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

  • ️Thu Jan 01 2015

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

Christian Jansen et al. PLoS One. 2015.

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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Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to J.T.), J. & W. Hector-Foundation (M60.2 to J.T.), unrestricted research grants from Roche Austria (to M.P.R.), MSD Austria (to M.P.R.), DZIF TTU HIV Project 05.803, and the German Center for Infection Research (DZIF), Research and Education program of the Medical Faculty of the University of Cologne, German Competence Network for Viral Hepatitis (Hepnet), German Ministry of Education and Research (BMBF), Grant No 01KI0601 (to M.O.), and German Liver Foundation (to M.O.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.