was no benefit in terms of mortality, readmission rate, recurrence of ascites, hepatic encephalopathy, and GI bleeding.
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10
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Wong YJ, Lum HM, Tan PT, Teo EK, Tan J, Kumar R, Thurairajah PH. Clinical implications of prompt ascitic drain removal in cirrhosis with refractory ascites. Singapore Med J 2021; 62:659-664. [PMID: 33866716 PMCID: PMC8804429 DOI: 10.11622/smedj.2021049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Large-volume paracentesis (LVP) is the first-line treatment for decompensated cirrhosis with refractory ascites. While ascitic drain removal (ADR) within 72 hours of the procedure was once considered safe, it was uncertain whether ADR within 24 hours could further reduce the risk of ascitic drain-related bacterial peritonitis (AdBP). This study aimed to investigate the association between the timing of ADR and the presence of AdBP. METHODS All patients with cirrhosis with refractory ascites who underwent LVP in our institution from 2014 to 2017 were studied. AdBP was diagnosed based on an ascitic fluid neutrophil count ≥ 250 cells/mm3 or positive ascitic fluid culture following recent paracentesis within two weeks. RESULTS A total of 131 patients who underwent LVP were followed up for 1,806 patient-months. Their mean age was 68.3 ± 11.6 years, and 65.6% were male. Their mean Model for End-Stage Liver Disease score was 15.2. The overall incidence of AdBP was 5.3%. ADR beyond 24 hours was significantly associated with a longer median length of stay (five days vs. three days, p < 0.001), higher risk of AdBP (0% vs. 8.9%, p = 0.042) and acute kidney injury (AKI) following LVP (odds ratio 20.0, 95% confidence interval 2.4-164.2, p = 0.021). The overall survival was similar in patients who underwent ADR within and beyond 24 hours of LVP. CONCLUSION ADR within 24 hours of LVP is associated with a reduced risk of AdBP and AKI. As AdBP is associated with resistant organisms and AKI, we recommend prompt ADR within 24 hours, especially in patients who have Child-Pugh class C alcoholic cirrhosis.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Huey Ming Lum
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Pei Ting Tan
- Clinical Trial & Research Unit, Changi General Hospital, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Jessica Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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11
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Intra-abdominal hypertension and abdominal compartment syndrome. Curr Probl Surg 2021; 58:100971. [PMID: 34836571 DOI: 10.1016/j.cpsurg.2021.100971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 02/10/2021] [Indexed: 11/21/2022]
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12
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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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13
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Chaney A. A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis. Clin Exp Gastroenterol 2021; 14:385-396. [PMID: 34675586 PMCID: PMC8502008 DOI: 10.2147/ceg.s323778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022] Open
Abstract
The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.
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Affiliation(s)
- Amanda Chaney
- Department of Transplant, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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14
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Li C, Xiang W, Wu M, Zhang H, Cheng J, Yang T, Mai J, Chi X, Gao X, Ding Y, Niu J. A randomized dose-escalation study on the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of a novel recombinant human albumin in healthy subjects. Eur J Pharm Sci 2021; 165:105923. [PMID: 34229078 DOI: 10.1016/j.ejps.2021.105923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/19/2021] [Accepted: 06/28/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Recombinant human albumin (rHA) is an alternative to human serum albumin (HSA) for treating ascites in cirrhosis patients. This study was to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics/pharmacodynamics (PK/PD) of rHA in healthy subjects to guide the design for further clinical trials. METHODS Healthy subjects aged 18-55 years were enrolled in this double-blinded, first-in-human, placebo-controlled single ascending dose (SAD) (1.25, 5, 10, 20, or 30g) and positive-controlled multiple-dose study (3-day treatment of 10g/day for three cycles every three weeks). The safety was assessed by adverse events (AEs). Antibodies (IgE and IgD) and cytokines were analyzed for immunogenicity. Serum albumin levels and changes in plasma colloid osmotic pressure (PCOP) and hematocrit (HCT) were measured for PK/PD analysis. RESULTS rHA was well tolerated as all AEs were assessed as mild or moderate. No severe allergy or difference in the incidence of AEs was observed among the different cohorts in the SAD study or in the different cycles in the multiple-dose study. The incidence of AEs was similar for the rHA and HSA cohort. Antibodies or cytokines showed no changes after drug administration. As expected, serum albumin levels and PCOP increases, and HCT ratio decreases were dose-related with significant differences (p < 0.01). No differences were observed between rHA and HSA. CONCLUSION rHA is safe and well-tolerated in healthy Chinese subjects. rHA and HSA exhibited similar safety, tolerability, and PK/PD profiles. The results support further evaluation of rHA treatment in cirrhotic patients with ascites. The clinical trial registration numbers are CTR20191221 (http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml).
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Affiliation(s)
- Cuiyun Li
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Wei Xiang
- Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China.
| | - Min Wu
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Hong Zhang
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Jianqiu Cheng
- Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China.
| | - Tao Yang
- Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China.
| | - Jiajia Mai
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Xiumei Chi
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Xiuzhu Gao
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Yanhua Ding
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
| | - Junqi Niu
- Department of Hepatology, First Hospital, Jilin University, Changchun, 130021, Jilin, China.
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15
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Bernal W, Karvellas C, Saliba F, Saner FH, Meersseman P. Intensive care management of acute-on-chronic liver failure. J Hepatol 2021; 75 Suppl 1:S163-S177. [PMID: 34039487 DOI: 10.1016/j.jhep.2020.10.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023]
Abstract
The syndrome of acute-on-chronic liver failure combines deterioration of liver function in a patient with chronic liver disease, with the development of extrahepatic organ failure and high short-term mortality. Its successful management demands a rapid and coherent response to the development of dysfunction and failure of multiple organ systems in an intensive care unit setting. This response recognises the features that distinguish it from other critical illness and addresses the complex interplay between the precipitating insult, the many organ systems involved and the disordered physiology of underlying chronic liver disease. An evidence base is building to support the approaches currently adopted and outcomes for patients with this condition are improving, but mortality remains unacceptably high. Herein, we review practical considerations in critical care management, as well as discussing key knowledge gaps and areas of controversy that require further focussed research.
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Affiliation(s)
- William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS, United Kingdom.
| | - Constantine Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G-2X8, Canada
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris SACLAY, INSERM Unit 1193, Villejuif, France
| | - Fuat H Saner
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum Essen Hufelandstr. 55 45 147, Essen, Germany
| | - Philippe Meersseman
- Medical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium
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16
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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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17
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Wong YJ, Kumar R, Chua YJJ, Ang TL. Long-term albumin infusion in decompensated cirrhosis: A review of current literature. World J Hepatol 2021; 13:421-432. [PMID: 33959225 PMCID: PMC8080546 DOI: 10.4254/wjh.v13.i4.421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/22/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.
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Affiliation(s)
- Yu Jun Wong
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Rahul Kumar
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Yu Jing Jonathan Chua
- Department of Internal Medicine, Yong Loo Lin School of Medicine, Singapore 117597, Singapore
| | - Tiing Leong Ang
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore.
