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.

Individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles modeled from acute HIV infection

“…sCD27 and sTIM-3 levels at enrollment also differed between individuals who achieved normalization versus those with persistent CD4/ CD8 T-cell inversion. These results are interesting given the known involvement of both markers with T-cell functionality and HIV disease pathogenesis (23). CD27 expression on T cells is functionally active (58,59), and elevated levels of sCD27 in plasma are a surrogate marker of immune activation and predictor of morbidity among PWH receiving suppressive ART (60,61).…”

“…As noted, a subset of participants underwent cellular immunophenotyping because this procedure was designated as optional in the parent protocol. Methods are summarized hereinafter with more detail available in prior publications (18)(19)(20)(21)(22)(23).…”

Derangement of Liver Enzymes, Hyperglycemia, Anemia, and Associated Factors among HIV-Infected Patients Treated with Tenofovir Disoproxil Fumarate-Based Regimen in Ethiopia: A Prospective Cohort Study

“…Particularly, in tenofovir disoproxil fumarate-based regimen hepatotoxicity was revealed in case reports [15][16][17]. Furthermore, various studies found elevation of liver enzymes in TDF-based regimen [18][19][20][21], and a study in China found that 48.1% of participants had hepatotoxicity following TDF-based regimen [22]. Hepatic histological damage is also found in animal study [23].…”

Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation

“…Although most modern ART regimens are considered less hepatotoxic than previously used ‘first generation’ drugs [ 6 ], their short-term and long-term effects on the liver need to be further investigated. Some studies indicate that early and continued ART leads to improved liver-specific health outcomes [ 18 , 19 ], whereas others describe the opposite with symptoms of drug-related toxicity and metabolic dysregulation exacerbating liver injury [ 20 , 21 ]. Given this complex interplay of pathogenic and protective mechanisms, HIV-associated and ART-associated effects on the liver require further study.…”