MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma

Table 1 miRNAs patterns in studies enrolling hepatocellular carcinoma patients with hepatitis B virus-related infection

References, period and state	Characteristics of the study	miRNAs Up-regulated	miRNAs Down-regulated	Conclusions
Bandopadhyay M, BMC Cancer, 2014 India Period: NR	Tissue samples obtained from: -16 healthy subjects -16 patients with advanced liver diseases (HBV positive cirrhosis and HCC)	ND	Decreased miR-21, miR-222 and miR-145 expression in patients with advanced liver diseases and HCC in comparison with healthy individuals	Differential modulation of miRNAs expression by HBx protein
Cheong JY, J Korean Med Sci, 2014 Korea Period: NR	Serum samples from: 1439 individuals with either past/ present evidence of HBV infection: -HCC: 417; -LC: 305; -CHB: 313; -SR: 404.	NR	Higher rate of HBV persistence after infection subjects with miR-604 rs2368392 T allele in comparison with miR-604 rs2368392 C allele. Patients with miR-604 T allele may have a higher risk for HBV chronicity Higher rate of the miR-604 T allele in the chronic carrier without HCC	pre-miR-604 rs2368392 polymorphism might confer genetic susceptibility to the occurrence of HCC in HBV related chronic liver disease, and HBV persistence after HBV infection
Connolly E, The American Journal of Pathology, 2008 China Period: NR	Human HCC samples and matched non-tumor liver tissue (19 sets) were obtained from surgical resections of anonymous donors	Up-regulation of miR-17-92 (miR-17, miR-19a, miR-20, and miR-92) and miR-21 occurs in precancerous stages of liver disease and in HCC in comparison with normal liver	NR	The combination of assays presented in the present study supports a role for the miR-17-92 polycistron (all six members) or miR-21 in the maintenance of the malignant transformation of hepatocytes
Coppola N, PLoS One, 2013 Italy Period: April 2007 - March 2011	Tissue samples obtained from: twenty-seven consecutive HBsAg/anti-HBe/HBV-DNA-positive Caucasian patients who were naive to nucleos(t)ide analogues and interferon therapy	Higher miR-125a-5p liver concentrations observed in patients with HBV-DNA plasma levels > 103 IU/mL	NR	In HBsAg/anti-HBe-positive patients, the liver miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression
Dang YW, Asian Pac J Cancer Prev, 2014 China Period: March 2010 and December 2011	89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissue 74/89 pairs were obtained from HBV-related HCC samples	NR	Remarkably downregulation of miR-152 expression in HCC compared to that in adjacent hepatic tissues Lower expression was observed in HBV positive group than in the negative one	miR-152 underexpression is associated with hepatocarcinogenesis, acting as a tumor suppressor miRNA, its lack is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis
Fan MQ, Journal of Experimental and Clinical Cancer Research, 2013 China Period: 2002 -2007, patients were followed until December 2010	100 patients with HCC, undergoing LT 95/100 patients with HBV related cirrhosis Specimens obtained from formalin-fixed paraffin-embedded tissue	NR	Down-regulation of miRNA 20a	miR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Its down-regulation increases the proliferation abilities of HCC cells. miR-20a may represent a novel Potential therapeutic target and biomarker for survival of HCC patients
Fu Y, Oncol Letters, 2013 China Period: NR	Serum and tissues (paired tissue specimens from 25 HCC tissues and adjacent noncancerous hepatic tissues (20 HBV-related HCC) were obtained from patients undergoing surgical resection and compared with 20 healthy subjects	miR-101 is upregulated in human HBV-related HCC serum	miR-101 is downregulated in human HBV-related HCC tissues	Serum miR-101 expression was closely associated with tumoral size of HCC-patients and provides a promising biochemical marker of HBV-related HCC
