Research Article

Evaluation of miR-122 Serum Level and IFN-λ3 Genotypes in Patients with Chronic HCV and HCV-Infected Liver Transplant Candidate

Author(s): Javad Moayedi, Tayebeh Hashempour*, Zahra Musavi, Ehsan Arefian, Mahmood Naderi, Mohamad Reza Heidari, Behzad Dehghani, Zahra Hasanshahi and Shahin Merat

Volume 10 , Issue 1 , 2021

Published on: 17 December, 2020

Page: [58 - 65] Pages: 8

DOI: 10.2174/2211536609666201217101414

Price: $65


Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease.

Objective: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease.

Methods: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured.

Results: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage.

Conclusion: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Keywords: Hepatitis C virus, liver transplant candidates, miR-122, ALT, AST, Chronic Hepatitis C (CHC).

Graphical Abstract
Sarvari J, Mojtahedi Z, Kuramitsu Y, et al. Comparative proteomics of sera from HCC patients with different origins. Hepat Mon 2014; 14(1): e13103.
[PMID: 24497876]
Hashempoor T, Alborzi AM, Moayedi J, et al. A decline in anti-core+ 1 antibody titer occurs in successful treatment of patients infected with hepatitis C virus. Jundishapur J Microbiol 2018; 11(2): e58294.
Alborzi AM, Bamdad T, Davoodian P, Hashempoor T, Nejatizadeh AA, Moayedi J. Insights into the role of HCV plus-/minus strand RNA, IFN-γ and IL-29 in relapse outcome in patients infected with HCV. Asian Pac J Allergy Immunol 2015; 33(3): 173-81.
[PMID: 26342113]
Lin J, Wu J-F, Zhang Q, Zhang H-W, Cao G-W. Virus-related liver cirrhosis: Molecular basis and therapeutic options. World J Gastroenterol 2014; 20(21): 6457-69.
[] [PMID: 24914367]
Asaoka T, Hernandez D, Tryphonopoulos P, et al. Clinical significance of intragraft miR-122 and -155 expression after liver transplantation. Hepatol Res 2015; 45(8): 898-905.
[] [PMID: 25220676]
Freeman ZT, Cox AL. Lessons from nature: Understanding immunity to HCV to guide vaccine design. PLoS Pathog 2016; 12(6): e1005632.
[] [PMID: 27362419]
Yaghobi R, Kazemi M, Geramizadeh B, Malek SH, Moayedi J. Significance of occult hepatitis c virus infection in liver transplant patients with cryptogenic cirrhosis. Exp Clin Transplant 2018; 16(5): 1-4.
[PMID: 30346262]
Laterza OF, Scott MG, Garrett-Engele PW, Korenblat KM, Lockwood CM. Circulating miR-122 as a potential biomarker of liver disease. Biomarkers Med 2013; 7(2): 205-10.
[] [PMID: 23547815]
Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67(1): 6-19.
[] [PMID: 29122851]
Fallatah HI. Noninvasive biomarkers of liver fibrosis: An overview. Adv Hepatol 2014; 2014(357287): 1-15.
Halász T, Horváth G, Pár G, et al. miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan. World J Gastroenterol 2015; 21(25): 7814-23.
[] [PMID: 26167081]
Motawi TM, Sadik NA, Shaker OG, Ghaleb MH. Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer. Tumour Biol 2016; 37(7): 9865-74.
[] [PMID: 26812693]
Wang K, Yuan Y, Cho J-H, McClarty S, Baxter D, Galas DJ. Comparing the microRNA spectrum between serum and plasma. PLoS One 2012; 7(7): e41561.
[] [PMID: 22859996]
Butt AM, Raja AJ, Siddique S, et al. Parallel expression profiling of hepatic and serum microRNA-122 associated with clinical features and treatment responses in chronic hepatitis C patients. Sci Rep 2016; 6: 21510.
[] [PMID: 26898400]
Hu J, Xu Y, Hao J, Wang S, Li C, Meng S. MiR-122 in hepatic function and liver diseases. Protein Cell 2012; 3(5): 364-71.
[] [PMID: 22610888]
Shimakami T, Yamane D, Jangra RK, et al. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA 2012; 109(3): 941-6.
[] [PMID: 22215596]
García-Sastre A, Evans MJ. MiR-122 is more than a shield for the hepatitis C virus genome. Proc Natl Acad Sci USA 2013; 110(5): 1571-2.
[] [PMID: 23324744]
Li X-N, Yang H, Yang T. MiR-122 inhibits hepatocarcinoma cell progression by targeting LMNB2. Oncol Res 2020; 28(1): 41-9.
[] [PMID: 31558184]
Roderburg C, Benz F, Vargas Cardenas D, et al. Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases. Liver Int 2015; 35(4): 1172-84.
[] [PMID: 25039534]
Köberle V, Waidmann O, Kronenberger B, et al. Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy. J Viral Hepat 2013; 20(8): 530-5.
[] [PMID: 23808991]
Bihrer V, Friedrich-Rust M, Kronenberger B, et al. Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol 2011; 106(9): 1663-9.
[] [PMID: 21606975]
Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 2011; 6(8): e23937.
[] [PMID: 21886843]
Starkey Lewis PJ, Dear J, Platt V, et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 2011; 54(5): 1767-76.
[] [PMID: 22045675]
Waidmann O, Bihrer V, Pleli T, et al. Serum microRNA-122 levels in different groups of patients with chronic hepatitis B virus infection. J Viral Hepat 2012; 19(2): e58-65.
[] [PMID: 22239527]
Xu J, Wu C, Che X, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011; 50(2): 136-42.
[] [PMID: 21229610]
Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010; 56(12): 1830-8.
[] [PMID: 20930130]
Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 2009; 28(40): 3526-36.
[] [PMID: 19617899]
Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 2009; 284(46): 32015-27.
[] [PMID: 19726678]
Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G, Voros D. Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog 2013; 52(4): 297-303.
[] [PMID: 22213236]
Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009; 461(7265): 798-801.
[] [PMID: 19759533]
Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461(7262): 399-401.
[] [PMID: 19684573]
Eurich D, Boas-Knoop S, Bahra M, et al. Role of IL28B polymorphism in the development of hepatitis C virus-induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy. Transplantation 2012; 93(6): 644-9.
[] [PMID: 22411462]
Sharafi H, Pouryasin A, Alavian SM, et al. Distribution of IL28B genotypes in Iranian patients with chronic hepatitis C and healthy individuals. Hepat Mon 2012; 12(12): e8387.
[] [PMID: 23550102]
Sarrazin C, Susser S, Doehring A, et al. Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011; 54(3): 415-21.
[] [PMID: 21112657]
Estrabaud E, Lapalus M, Broët P, et al. Reduction of microRNA 122 expression in IFNL3 CT/TT carriers and during progression of fibrosis in patients with chronic hepatitis C. J Virol 2014; 88(11): 6394-402.
[] [PMID: 24672032]
Su TH, Liu CH, Liu CJ, et al. Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C. Proc Natl Acad Sci USA 2013; 110(19): 7844-9.
[] [PMID: 23613588]
Hao J, Jin W, Li X, et al. Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol 2013; 87(1): 137-47.
[] [PMID: 23055569]
Shin JI, Eisenhut M. miR-122, IL28B genotype and the response to interferon in chronic hepatitis C virus infection. Nat Rev Immunol 2013; 13(12): 902.
[] [PMID: 24270782]
Lai M, Afdhal NH. Clinical utility of interleukin-28B testing in patients with genotype 1. Hepatology 2012; 56(1): 367-72.
[] [PMID: 22511388]
Melis R, Fauron C, McMillin G, et al. Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response. J Mol Diagn 2011; 13(4): 446-51.
[] [PMID: 21704279]
He J, Yu G, Li Z, Liang H. Influence of interleukin-28B polymorphism on progression to hepatitis virus-induced hepatocellular carcinoma. Tumour Biol 2014; 35(9): 8757-63.
[] [PMID: 24874053]
Alborzi A, Hashempour T, Moayedi J, Musavi Z, Pouladfar G, Merat S. Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients. Med Microbiol Immunol (Berl) 2017; 206(2): 165-74.
[] [PMID: 28214926]
Tang G, Shen X, Lv K, Wu Y, Bi J, Shen Q. Different normalization strategies might cause inconsistent variation in circulating microRNAs in patients with hepatocellular carcinoma. Med Sci Monit 2015; 21(1): 617-24.
[PMID: 25719241]
Li Y, Zhang L, Liu F, Xiang G, Jiang D, Pu X. Identification of endogenous controls for analyzing serum exosomal miRNA in patients with hepatitis B or hepatocellular carcinoma. Dis Markers 2015; 2015(893594): 893594.
[] [PMID: 25814782]
Schlosser K, McIntyre LA, White RJ, Stewart DJ. Customized internal reference controls for improved assessment of circulating MicroRNAs in disease. PLoS One 2015; 10(5): e0127443.
[] [PMID: 26010841]
Choi Y, Dienes H-P, Krawczynski K. Kinetics of miR-122 expression in the liver during acute HCV infection. PLoS One 2013; 8(10): e76501.
[] [PMID: 24124569]
Zhu H-T, Dong Q-Z, Wang G, et al. Identification of suitable reference genes for qRT-PCR analysis of circulating microRNAs in hepatitis B virus-infected patients. Mol Biotechnol 2012; 50(1): 49-56.
[] [PMID: 21567136]
Waidmann O, Köberle V, Brunner F, Zeuzem S, Piiper A, Kronenberger B. Serum microRNA-122 predicts survival in patients with liver cirrhosis. PLoS One 2012; 7(9): e45652.
[] [PMID: 23029162]
Trebicka J, Anadol E, Elfimova N, et al. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J Hepatol 2013; 58(2): 234-9.
[] [PMID: 23085648]
Júlia C, Daiane R, Rode MP, et al. MicroRNA profiles in serum samples from acute-on-chronic liver failure patients and miR-25-3p as a potential biomarker for survival prediction. Sci Rep 2020; 10(1): 1-12.
[PMID: 31913322]
Hussein RM, Anwar MM, Farghaly HS, Kandeil MA. Gallic acid and ferulic acid protect the liver from thioacetamide-induced fibrosis in rats via differential expression of miR-21, miR-30 and miR-200 and impact on TGF-β1/Smad3 signaling. Chem Biol Interact 2020; 324(109098): 109098.
[] [PMID: 32278740]
Merat S, Rezvan H, Nouraie M, et al. Seroprevalence of hepatitis C virus: The first population-based study from Iran. Int J Infect Dis 2010; 14(3)(Suppl. 3): e113-6.
[] [PMID: 20362479]
El-Garem H, Ammer A, Shehab H, et al. Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma. World J Hepatol 2014; 6(11): 818-24.
[] [PMID: 25429320]
Zekri AN, Youssef ASE-D, El-Desouky ED, et al. Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection. Tumour Biol 2016; 37(9): 12273-86.
[] [PMID: 27271989]
Gholami M, Ravanshad M, Alavian S-M, Baesi K, Moallemi S. Evaluation of miR-122 level in the plasma of chronically HCV infected patients. Mol Biol (Mosk) 2016; 50(2): 279-83.
[] [PMID: 27239848]
van der Meer AJ, Farid WR, Sonneveld MJ, et al. Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat 2013; 20(3): 158-66.
[] [PMID: 23383654]

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