Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic Therapy

Hepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.