Serum miR-122 as a Biomarker of Necroinflammation in Patients With Chronic Hepatitis C Virus Infection

Abstract

OBJECTIVES: The liver contains large amounts of microRNA-122 (miR-122), whereas other tissues contain only marginal amounts of this miRNA. MicroRNAs have also been found to circulate in the blood in a cell free form; their potential as readily accessible disease markers is currently evaluated. Here we investigated if the serum levels of miR-122 might be useful as disease parameter in patients with chronic hepatitis C virus (HCV) infection.METHODS: RNA was extracted from sera of patients with chronic HCV infection and healthy controls and was analyzed for miR-122 content by quantitative real-time reversetranscription PCR and for standard parameters of liver function. Liver biopsies from the same patients were examined for the histologic activity index (HAI) and the degree of fibrosis.RESULTS: Sera from patients with chronic HCV infection contained higher levels of miR-122 than sera from healthy controls. Serum miR-122 levels correlated well with markers of liver inflammatory activity, i. e. serum levels of alanine leucine transaminase (ALT) and aspartate transaminase, and the HAI score. In patients with persistently normal ALT levels, serum miR-122 levels did not differ from healthy controls. There was no correlation of serum miR-122 levels with serum albumin, international normalized ratio, liver fibrosis or serum HCV RNA.CONCLUSIONS: The serum level of miR-122 strongly correlates with serum ALT activity and with necroinflammatory activity in patients with chronic HCV infection and elevated ALT levels, but not with fibrosis stage and functional capacity of the liver.

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

“…Recent studies convincingly showed that miRNAs stably present in human serum or plasma samples by the carriers of exosomes or argonaute2 (Ago2) complex (16,17), and may be used as diagnostic markers in several cancers (18,19). Serum miR-122 has been implicated as a potential biomarker in drug-, alcohol-, hepatitis B virus-, or HCV-related liver diseases and HCC (20)(21)(22)(23)(24). However, the role of serum miR-122 in the management of CHC remains largely unknown and deserves further investigations.…”

MicroRNAs in Liver Disease: Bench to Bedside

“…40,44,45 Serum/plasma levels of miR-122 correlate with hepatic necro-inflammation, liver damage, cell death and increased aminotransferase levels in acute and chronic liver diseases. 44,[46][47][48][49] Interestingly, hepatic and circulating miR-122 levels do not correlate in NAFLD 14,39,[50][51][52][53][54][55] or viral hepatitis 41,47,49,56 although both have been statistically associated with various measures of disease severity in these studies. Together these studies show that miR-122 may play a role in most liver diseases.…”

“…58 MiRs are likely to have a role in viral hepatitis as cellular miRs play an important role in viral pathogenesis. 59 The level of plasma miR-122 exhibits an excellent correlation with the necroinflammatory activity of HBV 41 and HCV 47 infections. Altered miR expressions during virus infection include host miRs that target virus sequences and host genes to modulate and influence viral replication.…”

Liver Specific Serum Micro RNA122 as a Prognostic Marker in Egyptian Patients with Liver Cirrhosis

“…As well as in sera or plasma from humans and rodents upon toxic liver injury [20][21][22]. Moreover, circulating miR-122 has been proposed as a marker of infl ammation in patients with chronic hepatitis C viral infection [23].…”

“…(miRNAs, miRs) are small (18)(19)(20)(21)(22)(23)(24)(25) ribonucleotides) non-coding RNAs which function in transcriptional and post-transcriptional regulation of gene expression [11]. Circulating miRs are,in large part, derived from cells with damaged plasma membrane [12] and circulate in the blood freely and in a relatively stable form [13,14].…”