Document Type : Opinions, Commentaries
Authors
1 Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
2 Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.Founder of Egyptian Club of Ascites (ECA).
3 Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
4 Department of Hepatology, Gastroenterology and Infectious Diseases, Al-Azhar University, Egypt.
5 Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.
6 Department of Internal Medicine, Faculty of Medicine, Assuit University, Asuit, Egypt.
7 Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt.
8 Department of Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
9 Department of Medical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
10 Department of Gynecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
11 Department of Intervention Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
12 Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract
Highlights
Keywords
Main Subjects
INTRODUCTION
Ascites is defined as abnormal accumulation of fluid in the abdominal cavity [1]; Decompensated liver cirrhosis is the most common cause of ascites (around 80% of cases). Furthermore, ascites is the most common complication of cirrhosis as more than 50 % of patients with cirrhosis will develop ascites within 10 years after diagnosis [2]. The mechanism of ascites in cirrhosis is multifactorial due to severe sinusoidal portal hypertension and hepatic insufficiency, they lead to a circulatory dysfunction characterized by arterial splanchnic vasodilation, decreased effective blood volume, renal vasoconstriction with resulting sodium retention, and finally extracellular fluid retention [3].
The development of ascites is an independent predictor of severe impairment of QOL (emotional stress, disturbed social life, disturbed working) [4]. Moreover, cirrhotic ascites is associated with increased morbidities such as hyponatremia, hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP) and is linked with negative impact on survival (5-year survival 30%) [5].
Causes of ascites
In more than 80 % of cases of ascites, the underlying etiology is liver cirrhosis. The next common cause is cancer (10%), followed by heart failure (3%); tuberculosis (2%), dialysis and pancreatic disease (1%) in addition to other rare causes [6]. Myxedema and SLE rarely present with ascites, usually mild, need no special investigation or special treatment, and in both the clinical features of the disease predominates. Nephrotic syndrome: essentially a disease of children and needs no special workup. causes of ascites are shown in table 1
Evaluation of adults with ascites
Evaluation of adult patients presenting with ascites should include the following items:
- Clinical evaluation
- Imaging studies
- Laboratory studies
- Abdominal paracentesis and ascetic fluid examination
Clinical evaluation is an important initial step in evaluating patients presenting with a clinical picture suggestive of ascites. Skillful history taking & physical examination may help to reveal the possible underlying etiology of ascites. The onset of ascites is very important because the causes of rapidly developing ascites are quite different of those of a slowly developing one (TB, malignancy, HCC, hepatic venous outflow tract obstruction, BCS and SOS. Signs indicating liver diseases may include spider naevi, palmar erythema, and splenomegaly while the presence of peripheral edema, jugular venous congestion, third heart sound and pulmonary rales may indicate cardiac ascites. The presence of fever, lymphadenopathy should be noted for infections and malignancy. More than 1.5 (liter) ascites usually can be detected by abdominal examination [3].
Pelvi-abdominal Doppler ultrasound is the initial most cost-effective imaging modality in evaluating patients with ascites. It may provide information about the etiology of ascites, signs of portal hypertension (splenomegaly, portosystemic collaterals) and help in guidance of paracentesis. Complementary cross-sectional imaging (CT, MRI) may be needed in some cases [7].
Laboratory studies are usually nonspecific but base-line investigations should be conducted including blood picture to evaluate the presence of leukocytosis and thrombocytosis in cases of suspected systemic infection, while cytopenia may indicate hypersplenism and portal hypertension. Liver functions particularly serum albumin and prothrombin time evaluation is important in liver associated ascites. Urinary protein quantitation in addition to renal functions is important especially in cases of suspected nephrotic syndrome. Assessment of thyroid function is important in suspected myxedema ascites [8].Serum amylase and lipase may be evaluated in cases of suspected pancreatitis and many other investigations may be ordered according to the suspected diagnosis.
Abdominal paracentesis with ascetic fluid examination (physical & laboratory based) should be done in every case of ascites parallel to imaging studies. Ascitic fluid analysis should be done for cell count, total protein, albumin and cultures in all patients as well as other tests in selected cases. A serum to ascites albumin gradient (SAAG) ≥1.1 g/dl has 97% accuracy for diagnosis of ascites due to portal hypertension whether due to cirrhosis, BCS, SOS or PV thrombosis, <1.1= peritoneal disease which is TB or malignant infiltrations [9]. A neutrophil count (250/μl cut-off) should be obtained in each diagnostic tap, to diagnose SBP [10&11]. Ascitic fluid-based tests as well as additional tests are summarized in table 2.
Imaging studies
Abdominal ultrasound is the first line imaging to detect the presence of ascites and its quantity. Moreover, it may differentiate between some causes of ascites especially portal hypertensive and non-portal hypertensive etiologies. Abdominal CT may add value in detection of malignant ascites. While Doppler US may be helpful in detecting thrombosis and vascular liver diseases. But the abdominal US and CT may not be helpful in detecting peritoneal carcinomatosis.
