Measuring Intrahepatic Vascular Changes Using Contrast-Enhanced Ultrasonography to Predict the Prognosis of Alcoholic Hepatitis Combined with Cirrhosis: A Prospective Pilot Study

Abstract

Background/aims: Acute hepatic dysfunction combined with alcoholic hepatitis (AH) in alcoholic cirrhosis is related to hepatic hypo-perfusion secondary to intrahepatic necroinflammation, neoangiogenesis, and shunt. The hepatic vein arrival time (HVAT) assessed by microbubble contrast-enhanced ultrasonography (CEUS) is closely correlated with the severity of intrahepatic changes. We investigated the usefulness of HVAT to predict short-term mortality of AH in cirrhosis.

Methods: Thirty-nine patients with alcoholic cirrhosis (27 males) and AH were prospectively enrolled. HVAT study was performed within 3 days after admission using ultrasonic contrast (SonoVue^®). The primary outcome was 12-week mortality.

Results: Twelve-week mortality developed in nine patients. HVAT was significantly different between the mortality and survival groups (9.3±2.0 seconds vs 12.6±3.5 seconds, p=0.002). The odds ratio of a shortened HVAT for 12-week mortality was 1.481 (95% confidence interval, 1.050-2.090; p=0.025). The area under the receiver operating characteristic curve of HVAT for 12-week mortality was 0.787 (p=0.010). The combination of MDF and HVAT ≥11.0 seconds resulted in an 87.5% survival rate even if the MDF score ≥32; however, HVAT ＜11.0 seconds was related with mortality despite a MDF score＜32.

Conclusions: HVAT using microbubble CEUS could be a useful additional index to predict short-term mortality in patients with AH and cirrhosis.

Keywords: Hepatic veins; Hepatitis, alcoholic; Liver cirrhosis, alcoholic; Ultrasonography, contrast-enhanced.

Fig. 1

Study design and flow chart HVAT, hepatic vein arrival time.

Fig. 2

Hepatic vein arrival time (HVAT) measurement using microbubble contrast enhanced ultrasonography (CEUS). (A) Detection of hepatic vein (HV) enhancement. After contrast injection at 10 seconds of lead time, HV enhancement with microbubble contrast agent was detected (white circle is region of interest [ROI] to measure time intensity curves [TICs]). (B) TICs for HV enhancement intensity were drawn and HVAT was calculated as the time (in seconds) from injection to a sustained signal increase in the TIC to over 10% above baseline intensity point (the 10-second lead time [black arrow] should be subtracted from the measured time point [e.g., 17.5–10.0 seconds=7.5 seconds]).

Fig. 3

The additional benefit of using hepatic vein arrival time (HVAT) to make a prognosis based on a Maddrey’s Discriminant Function (MDF) score. Among patients with a baseline MDF of <32, only one mortality developed with a simultaneous HVAT of <11.0 seconds. However, when HVAT was ≥11.0 seconds, the survival rate was 87.5%, although the baseline MDF was ≥32.

Fig. 4

The additional benefit of using hepatic vein arrival time (HVAT) to make a prognosis based on Model for End-Stage Liver Disease (MELD) score. Only one mortality occurred in patients with a HVAT of <11.0 seconds and a MELD of <21. In contrast, 83.3% of patients with a HVAT of ≥11.0 seconds survived despite initially presenting a MELD of ≥21.