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Kumar R, Marrapu S. Dietary salt in liver cirrhosis: With a pinch of salt! World J Hepatol 2023; 15:1084-1090. [PMID: 37970619 PMCID: PMC10642432 DOI: 10.4254/wjh.v15.i10.1084] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/21/2023] [Accepted: 10/08/2023] [Indexed: 10/24/2023] Open
Abstract
Patients with liver cirrhosis are advised to limit their sodium consumption to control excessive fluid accumulation. Salt is the most common form in which sodium is consumed daily. Consequently, various recommendations urge patients to limit salt intake. However, there is a lack of consistency regarding salt restriction across the guidelines. Moreover, there is conflicting evidence regarding the efficacy of salt restriction in the treatment of ascites. Numerous studies have shown that there is no difference in ascites control between patients with restriction of salt intake and those without restriction. Moreover, patients with cirrhosis may have several negative effects from consuming too little salt, although there are no recommendations on the lower limit of salt intake. Sodium is necessary to maintain the extracellular fluid volume; hence, excessive salt restriction can result in volume contraction, which could negatively impact kidney function in a cirrhotic patient. Salt restriction in cirrhotic patients can also compromise nutrient intake, which can have a negative impact on the overall outcome. There is insufficient evidence to recommend restricted salt intake for all patients with cirrhosis, including those with severe hyponatremia. The existing guidelines on salt restriction do not consider the salt sensitivity of patients; their nutritional state, volume status and sodium storage sites; and the risk of hypochloremia. This opinion article aims to critically analyze the existing literature with regard to salt recommendations for patients with liver cirrhosis and identify potential knowledge gaps that call for further research.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India.
| | - Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Kumar R, Kumar S, Prakash SS. Compensated liver cirrhosis: Natural course and disease-modifying strategies. World J Methodol 2023; 13:179-193. [PMID: 37771878 PMCID: PMC10523240 DOI: 10.5662/wjm.v13.i4.179] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/05/2023] [Accepted: 06/27/2023] [Indexed: 09/20/2023] Open
Abstract
Compensated liver cirrhosis (CLC) is defined as cirrhosis with one or more decompensating events, such as ascites, variceal haemorrhage, or hepatic encephalopathy. Patients with CLC are largely asymptomatic with preserved hepatic function. The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors. The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis, as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years. Furthermore, early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition. With the advent of effective non-invasive tools for detecting hepatic fibrosis, more and more patients with CLC are currently being recognised. This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or, at the very least, prevent its progression. There are numerous emerging approaches for preventing or delaying decompensation in CLC patients. A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression, and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension. Additionally, addressing various cofactors (such as obesity, diabetes, dyslipidaemia, and alcoholism) and precipitating factors (such as infection, viral hepatitis, and hepatotoxic drugs) that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC. However, high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these disease-modifying techniques for CLC patients. This article discussed the natural history of CLC, risk factors for its progression, and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sabbu Surya Prakash
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Dhaliwal A, Merhzad H, Karkhanis S, Tripathi D. Covered transjugular intrahepatic portosystemic stent-shunt vs large volume paracentesis in patients with cirrhosis: A real-world propensity score-matched study. World J Clin Cases 2022; 10:11313-11324. [PMID: 36387790 PMCID: PMC9649539 DOI: 10.12998/wjcc.v10.i31.11313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/05/2022] [Accepted: 09/20/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Refractory ascites has a 1-year survival rate of 50%. In selected patients, treatment options include liver transplantation (LT) or transjugular intrahepatic portosystemic stent shunt (TIPSS).
AIM To assess the outcomes of patients who underwent a TIPSS compared to large volume paracentesis (LVP).
METHODS Retrospective study of patients who underwent a covered TIPSS or LVP for refractory or recurrent ascites over 7 years. Primary outcome was transplant-free survival (TFS). Further analysis was done with propensity score matching (PSM).
RESULTS There were 150 patients [TIPSS group (n = 75), LVP group (n = 75)]. Seven patients in the TIPSS group underwent LT vs 22 patients in the LVP group. Overall median follow up, 20 (0.47-179.53) mo. In the whole cohort, there was no difference in TFS [hazard ratio (HR): 0.80, 95% confidence interval (CI): 0.54-1.21]; but lower de novo hepatic encephalopathy with LVP (HR: 95%CI: 0.20-0.96). These findings were confirmed following PSM analysis. On multivariate analysis albumin and hepatocellular carcinoma at baseline were associated with TFS.
