Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cells. 2021 May 15;10(5):1212. doi: 10.3390/cells10051212.
After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist.
自 1996 年引入抗逆转录病毒治疗（ART）以来，艾滋病毒感染者（PLWH）的寿命大大延长，而发病率和死亡率的主要原因已经从机会性感染和艾滋病相关肿瘤转变为心血管疾病和肝脏疾病。HIV 本身可能通过多种途径导致肝损伤和随后的肝纤维化（LF）。除 HIV 外，病毒性肝炎、酒精性和非酒精性肝病也与 PLWH 的肝脏受累有关。另一个众所周知的肝毒性原因是 ART，这引起了人们对长期治疗中 LF 的临床严重关注。在这篇综述中，我们呈现了现有数据，并分析了 LF 与所有 ART 药物类别的关联。来自许多研究的已发表数据在某种程度上存在争议，因此仍然没有定论。在所有抗逆转录病毒药物中，核苷逆转录酶抑制剂，特别是地达诺辛和齐多夫定，似乎对 LF 的风险最大，而整合酶链转移抑制剂和进入抑制剂的风险最小。令人惊讶的是，尽管蛋白酶抑制剂经常导致胰岛素抵抗，但它们似乎与 LF 的显著风险无关。总之，大多数 ART 药物在长期治疗中是安全的，并且在没有肝脏相关合并症的情况下很少导致严重的 LF。