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18
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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: 221] [Impact Index Per Article: 55.3] [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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19
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Alsebaey A, Rewisha E, Waked I. High efficacy of low-dose albumin infusion in the prevention of paracentesis-induced circulatory dysfunction. EGYPTIAN LIVER JOURNAL 2020; 10:9. [DOI: 10.1186/s43066-020-0024-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 01/27/2020] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Large-volume paracentesis (LVP) is a main pillar in treating patients with tense ascites. Without plasma expanders use, paracentesis-induced circulatory dysfunction (PICD) is a common complication with decreased survival. The aim was to compare low-dose albumin (2 g/L ascitic fluid removed n = 85) with standard-dose albumin (6 g/L ascitic fluid removed, n = 25) for prevention of PICD. Liver function tests, urea, creatinine, CBC, and abdominal ultrasonography were done. Plasma renin activity (PRA) was measured at baseline and on the 6th day post-LVP. The delta change (Δ) = day 6 variable minus baseline variable value. PICD was defined as increase in PRA of > 50% of the baseline value.
Results
Patients in low-dose albumin group were mainly Child B compared with Child C (85.9% vs. 52%; p = 0.001), underwent less paracentesis volume (9.78 ± 3.56 vs. 12.52 ± 3.6 L; p = 0.001), but had higher baseline PRA (859.62 ± 1151.34 vs. 165.93 ± 95.34 pg/mL; p = 0.001). In both groups, the PRA increased at day 6 compared with the baseline (1141.57 ± 1433.01 vs. 859.62 ± 1151.34 pg/mL; p = 0.01) and (192.21 ± 80.99 vs. 165.93 ± 95.34 pg/mL; p = 0.01) respectively. Both groups were comparable for Δ PRA (281.95 ± 851.4 vs. 26.28 ± 30.2 pg/mL; p = 0.102) and PRA percent increase (10.97 ± 30.77 vs. 12.57 ± 14.87; p = 0.844). They had comparable PICD incidence (24.7% vs. 12%; p = 0.27). Females were more liable for PICD occurrence than males (OR 2.91, 95% CI 1.125–7.547, p = 0.028) and so Child B patients than Child C (OR 8.4, 95% CI 1.072–65.767, p = 0.043).
Conclusion
Low-dose albumin infusion is comparable to the standard-dose albumin for the prevention of PICD.
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20
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Pietrukaniec M, Migacz M, Żak-Gołąb A, Olszanecka-Glinianowicz M, Chudek J, Duława J, Holecki M. Could KIM-1 and NGAL levels predict acute kidney injury after paracentesis? - preliminary study. Ren Fail 2020; 42:853-859. [PMID: 32808849 PMCID: PMC7472504 DOI: 10.1080/0886022x.2020.1801468] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/15/2020] [Accepted: 07/15/2020] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Kidney dysfunction is a common complication in patients with severe liver cirrhosis. There is a need for discovery and validation of novel biomarkers for earlier AKI detection. The aim of this study was to determine if tubular injury markers: NGAL and KIM-1 could be helpful in the early diagnosis of AKI in patients undergoing therapeutic paracentesis. METHODS This preliminary study included 24 adult patients diagnosed with liver cirrhosis who had been hospitalized due to massive ascites requiring paracentesis. Pre- and post-paracentesis plasma samples were taken from each patient and biomarkers were measured. RESULTS Before paracentesis, the levels of serum and urinary NGAL were similar between patients and controls; while urinary KIM-1 was markedly increased in liver cirrhotic patients (0.76 vs. 0.24 ng/ml; respectively). Although urinary NGAL levels in AKI patients were 5-time greater than in non-AKI subgroup, the difference did not reach statistical significance (13.2 vs 1.5 pg/mL, p = 0.06). Serum NGAL level, post-procedure, was 3 times greater in AKI subgroup. CONCLUSION Kidney injury markers, especially serum NGAL, may be useful for the early detection of AKI. However, further research is required to determine if biomarkers of kidney injury may help identify patients with cirrhosis who would most likely benefit from early AKI prevention and treatment.
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Affiliation(s)
- Marta Pietrukaniec
- Department of Internal, Autoimmune and Metabolic Diseases, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland
| | - Maciej Migacz
- Department of Internal, Autoimmune and Metabolic Diseases, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Żak-Gołąb
- Department of Internal, Autoimmune and Metabolic Diseases, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland
| | | | - Jerzy Chudek
- Department of Internal Diseases and Oncological Chemotherapy, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland
| | - Jan Duława
- Department of Internal and Autoimmune Diseases, School of Health Science, Medical University of Silesia, Katowice, Poland
| | - Michał Holecki
- Department of Internal, Autoimmune and Metabolic Diseases, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland
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21
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Zaccherini G, Tufoni M, Bernardi M. Albumin Administration is Efficacious in the Management of Patients with Cirrhosis: A Systematic Review of the Literature. Hepat Med 2020; 12:153-172. [PMID: 33149707 PMCID: PMC7602890 DOI: 10.2147/hmer.s264231] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 09/18/2020] [Indexed: 12/15/2022] Open
Abstract
The use of albumin in patients with cirrhosis has been extensively discussed over recent years. Current treatment approaches depend on targeting related complications, aiming to treat and/or prevent circulatory dysfunction, bacterial infections and multi-organ failure. Albumin has been shown to prolong survival and reduce complications in patients with cirrhosis. This review aims to ascertain whether the use of albumin is justified in patients with cirrhosis. A systematic review of randomized controlled trials (RCTs) and meta-analyses evaluating albumin use in patients with cirrhosis published between 1985 and February 2020 was conducted; the quality and risk of bias of the included studies were assessed. In total, 45 RCTs and 10 meta-analyses were included. Based on the included evidence, albumin is superior at preventing and controlling the incidence of cirrhosis complications vs other plasma expanders. Recent studies reported that long-term albumin administration to patients with decompensated cirrhosis improves survival with a 38% reduction in the mortality hazard ratio compared with standard medical treatment alone. Albumin infusions are justified for routine use in patients with cirrhosis, and the use of albumin either alone or in combination with other treatments leads to clinical benefits. Long-term administration of albumin should be considered in some patients.
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Affiliation(s)
- Giacomo Zaccherini
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna 40138, Italy
| | - Manuel Tufoni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna 40138, Italy
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna 40138, Italy
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Wong YJ, Qiu TY, Tam YC, Mohan BP, Gallegos-Orozco JF, Adler DG. Efficacy and Safety of IV albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis. Dig Liver Dis 2020; 52:1137-1142. [PMID: 32586766 DOI: 10.1016/j.dld.2020.05.047] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023]
Abstract
UNLABELLED Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. AIM We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. METHODS We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. RESULTS A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I2=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I2=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I2=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I2=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). CONCLUSION Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.