CONCLUSION Covered TIPSS results in similar TFS compared to LVP in cirrhotic patients with advanced liver failure. Liver transplant assessment should be considered in all potential candidates for TIPSS. Further controlled studies are recommended to select appropriate patients for TIPSS.
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Affiliation(s)
- Amritpal Dhaliwal
- Department of Hepatology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, United Kingdom
- National Institute of Health and Care Research, Biomedical Research Centre Birmingham, University of Birmingham, Birmingham B15 2WB, United Kingdom
| | - Homoyoon Merhzad
- Department of Radiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, United Kingdom
| | - Salil Karkhanis
- Department of Radiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, United Kingdom
| | - Dhiraj Tripathi
- Department of Hepatology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, United Kingdom
- National Institute of Health and Care Research, Biomedical Research Centre Birmingham, University of Birmingham, Birmingham B15 2WB, United Kingdom
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Choudhury A, Kedarisetty CK, Vashishtha C, Saini D, Kumar S, Maiwall R, Sharma MK, Bhadoria AS, Kumar G, Joshi YK, Sarin SK. A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock. Liver Int 2017; 37:552-561. [PMID: 27633962 DOI: 10.1111/liv.13252] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 09/01/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND & AIMS The choice of vasopressor for treating cirrhosis with septic shock is unclear. While noradrenaline in general is the preferred vasopressor, terlipressin improves microcirculation in addition to vasopressor action in non-cirrhotics. We compared the efficacy and safety of noradrenaline and terlipressin in cirrhotics with septic shock. PATIENTS AND METHODS Cirrhotics with septic shock underwent open label randomization to receive either terlipressin (n=42) or noradrenaline (n=42) infusion at a titrated dose. The primary outcome was mean arterial pressure (MAP) >65 mm Hg at 48 h. RESULTS Baseline characteristics were comparable between the terlipressin and noradrenaline groups.SBP and pneumonia were major sources of sepsis. A higher proportion of patients on terlipressin were able to achieve MAP >65 mm of Hg (92.9% vs 69.1% P=.005) at 48 h. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin (33.3% vs 11.9%, P<.05). Terlipressin compared to noradrenaline prevented variceal bleed (0% vs 9.5%, P=.01) and improved survival at 48 h (95.2% vs 71.4%, P=.003). Percentage lactate clearance (LC) is an independent predictor of survival [P=.0001, HR=3.9 (95% CI: 1.85-8.22)] after achieving the target MAP.Therapy related adverse effect were comparable in both the arms (40.5% vs 21.4%, P=.06), mostly minor (GradeII-88%) and reversible. CONCLUSIONS Terlipressin is as effective as noradrenaline as a vasopressor in cirrhotics with septic shock and can serve as a useful drug. Terlipressin additionally provides early survival benefit and reduces the risk of variceal bleed. Lactate clearance is a better predictor of outcome even after achieving target MAP, suggesting the role of microcirculation in septic shock.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | | | - Deepak Saini
- Department of Critical care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sachin Kumar
- Department of Pulmonology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj K Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ajeet S Bhadoria
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Yogendra K Joshi
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Rifaximin and midodrine improve clinical outcome in refractory ascites including renal function, weight loss, and short-term survival. Eur J Gastroenterol Hepatol 2016; 28:1455-1461. [PMID: 27622998 DOI: 10.1097/meg.0000000000000743] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUNDS AND AIMS The occurrence of refractory ascites in nearly 17% of patients with decompensated cirrhosis is an unresolved issue. Advanced liver disease, functional renal impairment, and vascular insensitivity to vasopressors are the main causes of its refractoriness. Therefore, the aim of this study was to evaluate the impact on diuresis, weight loss, and short-term survival if midodrine and rifaximin were added to the diuretic therapy (DT). MATERIALS AND METHODS The study evaluated the eligibility of 650 patients with cirrhosis and refractory ascites who were selected during the period from November 2011 to May 2015. A total of 50 patients were excluded and finally 600 were selected and divided into the following groups: patients exposed to DT (n=200) as a control group, or DT with midodrine and rifaximin group (n=400). Body weight, mean arterial pressure, and glomerular filtration rate were determined. Plasma renin and aldosterone were also determined. Follow-up was performed after 2, 6, and 12 weeks, and then every 2 months for 24 months. RESULTS The mean arterial pressure was significantly higher in the midodrine and rifaximin group (P=0.000), and there was a highly significant weight loss after 12 weeks (12.5 kg) (P=0.000), a highly significant increase in serum sodium, urine output, and urinary sodium excretion (P=0.000), and creatinine clearance was more reduced in the control group. With rifaximin and midodrine, a complete response occurred in 310 (78%) patients, a partial response in 72 (18%), and no response in 18 (4%) versus 30 (15%), 110 (55%), and 60 (30%) in the control group, respectively (P=0.000). Midodrine and rifaximin significantly reduced paracentesis needs when compared with the controls (18 study patients vs. 75 DT-only patients, P=0.000). CONCLUSION Adding rifaximin and midodrine to DT enhanced diuresis in refractory ascites with improved systemic, renal hemodynamics and short-term survival.
