Alpsoy Anil, Adanir Haydar, Bayramoglu Zeynep, Elpek Gulsum Ozlem
Department of Pathology, Akdeniz University, Medical School, Antalya 07070, Turkey.
Department of Gastroenterology, Akdeniz University, Medical School, Antalya 07070, Turkey.
World J Hepatol. 2022 Jan 27;14(1):260-273. doi: 10.4254/wjh.v14.i1.260.
Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.
To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.
A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.
A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed ( < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores ( < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) ( < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR ( < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR.
In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.
慢性乙型病毒性肝炎（CHB）是一种潜在的危及生命的肝脏疾病，可能进展为肝衰竭和肝硬化。目前，尽管在CHB的随访和治疗中使用了不同实验室方法的组合，但这些方法在某些情况下的失败导致了开发新方法的必要性。在CHB中，包括乙型肝炎表面抗原（HBsAg）在内的病毒抗原的肝内表达模式与不同的炎症阶段相关。然而，许多研究集中在HBsAg染色的胞质内特性上，并且肝组织中的HBsAg阳性尚未通过客观定量方法进行评估。
研究基于图像分析的定量HBsAg表达及其染色模式与CHB临床病理因素及治疗的关系。
本研究纳入了140例初治CHB感染患者的肝活检标本。诊断后，所有患者接受恩替卡韦（0.5mg）治疗，并每3个月进行一次随访。通过图像分析确定每例活检标本全组织切片中肝组织免疫组化HBsAg（p-HBsAg）表达的百分比。免疫组化染色模式也根据3种先前定义的不同分类分别进行评估。
观察到p-HBsAg与血清乙型肝炎病毒（HBV）DNA和HBsAg水平呈正相关（<0.001）。年轻患者的p-HBsAg值显著高于老年患者。在HBeAg阳性病例中，根据HBeAg状态对组进行分类时，p-HBsAg与HBV DNA、肝炎活动指数（HAI）和纤维化评分相关（<0.001）。在该组中，p-HBsAg和HBsAg表达模式也与病毒学应答（VR）和血清学应答（SR）相关（<0.001）。多变量分析显示，p-HBsAg是VR或SR的独立预测因子（<0.001）。在HBeAg阴性患者中，尽管HBsAg表达模式与HAI和纤维化均相关，但未观察到p-HBsAg、临床病理因素与VR之间的关系。
在治疗前肝活检中，通过定量方法免疫组化测定HBsAg表达，除了其在细胞内的分布外，可能是治疗应答的良好预测指标，尤其是在HBeAg阳性病例中。