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Affiliation(s)
- Yu-Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | - Tian-Yu Qiu
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | - Yew-Chong Tam
- Education Resource Centre, Singapore General Hospital, Department of Medicine
| | - Babu P Mohan
- University of Arizona, Tucson, USA; Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Juan-F Gallegos-Orozco
- Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Douglas G Adler
- Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
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Arora V, Vijayaraghavan R, Maiwall R, Sahney A, Thomas SS, Ali R, Jain P, Kumar G, Sarin SK. Paracentesis-Induced Circulatory Dysfunction With Modest-Volume Paracentesis Is Partly Ameliorated by Albumin Infusion in Acute-on-Chronic Liver Failure. Hepatology 2020; 72:1043-1055. [PMID: 31849085 DOI: 10.1002/hep.31071] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 12/06/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Paracentesis-induced circulatory dysfunction (PICD) is a serious complication of large-volume (>5 L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute-on-chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest-volume paracentesis (MVP) and the role of albumin infusion. APPROACH AND RESULTS A total of 80 ACLF patients undergoing <5 L paracentesis were randomized to receive albumin (8 g/dL of ascitic fluid; n = 40) or no albumin (n = 40) and serially followed to detect PICD. Baseline characteristics were comparable between groups, including volume of ascitic tap (4.16 ± 0.23 versus 4.14 ± 0.27 L; P = 0.72) and plasma renin activity (PRA; 20.5 ± 7.03 versus 23.2 ± 8.24 ng/mL/hour; P = 0.12). PICD was more frequent in the no-albumin group than the albumin group (70% versus 30%; P = 0.001), with higher incidence of hepatic encephalopathy (50% versus 27.5%; P = 0.04), hyponatremia (67.5% versus 22.5%; P < 0.001), acute kidney injury (62.5% versus 30%; P = 0.001), and in-house mortality (62.5% versus 27.5%; P = 0.003). PRA of 25.15 ng/mL at day 3 had sensitivity and specificity of 71% and 68%, respectively, for development of PICD at day 6. Albumin infusion decreased the incidence of PICD at day 6 (odds ratio, 0.068; 95% confidence interval, 0.011-0.43; P = 0.005). CONCLUSIONS PICD is common and develops even with MVP in ACLF patients. Albumin infusion decreases the incidence of PICD and mortality in patients with ACLF. Clinical trial identifier: NCT02467348.
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Affiliation(s)
- Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amrish Sahney
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin Sarah Thomas
- Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rehmat Ali
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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24
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John S, Friedman LS. Portal Hypertensive Ascites: Current Status. CURRENT HEPATOLOGY REPORTS 2020; 19:226-234. [DOI: 10.1007/s11901-020-00524-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/20/2025]
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Tufoni M, Baldassarre M, Zaccherini G, Antognoli A, Caraceni P. Hemodynamic and Systemic Effects of Albumin in Patients with Advanced Liver Disease. CURRENT HEPATOLOGY REPORTS 2020; 19:147-158. [PMID: 32837825 PMCID: PMC7326530 DOI: 10.1007/s11901-020-00521-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Purpose of Review Albumin administration is recommended to prevent or treat specific complications of decompensated cirrhosis based on its capacity to expand plasma volume. However, the molecule also has many other biological properties that are unrelated to the oncotic activity. The purpose of this review is to examine the hemodynamic and systemic effects of albumin administration in patients with decompensated cirrhosis. Recent Findings Besides plasma expansion, albumin appears to act against inflammation, facilitate immunocompetence, and improve cardiac and endothelial function, thus antagonizing critical steps in the pathophysiological cascade underlying decompensated cirrhosis. Summary Increasing knowledge of the pathophysiological mechanisms of the disease, as well the pleiotropic properties of the molecule, provides the rationale for considering albumin as a multi-target disease-modifying agent in decompensated cirrhosis. Both oncotic and non-oncotic properties likely concur with the clinical benefits of long-term albumin administration recently demonstrated in these patients.
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Affiliation(s)
- Manuel Tufoni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Maurizio Baldassarre
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Agnese Antognoli
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
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26
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Ali B, Salim A, Alam A, Zuberi BF, Ali Z, Azam Z, Kamani L, Farooqi JI, Salih M, Nawaz AA, Chaudhry AA, Hashmi ZY, Siddique M. HEP-Net opinion on the management of ascites and its complications in the setting of decompensated cirrhosis in the resource constrained environment of Pakistan. Pak J Med Sci 2020; 36:1117-1132. [PMID: 32704299 PMCID: PMC7372671 DOI: 10.12669/pjms.36.5.2407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/09/2020] [Accepted: 05/20/2020] [Indexed: 11/30/2022] Open
Abstract
Approximately one half of patients develop ascites within 10 years of diagnosis of compensated cirrhosis. It is a poor prognostic indicator, with only 50% surviving beyond two years. Mortality worsens significantly to 20% to 50% at one year if the ascites becomes refractory to medical therapy. Pakistan has one of the highest prevalence of viral hepatitis in the world and patients with ascites secondary to liver cirrhosis make a major percentage of both inpatient and outpatient burden. Studies indicate that over 80% of patients admitted with ascites have liver cirrhosis as the cause. This expert opinion suggests proper assessment of patients with ascites in the presence of underlying cirrhosis. This expert opinion includes appropriate diagnosis and management of uncomplicated ascites, refractory ascites and complicated ascites (including spontaneous bacterial peritonitis (SBP) ascites, hepatorenal syndrome (HRS) and hyponatremia. The purpose behind this expert opinion is to help consultants, postgraduate trainees, medical officers and primary care physicians optimally manage their patients with cirrhosis and ascites in a resource constrained setting as is often encountered in a developing country like Pakistan.