Gao P, Hepatology, 2011 Hong Kong Period: NR	Formalin fixed, paraffin embedded materials obtained from: -16 patients with dysplastic nodules -29 HCC nodules from 24 patients	Up-regulation of miR-224 in pre-malignant DNs Up-regulation of miR-10b, miR-21, miR-221, and miR-224 in the small HCCs	Down-regulation of miR-145 and miR-199b in pre-malignant DNs Down-regulation of miR-145 and miR-199b in the small HCCs	miRNA deregulation is an early event and accumulated throughout the various steps of HBV-associated hepatocarcinogenesis. Down-regulation of miR-145 and miR- 199b and up-regulation of miR-224 were frequently observed in pre-malignant DNs and these changes persisted throughout HCC development miR-145 is a candidate tumor suppressive miRNA and may play an important role in HCC development
Giray BG, Mol Biol Rep, 2014 Turkey Period: NR	Plasma samples from: -66 HBV-positive patients (CHB: 24, cirrhosis: 22, HCC: 20) -28 healthy controls	mi125b-5p up-regulation in CHB, cirrhosis and HCC in comparison to healthy controls	miR-223-3p down regulation in CHB, cirrhosis and HCC in comparison to healthy controls	miR-125-5 p and miR-223 -3p could be used as novel non-invasive biomarkers of HBV-positive HCC in very early, even at CHB stage of liver disease
Gu H, Mol Cell Biochem, 2013 China Period: April 2001 - March 2009	Tissue samples obtained from 108 patients with HCC, undergoing surgical resection. HBsAg +: 92; HBsAg -: 16	Up-regulation of miR-372 associated with significant poorer recurrence-free survival and overall survival	NR	miR-372 may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients as well as a promoter of tumorigenicity of HCC and may be a prospective therapeutic target for this malignancy
Gui J, Clinical Science, 2011 China Period: November 2008 - January 2010	Serum samples from: 25 HBV-positive patients (LC: 10, HCC: 15) -10 age-matched healthy controls	Up-regulation of miR-885-5p, miR-574-3p, miR-224, miR-215 and miR-146a in the HCC and LC patients	NR	miR-885-5p is significantly elevated in the sera of patients with liver pathologies miRNAs could serve as novel complementary biomarkers for the detection and assessment of liver pathologies
Han Y, PLoS One, 2013 China Period: -September 2009 - June 2010 -October 2009 to September 2011	Serum samples from: 1,012 healthy controls, 302 HBV natural clearance subjects, 316 ASCs, 316 patients with CHB, 358 HBV-infected patients with LC, and 1,021 HBV-infected patients with HCC Pri-miR-34b/c rs4938723 HBV-HCC patients: 311 HBV-infected subjects without HCC: 210 Pre-miR-196a2 rs11614913 HBV-HCC patients: 255 HBV-infected subjects without HCC: 170	NR	NR	Association of pri-miR-34b/c rs4938723 with a significant increased risk of HCC, mainly in women No statistically significant association of pre-miR-196a2 rs11614913 with HCC risk. pre-miR-196a2 rs11614913 may enhance the effect of primiR-34b/c rs4938723 in women rs4938723 CC genotype and rs11614913 TC genotype might predispose the host to immune selection of T1674C/G, and G1896A, respectively The rs4938723 effect on HCC risk can be seriously affected by the HBV mutations
Hou J, Cancer Cell, 2011 China Period: NR	Tissue samples obtained from 40 HCC patients with CHB	NR	Consistent miR-199a/b-3p decrease in HCC, and its reduction significantly correlates with poor survival of HCC patients	miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases
Huang J, Hepatology, 2010 China Period: NR	20 HBV-related HCC tissues and the corresponding nearby noncancerous livers	NR	Down-regulation of miR-152 in human HBV-related HCC Tissues	Tumor suppressive role of miR-152 in the epigenetic aberration of HBV-related HCC and the potential development of miRNA-based targeted approaches for the treatment of HBV-related HCC
