Clinical frailty scale identifies covert and overt hepatic encephalopathy in patients with cirrhosis

【Objective】Frailty, a syndrome of reduced physical function and stress vulnerability, is increasingly recognized in hepatology but remains under-evaluated in Japan. This study investigated the association between frailty and hepatic encephalopathy (HE) in patients with cirrhosis.【Methods】We retrospectively analyzed 262 patients with cirrhosis hospitalized between 2013 and 2024, excluding those with prior overt HE (OHE). Frailty was defined as a Clinical Frailty Scale (CFS) score ≧5. Covert HE (CHE) was diagnosed using neuropsychological tests. Factors associated with CHE and OHE were analyzed using logistic regression and Fine-Gray models, adjusting for age, sex, BMI, ammonia, CHE, and liver function (MELD/albumin, Child-Pugh, ALBI)【Results】The median age was 65 years, and 41.2% were male. The underlying liver diseases included HBV (6.5%), HCV (16.0%), ALD (24.8%), MASLD (18.7%), and other causes (34.0%). The median MELD, Child-Pugh, and ALBI scores were 8, 6, and -2.28, respectively, with a median ammonia level of 56 μg/dL. 25 patients (9.5%) were classified as frail. CFS was independently associated with CHE (OR 2.13－2.69, p＜0.001) and OHE (SHR 1.38－1.51, p=0.006－0.047) for all models. OHE incidence was significantly higher in frail patients (1-year: 24.9% vs. 5.4%; 3-year: 33.3% vs. 11.2%; 5-year: 35.6% vs. 18.0%, p=0.009).【Conclusion】CFS was independently associated with the development of both CHE and OHE, regardless of liver function and ammonia levels. CFS is a simple and useful tool for predicting hepatic encephalopathy in patients with cirrhosis.