Laparoscopy
Laparoscopy is considered a minimally invasive technique for examination of peritoneal cavity and allow biopsy from peritoneum, liver, and some intra-abdominal lymph nodes in most of cases of un-explained ascites [12].
METHODOLOGY
The Egyptian Club of Ascites (ECA) is an experienced multidisciplinary team, founded in 2016 by prof. Nadia Abdelaaty Abdelkader aiming to unifying the guidelines regarding diagnosis and management of ascites. This will be reflected on Excellency in management of patients with ascites and offering them the best medical care and better quality of life.
The ECA vision is divided into three integrated phases:
Phase 1: construction of imminent group of academics and clinicians concerned with the management of ascites. The multidisciplinary consensus group included participants with expertise in the areas of Hepato-gastroenterology and inviting experts from other specialties concerned with ascites. At this stage, the group is connecting continuously by different ways including meetings, phone calls, webinars, emails, etc. Problem solving and discussion of difficult cases of ascites of unknown cause allover Egypt are the aims at this stage. An algorithm fitting the national resources is developed for diagnosis of ascites, to be an aid for primary care providers and specialist dealing with ascites cases.
A literature search was performed to identify and revise studies on the diagnosis of ascites. Working subgroups were selected and repeated workshops were conducted. An initial diagnostic algorithm was designed by the working subgroups, one -day conference in April 2017 was held by the ECA to revise and modify this algorithm using the voting method. The algorithm was applied in different university hospitals, to test validity. Algorithm was progressively revised through separate voting/commenting iterations and finalized at the consensus meeting. A one-day consensus conference was held by the ECA in April 2018 and the algorithm was finalized and approved by the group. A statement was accepted if >75% of participants voted.
Phase 2: Building an electronic network involving all experts and physician all over the country and abroad and starting data registry of cases of ascites of different etiologies for purposes of research and clinical trials. The ECA is establishing the Egyptian Ascites Registry, as a national, prospectively recruited observational cohort study with clinical, biochemical, radiological information using the online platform RED Cap representing the basis for multiple collaborative projects.
Phase 3: International connections are in the plan collaborative clinical and research work with International Club of Ascites (ICA).
The Egyptian Club of Ascites (ECA) had designed an algorithmic diagnostic workup for the evaluation of adult patients presenting with ascites in ECA conference 2017. This suggested algorithmic approach was deeply investigated and discussed in ECA conference 2018. Lastly, ECA experts from all centers in Egypt met on 14th November 2019, to put a consensus for an algorithmic approach for the evaluation of patients with ascites “The Egyptian club of Ascites (ECA) opinion”.
The Experts put the statements that representing different aspects of ascites diagnosis and voted for each point of this statements, A. accepted strongly, B. accepted with reservation (needs modification), C. Undecided, D. non-accepted, E. non-accepted strongly. A statement is considered accepted without modifications if 75% or more experts accept strongly for it. These statements were classified as follows:
- Section 1: Clinical evaluation for ascites (3 statements)
- Section 2: Imaging studies (10 statements)
- Section 3: Laboratory studies (2 statements)
- Section 4: Abdominal paracentesis and ascetic fluid examination (4 statements)
- Section 5: Imaging (US\CT) or laparoscopy guided biopsies (1 statement)
Recommendation statements for ascites diagnosis in Egypt. (Table 3)
According to these statements, the algorithm was designed .
Table (1): Causes of ascites.
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Portal Hypertension: Liver cirrhosis Alcoholic hepatitis Hepatic congestion (Congestive cardiac failure, constrictive pericarditis, sinusoidal obstruction syndrome and Budchiari syndrome) Portal vein thrombosis Non-cirrhotic portal hypertension |
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Malignancy Hepatocellular carcinoma Peritoneal carcinomatosis Mesothelioma Metastatic liver disease Other intra-abdominal malignancy Pseudomyxoma peritoneii |
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Infections Tuberculous peritonitis Spontaneous bacterial peritonitis Secondary bacterial peritonitis Chlamydia |
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Miscellaneous Pancreatitis Nephrotic syndrome Lymphatic obstruction Urinary leakage Hypoalbuminemia Protein losing enteropathy Severe malnutrition Ovarian diseases Familial Mediterranean fever Vasculitis Hypothyroidism Eosinophilic ascites Granulomatous peritonitis |
Table (2): Initial ascetic fluid-based tests as well as additional tests.