Huang YH, PLoS One, 2012 China Period: July 1998 - Aug 2004	Tissue samples obtained from: 228 patients with HCC, 12 with known better and poorer prognosis subjected for the first-step (pilot) study; 6 patients had a RFS time for more than 5 yr (better prognosis) and 6 had rapid relapse within six-month after operation (poorer prognosis)	High expression levels of miR-30c, miR-155, miR-432, miR-15b, and miR-30b associated with shorter RFS High miR-15a, miR-486-3p, and miR-381 expression significantly predicted a longer RFS High expression level of miR-29a, miR-486-3p, and miR-876-5p significantly predicted a longer OS	NR	Significant prognostic miRNA predictors identified through examination of miRNA expression levels in paraneoplastic liver tissues. Functional analysis of miR-155, suggested that the prognostic miRNA predictors identified under this strategy could serve as potential molecular targets for anticancer therapy
Jiang R, Clin Cancer Res, 2011 China Period: January 2001 - August 2009	Liver tissue obtained from: 116 HBV-related HCC patients 48 subjects with benign conditions	up-regulation of miR-22 in male tumor adjacent tissue	NR	Overexpression of miR-22 in male tumor adjacent tissue associated with down-regulated ERa expression, potentially causing the attenuation of the protective effect of estrogen and inducing increased IL-1a expression. These results may explain the high incidence of HBV-associated HCC in the male population
Kim HY, J Med Virol, 2014 South Korea Period: NR	Serum samples obtained from: 1439 Korean patients with either past or present HBV infection, -404 control subjects with spontaneous Recovery; -1035 subjects with chronic HBV (313 with chronic hepatitis B, 305 with liver cirrhosis, 417 with HCC)	NR	NR	Protective effect of miR-196a-2 rs12304647 CC genotype against development of HCC in comparison to the AA or AC genotypes in patients with chronic hepatitis and cirrhosis
Kwak MS, PLoS One, 2012 South Korea Period: January 2001 - August 2003	1439 Korean subjects with past or persistent HBV infection: SR: 404 CHB: 313 chronic LC: 305 HCC : 417	Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are upregulated in HCC	NR	Among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes
Lan SH, Hepatology, 2014 Taiwan Period: NR	Tissue and specimens, obtained from patients from Taiwan patients with HCC	The level of autophagy was low and inversely Correlated with miR-224 expression only in HBV associated HCC	NR	A noncanonical pathway links autophagy, miR-224, Smad4, and HBV-associated HCC
Li J, Biochemical and Biophysical Research Communications, 2011 China Period: NR	Serum samples of HCC were obtained from 46 patient (30 HBsAg positive) The healthy sera were collected from 50 age-matched healthy individuals who serves as normal controls	Serum miR-221, up-regulation in HCC, correlates with tumor size, cirrhosis and tumor stage	NR	Serum miR-221, upregulated in HCC, can provide predictive significance for prognosis of HCC patients
Li L, Digestive Diseases and Sciences, 2012 China Period: NR	Serum samples obtained from: HCC: 101 (HBsAg +) CLD and cirrhosis: 30 Healthy controls: 60	miR-18a significantly up-regulated in HBV- related HCC, chronic hepatitis or cirrhosis than those in healthy Controls	NR	Significant increase of elevated serum miR-18a in the patients of HBV-related HCC. It might serve as a novel noninvasive biomarker to distinguish patients with HBV-related HCC from healthy subjects, and further from those with HBV-related chronic hepatitis or cirrhosis