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Affiliation(s)
- Bushra Ali
- Bushra Ali, Fatima Memorial Medical and Dental College, Lahore, Pakistan
| | - Adnan Salim
- Adnan Salim, Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan
| | - Altaf Alam
- Altaf Alam, Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan
| | - Bader Faiyaz Zuberi
- Bader Faiyaz Zuberi, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Zeeshan Ali
- Zeeshan Ali, Jinnah Postgraduate Medical Centre, Karachi, Pakistan
| | - Zahid Azam
- Zahid Azam, NILGID, Dow University of Health Sciences, Karachi, Pakistan
| | - Lubna Kamani
- Lubna Kamani, Liaquat National Hospital, Karachi, Pakistan
| | | | - Muhammed Salih
- Muhammed Salih, Quaid e Azam International Hospital, Islamabad, Pakistan
| | - Arif Amir Nawaz
- Arif Amir Nawaz, Fatima Memorial Medical and Dental College, Lahore, Pakistan
| | | | | | - Masood Siddique
- Masood Siddique, Jinnah Memorial Hospital, Rawalpindi, Pakistan
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27
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Kulkarni AV, Kumar P, Singh S, Sharma M, Talukdar R, Murthy VH, Singh V, Reddy ND, Rao NP. Prevention of paracentesis‐induced circulatory dysfunction—A systematic review and network meta‐analysis. ACTA ACUST UNITED AC 2020. [DOI: 10.1002/ygh2.395] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Anand V. Kulkarni
- Department of Hepatology Asian Institute of Gastroenterology Hyderabad India
| | - Pramod Kumar
- Department of Hepatology Asian Institute of Gastroenterology Hyderabad India
| | - Siddharth Singh
- Department of Gastroenterology, and Division of Biomedical Informatics University of California San Diego La Jolla CA USA
| | - Mithun Sharma
- Department of Hepatology Asian Institute of Gastroenterology Hyderabad India
| | - Rupjyoti Talukdar
- Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India
| | | | | | - Nageshwar D Reddy
- Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India
| | - Nagaraja Padaki Rao
- Department of Hepatology Asian Institute of Gastroenterology Hyderabad India
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28
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Kulkarni AV, Kumar P, Sharma M, Sowmya TR, Talukdar R, Rao PN, Reddy DN. Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction: A Concise Review. J Clin Transl Hepatol 2020; 8:42-48. [PMID: 32274344 PMCID: PMC7132018 DOI: 10.14218/jcth.2019.00048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 02/16/2020] [Accepted: 02/23/2020] [Indexed: 12/16/2022] Open
Abstract
Annually, 10% of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis (LVP) is a frequently used therapeutic procedure. LVP, although a safe method, is associated with circulatory dysfunction in a significant percentage of patients, which is termed paracentesis-induced circulatory dysfunction (PICD). PICD results in faster reaccumulation of ascites, hyponatremia, renal impairment, and shorter survival. PICD is diagnosed through laboratory results, with increases of >50% of baseline plasma renin activity to a value ≥4 ng/mL/h on the fifth to sixth day after paracentesis. In this review, we discuss the pathophysiology and prevention of PICD.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Pramod Kumar
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - T R Sowmya
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rupjyoti Talukdar
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Padaki Nagaraj Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
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29
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Rudler M, Mallet M, Sultanik P, Bouzbib C, Thabut D. Optimal management of ascites. Liver Int 2020; 40 Suppl 1:128-135. [PMID: 32077614 DOI: 10.1111/liv.14361] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 12/27/2019] [Indexed: 02/13/2023]
Abstract
Ascites is the most common complication of cirrhosis, which develops in 5%-10% of patients per year. Its management is based on symptomatic measures including restriction of sodium intake, diuretics and paracentesis. Underlying liver disease must always be treated and may improve ascites. In some patients, ascites is not controlled by medical therapies and has a major impact on quality of life and survival. TIPS placement and liver transplantation must therefore be discussed. More recently, repeated albumin infusions and Alfapump® have emerged as new therapies in ascites. In this review, the current data on these different options are analysed and an algorithm to help the physician make clinical decisions is suggested.
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Affiliation(s)
- Marika Rudler
- Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Maxime Mallet
- Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Philippe Sultanik
- Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Charlotte Bouzbib
- Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France.,Sorbonne University, UPMC University Paris 06, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Dominique Thabut
- Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France.,Sorbonne University, UPMC University Paris 06, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
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30
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Benmassaoud A, Freeman SC, Roccarina D, Plaz Torres MC, Sutton AJ, Cooper NJ, Iogna Prat L, Cowlin M, Milne EJ, Hawkins N, Davidson BR, Pavlov CS, Thorburn D, Tsochatzis E, Gurusamy KS. Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev 2020; 1:CD013123. [PMID: 31978257 PMCID: PMC6984622 DOI: 10.1002/14651858.cd013123.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Approximately 20% of people with cirrhosis develop ascites. Several different treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative efficacy. OBJECTIVES To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 49 randomised clinical trials (3521 participants) in the review. Forty-two trials (2870 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, without other features of decompensation, having mainly grade 3 (severe), recurrent, or refractory ascites. The follow-up in the trials ranged from 0.1 to 84 months. All the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Approximately 36.8% of participants who received paracentesis plus fluid replacement (reference group, the current standard treatment) died within 11 months. There was no evidence of differences in mortality, adverse events, or liver transplantation in people receiving different interventions compared to paracentesis plus fluid replacement (very low-certainty evidence). Resolution of ascites at maximal follow-up was higher with transjugular intrahepatic portosystemic shunt (HR 9.44; 95% CrI 1.93 to 62.68) and adding aldosterone antagonists to paracentesis plus fluid replacement (HR 30.63; 95% CrI 5.06 to 692.98) compared to paracentesis plus fluid replacement (very low-certainty evidence). Aldosterone antagonists plus loop diuretics had a higher rate of other decompensation events such as hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding compared to paracentesis plus fluid replacement (rate ratio 2.04; 95% CrI 1.37 to 3.10) (very low-certainty evidence). None of the trials using paracentesis plus fluid replacement reported health-related quality of life or symptomatic recovery from ascites. FUNDING the source of funding for four trials were industries which would benefit from the results of the study; 24 trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 21 trials was unclear. AUTHORS' CONCLUSIONS Based on very low-certainty evidence, there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality, adverse events, or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites. Based on very low-certainty evidence, transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement. Based on very low-certainty evidence, aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement.
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Affiliation(s)
- Amine Benmassaoud
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Davide Roccarina
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | | | - Alex J Sutton
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Nicola J Cooper
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Laura Iogna Prat
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | | | | | - Neil Hawkins
- University of GlasgowHEHTAUniversity Ave Glasgow G12 8QQGlasgowUK
| | - Brian R Davidson
- University College LondonDivision of Surgery and Interventional ScienceLondonUKNW3 2QG
| | - Chavdar S Pavlov
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional ScienceLondonUKNW3 2QG
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
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Abstract
Ascites occurs in up to 70% of patients during the natural history of cirrhosis. Management of uncomplicated ascites includes sodium restriction and diuretic therapy, whereas that for refractory ascites (RA) is regular large-volume paracentesis with transjugular intrahepatic portosystemic shunt being offered in appropriate patients. Renal impairment occurs in up to 50% of patients with RA with type 1 hepatorenal syndrome (HRS) being most severe. Liver transplant remains the definitive treatment of eligible candidates with HRS, whereas combined liver and kidney transplant should be considered in patients requiring dialysis for more than 4 to 6 weeks or those with underlying chronic kidney disease.
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32
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Garbin N, Doyle P, Smith B, Taylor JG, Khan MH, Khalil Q, Valdastri P. Miniature Pump for Treatment of Refractory Ascites Based on Local Magnetic Actuation. J Med Device 2019. [DOI: 10.1115/1.4042460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
This paper presents the design, fabrication, and experimental validation of a novel low-cost implantable pump for the treatment of refractory ascites (RA) based on local magnetic actuation (LMA). A reciprocating positive displacement pump displaces liquid unidirectionally through magnetic coupling with a magnetic controller placed on the outside of the patient's body. The proposed solution is intuitive to use given an alignment algorithm that exploits externally placed magnetic field sensors (MFS). The implantable device has a catheter-like shape, is electronic free (no on-board battery), has low fabrication cost (<8 USD), and is able to generate a flow-rate of 3.65 L/h while effectively pumping fluids with various viscosity (1–5.5 cP). RA is commonly treated via costly paracentesis or invasive surgical placement of a transjugular portosystemic shunt (TIPS). The proposed solution can be implanted with minimally invasive techniques and can be used on a daily basis to drain a set amount of liquid, without requiring recurrent hospital visits.
