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Abstract：
UNASSIGNED: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers.
UNASSIGNED: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA.
UNASSIGNED: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples.
UNASSIGNED: Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA).
UNASSIGNED: HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes.
UNASSIGNED: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA.
UNASSIGNED: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples.
UNASSIGNED: Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA).
UNASSIGNED: HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes.
摘要：
未经证实：肝HBV抗原表达的模式已被描述，但未在单细胞分辨率下定量。我们将定量技术应用于慢性乙型肝炎患者的肝活检，并评估采样异质性，疾病阶段的影响，和核苷(t)ide(NUC)处理，以及肝脏和外周病毒生物标志物之间的相关性。
UNASSIGNED：使用新型四重免疫荧光测定和图像分析对HBV核心和HBsAg阳性的肝细胞进行定量。在NUC治疗前后，从HBeAg阳性（n=39）和HBeAg阴性（n=75）参与者进行活检分析。为了评估抽样效果，比较了在同一时间点收集的重复活检.血清或血浆样品的HBVDNA水平进行了评估，HBsAg,乙型肝炎核心相关抗原（HBcrAg），和HBVRNA。
未经证实：弥漫性分布的个体HBV核心+细胞和HBsAg+细胞病灶是最常见的染色模式。HBV核心和HBsAg阳性的肝细胞很少见。配对活检显示参与者体内HBV染色的大的局部变异，这在大型肝脏切除术中得到证实。NUC治疗与HBeAg阳性和HBeAg阴性参与者中HBV核心+细胞的中位频率>100倍降低相关，而HBsAg+细胞的减少没有统计学意义。在所有评估的时间点，HBeAg阴性参与者的HBV核心肝细胞的频率低于HBeAg阳性参与者。总HBV+肝细胞负荷与HBcrAg相关，HBVDNA，和HBVRNA仅在基线HBeAg阳性样品。
未经证实：HBV核心+肝细胞减少与HBeAg阴性状态和NUC治疗相关。个体肝脏中HBV阳性的变化是广泛的。肝脏和外围之间的相关性仅在可能指示cccDNA的生物标志物之间发现（HBV核心+和HBcrAg，HBVDNA，和RNA）。
未经证实：HBV感染肝肝细胞，它的基因组可以以两种形式存在，表达不同组的病毒蛋白：一个称为cccDNA的环状基因组，可以表达所有病毒蛋白，包括HBV核心和HBsAg蛋白，或插入宿主基因组通常表达HBsAg的线性片段，但不是HBV核心。我们使用新技术来确定表达HBV核心和HBsAg蛋白的肝细胞的百分比在一大组的肝活检。我们发现，表达的丰度和模式在患者组中甚至在单个肝脏内都不同，并且NUC治疗大大减少了核心表达肝细胞的数量。
UNASSIGNED：使用新型四重免疫荧光测定和图像分析对HBV核心和HBsAg阳性的肝细胞进行定量。在NUC治疗前后，从HBeAg阳性（n=39）和HBeAg阴性（n=75）参与者进行活检分析。为了评估抽样效果，比较了在同一时间点收集的重复活检.血清或血浆样品的HBVDNA水平进行了评估，HBsAg,乙型肝炎核心相关抗原（HBcrAg），和HBVRNA。
未经证实：弥漫性分布的个体HBV核心+细胞和HBsAg+细胞病灶是最常见的染色模式。HBV核心和HBsAg阳性的肝细胞很少见。配对活检显示参与者体内HBV染色的大的局部变异，这在大型肝脏切除术中得到证实。NUC治疗与HBeAg阳性和HBeAg阴性参与者中HBV核心+细胞的中位频率>100倍降低相关，而HBsAg+细胞的减少没有统计学意义。在所有评估的时间点，HBeAg阴性参与者的HBV核心肝细胞的频率低于HBeAg阳性参与者。总HBV+肝细胞负荷与HBcrAg相关，HBVDNA，和HBVRNA仅在基线HBeAg阳性样品。
未经证实：HBV核心+肝细胞减少与HBeAg阴性状态和NUC治疗相关。个体肝脏中HBV阳性的变化是广泛的。肝脏和外围之间的相关性仅在可能指示cccDNA的生物标志物之间发现（HBV核心+和HBcrAg，HBVDNA，和RNA）。
未经证实：HBV感染肝肝细胞，它的基因组可以以两种形式存在，表达不同组的病毒蛋白：一个称为cccDNA的环状基因组，可以表达所有病毒蛋白，包括HBV核心和HBsAg蛋白，或插入宿主基因组通常表达HBsAg的线性片段，但不是HBV核心。我们使用新技术来确定表达HBV核心和HBsAg蛋白的肝细胞的百分比在一大组的肝活检。我们发现，表达的丰度和模式在患者组中甚至在单个肝脏内都不同，并且NUC治疗大大减少了核心表达肝细胞的数量。