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Update on new aspects of the renin-angiotensin system in liver disease: clinical implications and new therapeutic options. Clin Sci (Lond) 2012; 123:225-39. [PMID: 22548407 DOI: 10.1042/cs20120030] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The RAS (renin-angiotensin system) is now recognized as an important regulator of liver fibrosis and portal pressure. Liver injury stimulates the hepatic expression of components of the RAS, such as ACE (angiotensin-converting enzyme) and the AT(1) receptor [AngII (angiotensin II) type 1 receptor], which play an active role in promoting inflammation and deposition of extracellular matrix. In addition, the more recently recognized structural homologue of ACE, ACE2, is also up-regulated. ACE2 catalyses the conversion of AngII into Ang-(1-7) [angiotensin-(1-7)], and there is accumulating evidence that this 'alternative axis' of the RAS has anti-fibrotic, vasodilatory and anti-proliferative effects, thus counterbalancing the effects of AngII in the liver. The RAS is also emerging as an important contributor to the pathophysiology of portal hypertension in cirrhosis. Although the intrahepatic circulation in cirrhosis is hypercontractile in response to AngII, resulting in increased hepatic resistance, the splanchnic vasculature is hyporesponsive, promoting the development of the hyperdynamic circulation that characterizes portal hypertension. Both liver fibrosis and portal hypertension represent important therapeutic challenges for the clinician, and there is accumulating evidence that RAS blockade may be beneficial in these circumstances. The present review outlines new aspects of the RAS and explores its role in the pathogenesis and treatment of liver fibrosis and portal hypertension.
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Mpabanzi L, Deutz N, Hayes PC, Dejong CHC, Olde Damink SWM, Jalan R. Overnight glucose infusion suppresses renal ammoniagenesis and reduces hyperammonaemia induced by a simulated bleed in cirrhotic patients. Aliment Pharmacol Ther 2012; 35:921-8. [PMID: 22360430 DOI: 10.1111/j.1365-2036.2012.05044.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 12/23/2011] [Accepted: 02/02/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND A simulated upper gastrointestinal (UGI) bleed in cirrhotic patients has been shown to induce hyperammonaemia. The kidney was the site of this exaggerated ammoniagenesis with alanine as substrate. Administration of alanine to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but resulted in increased ammoniagenesis. We hypothesise that reduced hepatic glycogen stores result in hyperglucagonaemia which may drive increased renal gluconeogenesis and therefore alanine uptake and renal ammoniagenesis. AIM To determine whether an overnight glucose infusion lowers renal ammoniagenesis by reducing hyperglucagonaemia and renal ammoniagenesis. METHODS Patients with decompensated cirrhosis were studied in a cross-over design. An UGI bleed was simulated via intragastric administration of an amino acids mixture mimicking the haemoglobin molecule after a 12-h overnight fast (F-group) or after a 12-h treatment with 20% glucose solution (G-group). RESULTS Before the simulated bleed the glucagon levels were 21 (15-31) pmol/L in the F-group and 15 (9-21) pmol/L in the G-group (P < 0.01). After the simulated bleed, arterial ammonia levels increased in both groups [F-group: 73-118 μmol/L (P = 0.01); G-group 64-87 μmol/L (P = 0.01)]. The enhancement of hyperammonaemia was significantly higher in the F-group (45 [19-71] μmol/L) compared with the G-group (23 [13-39] μmol/L) (P = 0.01). The difference in renal ammoniagenesis during the simulated bleed in the F-group was 399 (260-655) nmol/kg/bwt/min and was significantly higher than in the G-group 313 (1-498) nmol/kg/bwt/min (P = 0.05). CONCLUSIONS Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates ammonia levels. These observations have implications for the development of nutritional strategies in hyperammonaemic patients.