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Affiliation(s)
- Nicolo Garbin
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN 37212 e-mail:
| | | | - Byron Smith
- Senior Engineer, Medical Merge LLC, Brentwood, TN 37027 e-mail:
| | | | | | - Qasim Khalil
- Hospital Medicine Consultant, Abu Dhabi, 112412, United Arab Emirates e-mail:
| | - Pietro Valdastri
- Chair in Robotics & Autonomous Systems, School of Electronic and Electrical Engineering, University of Leeds, Leeds, LS2 9JT, UK e-mail:
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33
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Yamada Y, Inui K, Hara Y, Fuji K, Sonoda K, Hashimoto K, Kamijo Y. Verification of serum albumin elevating effect of cell-free and concentrated ascites reinfusion therapy for ascites patients: a retrospective controlled cohort study. Sci Rep 2019; 9:10195. [PMID: 31308465 PMCID: PMC6629637 DOI: 10.1038/s41598-019-46774-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 07/04/2019] [Indexed: 02/06/2023] Open
Abstract
Cell-free and concentrated ascites reinfusion therapy (CART) is frequently used to treat refractory ascites in Japan. However, its efficacy remains unclear. This controlled cohort study verified the serum albumin elevating effect of CART by comparisons with simple paracentesis. Ascites patients receiving CART (N = 88) or paracentesis (N = 108) at our hospital were assessed for the primary outcome of change in serum albumin level within 3 days before and after treatment. A significantly larger volume of ascites was drained in the CART group. The change in serum albumin level was +0.08 ± 0.25 g/dL in the CART group and −0.10 ± 0.30 g/dL in the paracentesis group (P < 0.001). The CART – paracentesis difference was +0.26 g/dL (95%CI +0.18 to +0.33, P < 0.001) after adjusting for potential confounders by multivariate analysis. The adjusted difference increased with drainage volume. In the CART group, serum total protein, dietary intake, and urine volume were significantly increased, while hemoglobin and body weight was significantly decreased, versus paracentesis. More frequent adverse events, particularly fever, were recorded for CART, although the period until re-drainage was significantly longer. This study is the first demonstrating that CART can significantly increase serum albumin level as compared with simple paracentesis. CART represents a useful strategy to manage patients requiring ascites drainage.
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Affiliation(s)
- Yosuke Yamada
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Keita Inui
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yuuta Hara
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Kazuaki Fuji
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Kosuke Sonoda
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Koji Hashimoto
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yuji Kamijo
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
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Runken MC, Caraceni P, Fernandez J, Zipprich A, Carlton R, Bunke M. The cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain. HEALTH ECONOMICS REVIEW 2019; 9:22. [PMID: 31278624 PMCID: PMC6734265 DOI: 10.1186/s13561-019-0237-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 06/17/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND Albumin is frequently prescribed in cirrhotic patients with acute decompensation. However, the true cost effectiveness of albumin use in cirrhotic patients is still under debate. OBJECTIVE To evaluate the cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain. METHODS A decision-tree economic model was developed to evaluate treatments for decompensated cirrhosis from the hospital perspective over a typical inpatient admission. The treatments for large volume paracentesis (LVP) were albumin vs saline, gelatin, or no fluid. The treatments for spontaneous bacterial peritonitis (SBP) were albumin plus antibiotics vs antibiotics alone. The treatments for hepatorenal syndrome (HRS) were albumin plus a vasoconstrictor vs a vasoconstrictor alone. Effectiveness inputs were literature-based. Cost inputs included pharmacy costs and medical complication costs of decompensated cirrhosis. The primary model assessments were incremental cost-effectiveness ratios (ICERs) per life saved and per quality-adjusted life-year (QALY). RESULTS Albumin was found to be both less costly and more effective relative to saline, gelatin, and no fluid for the treatment of LVP across all 3 countries. For SBP, albumin plus antibiotics was more clinically effective than antibiotics alone in all 3 countries. The combination of albumin plus antibiotics was less costly than antibiotics alone in Germany and Italy, making albumin a dominant treatment (ie, less costly and more effective). In the management of SBP in Spain, albumin plus antibiotics compared to antibiotics alone resulted in ICERs of €1516 per life saved and €3369 per QALY gained. Albumin plus a vasoconstrictor was both less costly and more effective than vasoconstrictor alone in the treatment of HRS across all 3 countries. CONCLUSION This analysis demonstrates that albumin is cost-effective in terms of lives saved and QALYs gained in the management of decompensated cirrhosis associated with LVP, SBP, or HRS.
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Affiliation(s)
- M. Chris Runken
- Grifols Shared Services North America (SSNA), Inc., Research Triangle Park, Raleigh, NC USA
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Alexander Zipprich
- Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | | | - Martin Bunke
- Senior Director Medical Affairs, Retrophin, San Diego, CA USA
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Simonetti RG, Perricone G, Nikolova D, Bjelakovic G, Gluud C. Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis. Cochrane Database Syst Rev 2019; 6:CD004039. [PMID: 31251387 PMCID: PMC6598734 DOI: 10.1002/14651858.cd004039.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Plasma volume expanders are used in connection to paracentesis in people with cirrhosis to prevent reduction of effective plasma volume, which may trigger deleterious effect on haemodynamic balance, and increase morbidity and mortality. Albumin is considered the standard product against which no plasma expansion or other plasma expanders, e.g. other colloids (polygeline , dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol have been compared. However, the benefits and harms of these plasma expanders are not fully clear. OBJECTIVES To assess the benefits and harms of any plasma volume expanders such as albumin, other colloids (polygeline, dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol versus no plasma volume expander or versus another plasma volume expander for paracentesis in people with cirrhosis and large ascites. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CNKI, VIP, Wanfang, Science Citation Index Expanded, and Conference Proceedings Citation Index until January 2019. Furthermore, we searched FDA, EMA, WHO (last search January 2019), www.clinicaltrials.gov/, and www.controlled-trials.com/ for ongoing trials. SELECTION CRITERIA Randomised clinical trials, no matter their design or year of publication, publication status, and language, assessing the use of any type of plasma expander versus placebo, no intervention, or a different plasma expander in connection with paracentesis for ascites in people with cirrhosis. We considered quasi-randomised, retrieved with the searches for randomised clinical trials only, for reports on harms. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We calculated the risk ratio (RR) or mean difference (MD) using the fixed-effect model and the random-effects model meta-analyses, based on the intention-to-treat principle, whenever possible. If the fixed-effect and random-effects models showed different results, then we made our conclusions based on the analysis with the highest P value (the more conservative result). We assessed risks of bias of the individual trials using predefined bias risk domains. We assessed the certainty of the evidence at an outcome level, using GRADE, and constructed 'Summary of Findings' tables for seven of our review outcomes. MAIN RESULTS We identified 27 randomised clinical trials for inclusion in this review (24 published as full-text articles and 3 as abstracts). Five of the trials, with 271 participants, assessed plasma expanders (albumin in four trials and ascitic fluid in one trial) versus no plasma expander. The remaining 22 trials, with 1321 participants, assessed one type of plasma expander, i.e. dextran, hydroxyethyl starch, polygeline, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus another type of plasma expander, i.e. albumin in 20 of these trials and polygeline in one trial. Twenty-five trials provided data for quantitative meta-analysis. According to the Child-Pugh classification, most participants were at an intermediate to advanced stage of liver disease in the absence of hepatocellular carcinoma, recent gastrointestinal bleeding, infections, and hepatic encephalopathy. All trials were assessed as at overall high risk of bias. Ten trials seemed not to have been funded by industry; twelve