Li LM, Cancer Research, 2010 China Period: September 2007 - July 2008	Serum samples from: -120 HCC-affected individuals; -135 HBV carriers; -48 HCV carriers; -210 controls	Serum up-regulation of miR-375, miR-92a, miR-10a, miR-223, miR-423, miR-23b/a, miR-342-3p, miR-99a, miR-122a, miR-125b, miR-150, and let-7c. in HBV positive patients with HCC in comparison with healthy controls	NR	The expression profile of serum miRNAs can serve as novel non-invasive biomarkers for the diagnosis of HBV infection and HBV positive HCC. The use of 3 miRNAs: miR-25, miR-375, and let-7f could be used to separate HCC cases from controls, miR-375 alone had high specificity and sensitivity in HCC prediction
Li T, Oncology Reports, 2014 China Period: NR	Tissue and plasma obtained from: 31 patients with HBV-related HCC 31 age- and gender-matched CHB patients	Tissue miRNA-21, miRNA-221, miRNA-148b and miRNA-186 over-expression	Tissue miRNA-99a, miRNA-27b, miRNA-378a, miRNA-378e and miRNA-30 down-regulation Tissue and plasma miRNA-139 down-regulation in HCC vs non-HCC patients	miRNA-139 is downregulated in both cancerous tissue and plasma of HCC. The plasma miRNA-139 is a possible diagnostic biomarker for identifying HCC patients while combined with other biomarkers, it is also a prognostic factor for indicating patient survival
Li W, Int J Cancer, 2008 China Period: NR	Specimens obtained obtained from: 78 human primary hepatocellular carcinoma (68 HBsAg +) and matched noncancerous liver tissues	84 miRNAs identified with deregulated expression in tissues from HCC patients. 69/84 miRNAs resulted differentially expressed in normal or non-tumour liver tissue vs cancerous hepatic tissue with 29 miRNAs up-regulated -Noncancerous vs normal liver tissue: 27 miRNAs differentially expressed, with 14 up-regulated in noncancerous liver specimens -HCC vs normal tissue: 55 differentially expressed miRNAs, with 29 up-regulated in HCC tissues	84 miRNAs identified with deregulated expression in tissues from HCC patients. 69/84 miRNAs resulted differentially expressed in normal or non-tumour liver tissue vs cancerous hepatic tissue with 40 miRNAs down-regulated Noncancerous vs normal liver tissue: 27 miRNAs differentially expressed, with 13 down-regulated in noncancerous liver specimens -HCC vs normal tissue: 55 differentially expressed miRNAs, with 26 down-regulated in HCC tissue	miRNA signature identified as a HCC diagnostic discriminator from both noncancerous and normal liver tissues. This is the first report to identify single miRNA correlated to the HCC prognosis, i.e., miR-125b as a HCC survival predictor
Liu AM, BMJ Open, 2012 China Period: 1990-2007	Serum and Cancerous/non tumors tissue samples collected from: - 96 cirrhotic patients with HCC (84 HBsAg positive) undergoing hepatectomy (exploration phase) -29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls (validation phase)	Exploration phase in resected tumour/adjacent non-tumour tissues: Upregulated miR in the AFP-low (< 400 ng/mL) HCC subgroup: miR-9, -9*, -15b, -21, -34c, -96, -130b, -183, -188, -196b, -216, -224, -301 and -324-5p Upregulated miR in all HCC samples of varying serum AFP levels: miR-15b, -21, -130b, -183, -224 and -301	Decreased serum miR-224 and miR-301 levels in HCC patients post-surgery in comparison with pre- surgery. Slight reduction of serum miR-15b and miR-130b levels in HCC patients post-surgery in comparison with pre- surgery	The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value (high sensitivity and accuracy) for HCC screening. This classifier also identified early-stage HCC cases that could not be detected by AFP
Liu Y, PLoS One, 2012 China Period: January 2006- December-10 Controls screened for the HBV/HCV markers in 2004 and 2009	Serum samples collected from: - 1300 HBV positive HCC cases, -1344 HBV persistent carriers; - 1344 subjects with HBV natural clearance people These patients were matched to the HCC cases on age and gender	NR	NR	A genetic variant in the promoter region of miR-106b-25 cluster might provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by affecting the expression of miR-106b-25 cluster A to G base change of rs999885 may have a protective effect on the probability to develop chronic HBV infection, but increased the risk of HCC in HBV persistent carriers