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Affiliation(s)
- L Mpabanzi
- Department of Surgery, Maastricht University Medical Centre, NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands
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Tzamouranis D, Alexopoulou A, Dourakis SP, Stergiou GS. Sodium handling is associated with liver function impairment and renin-aldosterone axis activity in patients with preascitic cirrhosis without hyponatremia. Ann Gastroenterol 2012; 25:254-257. [PMID: 24713869 PMCID: PMC3959362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Accepted: 04/01/2012] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND In cirrhotic patients awaiting liver transplantation, serum sodium concentration is related to prognosis. However, abnormalities in sodium homeostasis are evident even in the early preascitic stage of cirrhosis. We aimed to investigate whether parameters of renal sodium handling (serum sodium, urinary sodium and fractional exertion of sodium (FeNa%) correlate with markers of liver function and renin-aldosterone axis activity in patients with preascitic cirrhosis without hyponatremia. METHODS Patients with preascitic cirrhosis without hyponatremia underwent routine blood and urine laboratory tests, including markers of liver function impairment and sodium homeostasis. RESULTS Thirty eight cirrhotic patients (22 men) with mean age of 57.3±12.2 (SD) years were included. Twenty six and twelve patients were at Child-Pugh stage A and B cirrhosis respectively. Eighteen patients had a Model for End-stage Liver Disease (MELD) score of ≤9 and twenty had MELD >9. Serum sodium was found to differ significantly between Child-Pugh stage A and B cirrhotics (mean 142.8±2.0 mmol/L vs. 140.5±3.3 mmol/L, p<0.05). Serum sodium was also found to differ significantly between patients with MELD score ≤9 and >9 (mean 143.3±2.0 mmol/L vs. 140.9±2.8 mmol/L, respectively, p<0.01). Serum sodium correlated negatively with the international normalized ratio (INR) (r=-0.51, p<0.01), aldosterone (r=-0.40, p<0.05), Child-Pugh and MELD scores (r=-0.34, p<0.05 and r=-0.45, p<0.05 respectively). FeNa% correlated negatively with renin and aldosterone (r=-0.56, p<0.001 and r=-0.50, p<0.01 respectively). CONCLUSION Serum sodium concentration is a good surrogate marker of liver function impairment not only in late-stage liver cirrhosis before transplantation but also in the early preascitic stage.
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Affiliation(s)
- Dimitris Tzamouranis
- Hypertension Center, 3rd University Department of Medicine, Sotiria Hospital, Athens, Greece (Dimitris Tzamouranis, George S. Stergiou)
| | - Alexandra Alexopoulou
- 2nd Department of Medicine, Medical School, University of Athens, Hippokration General Hospital, Athens, Greece (Alexandra Alexopoulou, Spyros P. Dourakis),
Correspondence to: Dr Alexandra Alexopoulou, 40 Konstantinoupoleos St, 16342 Hilioupolis, Athens, Greece, Tel: +30 210 7774742, Fax: +30 210 7706871, e-mail:
| | - Spyros P. Dourakis
- 2nd Department of Medicine, Medical School, University of Athens, Hippokration General Hospital, Athens, Greece (Alexandra Alexopoulou, Spyros P. Dourakis)
| | - George S. Stergiou
- Hypertension Center, 3rd University Department of Medicine, Sotiria Hospital, Athens, Greece (Dimitris Tzamouranis, George S. Stergiou)
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Seo YS, Shah VH. Pathophysiology of portal hypertension and its clinical links. J Clin Exp Hepatol 2011; 1:87-93. [PMID: 25755320 PMCID: PMC3940250 DOI: 10.1016/s0973-6883(11)60127-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Accepted: 07/27/2011] [Indexed: 02/08/2023] Open
Abstract
Portal hypertension is a major cause of morbidity and mortality in patients with liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic vasodilatation, and development of collateral circulation have been considered as major factors for the development of portal hypertension. Recently, sinusoidal remodeling and angiogenesis have been focused as potential etiologic factors and various researchers have tried to improve portal hypertension by modulating these new targets. This article reviews potential new treatments in the context of portal hypertension pathophysiology concepts.
