Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis

Trebicka, Jonel; Anadol, Evrim; Elfimova, N; Strack, I.; Roggendorf, Michael; Viazov, Sergei; Wedemeyer, Inga; Drebber, Uta; Rockstroh, Jürgen K.; Sauerbruch, Tilman; Dienes, Hans‐Peter; Odenthal, Margarete

doi:10.1016/j.jhep.2012.10.015

Cited by 154 publications

(150 citation statements)

References 54 publications

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“…Although there is clear evidence for a close relation between miRNA-21 and hepatic fibrosis, the hepatic level of miRNA-21 correlates with the stage of liver fibrosis [21], and circulating miRNAs are expected to be affected by fibrosis progression [22]. Serum miRNA levels may initially rise following release from inflamed hepatocytes in HCV followed by a drop in the levels with fibrosis progression due to hepatocyte loss and accumulation of extracellular matrix [23]. A significant negative correlation between miRNA-21 levels and staging of liver fi-brosis in non-HCC group was reported in the present study.…”

Section: Discussionmentioning

confidence: 99%

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The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

Harfoush¹,

Meheissen²,

Elwafa³

et al. 2016

AiM

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Background: The discovery of miRNAs circulating in the peripheral blood has opened new directions of research to identify new non-invasive markers for diagnosis of diseases. Aim: The aim of the study was to evaluate the expression levels of circulating plasma miRNAs (miRNA-21 & miRNA-122) in Egyptian patients with chronic uncomplicated and complicated HCV. Patients & Methods: This study was conducted on 60 Chronic HCV infected patients. Patients were divided into three groups (20 patients each): uncomplicated HCV, cirrhosis, and hepatocellular carcinoma (HCC). All patients were subjected to laboratory investigations including complete blood picture, liver function tests. Expression levels of miRNA-21 and -122 in plasma using RT-PCR were determined. Results: MiR-NA-21showed significant fold increase in chronic uncomplicated HCV while significant fold decrease in cirrhotic and HCC groups (P = 0.036). On the other hand, miRNA-122 showed significant fold elevation in both chronic uncomplicated and cirrhotic groups and significant fold decrease in HCC group (P = 0.005). ROC curve analysis for miRNA-122 yielded 68.4% sensitivity and 100% specificity for the differentiation of HCC patients from non-HCC at a cutoff 0.184. Neither miRNA-21 nor miR-NA-122 was a successful predictor for HCC diagnosis. Conclusion: MiRNA-122 can be used as novel non-invasive biomarker for monitoring HCV related disease progression.

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Section: Discussionmentioning

confidence: 99%

“…In another study [29] miRNA-122 expression did not differ significantly between patients with HCC and liver cirrhosis alone. However, several studies have found that the level of serum miRNA-122 was significantly elevated in patients with HCC [23] [30] [31].…”

Section: Discussionmentioning

confidence: 99%

The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

Harfoush¹,

Meheissen²,

Elwafa³

et al. 2016

AiM

View full text Add to dashboard Cite

show abstract

“…Circulating miRNA profiles have been associated with HCV infection in previous studies, although many of these studies were performed in persons with long-term chronic infection in whom liver fibrosis also may have contributed to miRNA abundance (47,48). For example, changes in circulating miR-122 abundance have been reported in persons with chronic HCV infection and also in drug-induced liver injury (40) and nonalcoholic steatohepatitis (47).…”

Section: Discussionmentioning

confidence: 99%

Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

El-Diwany

Wasilewski

Witwer

et al. 2015

J Virol

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Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n ‫؍‬ 11) or persistence (n ‫؍‬ 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (P corrected < 0.05) and a decrease in miR-494 (P corrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n ‫؍‬ 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCEMicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe liver disease. We profiled plasma miRNAs in injection drug users before, during, and (in the people with resolution) after HCV infection. We discovered miRNA signatures of acute and persistent viremia and confirmed these findings two ways: (i) in a separate cohort of people with newly acquired HCV infection and (ii) in an HCV cell culture system. Our results demonstrate that acute HCV infection induces early changes in the abundance of specific plasma miRNAs that may affect the host response to HCV infection. H epatitis C virus (HCV) is a single-stranded positive-sense hepatotropic RNA virus that infects over 170 million people worldwide. Acute HCV infection progresses to chronic infection in ϳ75% of cases (1-3). Little is understood about early hostpathogen interactions due to a lack of representative animal models and the difficulty in studying acute HCV, which is largely asymptomatic.MicroRNAs (miRNAs) are 18-to 25-nucleotide noncoding RNA molecules with widespread gene network regulatory capacity. miRNAs are readily detectable in cell-free compo...

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“…Although the IFNL3 polymorphisms seem not to be associated with fibrosis (28,29), the IFNL3 CC genotype was associated with a state of enhanced immunity that can promote necroinflammation (30). Moreover, reports suggested a role of miR-122 in liver fibrosis (31,32). Since miR-122 regulates HCV replication, it is particularly interesting to investigate its role during fibrosis.…”

mentioning

confidence: 99%

Reduction of MicroRNA 122 Expression in IFNL3 CT/TT Carriers and during Progression of Fibrosis in Patients with Chronic Hepatitis C

Estrabaud

Lapalus

Broët

et al. 2014

J Virol

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The microRNA miR-122 is highly expressed in the liver and stimulates hepatitis C virus (HCV) replication in vitro. IFNL3 (lambda-3 interferon gene) polymorphisms and the expression of miR-122 have been associated with sustained virological response (SVR) to treatment with pegylated interferon plus ribavirin in patients with chronic hepatitis C (CHC). We investigated, in vivo, the relationship between miR-122 expression, IFNL3 polymorphism, fibrosis, and response to PEG-IFN plus ribavirin. IMPORTANCEmiR-122 plays a crucial role during HCV infection. Moreover, it was reported that miR-122 binding within the HCV genome stimulates its replication. Moreover, miR-122 is highly expressed within hepatocytes, where it regulates many cellular pathways. A reduction of miR-122 expression has been suggested to be associated with responsiveness to IFN-based therapy in patients with chronic hepatitis C. Several independent genome-wide association studies reported a strong association between IFNL3 polymorphism and responsiveness to IFN-based therapy. We report here a strong association between the expression of miR-122 and IFNL3 polymorphism that is independent of the response to the treatment. Our data suggest that modification of miR-122 expression may play an important role in the molecular mechanism associated with IFNL3 polymorphism. Moreover, we report a reduction of miR-122 at more advanced stages of fibrosis in patients with chronic hepatitis C.

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Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis

Cited by 154 publications

References 54 publications

The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

Reduction of MicroRNA 122 Expression in IFNL3 CT/TT Carriers and during Progression of Fibrosis in Patients with Chronic Hepatitis C

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