van Welzen Berend J, Mudrikova Tania, El Idrissi Ayman, Hoepelman Andy I M, Arends Joop E
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU) Utrecht, Utrecht, The Netherlands.
Infect Dis Ther. 2019 Mar;8(1):33-50. doi: 10.1007/s40121-018-0229-7. Epub 2019 Jan 3.
The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.
尽管在艾滋病毒和病毒性肝炎的治疗方面取得了进展，但艾滋病毒感染患者中与肝脏相关的发病率仍然很高。特别是，非酒精性脂肪性肝病（NAFLD）的影响很大，患病率高达50%。NAFLD的发病机制以及进展为非酒精性脂肪性肝炎（NASH）的原因仍未完全阐明，但胰岛素抵抗、线粒体功能障碍和血脂异常似乎是主要驱动因素。艾滋病毒感染本身和联合抗逆转录病毒疗法（cART）都可能以各种方式促成NAFLD/NASH的发展。由于持续的与艾滋病毒相关的免疫激活与胰岛素抵抗有关，需要尽早开始cART以限制其持续时间。此外，早期使用的核苷类逆转录酶抑制剂和蛋白酶抑制剂也与NAFLD/NASH的发展有关。因此，有风险的患者应接受具有更有利代谢特征的抗逆转录病毒药物。尽管有某些药物可用于特定亚组，但只有体重减轻被认为是所有NAFLD/NASH患者的有效治疗方法。由于NASH患者有发展为肝硬化和肝细胞癌的风险，几种非抗纤维化和抗纤维化药物正在临床试验中进行研究，以扩大治疗选择。艾滋病毒阳性患者中NAFLD/NASH的流行病学和病因在不久的将来可能会发生变化。目前的指南建议尽早开始使用不太可能诱发胰岛素抵抗、线粒体功能障碍和血脂异常的cART。相比之下，由于健康预期寿命的增加，这一人群将出现更多传统的NAFLD/NASH风险因素。治疗艾滋病毒的医生应了解NAFLD/NASH的病因、发病机制和治疗方法，以便识别和治疗有风险的患者。