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Key Words
- AT, angiotensin
- ET-1, endothelin-1
- HSC, hepatic stellate cell
- HVPG, hepatic venous pressure gradient
- NO, nitric oxide
- PDGF, platelet-derived growth factor
- PIGF, placenta! growth factor
- RAS, renin-angiotensin system
- RCT, randomized controlled trial
- VEGF, vascular endothelial growth factor
- angiogenesis
- eNOS, endothelial nitric oxide synthase
- pathophysiology
- portal hypertension
- sinusoids
- treatment
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Affiliation(s)
- Yeon Seok Seo
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN - 55905, USA
| | - Vijay H Shah
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN - 55905, USA,Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN - 55905, USA,Address for correspondence: Dr Vijay H Shah, Gastroenterology Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN - 55905, USA
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Stadlbauer V, Wright GAK, Banaji M, Mukhopadhya A, Mookerjee RP, Moore K, Jalan R, Moore K, Jalan R. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008; 134:111-9. [PMID: 18166350 DOI: 10.1053/j.gastro.2007.10.055] [Citation(s) in RCA: 135] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2007] [Accepted: 09/13/2007] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS It has been proposed that activation of the sympathetic nervous system causes a rightward shift in the renal autoregulatory curve such that renal blood flow is critically dependent on renal perfusion pressure and that this contributes to the development of the hepatorenal syndrome. The aims of the study were to determine the relationship of renal blood flow and renal perfusion pressure in patients with liver cirrhosis and the effect on renal hemodynamics following insertion of a transjugular intrahepatic portosystemic shunt (TIPS). METHODS Fifty-six patients were recruited into groups (1) with no ascites, (2) with diuretic-responsive ascites, (3) with intractable ascites, (4) with type II hepatorenal syndrome, and (5) requiring a TIPSs for refractory ascites. We measured cardiac hemodynamics, renal blood flow, renal perfusion pressure, and portal pressure and norepinephrine levels and mathematically modeled the renal autoregulatory curve. RESULTS Renal blood flow correlated with renal perfusion pressure (r(2) = 0.78; P < .001) and inversely with the hepatic venous pressure gradient (r(2) = 0.61; P < .0001) and plasma norepinephrine levels (r(2) = 0.78; P < .0001). Norepinephrine levels increased with increasing disease severity, and this was associated with a rightward and downward shift of the renal blood flow/renal perfusion pressure autoregulatory curve. TIPS insertion reduced portal pressure and plasma norepinephrine levels (P < .001), and the renal blood flow/renal perfusion pressure curve was shifted upward. CONCLUSIONS The relationship between renal blood flow and renal perfusion pressure involves a critical interplay between the sympathetic nervous system and the kidney. TIPS insertion decreases sympathetic activation and improves renal function through positive effects on renal blood flow autoregulation.
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Affiliation(s)
- Vanessa Stadlbauer
- Liver Failure Group, Institute of Hepatology, Division of Medicine, University College London, London, England
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Senzolo M, Cholongitas E, Tibballs J, Burroughs A, Patch D. Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome. Eur J Gastroenterol Hepatol 2006; 18:1143-50. [PMID: 17033432 DOI: 10.1097/01.meg.0000236872.85903.3f] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Ascites is the most common complication of liver cirrhosis and when it develops mortality is 50% at 5 years, apart from liver transplantation. Large volume paracentesis has been the only option for ascites refractory to medical treatment. The role of transjugular intrahepatic portosystemic shunt in the management of diuretic-resistant ascites has been evaluated in many cohort studies and five randomized trials up to now, clearly showing improvement in natriuresis and clinical efficacy. It, however, remains unclear how transjugular intrahepatic portosystemic shunt affects survival and quality of life, because hospital admissions owing to worsening encephalopathy may counterbalance the reduced need of paracentesis. What is clear is that the patient selection is critical. About 30% of patients with ascites develop hepatorenal syndrome at 5 years, leading to high mortality in its severe and progressive form. As its main pathogenetic factor is derangement of circulatory function owing to portal hypertension, these patients may benefit from transjugular intrahepatic portosystemic shunt, but this has been shown only in small series, in which mortality remains very high, owing to the underlying poor liver function.
