Liver function test abnormalities in a longitudinal cohort of Thai individuals treated since acute HIV infection

Abstract

Introduction: Liver disease is a common cause of non-AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation.

Methods: We measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non-parametric tests and multivariate logistic regression.

Results: Sixty-six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V (p = 0.001) and baseline HIV RNA >6 log₁₀ copies/mL (p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis (p < 0.001), baseline plasma HIV RNA levels <6 log₁₀ copies/mL (p < 0.001), abnormal baseline ALT (p < 0.001), baseline CD4 >350 cells/μL (p = 0.03) and older age (p = 0.03). Individuals initiating efavirenz-based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non-efavirenz-based regimens (p = 0.003).

Conclusions: One in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV-associated and ART-associated processes, which may change over time.

Keywords: Acquired Immunodeficiency Syndrome; HIV; Thailand; acute HIV; anti-HIV agents; antiretroviral agents; liver function tests.

Figure 1

(a) ALT levels stratified by Fiebig stage at diagnosis. (b) ALT levels stratified by the presence or absence of acute retroviral syndrome at diagnosis. (c) ALT levels stratified by HIV plasma RNA level at diagnosis. (d) ALT correlates with HIV RNA. I indicates statistically significant compared with Fiebig I, II indicates statistically significant compared with Fiebig II.

Figure 2

(a) Longitudinal ALT levels to 48 weeks according to the presence or absence of acute retroviral syndrome at diagnosis. (b) Longitudinal ALT levels to 48 weeks by Fiebig stage at diagnosis. (c) Longitudinal ALT levels according to ART regimen initiated at the time of diagnosis.

Figure 3

Trends to 144 weeks based upon (a) Fiebig stage at diagnosis and (b) presence of ALT elevations at baseline.

Figure 4

(a) GGT levels stratified by Fiebig stage at diagnosis. (b) GGT levels stratified by the presence or absence of acute retroviral syndrome at diagnosis. (c) GGT levels stratified by HIV plasma RNA level at diagnosis. (d) GGT correlates with HIV RNA at baseline. (e) GGT correlates with ALT at baseline. I indicates statistically significant compared with Fiebig I, II indicates statistically significant compared with Fiebig II.

Figure 5

(a) Total bilirubin levels stratified by Fiebig stage at diagnosis. (b) Total bilirubin levels stratified by the presence or absence of acute retroviral syndrome at diagnosis. (c) Total bilirubin levels stratified by HIV plasma RNA level at diagnosis. (d) Total bilirubin inversely correlates with HIV RNA. (e) Total bilirubin does not correlate with ALT at baseline. (f) Longitudinal total bilirubin levels to 48 weeks by Fiebig stage at diagnosis. I indicates statistically significant compared with Fiebig I, II indicates statistically significant compared with Fiebig II.