Transjugular intrahepatic portosystemic shunt for hepatorenal syndrome: A systematic review and meta-analysis

Abstract

Background

Hepatorenal syndrome is a severe complication of advanced liver diseases with a dismal prognosis.

Aims

This systematic review and meta-analysis aims to explore the efficacy and safety of transjugular intrahepatic portosystemic shunt for the treatment of hepatorenal syndrome.

Method

Publications were searched via PubMed and EMBASE databases. The pooled proportion and mean difference were calculated by using a random-effect model.

Results

Nine publications were included, in which 128 patients with hepatorenal syndrome were treated with transjugular intrahepatic portosystemic shunt. The pooled short-term and 1-year survival rates were 72% and 47% in type 1 hepatorenal syndrome and 86% and 64% in type 2 hepatorenal syndrome. No lethal procedure-related complications were observed. The pooled rate of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt was 49%. The pooled rate of renal function improvement after transjugular intrahepatic portosystemic shunt was 93% in type 1 hepatorenal syndrome and 83% in any type of hepatorenal syndrome. After transjugular intrahepatic portosystemic shunt, serum creatinine, blood urea nitrogen, serum sodium, sodium excretion, and urine volume were significantly improved; by comparison, serum bilirubin slightly increased, but the difference was not statistically significant.

Conclusion

Limited evidence suggested a potential survival benefit of transjugular intrahepatic portosystemic shunt in patients with hepatorenal syndrome but with a high incidence of hepatic encephalopathy.

Introduction

Hepatorenal syndrome (HRS) is a functional kidney injury developing in advanced liver diseases [1]. It is characterized by a reduced glomerular filtration rate (GFR) together with circulatory dysfunction in the absence of obvious organic kidney diseases, nephrotoxic drugs, and shock [[2], [3]]. There are 2 types of HRS. HRS-1 is a rapidly progressive acute renal failure that frequently develops in relationship with a precipitating factor, such as acute deterioration of hepatic function or infection [1]. It is characterized by a doubling of serum creatinine to greater than 2.5 mg/dl (221 μmol/l) in less than 2 weeks [3]. In contrary, HRS-2 is a more chronic form of HRS with a steady but moderate degree of functional renal failure, often occurring in patients with refractory ascites. The 3-month survival rate of cirrhotic patients with HRS is 15% [4]. The median survival time of HRS-1 and HRS-2 is about 2 weeks and 4–6 months, respectively.

Currently, liver transplantation is the best therapy for HRS [1]. However, the hepatic donor is often lacking, the cost is high, and many patients are being excluded due to age, comorbidity, or alcohol consumption. Vasoconstrictors combined with albumin are effective in the treatment of HRS. Several systematic reviews with meta-analyses showed the improvement or reversal of HRS by vasoconstrictors [[5], [6], [7], [8], [9]], but the survival benefit was mild or questionable [[10], [11]], and the relapse could not be prevented [9]. The role of transjugular intrahepatic portosystemic shunt (TIPS) for the management of HRS remains controversial. The shunt reduces portal hypertension and ameliorates circulatory dysfunction [12]. The main adverse effects comprise hepatic encephalopathy (HE) and worsening of liver function. In experienced hands, the intervention is safe with a technical mortality approaching zero [13]. The Italian liver community suggests TIPS for HRS-2 associated with refractory/recidivate ascites, but not in unselected patients with HRS-1 [14]. Similarly, the German guideline recommends TIPS as the first-line treatment in patients with refractory ascites with or without HRS [15]. The practice guideline of the European Association for the Study of the Liver Diseases states that TIPS may improve the renal function but data is insufficient to recommend TIPS for both HRS-1 and HRS-2 [1]. The practice guideline of the American Association for the Study of Liver Diseases recommends that TIPS is of investigatory use for the treatment of HRS and that further studies are required [16].

HRS-1 is a relatively rare disease. Only few studies on TIPS for HRS-1 including few patients are available [1]. In contrast, HRS-2 is rather common [1]. Most of patients with tense or refractory ascites may have HRS-2 [1]. As demonstrated previously and summarized recently, renal function improves after TIPS [17]. However, the primary endpoints of the majority of these studies were ascites and survival, but not reversal of HRS. Patients are not defined according to renal function and, therefore, the samples may be mixed up including patients with normal renal function, HRS-2, and even HRS-1. In addition, a false diagnosis of HRS is relatively common and a proper diagnosis may not be guaranteed in these studies [2]. This is why studies devoted to the treatment of refractory ascites are not sufficiently appropriate to assess the effect of TIPS on HRS.

The purpose of this systematic review and meta-analysis is to explore the efficacy and safety of TIPS for the treatment of HRS.