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Affiliation(s)
- Marco Senzolo
- Liver Transplantation and Hepatobiliary Unit, Royal Free & University College Medical School, London, UK
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Affiliation(s)
- K P Moore
- The UCL Institute of Hepatology, Royal Free and University College Medical School, UCL, Rowland Hill St, London NW3 2PF, UK.
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Berzigotti A, Casadei A, Magalotti D, Castaldini N, Losinno F, Rossi C, Zoli M. Renovascular Impedance Correlates with Portal Pressure in Patients with Liver Cirrhosis. Radiology 2006; 240:581-6. [PMID: 16801365 DOI: 10.1148/radiol.2401050585] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE To prospectively evaluate, in patients with liver cirrhosis, the correlation between the renovascular impedance measured by using color flow and pulsed wave Doppler ultrasonography (US) and the portal pressure measured by using the hepatic venous pressure gradient (HVPG). MATERIALS AND METHODS The study was approved by the senior staff committee (comparable to institutional review board) of the university hospital, and written informed consent was obtained from all patients. Thirty-one patients with cirrhosis (22 men, nine women; mean age, 57.6 years +/- 8.8 [standard deviation]) and esophageal varices were consecutively enrolled in the study. Having fasted, the patients underwent color flow and pulsed wave Doppler US of the right interlobar renal artery (RRA) and the left interlobar renal artery (LRA). The resistance index (RI) and pulsatility index (PI) were determined. On the same day, with fluoroscopic guidance, a 5-F balloon-tipped catheter was advanced, via the right basilic vein, into the right hepatic vein; HVPG was calculated as the difference between the wedged and free hepatic pressures. All measurements were performed in triplicate, and permanent tracings were recorded. Correlations were made by using the Pearson test. The positive predictive value of renovascular impedance for detection of severe portal hypertension was determined. RESULTS Mean RI and PI values were 0.67 +/- 0.07 and 1.21 +/- 0.25, respectively, for the RRA, and 0.68 +/- 0.07 and 1.24 +/- 0.26, respectively, for the LRA. All patients had portal hypertension (mean HVPG, 19.3 mm Hg +/- 4.7; range, 11.5-33.5 mm Hg). Neither portal pressure nor renal impedance correlated with Child-Pugh score for cirrhosis. Renal artery impedance indexes correlated with the HVPG (for RRA RI: R = 0.424, P = .03; for RRA PI: R = 0.402, P = .04; for LRA RI: R = 0.352, P = .05; for LRA PI: R = 0.393, P = .02). A higher-than-normal renal impedance had a high positive predictive value (RRA RI and PI, 100%; LRA RI, 92%; LRA PI, 84%) for the detection of severe portal hypertension. CONCLUSION Renovascular impedance had a direct correlation with HVPG.
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Affiliation(s)
- Annalisa Berzigotti
- Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Università di Bologna, Policlinico S. Orsola-Malpighi, via Albertoni 15-40138 Bologna, Italy
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Møller S, Bendtsen F, Henriksen JH. Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume. Scand J Gastroenterol 2006; 41:451-8. [PMID: 16635914 DOI: 10.1080/00365520500292962] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants of the RAAS, including the CBV. Circulating plasma renin concentrations were measured using an immunoradiometric assay. RESULTS Arterial renin concentrations were significantly higher in the patients than in the controls (p < 0.003). Plasma renin correlated significantly with several indicators of liver dysfunction and splanchnic and systemic haemodynamics (r = - 0.56-0.55), but only weakly with CBV (r = - 0.25, p < 0.02). In a multivariate regression analysis, plasma renin was determined by serum sodium, alkaline phosphatases and systolic blood pressure (p < 0.04 to p < 0.001). CONCLUSIONS CBV correlates weakly with circulating renin, and activation of the RAAS can therefore only partly be considered as an indicator of central hypovolaemia. Mechanisms other than central hypovolaemia relating to the liver disease and portal hypertension contribute significantly to the RAAS activation.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology, University of Copenhagen, Denmark.
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Xu XB, Cai JX, Leng XS, Dong JH, Zhu JY, He ZP, Wang FS, Peng JR, Han BL, Du RY. Clinical analysis of surgical treatment of portal hypertension. World J Gastroenterol 2005; 11:4552-9. [PMID: 16052687 PMCID: PMC4398707 DOI: 10.3748/wjg.v11.i29.4552] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the experience in surgery for 508 patients with portal hypertension and to explore the selection of reasonable operation under different conditions.
