New challenge of hepatorenal syndrome: Prevention and treatment

Abstract

Hepatorenal syndrome (HRS) remains one of the major therapeutic challenges in hepatology today. The pathogenesis is complex, but the final common pathway seems to be that sinusoidal portal hypertension, in the presence of severe hepatic decompensation, leads to splanchnic and systemic vasodilatation and decreased effective arterial blood volume. Renal vasoconstriction increases concomitantly, renal hemodynamics worsens, and renal failure occurs. Renal failure was shown 15 years ago to be potentially reversible after liver transplantation. This potential reversibility together with increased understanding of the pathogenesis has led to successful preliminary attempts to reverse HRS nonsurgically with combinations of splanchnic vasoconstrictors and colloid volume expansion, insertion of transjugular intrahepatic portovenous shunt radiologically, and improved forms of dialysis. Recent classification of HRS into the acute onset or severe type 1 with virtually 100% mortality and the more insiduous less severe type II promises to shed more light on the pathogenesis of HRS, especially on the currently unrecognized precipitating factors. It is hoped that this classification will be included in the necessary and carefully performed clinical trials, which should lead to clearer indications for the available therapies. The challenge now is to use all this information to improve our management of cirrhotic patients to prevent occurrence of HRS in the future. (HEPATOLOGY 2001;34:1242-1251.)Progressive oliguric renal failure is a common and severe complication in patients with advanced liver disease. In a large prospective follow-up study of cirrhotic patients with ascites, development of renal failure occurred in 18% and 39% of the patients at 1 year and at 5 years, respectively, with a median survival of 1.7 weeks or a 90% mortality at 10 weeks. 1 Hepatorenal syndrome (HRS) originally referred to occurrence of renal failure following biliary surgery. 2 The definitions of HRS gradually evolved to describe the renal failure observed in patients with liver failure associated with low urinary sodium levels and absence of renal pathology. 3 A recent consensus conference further defined HRS as types I and II with the following diagnostic criteria: type I HRS is characterized by rapidly progressive renal failure with a doubling of serum creatinine to a level greater than 2.5 mg/dL or a halving of the creatinine clearance to less than 20 mL/min in less than 2 weeks; type II HRS is a more chronic form with a slowly progressive increase in serum creatinine level to greater than 1.5 mg/dL or a creatinine clearance of less than 40 mL/min 4 and has a corresponding better prognosis. Until recently, liver transplantation was the only definitive treatment for HRS. 5,6 However, even then, the reported survival rates of these HRS patients posttransplantation have been less than in transplanted patients with normal renal function, and the return of renal function to normal may be delayed for months or years. 7,8 Furthermore, liver transplanta...

The use of vasoconstrictors in patients with cirrhosis: Type 1 HRS and beyond

“…16 HRS is a life-threatening complication of cirrhosis. [17][18][19][20][21][22][23] ; the spontaneous median survival time is less than 2 weeks and the probability of survival at 1 month is very low (25%). 17 Liver transplantation is the only treatment that can cure end-stage cirrhosis.…”

“…17 Liver transplantation is the only treatment that can cure end-stage cirrhosis. [18][19][20][21][22] However, patients who undergo transplantation with HRS have a lower probability of postoperative survival and a higher probability of developing postoperative complications than patients without HRS. 20,21 Therefore, measures that bridge patients to liver transplantation are needed.…”

The use of terlipressin in hepatorenal syndrome

“…Once renal vasoconstriction develops, intrarenal mechanisms likely contribute to the perpetuation of HRS, which may explain why HRS can follow a rapidly deteriorating course, even if there is reversal of the triggering event. 1,3,6 Diagnosis HRS is a functional disorder that has no pathognomonic fi ndings and is considered a diagnosis of exclusion. Therefore it is important to rule out all other potential causes of renal failure (i.e., prerenal azotemia, glomerulonephritis, acute tubular necrosis, drug-induced nephrotoxicity, etc.)…”

The natural history and management of hepatorenal disorders: from pre-ascites to hepatorenal syndrome

“…1 It is therefore important to understand the pathogenesis of the natural history of this complication of cirrhosis, and if possible prevent its development.…”