Migliavacca Center for the Study of Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
Hepatology. 2013 Mar;57(3):890-6. doi: 10.1002/hep.25749. Epub 2012 Dec 20.
Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN-alpha therapy. A post-treatment response was defined as hepatitis B surface antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow-up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and 11 (11%) had TT, with the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC, genotype carriers (P=0.039). Baseline HBV DNA levels<6 log cp/mL (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16; 95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% CI: 1.1-13.2; P=0.025) independently predicted HBsAg clearance.
IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in the pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of HBV.
探讨白细胞介素 28B（IL28B）多态性与慢性丙型肝炎患者干扰素（IFN）诱导的病毒清除之间的关系。这种关系是否也适用于难以治愈的乙型肝炎 e 抗原（HBeAg）阴性慢性乙型肝炎（CHB）患者尚不清楚。
对 101 例 HBeAg 阴性（92%基因型 D）、代偿性 CHB（84%男性，46 岁；乙型肝炎病毒[HBV]DNA：6.0 log cp/mL；丙氨酸氨基转移酶[ALT]：136 IU/L；42%有肝硬化）患者进行了中位 11 年（范围，1-17）的随访，这些患者在中位 23 个月（范围，10-48）的标准或聚乙二醇（Peg）-IFN-α治疗后，中位随访 11 年。以 HBsAg 清除伴或不伴乙型肝炎表面抗体（抗-HBs）血清转换来定义治疗后应答。采用 Custom TaqMan SNP Genotyping Assays（Applied Biosystems，Carlsbad，CA）检测血清样本中 IL28B 基因座的 rs12979860（C>T）基因型。
在中位 11 年的治疗后随访中，21 例（21%）患者血清 HBsAg 清除，其中 15 例患者抗-HBs 滴度>10 IU/mL。48 例（47%）患者为 CC 基因型，42 例（42%）为 CT 基因型，11 例（11%）为 TT 基因型，等位基因频率为 C 等位基因 68%，T 等位基因 32%。CC 基因型患者血清 HBsAg 清除率为 29%（n=14），而非 CC 基因型患者为 13%（n=7）（P=0.039）。HBV DNA 水平<6 log cp/mL（比值比[OR]，11.9；95%置信区间[CI]：2.8-50.6；P=0.001）、ALT 水平>136 IU/L（OR，6.5；95%CI：1.8-22.5；P=0.003）、IFN 持续时间（OR，1.16；95%CI：1.02-1.31；P=0.021）和 CC 基因型（OR，3.9；95%CI：1.1-13.2；P=0.025）独立预测 HBsAg 清除。
IL28B 多态性是治疗结束时 IFN 相关 HBsAg 血清学清除的另一个预测因素，可用于 HBeAg 阴性慢性感染 D 基因型 HBV 的患者的治疗前分层。
