Liver cancer risk and prevention among persons living with HIV/AIDS

描述(申请人提供)：由于抗逆转录病毒治疗，艾滋病毒/艾滋病患者(PLWHA)的寿命更长；然而，肝癌等非艾滋病定义癌症的负担随着时间的推移而增加。这一人群的老龄化、免疫功能受损以及肝癌危险因素的高发，丙型肝炎病毒、乙肝病毒、酗酒和依赖导致PLWHA中肝癌发病率的上升。这项拟议的研究的目的是确定肝癌的高危患者，并审查肝癌预防方法在PLWHA人群中的影响。 来自退伍军人事务中央癌症登记中心的癌症诊断将与退伍军人老龄化队列研究(Vacs)的数据联系起来，该研究是对在美国接受护理的艾滋病毒感染退伍军人的前瞻性观察队列。Vacs虚拟队列成立于1996年，包括40,000多名艾滋病毒感染者和性别、年龄、种族和诊所匹配的未感染艾滋病毒的退伍军人队列。有超过15年的诊所就诊和实验室测试的跟踪数据。 FIB-4是一种公认的肝纤维化和肝硬变的标志物，是根据常规实验室(丙氨酸转氨酶、天冬氨酸转氨酶、血小板计数)和年龄计算得出的。在PLWHA中，一次性检测FIB-4与随后的肝癌发展密切相关。这项拟议的工作将调查在多个时间点测量的FIB-4的效果，以确定FIB-4的变化是否能够更好地预测肝癌。这将通过对已知的肝癌风险因素和艾滋病毒相关风险因素进行调整的混合效应纵向回归模型来完成。除了在PLWHA中更有效地使用FIB-4外，还将在一组未感染艾滋病毒的受试者中进行额外的分析，以确定FIB-4‘S识别高危患者的能力是否因艾滋病毒状况而不同。 在确定了肝癌的高危患者后，重点转向预防。虽然乙肝病毒和丙型肝炎病毒的治疗、预防体重增加和危险的戒酒被认为有助于预防肝癌，但尚未量化预防策略的组合如何影响PLWHA的肝癌预防。除了肝脏的生物标志物外，还将纵向探索病毒性肝炎治疗、肥胖和体重以及糖尿病控制的临床生物标志物和措施。 在高危艾滋病毒感染者的子集中评估这些因素对肝癌预防的相对影响，以及对临床医生和高危患者最有意义的是什么。 这项建议的培训部分将包括：1)高级流行病学和统计讲习班，2)艾滋病毒、癌症生物学和医学研讨会，3)跟踪医生以增加临床知识和经验，4)两位知名流行病学研究人员的指导，以及5)与艾滋病毒、癌症流行病学和生物统计学研究人员的合作。

DESCRIPTION (provided by applicant): Persons living with HIV/AIDS (PLWHA) have longer lifespans, thanks to antiretroviral treatment; however, the burden of non-AIDS-defining cancers, such as liver cancer, is increasing over time. The aging of this population, impaired immune function, and high prevalence of liver cancer risk factors hepatitis C virus, hepatitis B virus, an alcohol abuse and dependency contribute to the rising incidence of liver cancer among PLWHA. The purpose of the proposed study is to identify high-risk patients for the development of liver cancer and review the impact of liver cancer prevention methods in the population of PLWHA. Cancer diagnoses from the Veterans Affairs Central Cancer Registry will be linked with data from the Veterans Aging Cohort Study (VACS), a prospective, observational cohort of HIV-infected veterans in care in the United States. The VACS virtual cohort was established in 1996 and includes over 40,000 HIV-infected subjects and a sex-, age-, race-, and clinic site-matched cohort of HIV-uninfected veterans. Over 15 years of follow-up data on clinic visits and laboratory tests are available. FIB-4, an established marker of liver fibrosis and cirrhosis, is calculated from routine labs (alanine transaminase, aspartate transaminase, platelet count) and age. In PLWHA, a one-time measure of FIB-4 was strongly associated with subsequent development of liver cancer. The proposed work will investigate the effect of FIB-4 measured at multiple time points to see whether changes in FIB-4 are better able to predict liver cancer. This will be done with mixed-effects longitudinal regression models adjusting for known liver cancer risk factors and HIV-related risk factors. In addition to more efficient use of FIB-4 among PLWHA, additional analyses will be conducted in a cohort of HIV-uninfected subjects to determine if FIB-4's ability to identify high-risk patients differs by HIV status. After identifying high-risk patients for liver cancer, the focus then turns to prevention. While hepatitis B virus and hepatitis C virus treatment, prevention of weight gain, and hazardous alcohol consumption cessation are hypothesized to contribute to liver cancer prevention, it has not yet been quantified how the combination of prevention strategies impacts liver cancer prevention in PLWHA. Clinical biomarkers and measures of viral hepatitis treatment, obesity and weight, and diabetes control will be explored longitudinally in addition to biomarkers of liver function in a subset of high-risk HIV-infected subjects to assess the relative impact of these factors on liver cancer prevention and what will be most informative to clinicians and patients at high risk. The training component of this proposal will include: 1) advanced epidemiologic and statistical workshops, 2) seminars on HIV, cancer biology, and medicine, 3) shadowing of physicians to increase clinical knowledge and experience, 4) mentorship from two established epidemiologic researchers, and 5) collaboration with researchers in HIV and cancer epidemiology and biostatistics.