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Clinical and Experimental Medicine Mar 2024Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is... (Review)
Review
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
Topics: Humans; Ascites; Ammonia; Liver Cirrhosis; Albumins; Protein Isoforms
PubMed: 38551716
DOI: 10.1007/s10238-024-01315-1 -
Thrombosis and Haemostasis Mar 2022Development of ascites is the most common form of decompensation of cirrhosis. We aimed to investigate the coagulation system in ascitic fluid and plasma of patients...
Development of ascites is the most common form of decompensation of cirrhosis. We aimed to investigate the coagulation system in ascitic fluid and plasma of patients with cirrhosis. We determined coagulation parameters and performed clotting and fibrinolysis experiments in ascitic fluid and plasma of thoroughly characterized patients with cirrhosis and ascites ( = 25) and in plasma of patients with cirrhosis but without ascites ( = 25), matched for severity of portal hypertension. We also investigated plasma D-dimer levels in an independent cohort of patients ( = 317) with clinically significant portal hypertension (HVPG ≥ 10 mmHg), grouped according to ascites severity. Ascitic fluid was procoagulant in a clotting assay. The procoagulant potential of ascitic fluid was abolished by depletion of extracellular vesicles from ascitic fluid by filtration or by addition of a tissue factor-neutralizing antibody. Compared with plasma, extracellular vesicle-associated tissue factor activity was high in ascitic fluid, while activities of other coagulation factors were low. The extracellular vesicle-depleted fraction of ascitic fluid induced fibrinolysis, which was prevented by aprotinin, indicating the presence of plasmin in ascitic fluid. Plasma peak thrombin generation and parameters reflecting fibrinolysis were independently associated with the presence of ascites. Finally, plasma D-dimer levels were independently linked to ascites severity in our second cohort comprising 317 patients. In conclusion, coagulation and fibrinolysis become activated in ascites of patients with cirrhosis. While tissue factor-exposing extracellular vesicles in ascitic fluid seem unable to pass the peritoneal membrane, fibrinolytic enzymes get activated in ascitic fluid and may re-enter the systemic circulation and induce systemic fibrinolysis.
Topics: Ascites; Ascitic Fluid; Austria; Blood Coagulation Factors; Blood Coagulation Tests; Cohort Studies; Correlation of Data; Disease Progression; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Severity of Illness Index
PubMed: 34020489
DOI: 10.1055/a-1515-9529 -
World Journal of Gastroenterology Mar 2015Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. The development of ascites in patients with cirrhosis... (Review)
Review
Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. The development of ascites in patients with cirrhosis is multi-factorial. Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone (ADH). The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solute- free water. This leads to additional compensatory mechanisms including non-osmotic secretion of ADH, also known as arginine vasopressin, further worsening excess water retention and thereby hyponatremia. Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic marker both before and after liver transplant. The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious. In this review, we discuss the pathophysiology and various treatment modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with cirrhosis.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Ascites; Fluid Therapy; Humans; Hypertension, Portal; Hyponatremia; Liver Cirrhosis; Patient Selection; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Water-Electrolyte Balance
PubMed: 25805925
DOI: 10.3748/wjg.v21.i11.3197 -
Saudi Journal of Gastroenterology :... 2014Cirrhosis affects millions of people throughout the world. Two of the most serious complications of liver cirrhosis are ascites and spontaneous bacterial peritonitis... (Review)
Review
Cirrhosis affects millions of people throughout the world. Two of the most serious complications of liver cirrhosis are ascites and spontaneous bacterial peritonitis (SBP). The development of ascites is related to the severity of portal hypertension and is an indicator of increased mortality. Although sodium restriction and diuretic therapy have proven effective, some patients may not respond appropriately or develop adverse reactions to diuretic therapy. In such cases, interventions such as transjugular intrahepatic portosystemic shunt (TIPS) placement are warranted. SBP is a complication of ascites that confers a very high mortality rate. Recognition and prompt treatment of this condition is essential to prevent serious morbidity and mortality. Initiation of prophylaxis in SBP remains controversial. Given the burden of liver cirrhosis on the health care system, ascites and SBP will continue to provide challenges for the primary care provider, hospitalist, internist, and gastroenterologist alike.
Topics: Ascites; Bacterial Infections; Diagnostic Imaging; Diuretics; Humans; Liver Cirrhosis; Peritonitis; Portasystemic Shunt, Transjugular Intrahepatic; United States
PubMed: 25253362
DOI: 10.4103/1319-3767.141686 -
The Korean Journal of Gastroenterology... Feb 2024Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In... (Review)
Review
Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In most cases, hepatic hydrothorax is seen in patients with ascites. However, ascites is not always found at diagnosis and is not clinically detected in 20% of patients with hepatic hydrothorax. Some patients have no symptoms and incidental findings on radiologic examination lead to the diagnosis of the condition. In the majority of cases, the patients present with symptoms such as dyspnea at rest, cough, nausea, and pleuritic chest pain. The diagnosis of hepatic hydrothorax is based on clinical manifestations, radiological features, and thoracocentesis to exclude other etiologies such as infection (parapneumonic effusion, tuberculosis), malignancy (lymphoma, adenocarcinoma) and chylothorax. The management strategy involves a stepwise approach of one or more of the following: Reducing ascitic fluid production, preventing fluid transfer to the pleural space, fluid drainage from the pleural cavity, pleurodesis (obliteration of the pleural cavity), and liver transplantation. The complications of hepatic hydrothorax are associated with significant morbidity and mortality. The complication that causes the highest morbidity and mortality is spontaneous bacterial empyema (also called spontaneous bacterial pleuritis).
