HIV Infection and Antiretroviral Therapy Impair Liver Function in People Living with HIV: Systematic Review and Meta-Analysis

Abstract

Background: The use of antiretroviral therapy (ART) has improved the lives of people living with HIV (PLWH). However, its use is associated with secondary complications, notably hepatotoxicity. This systematic review and meta-analysis assess the effects of HIV infection and ART on liver function in PLWH. Method: A comprehensive literature search was performed in PubMed, Scopus, and Google Scholar from inception to 12 February 2025. Studies analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in PLWH undergoing ART, those who are ART-naïve, and HIV-negative individuals were considered. Data analysis was performed using a meta-analysis web tool, and the results were reported as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Twenty-six studies were included in the meta-analysis. The findings showed an increase in AST, SMD = 1.85 (0.93 to 2.78, p < 0.0001, I² = 93.8%), and ALT, SMD = 2.65 (1.25 to 4.04, p = 0.0002, I² = 97.8%) in PLWH who were naïve compared with those who were HIV negative. Additionally, there was a pronounced elevation in AST, SMD = 1.49 (0.48 to 2.50, p = 0.0038, I² = 98%); ALT, SMD = 2.30 (1.14 to 3.45, p < 0.0001, I² = 98%); and ALP, SMD = 1.40 (0.55 to 2.26, p < 0.01, I² = 97%) in PLWH exposed to ART compared with HIV-negative individuals. However, there was no significant difference in ALP, SMD = 0.53 (-0.92 to 1.98, p = 0.4726, I² = 98%) between PLWH who were ART-naïve and HIV-negative individuals. Conclusions: The results show that HIV infection and ART administration are associated with elevated liver function test enzymes, suggesting that each may contribute to liver dysfunction among PLWH. These results highlight the dual risk posed by HIV infection and ART exposure.

Keywords: ALP; ALT; AST; HIV; antiretroviral therapy; hepatotoxicity; liver function; meta-analysis; systematic review.

Figure 6

Pathways by which HIV infection and ART contribute to liver dysfunction [81]. Created using Biorender. INF-γ: interferon-gamma; TNF-α: tumor necrosis factor alpha; IL-6: interleukin-6; ROS: reactive oxygen species; ART: antiretroviral therapy; HIV: human immunodeficiency virus.

Figure 1

A PRISMA flow diagram showing the study selection procedure.

Figure 2

(A) Random effect meta-analysis evaluating the effect of HIV on aspartate aminotransferase in ART-naïve PLWH compared with the HIV-negative group [32,34,35,36,47,49,50,51,52,54,55,56,58,59,60,61,62]. (B) Random effect meta-analysis evaluating the effect of ART on aspartate aminotransferase in PLWH on ART compared with the HIV-negative group [32,34,35,36,37,38,46,47,48,49,51,52,53,54,55,56,58,59,60,61,62,63,64,65]. The solid line shows the line of no effect, the dashed line shows the effect size, the green block shows the weight of the study, the horizontal line crossing the green block shows the confidence intervals, and the diamond plot shows the combined effect size.

Figure 3

(A) Random effect meta-analysis evaluating the effect of no ART on alanine aminotransferase in ART-naïve PLWH compared with the HIV-negative group [32,34,35,36,47,49,50,51,52,54,55,56,57,58,59,60,61,62]. (B) Random effect meta-analysis evaluating the effect of ART on alanine aminotransferase in PLWH on ART compared with the HIV-negative group [32,34,35,36,37,38,46,47,48,49,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65]. The solid line shows the line of no effect, the dashed line shows the effect size, the green block shows the weight of the study, the horizontal line crossing the green block shows the confidence intervals, and the diamond plot shows the combined effect size.

Figure 4

(A) Random effect meta-analysis evaluating the effect of no ART on alkaline phosphatase in ART-naïve PLWH compared with the HIV-negative group [32,34,35,36,47,49,52,55,56,57,59,60,62]. (B) Random effect meta-analysis evaluating the effect of ART on alkaline phosphatase in PLWH on ART compared with the HIV-negative group [32,34,35,36,37,38,47,48,49,52,53,55,56,57,59,60,62,65]. The solid line shows the line of no effect, the dashed line shows the effect size, the green block shows the weight of the study, the horizontal line crossing the green block shows the confidence intervals, and the diamond plot shows the combined effect size.

Figure 5

Funnel plots depicting the evidence of potential bias across the included studies in the meta-analysis. (A) Studies that assessed AST in ART-naïve PLWH compared with HIV-negative individuals. (B) Studies on the effect of PLWH on ART compared with HIV-negative individuals on AST. (C) Studies on ALT in ART-naïve PLWH compared with that in HIV-negative individuals. (D) Studies on the effect of ART on ALT in PLWH compared with that HIV-negative individuals. (E) Studies on ALP in ART-naïve PLWH compared with that in HIV-negative individuals. (F) Studies on the effect of ART on ALP. The individual dot shows the study included.

Figure 5

Funnel plots depicting the evidence of potential bias across the included studies in the meta-analysis. (A) Studies that assessed AST in ART-naïve PLWH compared with HIV-negative individuals. (B) Studies on the effect of PLWH on ART compared with HIV-negative individuals on AST. (C) Studies on ALT in ART-naïve PLWH compared with that in HIV-negative individuals. (D) Studies on the effect of ART on ALT in PLWH compared with that HIV-negative individuals. (E) Studies on ALP in ART-naïve PLWH compared with that in HIV-negative individuals. (F) Studies on the effect of ART on ALP. The individual dot shows the study included.