trials were considered unclear about funding; and five trials were considered funded by industry or a for-profit institution.We found no evidence of a difference in effect between plasma expansion versus no plasma expansion on mortality (RR 0.52, 95% CI 0.06 to 4.83; 248 participants; 4 trials; very low certainty); renal impairment (RR 0.32, 95% CI 0.02 to 5.88; 181 participants; 4 trials; very low certainty); other liver-related complications (RR 1.61, 95% CI 0.79 to 3.27; 248 participants; 4 trials; very low certainty); and non-serious adverse events (RR 1.04, 95% CI 0.32 to 3.40; 158 participants; 3 trials; very low certainty). Two of the trials stated that no serious adverse events occurred while the remaining trials did not report on this outcome. No trial reported data on health-related quality of life.We found no evidence of a difference in effect between experimental plasma expanders versus albumin on mortality (RR 1.03, 95% CI 0.82 to 1.30; 1014 participants; 14 trials; very low certainty); serious adverse events (RR 0.89, 95% CI 0.10 to 8.30; 118 participants; 2 trials; very low certainty); renal impairment (RR 1.17, 95% CI 0.71 to 1.91; 1107 participants; 17 trials; very low certainty); other liver-related complications (RR 1.10, 95% CI 0.82 to 1.48; 1083 participants; 16 trials; very low certainty); and non-serious adverse events (RR 1.37, 95% CI 0.66 to 2.85; 977 participants; 14 trials; very low certainty). We found no data on heath-related quality of life and refractory ascites. AUTHORS' CONCLUSIONS Our systematic review and meta-analysis did not find any benefits or harms of plasma expanders versus no plasma expander or of one plasma expander such as polygeline, dextrans, hydroxyethyl starch, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus albumin on primary or secondary outcomes. The data originated from few, small, mostly short-term trials at high risks of systematic errors (bias) and high risks of random errors (play of chance). GRADE assessments concluded that the evidence was of very low certainty. Therefore, we can neither demonstrate or discard any benefit of plasma expansion versus no plasma expansion, and differences between one plasma expander versus another plasma expander.Larger trials at low risks of bias are needed to assess the role of plasma expanders in connection with paracentesis. Such trials should be conducted according to the SPIRIT guidelines and reported according to the CONSORT guidelines.
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Affiliation(s)
- Rosa G Simonetti
- Cochrane Hepato‐Biliary GroupBlegdamsvej 9, 7811CopenhagenDenmark2100
| | - Giovanni Perricone
- Azienda Socio‐Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaS.C. Epatologia e GastroenterologiaPiazza Ospedale Maggiore, 3MilanItaly20162
- UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free HospitalLiver Failure GroupLondonUK
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Goran Bjelakovic
- Medical Faculty, University of NisDepartment of Internal MedicineZorana Djindjica 81NisSerbia18000
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Stratmann K, Fitting D, Zeuzem S, Bojunga J, Trebicka J, Friedrich-Rust M, Dultz G. Establishing an indwelling peritoneal catheter as a standard procedure for hospitalized patients with ascites: Retrospective data on feasibility, effectiveness and safety. United European Gastroenterol J 2019; 7:673-681. [PMID: 31210945 DOI: 10.1177/2050640619842442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 03/13/2019] [Indexed: 12/16/2022] Open
Abstract
Background The use of an indwelling peritoneal catheter system in hospitalized patients with ascites could facilitate patient management by the prevention of repetitive abdominal paracentesis. Despite these possible benefits, the use of indwelling catheters is not widely established. Objective This retrospective study aimed to evaluate the feasibility, effectiveness and safety of the use of an indwelling catheter for ascites drainage in the clinical routine. Methods This retrospective study included all indwelling peritoneal catheter placements in our department in hospitalized patients with cirrhosis between 2014 and 2017. Results A total of 324 indwelling catheter placements for ascites in 192 hospitalized patients with cirrhosis were included. The catheter (7F, 8 cm) was placed ultrasound-assisted bed-side on the hospital ward. The technical success rate of the catheter placement was 99.7% (323/324). In 17.5% (64/324) the catheter was placed to optimize ascitic drainage prior to an abdominal intervention (e.g. transjugular intrahepatic portosystemic shunt). The median time of catheter retention was 48 hours (8-168 hours) and the median cumulative amount of drained ascites 8000 ml (550-28,000). The most common adverse event was acute kidney injury (49/324, 15.1%); the risk was particularly higher in patients with a Model for End-Stage Liver Disease (MELD) score ≥ 16 (p = 0.028; odds ratio 2.039). Ascitic fistula after catheter removal was observed in 9.6% (31/324). Catheter-related infections occurred in 4.3% (14/324), and bleeding was documented in three cases (0.8%) with one major bleeding (0.3%). Conclusion The placement of an indwelling catheter for repetitive ascitic drainage in hospitalized patients with cirrhosis can be established in the clinical routine, facilitating patient management. High-MELD patients especially have to be monitored for acute kidney injury.
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Affiliation(s)
- Katharina Stratmann
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Daniel Fitting
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Jörg Bojunga
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Jonel Trebicka
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Mireen Friedrich-Rust
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
| | - Georg Dultz
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany
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Simonetto DA, Liu M, Kamath PS. Portal Hypertension and Related Complications: Diagnosis and Management. Mayo Clin Proc 2019; 94:714-726. [PMID: 30947834 DOI: 10.1016/j.mayocp.2018.12.020] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 12/11/2018] [Accepted: 12/21/2018] [Indexed: 02/06/2023]
Abstract
Portal hypertension is a major complication of cirrhosis, and its consequences, including ascites, esophageal varices, hepatic encephalopathy, and hepatorenal syndrome, lead to substantial morbidity and mortality. The past several decades have seen major improvements in the clinical management of complications of portal hypertension, resulting in substantial gains in patient outcomes. However, important challenges remain. This review focuses on the pathophysiology and diagnosis of portal hypertension and discusses general approaches in the management of patients with ascites as a result of portal hypertension.
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Affiliation(s)
| | - Mengfei Liu
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Neong SF, Adebayo D, Wong F. An update on the pathogenesis and clinical management of cirrhosis with refractory ascites. Expert Rev Gastroenterol Hepatol 2019; 13:293-305. [PMID: 30791777 DOI: 10.1080/17474124.2018.1555469] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates. Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy. Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy.
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Affiliation(s)
- Shuet Fong Neong
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
| | - Danielle Adebayo
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
| | - Florence Wong
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
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Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study. Eur J Gastroenterol Hepatol 2019; 31:345-351. [PMID: 30312183 DOI: 10.1097/meg.0000000000001277] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment. Less costly treatment alternatives such as vasoconstrictors have been investigated, but the results are controversial. Midodrine, an oral α1-adrenergic agonist, increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure. Our aim is to assess whether or not morbidity in terms of renal dysfunction, hyponatremia, systemic, or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine. PATIENTS AND METHODS Seventy-five patients with cirrhosis and refractory ascites were randomized to receive albumin infusion, oral midodrine for 2 days, or oral midodrine for 30 days after therapeutic large volume paracentesis (LVP). The primary endpoints were development of renal impairment or hyponatremia, change in systemic and portal hemodynamics, cost, and mortality in the short-term and long-term follow-up. RESULTS No significant difference was found between groups in the development of renal impairment, hyponatremia, or mortality 6 and 30 days after LVP. A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group. Renal perfusion improved significantly with the midodrine intake for 30 days only. The cost of midodrine therapy was significantly lower than albumin. CONCLUSION Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost. Long-duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion.