Topics: Humans; Hydrothorax; Ascites; Pleural Effusion; Liver Cirrhosis; Liver Transplantation
PubMed: 38389460
DOI: 10.4166/kjg.2023.107 -
BMC Cancer Mar 2022Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including...
BACKGROUND
Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute.
METHODS
We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute.
RESULTS
The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids.
CONCLUSIONS
The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.
Topics: Adult; Aged; Aged, 80 and over; Ascites; Cell- and Tissue-Based Therapy; Cell-Free System; Cross-Sectional Studies; Digestive System Neoplasms; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Retrospective Studies; Treatment Outcome
PubMed: 35287609
DOI: 10.1186/s12885-022-09298-6 -
Clinical Chemistry and Laboratory... Jun 2024Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous... (Review)
Review
Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.
Topics: Humans; Ascites; Ascitic Fluid; Algorithms; Diagnosis, Differential
PubMed: 38112289
DOI: 10.1515/cclm-2023-1112 -
World Journal of Gastroenterology Oct 2015Malignant ascites affects approximately 10% of patients with gastric cancer (GC), and poses significant difficulties for both patients and clinicians. In addition to the... (Review)
Review
Malignant ascites affects approximately 10% of patients with gastric cancer (GC), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in GC patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points (named "five-point method") on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, "Clinical Benefit Response in GC (CBR-GC)", was recently introduced to measure the efficacy of chemotherapy for malignant ascites of GC. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for GC patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a standard treatment based on the available guidelines, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), laparoscopic HIPEC alone, intravenous chemotherapy, intraperitoneal chemotherapy, and molecular targeting therapy. Although each treatment option is valid, further research is imperative to establish the optimal choice for each patient.
Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Cytoreduction Surgical Procedures; Diagnostic Imaging; Humans; Hyperthermia, Induced; Incidence; Molecular Targeted Therapy; Palliative Care; Predictive Value of Tests; Risk Factors; Stomach Neoplasms; Treatment Outcome
PubMed: 26494952
DOI: 10.3748/wjg.v21.i39.10936 -
BMC Gastroenterology Sep 2022Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those...
BACKGROUND
Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.
METHODS
241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.
RESULTS
Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.
CONCLUSIONS
Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
Topics: Ascites; Ascitic Fluid; Humans; Hypertension, Portal; Liver Neoplasms; Pancreatic Neoplasms; Peritoneal Neoplasms
PubMed: 36064324
DOI: 10.1186/s12876-022-02487-4 -
JAMA Network Open Jul 2023The potential association of low-volume paracentesis of less than 5 L with complications in patients with ascites remains unclear, and individuals with cirrhosis and...
IMPORTANCE
The potential association of low-volume paracentesis of less than 5 L with complications in patients with ascites remains unclear, and individuals with cirrhosis and refractory ascites (RA) treated with devices like Alfapump or tunneled-intraperitoneal catheters perform daily low-volume drainage without albumin substitution. Studies indicate marked differences regarding the daily drainage volume between patients; however, it is currently unknown if this alters the clinical course.
OBJECTIVE
To determine whether the incidence of complications, such as hyponatremia or acute kidney injury (AKI), is associated with the daily drainage volume in patients with devices.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study of patients with liver cirrhosis, RA, and a contraindication for a transjugular intrahepatic portosystemic shunt who received either device implantation or standard of care (SOC; ie, repeated large-volume paracentesis with albumin infusion), and were hospitalized between 2012 and 2020 were included. Data were analyzed from April to October 2022.
INTERVENTIONS
Daily ascites volume removed.
MAIN OUTCOMES AND MEASURES
The primary end points were 90-day incidence of hyponatremia and AKI. Propensity score matching was performed to match and compare patients with devices and higher or lower drainage volumes to those who received SOC.
RESULTS
Overall, 250 patients with RA receiving either device implantation (179 [72%] patients; 125 [70%] male; 54 [30%] female; mean [SD] age, 59 [11] years) or SOC (71 [28%] patients; 41 [67%] male; 20 [33%] female; mean [SD] age, 54 [8]) were included in this study. A cutoff of 1.5 L/d or more was identified to estimate hyponatremia and AKI in the included patients with devices. Drainage of 1.5 L/d or more was associated with hyponatremia and AKI, even after adjusting for various confounders (hazard ratio [HR], 2.17 [95% CI, 1.24-3.78]; P = .006; HR, 1.43 [95% CI, 1.01-2.16]; P = .04, respectively). Moreover, patients with taps of 1.5 L/d or more and less than 1.5 L/d were matched with patients receiving SOC. Those with taps of 1.5 L/d or more had a higher risk of hyponatremia and AKI compared with those receiving SOC (HR, 1.67 [95% CI, 1.06-2.68]; P = .02 and HR, 1.51 [95% CI, 1.04-2.18]; P = .03), while patients with drainage of less than 1.5 L/d did not show an increased rate of complications compared with those receiving SOC.
CONCLUSIONS AND RELEVANCE
In this cohort study, clinical complications in patients with RA performing low-volume drainage without albumin infusion were associated with the daily volume drained. Based on this analysis, physicians should be cautious in patients performing drainage of 1.5 L/d or more without albumin infusion.
Topics: Humans; Male; Female; Middle Aged; Paracentesis; Ascites; Cohort Studies; Retrospective Studies; Hyponatremia; Liver Cirrhosis; Albumins; Acute Kidney Injury
PubMed: 37410459
DOI: 10.1001/jamanetworkopen.2023.22048