Liu Y, J Med Virol, 2014 China Period: April 2008 - November 2011 Newly diagnosed HCC patients included from January 2006 - December 2010 HBV carriers and patients with signs oif past HBv infection, screened from 2004 to 2009	Samples obtained from: 29 pairs of HCC and adjacent noncancerous liver tissues	NR	In noncancerous liver tissues, subjects with a CA genotype exhibited significantly lower expression level of pri-miR-122 than those carrying the CC genotype. Positive or inverse correlation between the expression levels of pri-miR-122 and mature miR-122 were observed in HCC tissues or oncancerous tissues, respectively	The C to A base change of rs4309483 may alter the expression of miR-122, thus providing protective effect from chronic HBV infection but an increased risk for HCC in HBV carriers
Meng FL, Med Oncol, 2014 China Period: January 2009 - December 2011	Tissue obtained from: 84 patients with HBV-related HCC 31 with CLDs 46 with healthy controls	Tissue miR-24-3p over-expression in HCC in comparison with healthy controls and CLD	NR	The combination of serum miR-24-3p and AFP improves the diagnostic accuracy for HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an independent predictor of overall survival and disease free-survival. In patients with HBV-related HCC
Qi, F, PLoS One, 2014 China Period: NR	Serum samples obtained from 331 patients with HBV-related HCC in either intermediate or advanced stage of disease without surgery	NR	NR	miR-106b-25 cluster plays oncogenic roles in cancers through influencing tumor growth, cell survival, and angiogenesis. rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) . rs999885 variant could influence miR-106b-25 expression and the expression levels of miR-106b-25 were significantly higher in AG/GG carriers than that in AA carriers G allele of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese
Qi P, PLoS One, 2011 China Period: NR	Study divided into four phases. Serum samples obtained from: (I phase) -10 HBV-positive HCC patients and -10 age- and sex-matched healthy subjects; (II phase) before surgery, sera from another 48 HBV-positive HCC patients, from 48 chronic HBV infection patients without HCC and 24 age- and sex-matched healthy subjects; (III phase) 14 HCC patients before and after surgery, (IV phase) correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients	Up-regulation of serum miR-122, miR-222 and miR-223 in HCC patients in comparison with healthy controls	Down-regulation of serum miR-21 in HCC patients in comparison with healthy controls	Serum miR-122 might serve as a novel and potential biomarker for detection of HCC in healthy subjects and it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients
Tan Y, PLoS One, 2014 China Period: August 2010 - June 2013	Serum samples obtained from: HCC: 261, LC: 133; Healthy controls:173	up-regulation: miR-190b; miR-141-3p; miR-4532; mir-6127; miR-99b-3p; miR-1228-5p between HCC and healthy controls up-regulation: miR-206, mir-1285-1-p5, miR-10a-5p ,miR-511-5p, miR-433-3p between HCC and cirrhosis groups	Down-regulation: miR-30a-3p; miR-199a-5p ; let-7f-5p ; miR-122-5p ; miR-192-5p; miR-98-5p; miR-574-3p; miR-30e-3p; miR-6852-5p between HCC and healthy controls Down-regulation: miR-100-5p; miR-483-5p, miR-584-5p; miR-28-5p miR-30b-5p; miR-30c-5p ; miR-26a-5p; miR-4454; let-7e-5p; let-7c-5p; miR-4433b-5p between HCC and cirrhosis groups	A serum panel of miRNA with considerable clinical value in HCC diagnosis was identified. miR-206, miR-141-3p, miR-433-3p, miR-1228-5p, miR-199a-5p, miR-122-5p, miR-192-5p, and hsa-miR-26a-5p as potential circulating markers for HCC diagnosis
