Comparative impact of antiretroviral therapy on liver function among HIV infected pregnant women with and those without pre-eclampsia in South Africa

Abstract

Background: Pregnant women living with HIV (PWLWHIV) are at increased risk of adverse pregnancy outcomes, including pre-eclampsia (PE), a multisystem hypertensive disorder characterised by endothelial dysfunction, systemic inflammation, and organ damage. Both HIV infection and antiretroviral therapy (ART) are associated with hepatic impairment; their synergistic impact on maternal liver function in the context of pre-eclampsia remains unclear, especially in HIV-endemic regions. Aim: This study aimed to evaluate the effects of HIV infection and ART exposure on maternal liver function and systemic inflammation during pregnancy, with particular emphasis on the modifying role of pre-eclampsia. Method: A mixed-methods approach was utilised, combining systematic reviews and metaanalyses with observational cohort studies. Systematic reviews and meta-analyses assessed the impact of PE, HIV infection, and ART exposure on hepatic biomarkers, particularly aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin. The clinical component included cohorts stratified by PE and HIV status to evaluate inflammatory markers and liver function parameters. Plasma levels of AST, ALT, placental alkaline phosphatase (PLAP), and C-reactive protein (CRP) were measured and compared among groups to evaluate hepatic impairment, placental involvement, and systemic inflammation. Results: Meta-analytic data revealed a substantial association between PE and increased maternal liver enzymes, indicative of hepatocellular damage. HIV infection and ART exposure were independently associated with elevated AST and ALT levels in comparison to HIVnegative controls. The clinical observations validated these results, demonstrating markedly elevated AST and ALT levels in pre-eclamptic women, with the most pronounced increases noted in those with concurrent HIV infection and pre-eclampsia. PLAP levels were significantly altered in PE, especially in HIV-positive women, indicating placental dysfunction and potential placental-hepatic interplay. CRP concentrations were elevated in PE and further rose with illness severity, with HIV-positive women displaying greater baseline inflammatory levels. The simultaneous presence of HIV and PE led to the greatest inflammatory burden. Conclusion: These findings demonstrate that liver dysfunction during pregnancy is influenced by the complex interplay between HIV infection, ART exposure, and pre-eclampsia. The results indicate that hepatic abnormalities in PWLWHIV cannot be solely attributed to HIV, ART, or PE, but rather to their combined effects. Therefore, an improved monitoring of liver function and inflammatory markers in high-risk pregnancies may facilitate early identification of hepatic involvement and maternal risk assessment, especially in HIV-endemic areas like South Africa.

Boemo Basadi ba baimana bao ba phelago le HIV ba lebane le kotsi ye kgolo ya mathata a a amanago le boimana, go swana le pre-eclampsia (PE), ye e lego bolwetši bja kgatelelo ya madi bjo bo amago mekgwa ye mentši ya mmelo bjo bo akaretšago go senyega ga methapo ya madi, go ruruga ga mmele ka kakaretšo, le go senyega ga ditho. Tšoaetšo ya HIV le kalafo ya diantiretroviral (ART) ka bobedi di amahanngwa le go senyegega ga sebete; le ge go le bjalo, khuetšo ya tšona ye e kopanego godimo ga mošomo wa sebete sa bomme maemong a preeclampsia ga sešo sa hlaloswa gabotse, kudu dinageng tšeo HIV e atilego kudu. Maikemišetšo Maikemišetšo a nyakišišo ye e be e le go hlahloba ditlamorago tša tšoaetšo ya HIV le kalafo ya ART godimo ga mošomo wa sebete sa bomme le go rurušega nakong ya boimana, ka go lebanya kudu le khuetšo ya pre-eclampsia. Mokgwa Go dirišitšwe mokgwa wa mixed-methods, wo o kopantšego ditlhahlobo tša tsamaiso (systematic reviews) le meta-analyses le dithuto tše mmalwa tša di-cohort. Ditlhahlobo tša tsamaiso le meta-analyses di lekotše khuetšo ya pre-eclampsia, tšoaetšo ya HIV le go pepentšhwa go ART godimo ga di-biomarker tša sebete, e lego aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), le bilirubin ya kakaretšo ya serum. Dithuto tša kliniki di akaretša di-cohort tše mmalwa tšeo di nyakišišitšego go rurušega le mošomo wa sebete go basadi ba baimana bao ba arotšwego go ya ka maemo a PE le HIV. Maemo a plasma a AST, ALT, placental alkaline phosphatase (PLAP), le C-reactive protein (CRP) a lekantšwe le go bapetšwa magareng ga dihlopha go lekola go senyega ga sebete, go tsenela ga placenta, le go rurušega ga mmele ka kakaretšo. Dipoelo Dipoelo tša meta-analysis di bontšhitše kgokagano ye kgolo magareng ga pre-eclampsia le koketšego ya di-enzyme tša sebete sa bomme, e lego sešupo sa go senyega ga disele tša sebete. Tšoaetšo ya HIV le go šomišwa ga ART ka bonngwe di amantšwe le maemo a godimo a AST le ALT ge di bapetšwa le basadi bao ba se nago HIV. Ditemogo tša kliniki di netefaditše dipoelo tše, ka go bontšha koketšego ye kgolo ya AST le ALT go basadi bao ba nago le preeclampsia, ka maemo a godimo kudu go bao ba nago le tšoaetšo ya HIV le pre-eclampsia ka nako e tee. Maemo a PLAP a fetogile kudu go PE, kudu go basadi ba HIV-positive, se se bontšhago go se šome gabotse ga placenta le tswalano ya placenta le sebete. Maemo a CRP a be a phagame go PE gomme a oketša le go tia ga bolwetši, go basadi ba nang leHIVvi positive ba bontšha maemo a godimo a go rurušega go tšwa mathomong. Go ba gona ka nako e tee ga HIV le PE go lebile go morwalo wo mogolo kudu wa go rurušega. Mafetšo Mošomo wo o tšweleditšwego mo porojekeng ye o bontšha gore go se šome gabotse ga sebete go tšwa go tswalano ya tšoaetšo ya HIV, go šomitšwa ga ART, le boimana, gomme go ka amana gape le pre-eclampsia. Dipoelo di bontšha gore diphetogo tša sebete go basadi ba baimana bao ba phelago ka twatši ya HIV di ka se hlaloswe ka HIV, ART goba PE fela, eupša di tšwa go ditlamorago tša tšona tše di kopanego. Ka fao, go tokafatša go hlokomelwa ga mošomo wa sebete le di-marker tša go rurušega go boimana bjo bo lego kotsing go ka thuša go lemoga ka pela go tsenela ga sebete le go lekola kotsi ya bomme, kudu dinageng tšeo HIV e atilego kudu go swana le Afrika Borwa.