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Patil V, Jain M, Venkataraman J. Paracentesis-induced acute kidney injury in decompensated cirrhosis - prevalence and predictors. Clin Exp Hepatol 2019; 5:55-59. [PMID: 30915407 PMCID: PMC6431093 DOI: 10.5114/ceh.2019.83157] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Accepted: 09/13/2018] [Indexed: 12/22/2022] Open
Abstract
AIM OF THE STUDY A subgroup of cirrhotic patients undergoing therapeutic paracentesis develop acute kidney injury (AKI) despite adequate colloidal replacement.The aim of the study was to determine the prevalence and predictors of paracentesis-induced AKI in cirrhotic patients with normal baseline renal parameters and adequate colloidal replacement. MATERIAL AND METHODS This prospective, observational analytical study was undertaken between April 2015 and April 2017. All patients undergoing therapeutic paracentesis were enrolled as per inclusion and exclusion criteria. Based on Acute Kidney Injury Network (AKIN) criteria for AKI, comparative analysis was performed between those developing and not developing AKI for demography, renal parameters, frequency and quantity of paracentesis per session. Univariate and multivariate regression analyses were performed to determine the predictors of AKI. RESULTS Altogether, 177 patients underwent 859 therapeutic paracenteses. Ninety-four paracentesis sessions resulted in an AKI (10.9%). The median number of paracenteses was 10 (range 1-25) and the median volume of fluid drained per paracentesis was 6 l (1-20 l). In univariate analysis, younger age (p < 0.02), higher MELD (Model For End-Stage Liver Disease) score (p < 0.0001), CTP (Child-Turcotte-Pugh) class C (p < 0.017) and prior history of renal dysfunction (p < 0.0001) were significantly associated with AKI. For each liter of fluid drained, the risk of AKI increased by 1.24 times. Frequency of paracentesis did not influence the AKI. In multivariate logistic regression, the significant predictors of AKI were past renal dysfunction, a higher MELD and volume of fluid tapped at paracentesis. CONCLUSIONS Post-paracentesis AKI occurs in 10.9% of cases, despite adequate colloid replacement. For each 1 l of fluid drained during paracentesis, the risk of AKI increased by 1.24 times.
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Di Pascoli M, Fasolato S, Piano S, Bolognesi M, Angeli P. Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites. Liver Int 2019; 39:98-105. [PMID: 30230204 DOI: 10.1111/liv.13968] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 08/02/2018] [Accepted: 09/12/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND & AIMS In patients with cirrhosis, the clinical benefit of the treatment with human albumin for ascites is debated, and no data are available regarding refractory ascites. In this study, in patients with cirrhosis and refractory ascites, we assessed the effect of long-term albumin administration on emergent hospitalization and mortality. METHODS Seventy patients with cirrhosis and refractory ascites, followed at the Unit of Internal Medicine and Hepatology, University and General Hospital of Padova, Italy, were included into the study. Forty-five patients were non-randomly assigned to receive long-term administration of human albumin at the doses of 20 g twice per week (n = 45), in addition to standard medical of care (SOC), and compared to those followed according to SOC. Patients were followed up to the end of the study, liver transplantation or death. RESULTS The cumulative incidence of 24-month mortality was significantly lower in patients treated with albumin than in the group of patients treated with SOC (41.6% vs 65.5%; P = 0.032). The period free of emergent hospitalization was significantly longer in patients treated with long-term administration of albumin (P = 0.008). Analysing separately the causes of inpatient admission, patients treated with albumin showed a reduction in the incidence of overt hepatic encephalopathy, ascites, spontaneous bacterial peritonitis (SBP) and non-SBP infections. In addition, a non-significant trend towards a reduced probability of hepatorenal syndrome was observed. CONCLUSION In patients with cirrhosis and refractory ascites, long-term treatment with albumin improves survival and reduces the probability of emergent hospitalizations.
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Affiliation(s)
- Marco Di Pascoli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Silvano Fasolato
- 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
| | - 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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Abstract
Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes 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 paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
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Affiliation(s)
- Danielle Adebayo
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Shuet Fong Neong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
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KASL clinical practice guidelines for liver cirrhosis: Ascites and related complications. Clin Mol Hepatol 2018; 24:230-277. [PMID: 29991196 PMCID: PMC6166105 DOI: 10.3350/cmh.2018.1005] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 04/06/2018] [Indexed: 02/07/2023] Open
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Katsounas A, Canbay A. Intensive Care Therapy for Patients with Advanced Liver Diseases. Visc Med 2018; 34:283-289. [PMID: 30345286 DOI: 10.1159/000492088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Decompensated cirrhosis is characterized by high hospitalization rates and costs, frequent readmissions, and poor short-term survival. Patients admitted to the hospital with acute variceal bleeding and/or hepatic encephalopathy and/or renal dysfunction are at serious risk for developing infection and/or sepsis; in turn, this renders them highly susceptible to the development of multi-system organ failure. The lack of standardized intensive care unit management protocols in patients with cirrhosis along with only few data reports from longitudinal clinical trials makes it difficult for hepatologists and critical care specialists to provide uniform evidence for clinical practice that could safely consolidate favorable outcomes such as lower hospitalization rates and/or mortality. Based on a rigorous online search of the scientific literature as well as a longtime clinical experience of the authors in the field of hepatology and critical care medicine, this work represents a focused effort to elucidate the specific bio-morbidity of advanced liver diseases in relation to the aforementioned challenges in clinical management. Further meta-analyses and/or systematic reviews are needed to enable clinicians to develop more effective strategies to bridge patients with decompensated liver disease to recompensation or liver transplantation.
