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  • Improving Treatment Outcomes in Hepatorenal Syndrome
    Individuals with advanced liver disease are at risk for severe complications. One of these potential issues is the often fatal hepatorenal syndrome. It is a condition that is becoming more common as the number of cases of advanced liver disease, including cirrhosis, continues to rise in US patients. The critical need of patients experiencing hepatorenal syndrome is to undergo liver transplantation, but with limited donor organs and long waiting lists, patients have severely reduced chances for survival. Pharmacological intervention prior to transplantation, therefore, has extreme importance. Recently, terlipressin became the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome.

    The reported incidence of hepatorenal syndrome is approximately 10 percent of individuals diagnosed with cirrhosis and ascites. Cases of advanced cirrhosis and ascites are where most hepatorenal syndrome occurs; however, other forms of liver disease can also result in the syndrome, including fulminant hepatic failure. The International Ascites Club, established to promote and support ongoing scientific research devoted to advanced cirrhosis, defined the commonly accepted criteria used to diagnose hepatorenal syndrome. They include:
    • Advanced liver failure with portal hypertension
    • High creatine levels
    • Renal failure not attributable to other causes (eg, bacterial infection)
    • Renal function that fails to improve after withdrawal of diuretics and expansion of plasma with albumin
    • Urinalysis indicates low protein levels, with no uropathy or parenchymal renal disease
    With hepatorenal syndrome, the kidneys do not acquire structural damage, but its effect of rapid reduction in kidney function becomes a life-threatening situation. Patients who need to be hospitalized due to rapidly progressing renal failure would be classified as having hepatorenal syndrome type 1. When the filtration performance of the system becomes so impaired that the results are edema between tissues and organs, oliguria, and azotemia, the patient’s expected survival time is often as low as two weeks. Hepatorenal syndrome type II has a slower progression. A distinct characteristic of this subtype is that it is diuretic resistant. Due to the dire timeline related to type 1, treatment and intervention for it are extremely important in order to extend patient survival. The new FDA approval for Terlivaz (terlipressin) is indicated for improvement of kidney function in adults with hepatorenal syndrome with a rapid reduction in kidney function. According to its prescribing information, terlipressin is thought to increase renal blood flow by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure. This effect works to correct circulatory dysfunction and intrarenal vasoconstriction, thereby lowering creatine levels and improving urinary function. When the malfunctions subside, kidney self-regulation can resume as normal. There are serious warnings associated with terlipressin, and a boxed warning is included on the label. The drug may cause serious or fatal respiratory failure. Patient oxygenation saturation must be assessed before initiation of the therapy, and monitoring for hypoxia must be performed throughout treatment.

    Research for using terlipressin is ongoing, and multiple abstracts for presentation have been rolling out in the two months since FDA approval of the drug, bringing discussion of the scope of related clinical and health outcomes to the forefront. Clinicians should all be aware of the severity of the complications of cirrhosis and be sure patients are intensively managed by specialists to assist with early diagnosis and implementing vital, life-extending/life-saving therapies. Stay informed about emergent drug information, including treatment options for hepatorenal syndrome, by updating or registering your profile to receive email alerts and other critical drug information updates from PDR. You can also stay current by using the official PDR app, mobilePDR, available for free from your favorite app stores.