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

Abstract

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores

“…In our study, the prevalence of liver fibrosis at the last visit in individuals with HIV mono-infection was of 8.1% using the APRI score and of 9% using the Fib-4 score, comparable with data from studies using non-invasive methods (20, 23,33,44). Additionally, the current study showed a significant increase of APRI and Fib-4 scores over time in this group with high CD4 T cell counts and relatively good real-life adherence to ART.…”

“…Hence, it is probable that similar to patients with chronic hepatitis B (53), distinct lower thresholds liver fibrosis are needed in PLWH on extensive ART. Sterling et al (34) have indicated lower optimal cut-offs for both APRI and Fib-4 scores in treated patients, while other authors have underlined the discordant results obtained using traditional APRI and Fib-4 cut-offs in PLWH without elevated transaminases (44). Nevertheless, considering the increase of the scores found over time in the cases with HIV mono-infection, a rigorous follow-up using at least serum-based scores should be considered in all PLWH on prolonged ART, irrespective on the presence of elevated transaminases or of other viral coinfections.…”

Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy

“…Interestingly, the plasma levels of the IFN-stimulated genes OAS1 and IP-10 were also significantly elevated in PLWH receiving cART compared with healthy individuals ( Figure 7, D and E ). Taken together, HIV/cART-induced pathogenic M2-macrophages and activation of IFN signaling may also play a role in increased risk of liver diseases reported in PLWH receiving ART ( 45 – 47 ).…”

“…ART has significantly improved the lifespan of PLWH. Because most drugs are metabolized by the liver, even low hepatotoxicity becomes an important clinical issue for PLWH with long-term cART ( 45 – 47 ). Therefore, monitoring PLWH with stable cART for potential emergence of liver injury and disease should continue to be of clinical importance.…”

Regional variation in NAFLD prevalence and risk factors among people living with HIV in Europe: a meta-analysis

“…After reviewing the full texts, a total of 36 studies met the inclusion criteria and were included in the final analysis ( 11 , 30–64 ) ( Figure 1 ). These studies were all from European countries, including the United Kingdom ( 42 , 46 ), France ( 31 , 35 , 38–40 , 64 ), Belgium ( 39 , 40 ), Greece ( 30 , 41 ), Italy ( 11 , 34 , 44 , 48 , 53 , 62 ), Spain ( 33 , 45 , 50 , 51 , 55 , 56 ), Denmark ( 36 ), Finland ( 37 , 57 ), Germany ( 32 , 39 , 40 , 43 , 49 , 58 , 63 ), Switzerland ( 54 ), Serbia ( 47 , 61 ), Austria ( 59 ), and Turkey ( 52 , 60 ) ( Supplementary Table S1 ). Most of the studies were cross-sectional in design, with a few prospective cohort studies.…”