METHODS: The data of 508 patients with portal hypertension treated surgically in 1991-2001 in our centers were analyzed. Of the 508 patients, 256 were treated with portaazygous devascularization (PAD), 167 with portasystemic shunt (PSS), 62 with selective shunt (SS), 11 with combined portasystemic shunt and portaazygous devascularization (PSS+PAD), 9 with liver transplantation (LT), 3 with union operation for hepatic carcinoma and portal hypertension (HCC+PH).
RESULTS: In the 167 patients treated with PSS, free portal pressure (FPP) was significantly higher in the patients with a longer diameter of the anastomotic stoma than in those with a shorter diameter before the operation (P<0.01). After the operation, FPP in the former patients markedly decreased compared to the latter ones (P<0.01). The incidence rate of hemorrhage in patients treated with PAD, PSS, SS, PSS+PAD, and HCC+PH was 21.09% (54/256), 13.77 (23/167), 11.29 (7/62), 36.36% (4/11), and 100% (3/3), respectively. The incidence rate of hepatic encephalopathy was 3.91% (10/256), 9.58% (16/167), 4.84% (3/62), 9.09% (1/11), and 100% (3/3), respectively while the operative mortality was 5.49% (15/256), 4.22% (7/167), 4.84% (3/62), 9.09% (1/11), and 66.67% (2/3) respectively. The operative mortality of liver transplantation was 22.22% (2/9).
CONCLUSION: Five kinds of operation in surgical treatment of portal hypertension have their advantages and disadvantages. Therefore, the selection of operation should be based on the actual needs of the patients.
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Affiliation(s)
- Xin-Bao Xu
- Department of Hepatobiliary Surgery, People's Hospital, Peking University, Beijing 100044, China.
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Møller S, Henriksen JH. Review article: pathogenesis and pathophysiology of hepatorenal syndrome--is there scope for prevention? Aliment Pharmacol Ther 2004; 20 Suppl 3:31-41; discussion 42-3. [PMID: 15335398 DOI: 10.1111/j.1365-2036.2004.02112.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research into the pathophysiology of ascites and HRS has stimulated new enthusiasm in their prevention and treatment. Patients with HRS have hyperdynamic circulatory dysfunction with reduced arterial blood pressure and reduced central blood volume, owing to preferential splanchnic arterial vasodilatation. Activation of potent vasoconstricting systems, including the sympathetic nervous and renin-angiotensin-aldosterone systems, counteracts the arterial vasodilatation and leads to a pronounced renal vasoconstriction with renal hypoperfusion, a reduced glomerular filtration rate, and intense sodium-water retention. Thus prevention of HRS should seek to improve liver function, limit arterial hypotension and central hypovolaemia, and reduce renal vasoconstriction and the renal and interstitial pressures. Portal pressure can be reduced with beta-adrenergic blockers and transjugular intrahepatic portosystemic shunt (TIPS). Precipitating events, like infections, bleeding, and postparacentesis circulatory syndrome, should be treated to avoid further circulatory failure. Improvement in arterial blood pressure and central hypovolaemia can be achieved with vasoconstrictors, such as terlipressin (Glypressin), and plasma expanders such as human albumin. In the future endothelins, adenosine antagonists, long-acting vasoconstrictors, and antileukotriene drugs may play a role in preventing and treating HRS.
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Affiliation(s)
- S Møller
- Department of Clinical Physiology, Hvidovre Hospital, University of Copenhagen, Denmark.
