Yim Sun Young, Kim Tae Hyung, Jun Suh Sang, Kim Eun Sun, Keum Bora, Seo Yeon Seok, Yim Hyung Joon, Jeen Yoon Tae, Chun Hoon Jai, Lee Hong Sik, Um Soon Ho, Kim Chang Duck, Won Nam Hee, Ryu Ho Sang
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Department of Pathology, Korea University College of Medicine, Seoul, Korea.
Gut Liver. 2017 May 15;11(3):417-425. doi: 10.5009/gnl16148.
BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB).
We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system.
In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05).
Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.
背景/目的：我们旨在阐明慢性乙型肝炎（CHB）患者中乙肝表面抗原（HBsAg）/乙肝核心抗原（HBcAg）与疾病状态及治疗反应之间的关联。
我们调查了171例经活检证实接受恩替卡韦治疗的CHB患者（109例乙肝e抗原[HBeAg]阳性，62例HBeAg阴性）。当≥10%的肝细胞染色时，HBcAg表达为阳性，并分为核型、混合型和胞质型。HBsAg表达为胞质内（弥漫型、球状型和膜下型）和膜型。组织学活动指数（HAI）和纤维化分期遵循Ishak系统。
在HBeAg阳性患者中，当HBcAg阳性患者的HBcAg表达从细胞核转移到细胞质，以及HBcAg阴性患者的HBsAg表达从非膜下型转变为膜下型时，观察到年龄较大、HAI评分增加、纤维化进展和病毒载量降低（均p<0.05）。在HBeAg阴性患者中，只有胞质内HBsAg表达模式与ALT水平降低和病毒血症具有临床相关性。在没有病毒学反应良好预测指标的HBeAg阳性患者中，HBcAg阴性和膜型HBsAg表达预测病毒学反应更好（均p<0.05）。HAI增加或缺乏HBcAg表达的患者HBeAg血清学转换的概率更高（均p<0.05）。较高的血清HBsAg水平和肝细胞HBcAg阳性分别与治疗第一年和第一年之后血清HBsAg降低相关（均p<0.05）。
肝细胞HBcAg/HBsAg表达是疾病状态和预测治疗反应的良好标志物。
