Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

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 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.

Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection

“…Liver disease is one of the major causes of morbidity and mortality in PLWH [ 17 , 18 ]. As far as liver fibrosis is concerned, available studies report that its prevalence in HIV-infected patients ranges from 1.4% to 63% according to different populations [ 20 , 28 , 29 , 55 , 56 ].…”

“…Currently available antiretroviral drugs have dramatically changed the landscape of HIV infection, reducing mortality for any reason but increasing the impact of aging-related comorbidities. However, even if many controversies still exist, the potential impact of some antiretroviral drugs in mid- and long-term liver abnormalities is known, in particular due to first-generation NRTIs, such as AZT and PIs [ 17 , 38 ]. In our study, we observed an effect of longer cumulative atazanavir exposure on liver stiffness measurements by TE, according to previous literature data.…”

“…In clinical practice, non-invasive methods are widely used to estimate of liver fibrosis. The non-invasive methods could identify PLWH at higher risk of severe liver injury, and liver fibrosis stratification may help to determine those who may benefit from lifestyle changes, including healthy diet, weight loss, physical exercise and metabolic disorder control, and potential pharmacologic interventions [ 17 , 18 , 20 ]. Non-invasive assessment of liver fibrosis can be performed (i) by biological approaches, quantifying serum biomarkers, with FIB-4 and APRI being the most used scores, or (ii) by a physical approach, measuring liver stiffness by TE.…”

“…Severe liver fibrosis is associated with poor long-term liver-related outcomes and mortality, and PLWH are at higher risk of multifactorial liver injuries than people without HIV [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients – a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown

“…It is estimated that each year of NRTI treatment may add an 11% risk to NAFLD ( 206 ). However the progression of NAFLD to liver fibrosis is a rare and lengthy process ( 208 ). The metabolic and inflammatory mechanisms generated by HIV and ART are depicted in the Figure 2 .…”