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Jalan R, Kapoor D. Enhanced renal ammonia excretion following volume expansion in patients with well compensated cirrhosis of the liver. Gut 2003; 52:1041-5. [PMID: 12801964 PMCID: PMC1773725 DOI: 10.1136/gut.52.7.1041] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS In patients with cirrhosis, hepatic encephalopathy is often precipitated by dehydration. This study tests the hypothesis that volume expansion in cirrhotic patients increases renal ammonia excretion. PATIENTS AND METHODS Sixteen well compensated cirrhotic patients (mean Pugh score 6.7 (SEM 0.4)) were studied after an overnight fast. One litre of 0.9% saline was administered to patients intravenously over one hour. Plasma and urinary ammonia and sodium, renal plasma flow (RPF), glomerular filtration rate (GFR), plasma renin activity (PRA), and angiotensin II (ANG II) were measured before, during, and two hours after saline infusion. RESULTS Saline infusion resulted in a significant reduction in plasma ammonia (93 (SEM 7) to 56 (4) micromol/l; p<0.05) and RPF and GFR increased (p<0.05). Urinary ammonia excretion increased (p<0.05) significantly. There was a significant reduction in ANG II and PRA (p<0.05 for each) and the change in ammonia excretion correlated directly with the change in urinary sodium excretion (p<0.007), ANG II (p<0.002), and PRA (p<0.01). The mean increase in urinary ammonia excretion during the observation period was 1.08 mmol. Assuming a volume of distribution of 45 litres, the corresponding change in whole body ammonia during the same period was 1.67 mmol. CONCLUSION The results of this study suggest that volume expansion reduces plasma ammonia concentration by increasing ammonia excretion and reducing ammoniagenesis.
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Affiliation(s)
- R Jalan
- Liver Failure Group, Institute of Hepatology, University College London Medical School, 69-75 Chenies Mews, London, UK.
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Fukui H. Does angiotensin II type 1 receptor blockade offer a clinical advantage to cirrhotics with ascites? J Gastroenterol 2002; 37:235-7. [PMID: 11931541 DOI: 10.1007/s005350200029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Wong F, Liu P, Blendis L. The mechanism of improved sodium homeostasis of low-dose losartan in preascitic cirrhosis. Hepatology 2002; 35:1449-58. [PMID: 12029630 DOI: 10.1053/jhep.2002.33637] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Renal sodium retention on standing is one aspect of the abnormal renal sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal sodium retention on high, 200-mmol sodium/d diet in these patients and restore them to sodium balance. Therefore, the effect of 7.5 mg of losartan on sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 age- and sex-matched controls on the same sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to sodium balance. In addition, it blunted the fall in erect posture- induced renal sodium excretion by a reduction in proximal and distal tubular reabsorption of sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered sodium load compared with controls, and despite activation of the systemic renin-angiotensin-aldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture - induced sodium retention in preascitic cirrhosis supports the suggestion that the pathophysiology of sodium retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture.
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Affiliation(s)
- Florence Wong
- Department of Medicine, Divisions of Gastroenterology and Cardiology, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
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Schepke M, Werner E, Biecker E, Schiedermaier P, Heller J, Neef M, Stoffel-Wagner B, Hofer U, Caselmann WH, Sauerbruch T. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology 2001; 121:389-95. [PMID: 11487548 DOI: 10.1053/gast.2001.26295] [Citation(s) in RCA: 104] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension. This randomized, placebo-controlled, double-blind study aimed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis. METHODS Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week. Systemic hemodynamics, kidney and liver function parameters were recorded regularly; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7. RESULTS Irbesartan reduced the hepatic venous pressure gradient by 12.2% +/- 6.6% (P < 0.05) and mean arterial pressure by 5.3% +/- 4.0% in 13 of 18 verum patients. In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan. In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan. Four of five patients with baseline renin >900 microU/mL developed treatment-limiting hypotension. CONCLUSIONS The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure.
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Affiliation(s)
- M Schepke
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany.
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Abstract
Advances in the understanding of the pathophysiology of sodium retention and ascites formation in cirrhosis has helped improve the treatment of ascites in these patients. It is likely that further unraveling of these pathophysiologic changes will lead to the development of novel and better treatment options. For example, the development of aquaretic agents for the management of hyponatremia in cirrhosis may allow more effective use of diuretic therapy. The ultimate challenge is to use the understanding of the pathophysiology to develop new strategies to prevent the development of ascites in cirrhosis.
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Affiliation(s)
- F Wong
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University of Toronto, Ontario, Canada.
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Abstract
It is important to diagnose portal hypertension owing to its devastating complications. Clinicians need to be able to recognize physical signs and symptoms associated with portal hypertensive states. When in doubt, appropriate diagnostic measures need to be performed and a definite diagnosis made. Hepatic venous pressure gradient (HVPG) is often used as a surrogate measurement of portal pressure. HVPG can be obtained safely and conveniently on an outpatient basis. It can also be used to assess efficacy of various treatment modalities. Knowledge of pathophysiology of portal hypertension has provided the basis for further trials in both novel treatment modalities and diagnostic methods.
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Affiliation(s)
- S Wongcharatrawee
- Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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