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Affiliation(s)
- Antonios Katsounas
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Ali Canbay
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1759] [Impact Index Per Article: 251.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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Fukui H, Kawaratani H, Kaji K, Takaya H, Yoshiji H. Management of refractory cirrhotic ascites: challenges and solutions. Hepat Med 2018; 10:55-71. [PMID: 30013405 PMCID: PMC6039068 DOI: 10.2147/hmer.s136578] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Among the various risky complications of liver cirrhosis, refractory ascites is associated with poor survival of cirrhotics and persistently worsens their quality of life (QOL). Major clinical guidelines worldwide define refractory ascites as ascites that cannot be managed by medical therapy either because of a lack of response to maximum doses of diuretics or because patients develop complications related to diuretic therapy that preclude the use of an effective dose of diuretics. Due to the difficulty in receiving a liver transplantation (LT), the ultimate solution for refractory ascites, most cirrhotic patients have selected the palliative therapy such as repeated serial paracentesis, transjugular intrahepatic portosystemic shunt, or peritoneovenous shunt to improve their QOL. During the past several decades, new interventions and methodologies, such as indwelling peritoneal catheter, peritoneal-urinary drainage, and cell-free and concentrated ascites reinfusion therapy, have been introduced. In addition, new medical treatments with vasoconstrictors or vasopressin V2 receptor antagonists have been proposed. Both the benefits and risks of these old and new modalities have been extensively studied in relation to the pathophysiological changes in ascites formation. Although the best solution for refractory ascites is to eliminate hepatic failure either by LT or by causal treatment, the selection of the best palliative therapy for individual patients is of utmost importance, aiming at achieving the longest possible, comfortable life. This review briefly summarizes the changing landscape of variable treatment modalities for cirrhotic patients with refractory ascites, aiming at clarifying their possibilities and limitations. Evolving issues with regard to the impact of gut-derived systemic and local infection on the clinical course of cirrhotic patients have paved the way for the development of a new gut microbiome-based therapeutics. Thus, it should be further investigated whether the early therapeutic approach to gut dysbiosis provides a better solution for the management of cirrhotic ascites.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan,
| | - Hideto Kawaratani
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan,
| | - Kosuke Kaji
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan,
| | - Hiroaki Takaya
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan,
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan,
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Ferrarese A, Tikhonoff V, Casiglia E, Angeli P, Fasolato S, Faggian D, Zanetto A, Germani G, Russo FP, Burra P, Senzolo M. Hemodynamic Evaluation of Nonselective β-Blockers in Patients with Cirrhosis and Refractory Ascites. Gastroenterol Res Pract 2018; 2018:4098210. [PMID: 29861720 PMCID: PMC5971311 DOI: 10.1155/2018/4098210] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 04/10/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Nonselective β-blockers (NSBB) have been associated with increased incidence of paracentesis-induced circulatory dysfunction (PICD) and reduced survival in patients with cirrhosis and refractory ascites. AIM To prospectively evaluate a hemodynamic response to NSBB in cirrhotics listed for liver transplantation with refractory ascites undergoing large volume paracentesis (LVP). METHODS Patients with cirrhosis and refractory ascites, with an indication to start NSBB in primary prophylaxis for variceal bleeding, were enrolled. During two consecutive LVP, while being, respectively, off and on NSBB, cardiac output (CO), systemic vascular resistances (SVR), peripheral vascular resistances (PVR), and plasma renin activity (PRA) were noninvasively assessed. RESULTS Seventeen patients were enrolled, and 10 completed the study. Before NSBB introduction, SVR (1896 to 1348 dyn·s·cm-5; p = 0.028) and PVR (47 to 30 mmHg·min·dl·ml-1; p = 0.04) significantly decreased after LVP, while CO showed an increasing trend (3.9 to 4.5 l/m; p = 0.06). After NSBB introduction, LVP was not associated with a significant increase in CO (3.4 to 3.8 l/m; p = 0.13) nor with a significant decrease in SVR (2002 versus 1798 dyn·s·cm-5; p = 0.1). Incidence of PICD was not increased after NSBB introduction. CONCLUSION The negative inotropic effect of NSBB was counterbalanced by a smaller decrease of vascular resistances after LVP, probably due to splanchnic β2-blockade. This pilot study showed that NSBB introduction may be void of detrimental hemodynamic effects after LVP in cirrhotics with refractory ascites.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | | | - Paolo Angeli
- Department of Medicine, Padua University Hospital, Padua, Italy
| | | | - Diego Faggian
- Laboratory Medicine, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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MacIntosh T. Emergency Management of Spontaneous Bacterial Peritonitis - A Clinical Review. Cureus 2018; 10:e2253. [PMID: 29721399 PMCID: PMC5929973 DOI: 10.7759/cureus.2253] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 02/16/2018] [Indexed: 12/11/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) has a high mortality rate; early antimicrobial therapy is essential for improving patient outcomes. Given that cirrhotic patients are often coagulopathic, the perceived risk of bleeding may prevent providers from performing a paracentesis and ruling out this potentially deadly disease. We examine the pathophysiology and risk factors for SBP, and current guidelines for its diagnosis and treatment. We then review the time-sensitive nature of performing a paracentesis, and the current controversies and contraindications for performing this procedure in patients at risk for SBP. Cirrhotic patients with ascites and clinical suspicion for SBP-abdominal pain or tenderness, fever or altered mental status-should have a diagnostic paracentesis. Although most patients with cirrhosis and liver dysfunction will have prolonged prothrombin time, paracentesis is not contraindicated. Limited data support platelet administration prior to paracentesis if <40,000-50,000/μL. Timely antimicrobial therapy includes a third-generation cephalosporin for community-acquired infection; nosocomial infections should be treated empirically with a carbapenem or with piperacillin-tazobactam, or based on local susceptibility testing. Patients with gastrointestinal (GI) hemorrhage should receive ceftriaxone prophylactically for GI hemorrhage. SBP has a high mortality rate. Early diagnosis and antimicrobial therapy are essential for improving patient outcomes. Cirrhotic patients with ascites with clinical suspicion for SBP, abdominal pain or tenderness, altered mental status or fever should have a diagnostic paracentesis performed prior to admission unless platelets <40,000-50,000/μL.
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Stirnimann G, Berg T, Spahr L, Zeuzem S, McPherson S, Lammert F, Storni F, Banz V, Babatz J, Vargas V, Geier A, Stallmach A, Engelmann C, Trepte C, Capel J, De Gottardi A. Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis. Aliment Pharmacol Ther 2017; 46:981-991. [PMID: 28940225 PMCID: PMC5698811 DOI: 10.1111/apt.14331] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 04/17/2017] [Accepted: 08/30/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427.
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Walayat S, Martin D, Patel J, Ahmed U, N Asghar M, Pai AU, Dhillon S. Role of albumin in cirrhosis: from a hospitalist's perspective. J Community Hosp Intern Med Perspect 2017. [PMID: 28634518 PMCID: PMC5463675 DOI: 10.1080/20009666.2017.1302704] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Albumin, a negatively charged globular protein encoded on chromosome 4, is one of the most abundant proteins in the plasma and accounts for approximately 75% of plasma oncotic pressure. The role of albumin in the management of various disease states has shown to be beneficial historically. Low serum albumin is a predictor of mortality and poor outcomes. In cirrhotics undergoing paracentesis, albumin infusion prevents rapid re-accumulation of ascitic fluid while simultaneously decreasing the risk of post-paracentesis related circulatory dysfunction. Additionally, albumin is utilized in patients with hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP). Overall, albumin appears to be an effective pharmacological agent in the management of cirrhosis and its complications.
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Affiliation(s)
- Saqib Walayat
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Daniel Martin
- Department of Gastroenterology and Hepatology, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Jaymon Patel
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Umair Ahmed
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Muhammad N Asghar
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA.,Department of Medicine, CMH Lahore Medical College, Lahore, Pakistan
| | - Aparna U Pai
- Department of Internal Medicine, Palos Community Hospital, Palos Heights, IL, USA
| | - Sonu Dhillon
- Department of Gastroenterology and Hepatology, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
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