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Initial tests (II-2;1) 5 |
Additional tests 6 |
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- Cell count with differentiation |
- Glucose conc (malignancy, bowel perf, inf.) |
|
- Total protein concentration |
- LDH (malignancy, bowel perf, malignancy) |
|
- Albumin concentration (and SAAG) |
- Gram stain |
|
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- Amylase concentration (Panc, bowel perforation) |
|
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- Cytological exam (?? CEA) |
|
- Triglycerides (chylous ascites) |
|
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- Bilirubin concentration(bowel or biliary perforation) |
|
|
- TB work-up |
Table (3): Recommendations for ascites diagnosis in Egypt.
|
Section 1: Clinical evaluation for ascites |
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Statement 1.1 Clinical evaluation is an important initial step in evaluating patients presenting with a clinical picture suggestive of ascites. |
|
Statement 1.2 Skillful history taking & physical examination may help to reveal the possible underlying etiology of ascites. |
|
Statement 1.3 At a volume of more than 1.5 (liter) ascites usually can be detected by physical examination |
|
Section 2: Imaging studies |
|
Statement 2.1 Pelvi-abdominal Doppler ultrasound with color Doppler is the initial most cost-effective imaging modality in evaluating patients with ascites |
|
Statement 2.2 Complementary cross-sectional imaging (CT, MRI) may be needed in some cases. |
|
Statement 2.3 Liver coarseness, the irregular border and attenuated hepatic viens of liver can be clearly seen in case of (cirrhotic) ascites. |
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Statement 2.4 Prominent hepatic veins ending into dilated IVC denoting hepatic venous congestion. |
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Statement 2.5 Attenuated or thrombosed hepatic veins with IVC web or thrombosis suggesting Budd Chiari syndrome. Portal veins thrombosis. |
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Statement 2.6 Bilateral swollen kidneys with prominent papillae suggesting acute renal insult or nephritic syndrome. |
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Statement 2.7 Heterogenous pancreas with peri pancreatic fluid collection or left pleural effusion suggesting pancreatic ascites. |
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Statement 2.8 Omental hetergeniety or masses suggesting omental malignancy, best seen in the left hypochondrial region, peritoneal masses (, adhesions or septations) suggesting deposits or TB. |
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Statement 2.9 Intra-abdominal or mesenteric lymphadenopathy suggesting metastasis, lymphoma, or TB. |
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Statement 2.10 Internal echoes or adhesions in the ascitic fluid suggesting local cause of ascites or spontaneous bacterial peritonitis in the presence of cirrhosis. |
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Section 3: Laboratory studies |
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Statement 3.1 Lab studies are usually nonspecific but base-line investigations should be conducted including CBC, Liver & renal profiles, Serum & Urine electrocytes (and) as well as assessment of thyroid function. |
|
Statement 3.2 Other specific laboratory investigations e.g. tumor markers may be ordered according to the suspected diagnosis. |
|
Section 4: Abdominal paracentesis and ascetic fluid examination |
|
Statement 4.1 Abdominal paracentesis with ascetic fluid examination (physical & lab- based) should be done parallel to imaging studies |
|
Statement 4.2 Initial tests for ascetic fluid as cell count, total protein and albumin should be done for all patients. |
|
Statement 4.3 Additional tests as (Glucose, LDH, Gram stain, Amylase, Cytological exam, CEA, Triglycerides, Bilirubin, TB work-up) may be needed in some cases |
|
Statement 4.4 A serum to ascites albumin gradient (SAAG) ≥1.1 g/dl has 97% accuracy for diagnosis of ascites due to portal hypertension |
|
Section 5: Imaging (US\CT) or laparoscopy guided biopsies |
|
Statement 5.1 Whenever, imaging and ascetic fluid-based tests fail to reveal the underlying etiology of ascites, either imaging or laparoscopy guided biopsies from any suspected intra-abdominal lesions is indicated. |
CONCLUSION
A consensus on the diagnostic workup of adult patients with ascites was developed by the ECA hoping that it would enable for a judicious use of investigational methods in this field. We just suggest an approach to diagnosis of ascites based on our expert opinions from different Egyptian universities according to availability, finance and effectiveness of different tools to reach the diagnosis in our centers. We have already used this algorithm in our university hospitals (Cairo, Ain Shams, Alazhar, Assuit, Minia , Zagazik, Benha,..) With great success. (ECA algorithm attached).
Ethical approval: not applicable
Consent for publication: not applicable
Funding: none
Availability of data: not applicable
Competing interests: none
Acknowledgement:
Authors acknowledge the help of Dr. Ahmad Fouad, Mohamad AboZaid, Ahmad Nagah, Zakaria Hamd Allah, Enas Soliman, Amr Alaa, Safia Ramadan, Ibrahim Abdul-Hakim, Mahmoud Farrag, Shaimaa Abdulrahman, Esraa Hassan, Aya Sami: members of Ascites Study Group (ASG) in Tropical Medicine department, Ain Shams University. Also, authors would like to thank all ECA members in different Egyptian universities.
Author’s contribution:
Mohammad A. Sakr and Nadia Abdelaaty Abdelkader prepared and drafted the article, suggested the concept and designed the algorithm. Other contributing authors revised the article for important intellectual content.
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