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. 2015 Feb 3;10(2):e0116768.
doi: 10.1371/journal.pone.0116768. eCollection 2015.

Circulating miRNA-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection

Christian Jansen  1 , Thomas Reiberger  2 , Jia Huang  3 , Hannah Eischeid  3 , Robert Schierwagen  1 , Mattias Mandorfer  2 , Evrim Anadol  1 , Philipp Schwabl  2 , Carolynne Schwarze-Zander  1 , Ute Warnecke-Eberz  4 , Christian P Strassburg  1 , Jürgen K Rockstroh  5 , Markus Peck-Radosavljevic  2 , Margarete Odenthal  3 , Jonel Trebicka  1
Affiliations

Circulating miRNA-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection

Christian Jansen et al. PLoS One. .

Abstract

Background: Introduction of combined antiretroviral therapy (cART) has improved survival of HIV infected individuals, while the relative contribution of liver-related mortality increased. Especially in HIV/HCV-coinfected patients hepatic fibrosis and portal hypertension represent the main causes of liver-related morbidity and mortality. Circulating miRNA-122 levels are elevated in HIV patients and have been shown to correlate with severity of liver injury. However, the association of miRNA-122 levels and hepatic fibrosis and portal hypertension remains to be explored in HIV/HCV coinfection.

Methods: From a total of 74 (31% female) patients with HIV/HCV coinfection were included. Serum levels of miRNA-122 were analyzed by quantitative polymerase chain reaction (PCR) and normalized to SV-40 spike-in RNA. Hepatic venous pressure gradient (HVPG) was measured in 52 (70%) patients and the fibrosis stage was determined in 63 (85%) patients using transient elastography.

Results: The levels of circulating miRNA-122 were increased in HIV/HCV coinfected patients and significantly correlated with the alanine aminotransferase (ALT) (rs = 0.438; p<0.001) and aspartate transaminase AST values (rs = 0.336; p = 0.003), but not with fibrosis stage (p = n.s.). Interestingly, miRNA-122 levels showed an inverse correlation with hepatic venous pressure gradient (HVPG) (rs = -0.302; p = 0.03).

Conclusion: Elevated miRNA-122 levels are associated with liver injury, and with low HVPG. Though, miRNA-122 levels are not suitable to predict the degree of fibrosis, they might function as indicators for portal hypertension in HIV/HCV coinfected patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The Venn-diagram depicts the number of patients receiving HVPG-measurements and fibroscan.
Circulating miRNA-122 levels were measured in seventy-four patients with HIV/HCV coinfection. Hepatic venous pressure gradient (HVPG) was measured in fifty-two patients. The fibrosis stage was determined using transient elastography in 63 patients.
Figure 2
Figure 2. Serum levels of circulating miRNA-122 correlation with ALT-levels and HVPG in HIV/HCV co-infected patients, as well as HVPG with FibroScan.
HVPG correlates (rs = 0.689; p = 1.47*10−7) with transient elastography assessed by FibroScan© (A). The levels of circulating miRNA-122 measured in peripheral blood showed significant correlations with ALT (rs = 0.438; p<0.001) (B) and AST (rs = 0.336; p = 0.003) (C). The levels of circulating miRNA-122 measured in peripheral blood showed significant (rs = 0.−302; p = 0.03) inverse correlation with HVPG (D). Data were presented using Spearman coefficient rs and p-values. The levels of miRNA-122 were normalized to SV40 and shown as the x-fold of SV40.
Figure 3
Figure 3. miRNA-122 could not predict portal hypertension.
AUROC analysis demonstrated that we unfortunatelydid not succeeded to define a cut-off value to predict portal hypertension. (A) AUC of 0.639 (p = 0.214) for detecting an HVPG of 5mmHG. (B) AUC of 0.73 (p = 0.274) for detecting an HVPG of 10mmHg—indicating clinically significant portal hypertension.
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