@article{3102441,
    title = "Liver fibrosis during antiretroviral treatment in hiv-infected individuals. Truth or tale?",
    author = "Bakasis, A.-D. and Androutsakos, T.",
    journal = "Cell Stem Cell",
    year = "2021",
    volume = "10",
    number = "5",
    publisher = "MDPI",
    issn = "1934-5909",
    doi = "10.3390/cells10051212",
    keywords = "abacavir;  alanine aminotransferase;  antiretrovirus agent;  aspartate aminotransferase;  aspartic proteinase;  chemokine receptor CCR5;  chemokine receptor CCR5 antagonist;  chemokine receptor CXCR4;  cytochrome P450;  darunavir;  didanosine;  dolutegravir;  efavirenz;  emtricitabine;  enfuvirtide;  Gag Pol protein;  gamma glutamyltransferase;  gelatinase A;  gelatinase B;  Human immunodeficiency virus fusion inhibitor;  indinavir;  integrase inhibitor;  itolizumab;  lamivudine;  lipopolysaccharide;  lopinavir;  maraviroc;  metalloproteinase;  monocyte chemotactic protein 1;  nevirapine;  nonnucleoside reverse transcriptase inhibitor;  polyprotein;  proteinase inhibitor;  rilpivirine;  ritonavir;  RNA directed DNA polymerase inhibitor;  STAT1 protein;  stavudine;  tenofovir alafenamide;  tenofovir disoproxil;  tissue inhibitor of metalloproteinase 1;  tissue inhibitor of metalloproteinase 2;  toll like receptor 4;  transforming growth factor beta1;  triacylglycerol;  tumor necrosis factor;  very low density lipoprotein;  zalcitabine;  zidovudine;  anti human immunodeficiency virus agent;  enzyme inhibitor, alanine aminotransferase blood level;  allergic reaction;  antiretroviral therapy;  apoptosis;  aspartate aminotransferase to platelet ratio index;  CD4 lymphocyte count;  CD4+ T lymphocyte;  DNA fragmentation;  DNA strand;  drug design;  dyslipidemia;  elastography;  fatty liver;  fibrogenesis;  Fibrosis-4 Index;  gamma glutamyl transferase blood level;  genotype;  hepatic stellate cell;  hepatitis;  homeostasis model assessment;  human;  Human immunodeficiency virus infected patient;  Human immunodeficiency virus infection;  hypertransaminasemia;  insulin resistance;  lactic acidosis;  lipodystrophy;  liver biopsy;  liver fibrosis;  liver injury;  liver regeneration;  liver stiffness;  liver toxicity;  long term care;  mitochondrial toxicity;  myopathy;  non-cirrhotic portal hypertension;  nonalcoholic fatty liver;  nonhuman;  oxidative phosphorylation;  oxidative stress;  peripheral neuropathy;  Review;  T cell depletion;  transient elastography;  virus load;  virus replication;  virus transmission;  Human immunodeficiency virus infection;  liver cirrhosis, Anti-HIV Agents;  Enzyme Inhibitors;  HIV Infections;  Humans;  Liver Cirrhosis",
    abstract = "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 inhibi-tors 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland."
}