BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.
An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD , of IrsiCaixa AIDS Research Institute in Badalona, Spain.
“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.
Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.
They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.
Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.
“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.
Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said
The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.
A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.
“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.
The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.
SOURCE: Martinez MA et al. CROI 2018, abstract 639 .