Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

Abstract

This is a comprehensive guidance on the diagnosis, evaluation, and management of ascites and hepatorenal syndrome (HRS) in patients with chronic liver disease from the American Association for the Study of Liver Diseases (AASLD). It replaces the prior AASLD guideline on the same topic published in 2012 (Table 1).(1) Because this guidance represents an update covering nearly a decade, numerous changes are made. Instead of enumerating the individual changes, the following list represents noticeable revisions: This AASLD Guidance provides a data-supported approach to the management of ascites and HRS. It differs from the AASLD Guidelines, which are supported by systematic reviews of the literature, formal rating of the quality of the evidence, and strength of the recommendations. In contrast, this Guidance was developed by consensus of an expert panel and provides guidance statements based on comprehensive review and analysis of the literature on the topics, with oversight provided by the AASLD Practice Guidelines Committee. The AASLD Practice Guidelines Committee chose to perform a Guidance on this topic because a sufficient number of randomized controlled trials were not available to support meaningful systematic reviews and meta-analyses. Hepatic decompensation, defined by ascites, hepatic encephalopathy, and portal hypertensive gastrointestinal bleeding, is an important landmark in the natural history of cirrhosis.(2) Ascites is commonly the first decompensation-defining event, with 5%-10% of patients with compensated cirrhosis developing ascites per year.(3) The development of ascites is associated with a reduction in 5-year survival from 80% to 30%,(4) which is due in part to patients with ascites being prone to additional complications, such as bacterial infections, electrolyte abnormalities, HRS, and nutritional imbalances, and, consequently, further clinical decline.(5) Patients with cirrhosis who develop clinically significant ascites and related complications should be considered for referral for liver transplantation (LT) evaluation and, when appropriate, palliative care.(6) HRS is a late complication of cirrhosis that accounted for 3.2% of all hospital discharges related to cirrhosis according to a 2012 study based on a large inpatient health care database of patients representative of community hospitals in the United States.(4) Moreover, the number of HRS discharges in the United States has increased significantly in the past 2 decades.(7) HRS was also associated with high inpatient mortality (~46%) as well as longer lengths of stay and higher costs of hospitalizations compared with cirrhosis discharges without HRS. Figure 1 summarizes the key steps in the pathogenesis of ascites and related complications discussed in this document. From the perspective of the management of ascites, pathogenetic events of importance are renal sodium retention, arterial underfilling, and portal hypertension, which may be mitigated by diuretics, albumin infusion, and portal decompressive procedures, respectively.(8, 9) More recently, the advent of vasopressin receptor antagonists provided further insights on the contribution of water retention in the pathogenesis of ascites.(10) Recent reviews provide more detailed discussion of the pathogenesis of ascites.(11-13) HRS is a functional renal failure resulting from hemodynamic changes occurring in patients with ascites and portal hypertension.(14) The primary pathophysiologic mechanism of HRS is reduced renal perfusion secondary to renal vasoconstriction mediated by increased activities of the sympathetic, renin-angiotensin-aldosterone, and vasopressin systems,(5) which may be further aggravated by decreased cardiac output in patients with cirrhosis-associated cardiomyopathy. In addition, systemic inflammation that is common among patients with decompensated cirrhosis may trigger immune-mediated renal injury.(15) Finally, emerging evidence suggests that renal autoregulation, a natural defense mechanism to maintain renal blood flow, is impaired in patients with cirrhosis, predisposing them to additional direct hemodynamic renal injury.(16) Together, structural kidney damage can follow severe and/or repeated episodes of such renal events.(17, 18) Although cirrhosis is the most common cause of ascites in the Western world, other potential causes should be considered, including malignancy, heart failure, tuberculosis, and pancreatic disease. The initial evaluation of ascites should include history, physical examination, abdominal doppler ultrasound, laboratory assessment of liver and renal function, serum and urine electrolytes, and a diagnostic paracentesis for analysis of the ascitic fluid (Fig. 2; Tables 2-4).(19, 20) In evaluating the etiology of ascites, the serum albumin ascites gradient is calculated by subtracting the ascitic fluid albumin from the serum albumin in simultaneously obtained samples.(21) A serum albumin ascites gradient ≥1.1 g/dL is highly suggestiv