Ascites without cirrhosis: finding differential diagnoses and treating correctly

Ascites is often equated with cirrhosis of the liver, but the causes can be much more diverse – ranging from malignant diseases and infections to rare syndromes.

Common causes of ascites

• In Western countries, cirrhosis of the liver is the main cause of ascites, accounting for around 85% of cases.
• The second most common cause is malignant diseases, accounting for around 7%, while heart failure and kidney disease account for only around 3%.
• It is estimated that more than 5% of ascites cases are due to two or more causes.
• In developing countries, cancer and tuberculosis are the main causes of ascites without cirrhosis.

Diagnostic ascites puncture is groundbreaking

The gold standard for etiological assessment is the analysis of ascites fluid. Diagnostic paracentesis should generally be performed for every new case of ascites. In addition to appearance, which can provide initial clues (cloudiness, milky or bloody appearance), albumin (serum-ascites albumin gradient, SAAG), total protein and cell count are among the most important markers for distinguishing between different causes of ascites.

Microbiology and cytology also play an important role in detecting infections or malignancies. Other parameters can also be determined if there is a specific suspicion (e.g. lipase or creatinine if the origin is in the pancreas or kidneys, cholesterol if malignant ascites is suspected).

Further examinations, such as imaging procedures, are also based on the initial clinical suspicion. Exploratory laparoscopy is considered the last resort for confirming the diagnosis.

Numerous diseases can be hidden behind the clinical findings of ascites. Even without cirrhosis, the origin may lie in the liver, as in Budd-Chiari syndrome, an obstruction of the hepatic veins, in which ascites occurs in over 80% of cases. It is treated by recanalisation through anticoagulation or invasive techniques and is therefore treated completely differently from ascites in the context of liver cirrhosis.

Important differential diagnoses for ascites: cancer and infections

Malignancies and infections are among the more common differential diagnoses. Malignant ascites is characterised by a low SAAG with a high concentration of total protein. In addition, there is an increase in cholesterol concentration to over 4.5 mmol/l. Primary cancers include ovarian, breast, colon, stomach and pancreatic cancer. New, promising approaches to intraperitoneal immunotherapy with antibodies or CAR-T cells are currently being evaluated.

One of the most important infectious causes of increased fluid accumulation in the peritoneal cavity is tuberculosis, which is particularly prevalent in developing countries. A total of 1–2% of all tuberculosis patients develop infectious ascites. An important diagnostic feature is a lymphocyte concentration of over 1000/mm3 in the ascites fluid.

The LDH/serum ratio is typically above 0.6 and the protein/serum protein ratio above 0.5. While interferon gamma release assays (IGRAs) are generally not recommended, PCR-based methods such as multiplex PCR are increasingly coming onto the market.

Rare causes of ascites

There are also other rare causes of ascites without cirrhosis that must be considered in diagnosis and treatment. These include gynaecological conditions such as ovarian cysts or endometriosis. Ruptures of the pancreatic duct, urinary tract or bladder are also possible, as are nephrotic syndrome and malnutrition. Rare diseases such as Gaucher's disease and Ormond's disease, as well as infections such as amoebiasis, Whipple's disease or brucellosis, are also possible causes.

The list goes on and shows that a thorough diagnosis is essential in cases of ascites in order to determine the cause. This, in turn, has a significant influence on the treatment, which can vary greatly depending on the etiology.