Lower levels of serum albumin are associated with impairment of cognitive function in cirrhotic patients with early-stage hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials of rifaximin in Japan

Abstract

Background Because covert hepatic encephalopathy (CHE) has been shown to affect the prognosis of cirrhotic patients, early diagnosis of HE is a prerequisite for preservation of patients’ quality of life and for prophylaxis of overt HE. Currently, neuropsychological tests are used for the diagnosis of early-stage HE including CHE. However, it would be inefficient to apply them to all cirrhotic patients. Thus, some biomarkers correlated with the above diagnostic modalities are available for screening examination. The aim of this study was to identify a clinical parameter to predict impairment of cognitive function in cirrhotic patients with early-stage HE.Methods This exploratory data analysis was based on the data from 172 patients with cirrhotic or idiopathic portosystemic shunt (PSS) in phase II/III trials of rifaximin in Japan. Their data at baseline before treatment with rifaximin were utilized to analyze the relationship between cognitive dysfunction and different clinical parameters We Classification and regression trees (CART) were constructed to identify clinical profiles related to cognitive dysfunction, as indicated by the prolongation of time required for the number connection test (NCT-B).Results CART analysis detected age 65 years as the variable for the initial split, and serum albumin level was selected as the variable for the second split among patients aged ≤ 65 years. In 27 cirrhotic patients aged ≤ 65 years without PSS, receiver-operating characteristic curve analysis revealed that the optimal albumin level cutoff point was 3.05 g/dL, and the area under the curve was 0.80 for the prolongation of NCT-B time, which was higher than that of other HE-related parameters including the branched-chain amino acids-to-tyrosine ratio (0.46), the prothrombin time–international normalized ratio (PT-INR) (0.68), serum ammonia (0.61), and total bilirubin (0.69).Conclusions Lower serum albumin level as a clinical biomarker associated with impaired cognitive function is available as a screening examination for early-stage HE in cirrhotic patients aged ≤ 65 years without PSS before undergoing neuropsychological tests.

Association between serum albumin and psychometric hepatic encephalopathy score in cirrhosis without overt hepatic encephalopathy

“…Lower levels of serum albumin may be associated with higher risk of overt HE and HE-associated mortality during hospitalizations in cirrhosis ([CSL STYLE ERROR: reference with no printed form.]). Our ndings align with other studies that suggest a positive association between albumin and PHES (Kaji et al 2020(Kaji et al , 2021. However, the relationship between albumin and covert hepatic encephalopathy remains controversial.…”

“…Hence, the identi cation of simple clinical indicators that demonstrate a signi cant association with the PHES can be instrumental in enhancing the diagnostic rate of CHE. Serum albumin is regarded as a prominent clinical indicator for evaluating liver function in cirrhosis and is frequently employed in the screening of early hepatic encephalopathy (Kaji et al 2020(Kaji et al , 2021. Nevertheless, the association between serum albumin levels and the Psychometric Hepatic Encephalopathy Score (PHES) remains a subject of controversy (Kimer et al 2021).…”