Original Contribution
Hepatic Filling Rate of a Microbubble Agent: A Novel Predictor of Long-Term Outcomes in Patients With Cirrhosis

https://doi.org/10.1016/j.ultrasmedbio.2014.04.014Get rights and content

Abstract

The aim of the study described here was to evaluate the significance of the hepatic filling rate of a perflubutane microbubble agent in predicting long-term outcomes and prognoses in 32 patients with cirrhosis (37–76 y, 20 females, Child–Pugh A16, B16). The time from delivery of the contrast agent to the hepatic artery to maximum enhancement of the liver parenchyma on the sonogram was defined as the hepatic filling rate (mean = 18.6 s). Hepatic filling rate did not correlate significantly with the Child–Pugh score or the model for end-stage liver disease score. However, the survival rate was lower (93.3% at 1 y, 60.2% at 3 y) and the rate of occurrence of hepatocellular carcinoma (HCC) was higher (13.3% at 1 y, 33.3% at 3 y) in the group with the slow filling rate (≥18 s) than in the group with the rapid filling rate (<18 s) (93.3% at 1 and 3 y for survival, 6.3% at 1 and 3 y for HCC occurrence). Hepatic filling rate may constitute a non-invasive marker for the occurrence of HCC and prognosis of cirrhosis.

Introduction

Cirrhosis is the end stage of all chronic liver diseases. Several clinical presentations caused by decompensation, such as variceal bleeding, ascites and hepatic encephalopathy, influence quality of life, as well as prognosis (Williams 2006). Furthermore, the risk of development of hepatocellular carcinoma (HCC) is serious because of its impact on long-term survival (Bruix and Sherman, 2011, Nissen and Martin, 2002). Unfortunately, at present, transplantation may be only the curative treatment for cirrhosis, and practical management requires prediction of the prognosis.

A previous study indicated that the presence or degree of portal hypertension is a significant factor determining the survival of patients with cirrhosis (Tandon and Garcia-Tsao 2006). Evaluation of blood flow in the liver may enable estimation of the potential liver function reserve. Because of its non-invasiveness, reliability and potential for real-time observation, currently, contrast-enhanced ultrasound (US) is one of the most popular imaging tools (Cosgrove, 2006, Quaia, 2007). Microbubble contrast agents were originally introduced to enhance the detection and characterization of focal hepatic lesions by US (Quaia, 2011, Rettenbacher, 2007). Thereafter, the applications broadened; many studies have reported the value of contrast-enhanced US in treatment support and evaluation of therapeutic responses (Guibal et al. 2013), and recent studies have reported the effectiveness of the technique in non-tumor liver disease, as in the grading of hepatic fibrosis and characterization of diffuse liver diseases (Lim et al., 2006, Maruyama et al., 2009, Staub et al., 2009). Analysis of the dynamic behavior of microbubbles may have further potential for providing detailed information in chronic liver disease.

On this basis, we designed a study to determine whether the dynamic behavior of microbubbles in the liver might help to estimate the potential liver function of patients with cirrhosis. We propose a novel contrast parameter—the hepatic filling rate of a microbubble agent—to express the overall hemodynamic condition of the liver, including the hepatic artery and portal vein. The aim of this study was to determine the value of the hepatic filling rate in predicting the long-term outcome and prognosis of patients with cirrhosis.

Section snippets

Study design

The study described here is a subgroup analysis using data collected in a prospective study of the relationship between grade of hepatic fibrosis and contrast-enhanced US findings, conducted with the approval of the institutional review board of our hospital (Ishibashi et al. 2010). Written informed consent was obtained from all patients, and the investigation was carried out in accordance with the Helsinki Declaration. This study was determined by the ethics committee of this hospital to have

Patients

This study comprised 32 patients with cirrhosis (age range, 37–76 y; mean ± SD, 61.4 ± 10.7; 12 males, 20 females). Cirrhosis was diagnosed on the basis of pathologic findings on needle biopsy in 29 patients (24 percutaneous, 5 transjugular) and resected specimens obtained during liver transplantation in 3 patients. There were 11 patients with compensated cirrhosis and 21 patients with decompensated cirrhosis, and 16 patients with Child-Pugh grade A and 16 with grade B (Table 1).

The reasons for

Discussion

Non-invasive predictors of long-term outcomes in cirrhosis are clinically informative in the practical management of patients. This study proposes a novel parameter based on time-related changes in microbubble behavior on contrast-enhanced US. The time points were determined to assess comprehensively the effect of hepatic inflow, that is, from delivery of the contrast agent to the hepatic artery as the start and maximum parenchymal enhancement as the end. The advantage of this starting point

Conclusions

This study indicates that the dynamic behavior of microbubbles in the liver can be used to grade the potential severity of cirrhosis. This contrast parameter may constitute a novel, non-invasive marker for the risk of HCC occurrence and the prognosis of patients with cirrhosis, independent of existing well-known parameters such as the Child–Pugh and MELD scores.

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Conflicts of Interest: The authors have indicated that they have no conflicts of interest regarding the content of this article.

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