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. 2025;93(4):411-418.
doi: 10.24875/CIRU.24000331.

Circulating histone H4 values can relate to disease severity in patients with alcoholic hepatitis and cirrhosis

İrfan Küçük  1 , Süleyman Baş  1 , Ersin Tural  2 , Mine Ergelen  3 , Musa Salmanoğlu  4 , Başak Çakır Güney  4 , Tuğba Akbaş Şimşek  5 , İdris Yıldırım  5 , Habip Yılmaz  6
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Free article

Circulating histone H4 values can relate to disease severity in patients with alcoholic hepatitis and cirrhosis

İrfan Küçük et al. Cir Cir. 2025.
Free article

Abstract
in English, Spanish

Objective: We aimed to evaluate whether serum histone H4 (sHH4) is associated with alcoholic liver disease (ALD) phenotypes.

Methods: This case-control study included 66 ALD patients and 47 healthy controls (HCs). Patients with ALD were classified into three groups: alcohol-associated steatotic liver, alcoholic hepatitis (AH), and alcoholic cirrhosis (AC). The HIST1H4A kit was used for the enzyme-linked immunosorbent assay of sHH4.

Results: In the AH patients, the median sHH4 value was the highest and the lowest in the HC (3572.32 ng/L vs. 451 ng/L, respectively, p = 0.002). In the AC group, the median sHH4 value was higher in the Child-Pugh classification B (CPC-B) group than in the CPC-A group (p = 0.026). Positive correlations existed between the sHH4 value and the duration of alcohol use and Maddrey's discriminant function scores in patients with AH (rho = 0.886, p = 0.019 for both). In the AC patients, a positive correlation was noted between the sHH4 values and The Model for End-stage Liver Disease Sodium scores (rho = 0.527, p = 0.006).

Conclusions: Increased sHH4 values might be a marker for the severity of AH and AC.

Objetivo: Evaluar si la histona sérica H4 (sHH4) está asociada con fenotipos de enfermedad hepática alcohólica.

Métodos: Estudio de casos y controles que incluyó 66 pacientes con enfermedad hepática alcohólica y 47 controles sanos. Los pacientes con enfermedad hepática alcohólica se clasificaron en tres grupos: hígado esteatósico asociado al alcohol, hepatitis alcohólica (HA) y cirrosis alcohólica (CA). Se utilizó el kit HIST1H4A para el ensayo de inmunoadsorción ligado a enzimas (ELISA) de sHH4.

Resultados: En los pacientes con HA, la mediana del valor de sHH4 fue más alta que en los controles sanos (3572.32 ng/L frente a 451 ng/L; p = 0.002). En el grupo con CA, el valor mediano de sHH4 fue mayor en los pacientes en clase B de Child-Pugh que en aquellos en clase A (p = 0.026). Hubo una correlación positiva entre el valor de sHH4 y la duración del consumo de alcohol y las puntuaciones MDF (Maddrey’s Discriminant Function) en los pacientes con HA (rho = 0.886; p = 0.019 para ambos). Se detectó una correlación positiva entre los valores de sHH4 y las puntuaciones MELD-Na (Model for End-stage Liver Disease Sodium) en los pacientes con CA (rho = 0.527; p = 0.006).

Conclusiones: Los valores elevados de sHH4 pueden ser un indicador de la gravedad de la HA y la CA.

Keywords: Alcoholic liver disease; Enfermedad hepática alcohólica; Gravedad; Histona H4; Histone H4; Severity.

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