Hepatorenal Syndrome and Novel Advances in its Management

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Abstract
Hepatorenal syndrome is a complication of end stage liver disease. It is a unique form of functional renal failure related to kidney vasoconstriction in the absence of underlying kidney pathology. Hepatorenal syndrome is classified into 2 types: type-1 HRS shows a rapid and progressive decline in renal function with a very poor prognosis (median survival of about 2 weeks); type-2 HRS has a more stable kidney failure, with a median survival of 6 months; its main clinical manifestation is refractory ascites. The most appropriate therapy for HRS is liver transplantation but only a minority of HRS patients undergo the procedure due to the high mortality; survival among liver transplant recipients is lower in HRS than among their counterparts without HRS. A large body of evidence, based on observational studies and randomized controlled trials, has been accumulated in the last decade showing that terlipressin represents a milestone in the management of HRS. According to our meta-analysis of randomized trials comparing terlipressin vs. placebo (five trials, n=243 patients), the pooled rate of patients who reversed HRS by terlipressin was 8.09 (95% CI, 3.52; 18.59) (P<0.001). Among vasoconstrictors, terlipressin (a V1 vasopressin agonist) is the most widely used; however, noradrenaline is another good choice. Vasoconstrictor drugs alone or with albumin reduce mortality compared with no intervention or albumin (RR of mortality, 0.82; 95% Confidence Intervals, 0.70; 0.96) (P<0.01). Two series of patients with HRS recurrence after the first treatment have recently shown that long-term therapy with terlipressin and albumin is beneficial as a bridge to liver transplant. Nevertheless, recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use and the recovery of renal function may also be partial in patients who are defined full responders. Renal replacement therapy should not be considered a first-line therapy for HRS Clinical trials are under way in order to assess efficacy and safety of novel therapeutic agents for the treatment of type-1 and type-2 HRS.

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