Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era

Abstract

Background As morbidity due to viral co-infections declines among HIV-infected persons, changes in liver related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV mono-infected patients in the combination antiretroviral therapy (cART) era. Methods Participants who were HBV and HCV seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase (ALT) elevations ≥ 1.25 times the upper limit of normal on at least two visits, for a duration of six months or more within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. Results Of 2,779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28 – 1.29). In an adjusted model, cLEE was associated with Hispanic/other ethnicity [Reference Caucasian: HR 1.744 (1.270 – 2.395)], non–nucleoside reverse transcriptase (NNRTI) based cART [Reference boosted protease inhibitors: HR 2.232 (1.378 – 3.616)], being cART naïve [HR 6.046 (3.686 – 9.915)] or having cART interruptions [HR 8.671 (4.651 – 16.164)]. African American race [HR 0.669 (0.510 – 0.877)] and integrase strand transfer inhibitor (INSTI) based cART [HR 0.222 (0.104 – 0.474)] were protective. Conclusions Our findings demonstrate initiation and continued use of cART is protective against cLEE and supports the hypothesis HIV infection directly impacts the liver. INSTI based regimens were protective and could be considered in persons with cLEE.

Liver steatosis and fibrosis in people with human immunodeficiency virus in West Africa and the relationship with hepatitis B virus coinfection

“…Multiple factors may contribute to increase the risk of liver disease in the context of human immunodeficiency virus (HIV) infection, including infectious and noninfectious comorbidities, metabolic disorders, and the possible direct effects of HIV infection and antiretroviral therapy (ART). [ 1 , 2 , 3 , 4 ] In a systematic review of 10 cross‐sectional studies of primarily men living with HIV in North America, Western Europe, China, and Japan, 35% met the definition of nonalcoholic fatty liver disease (NAFLD) based on imaging or liver histology. [ 1 ] Metabolic disorders and high CD4 cell counts were associated with NAFLD, whereas duration of HIV infection, duration of ART, HIV RNA load, and nadir CD4 cell counts were not.…”

Avaliação laboratorial da função hepática em pessoas iniciando a terapia antirretroviral com esquemas contendo Dolutegravir ou Efavirenz: estudo de coorte em Belo Horizonte, Brasil

“…A infecção pelo vírus HIV não tratada e uma elevada carga viral podem ocasionar um aumento nos níveis das transaminases hepáticas, devido à ação direta do vírus nas células hepáticas e ao processo inflamatório sistêmico. Em muitos casos a atividade anormal das transaminases ocorre de forma assintomática e é uma consequência da infecção pelo HIV, sendo necessário tratar a infecção pelo HIV, objetivando reduzir a carga viral e normalizar os índices das transaminases (Kim et al, 2008;Wood et al, 2021). Outros estudos mostraram correlação entre a carga viral do HIV e o grau de elevação das enzimas hepáticas, sendo observado uma redução dos níveis das transaminases à medida que a viremia diminui (Mata-Marín et al 2009;Dusingize et al 2015;Alghamdi et al 2016).…”

“…Estudos realizados por outros autores mostram que a elevação discreta nas enzimas geralmente é transitória e não necessita interrupção no tratamento. No entanto, se houver toxicidade grave (elevação > 5 vezes o limite superior da normalidade) ou se a pessoa apresentar sintomas graves, sugere-se trocar o tratamento (Martins et al, 2020;Wood et al, 2021). Em nosso estudo, o aumento da FAL foi discreto e permaneceu dentro do valor de referência (65 a 300 UI/L), sem indicar necessidade em mudar esquema de TARV.…”

Hepatic Toxicity Assessment in HIV’s Interaction with Reverse Transcriptase and Integrase Strand Transfer Inhibitors at a Military Hospital, Southsouth Nigeria

“…This suggests that elevations in one liver enzyme may be accompanied by elevations in the other, reflecting potential liver injury or inflammation. However, Wood et al 2021 reported that long-term use of INSTI-based ART reduces liver enzyme elevation by half compared to those on NNRTI [23]. This observed difference may, however, be due to differences in race, ethnicity, and study design.…”