Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Kaiser Permanente Mid-Atlantic States, Mid-Atlantic Permanente Research Institute, Rockville, Maryland.
JAMA Netw Open. 2021 Feb 1;4(2):e2037512. doi: 10.1001/jamanetworkopen.2020.37512.
People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era.
To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020.
HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation.
HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage.
Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection.
HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.
艾滋病毒感染者（PWH）通常同时感染乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HCV），导致肝细胞癌（HCC）的风险增加，但很少有队列研究有足够的能力描述 PWH 在联合抗逆转录病毒治疗（cART）时代 HCC 发病率和风险的趋势。
确定 HCC 发病率（IR）的时间趋势，并比较 cART 时代 PWH 中基于风险因素的比率。
设计、设置和参与者：这项队列研究使用了北美艾滋病队列协作研究和设计（NA-ACCORD）研究的数据，该研究于 1996 年至 2015 年进行。NA-ACCORD 汇集了来自美国和加拿大的 22 个 HIV 临床和间隔队列中 PWH 的个体水平数据。纳入了年龄在 18 岁及以上，具有可用 CD4 细胞计数和 HIV RNA 数据的 PWH。数据分析于 2020 年 3 月完成。
HBV 感染的定义是在观察期间的任何时间在血清或血浆中检测到 HBV 表面抗原、HBV e 抗原或 HBV DNA。HCV 感染的定义是在观察期间的任何时间在血清或血浆中检测到抗 HCV 血清阳性、HCV RNA 或可检测的基因型。
根据病历回顾或癌症登记处的链接确定 HCC 诊断。
在 109283 名 PWH 中，有 723441 人年的随访时间，基线时的中位（四分位距）年龄为 43（36-51）岁，93017 名（85.1%）为男性，44752 名（40.9%）为白人，44322 名（40.6%）为黑人，21343 名（19.5%）有 HCV 合并感染，6348 名（5.8%）有 HBV 合并感染，2082 名（1.9%）有三重感染；2015 年有 451 人被诊断为 HCC。在早期（1996-2000 年）和现代（2006-2015 年）cART 时代之间，HCC 的粗发病率从 0.28 增加到 0.75 例/1000 人年。在 HIV 单一感染或 HBV 合并感染的患者中，HCC 的发病率保持不变，但从 1996 年到 2015 年，HCV 合并感染的 PWH 的发病率（从 1996 年的 0.34 例/1000 人年增加到 2015 年的 2.39 例/1000 人年）或三重感染的发病率（从 1996 年的 0.65 例/1000 人年增加到 2015 年的 4.49 例/1000 人年）有所增加。最近的 HIV RNA 水平大于或等于 500 拷贝/mL（发病率比，1.8；95%CI，1.4-2.4）和 CD4 细胞计数小于或等于 500 个/μL（发病率比，1.3；95%CI，1.0-1.6）与现代 cART 时代 HCC 风险增加相关。与男男性行为者相比，注射毒品的人 HCC 风险更高（发病率比，2.0；95%CI，1.3-2.9），调整了 HBV-HCV 合并感染的因素。
从 1996 年到 2015 年，PWH 中 HCC 的发生率显著增加。同时感染病毒性肝炎、HIV RNA 水平较高或 CD4 细胞计数较低、以及注射毒品的 PWH，其 HCC 风险更高。
