Tripodo Claudio, Petta Salvatore, Guarnotta Carla, Pipitone Rosaria, Cabibi Daniela, Colombo Mario P, Craxì Antonio
Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
Antivir Ther. 2012;17(1):111-8. doi: 10.3851/IMP1957.
Here, we assessed the presence of intrahepatic follicular helper T-cells (T(FH)) in a cohort of consecutive genotype 1 (G1) chronic hepatitis C (CHC) patients comprising non-responders (NRs), relapsers (RRs) or those with sustained virological response (SVR) to pegylated interferon and ribavirin, and tested their relation with the response to antiviral treatment.
A total of 78 patients with G1 CHC (30 SVR, 15 RR and 33 NR), comparable for sex, age, viral load and fibrosis were evaluated by immunohistochemistry for liver content of PD1+Bcl6+ T(FH) cells. The number of T(FH) cells in the immunostained sections was counted out of five representative high-power microscopic fields (400×) relative to areas involved by the inflammatory infiltrate. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated.
The absolute number of liver T(FH) progressively increased from NR to RR to a maximum in SVR patients (14.2 ±12.5 versus 24.5 ±12.5 versus 59.2 ±27.1; P<0.001). The mean absolute number of liver T(FH) was 24.3 ±21.1 in 18 TT polymorphism patients, 31.7 ±29.5 in 43 TC and 47.8 ±27.8 in 17 CC (P=0.01). SVR was achieved in 27/35 (77.1%) of patients with T(FH)≥28 and in only 3/43 (6.9%) of those with T(FH)<28. Similarly, 15/17 (88.2%) CC patients achieved SVR, compared with 15/61 (24.6%) TT/TC subjects. With the combination of T(FH) at the threshold of 28 and the rs12979860 polymorphism, the ability to predict SVR strongly increased.
In G1 CHC patients, T(FH) cells are present in the hepatic inflammatory infiltrate. Their amount is proportional to the ultimate likelihood of SVR, with a progressive increase from NR to RR to SVR. Quantification of T(FH) cells in the liver biopsy of these patients adds useful prognostic information.
在此，我们评估了一组连续的基因1型（G1）慢性丙型肝炎（CHC）患者肝内滤泡辅助性T细胞（T(FH)）的存在情况，这些患者包括对聚乙二醇干扰素和利巴韦林治疗无应答者（NRs）、复发者（RRs）或获得持续病毒学应答（SVR）者，并测试了它们与抗病毒治疗应答的关系。
通过免疫组织化学评估78例G1 CHC患者（30例SVR、15例RR和33例NR）肝脏中PD1+Bcl6+ T(FH)细胞的含量，这些患者在性别、年龄、病毒载量和纤维化程度方面具有可比性。在免疫染色切片中，相对于炎症浸润所累及的区域，在五个代表性的高倍显微镜视野（400×）中计数T(FH)细胞的数量。还评估了IL28B rs12979860和rs8099917多态性。
肝脏T(FH)的绝对数量从NR到RR逐渐增加，在SVR患者中达到最高（14.2±12.5对24.5±12.5对59.2±27.1；P<0.001）。18例TT多态性患者肝脏T(FH)的平均绝对数量为24.3±21.1，43例TC患者为31.7±29.5，17例CC患者为47.8±27.8（P=0.01）。T(FH)≥28的患者中有27/35（77.1%）实现了SVR，而T(FH)<28的患者中只有3/43（6.9%）实现了SVR。同样，15/17（88.2%）的CC患者实现了SVR，相比之下，TT/TC受试者中为15/61（24.6%）。将T(FH)阈值设为28并结合rs12979860多态性，预测SVR的能力显著提高。
在G1 CHC患者中，T(FH)细胞存在于肝脏炎症浸润中。它们的数量与SVR的最终可能性成正比，从NR到RR再到SVR逐渐增加。对这些患者肝活检中T(FH)细胞进行定量可提供有用的预后信息。