Wei X, Cellular Signalling, 2013 China Period: NR	Serum and tissues (paired tissue specimens from HBV-related HCC tissues and adjacent noncancerous hepatic tissues)	NR	miR-132 is more frequently downregulated in HBV-positive HCCs tumor tissues than in adjacent noncancerous tissues and has a significant inverse correlation with HBx expression in HBV-related HCCs	miR-132 may play a tumor-suppressive role in HBV-related HCC development. Serum miR-132 levels are closely correlated with miR-132 expression levels in tumor tissues. miR-132 may be a promising biochemical marker and may have therapeutic applications in HBV-related HCC
Wen Y, Int J Cancer, 2015 China Period (3 phases): December 2010- December 2011 January 2010- December 2012 2004-2005	Multicenter, three-phase study to screen liver-originated HCC-associated plasma miRNAs in both plasma and tissue samples The training set consisted of 35 HCC cases and 50 cancer-free HBV carriers who were frequency matched for age and sex, whereas the validation set consisted of 32 HCC cases and 32 matched cancer-free HBV carriers	Up-regulation of miR-221, miR-222, miR-31	Down-regulation of miR-126, and miR-122a miR-223	miR-223 may represent a potential target in cancer therapy because it regulates Stathmin 1
Xiang Y, Mol Biol Rep, 2012 China Period: December 2009 - February 2011	Specimens obtained from: -100 patients with HCC (73 HBV positive); -100 patients with CHB; -100 healthy subjects	NR	NR	miRNA 499 polymorphisms is associated with susceptibility in HBV-related HCC in Chinese population. The risk of HCC development is increased in patients with miR-399 C/C was higher in comparison with subjects with miR 499 T/T
Xie Y, Cancer Biology and Therapy China Period: NR	Specimens and tissue samples obtained from: -67 HBV-HCC patients, -61 HBV-LC patients, -79 CHB patients, -30 Healthy subjects	Elevated miR-101 levels in the sera and liver tissues of HBV-LC patients and decreased in HBV-HCC patients	NR	Serum miR-101 as a potential biomarker for monitoring the development of HBV-HCC from HBV-LC and the development of HBV-LC from CHB
Xing TJ, Genetics and Molecular Research, 2014 China Period: NR	Serum samples obtained from: HCC: 20 patients; LC: 20 patients; CHB: 29 patients; ASC: 20 patients; Healthy controls: 20	Increased miRNA-122 levels in patients with HCC and CHB vs patients with HC, LC, and ASC	lower miRNA-29 serum levels in LC patients than those in the healthy controls	The elevation in miR-122 was correlated with liver damage in CHB patients and with the pathogenesis of liver cancer in HCC patients. The decrease in miR-29 expression was related to the incidence of liver fibrosis
Xu J, Molecular Carcinogenesis, 2011 China Period: NR	Serum samples obtained from: -101 patients with advanced primary HCC (78 HBsAg +), -48 patients with CHB, -89 healthy controls	Higher serum miR-21, miR-122, and miR-223 levels in patients with HCC or CHB, compared with healthy controls	NR	Serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC
Zhang H, WJG, 2012 China Period: NR	Serum samples obtained from patients with: -34 CHB, -20 NASH -34 healthy donors Serum samples from 10 CHB patients and 10 controls were subjected to miRNA microarray analysis to obtain serum miRNA profiles	Up-regulation of miR-122, miR-138, miR-638, hsv1-miR-H1, miR-575, miR-572, kshv-miR-K12-3, miR-1915, miR-623, miR-1268, miR-939, miR-498	Down-regulation of: miR-421, miR-598, miR-155, miR-424, miR-23b, miR-195, miR-487b, miR-224, miR-495, miR-181c, miR-654-3p, let-7e, miR-382, miR-171, miR-128, miR-625, miR-30e1, miR-139-5p, miR-30c, miR-744, miR-374b, miR-376c	Serum levels of miR-122, -572, -575, -638 and -744 are deregulated in patients with CHB or NASH. The levels of these miRNAs may serve as potential biomarkers for liver injury caused by CHB and NASH
Zhang T, Neoplasia, 2013 China Period: NR	Samples obtained from cancerous tissues of thirty-three patients with HBV-related HCC and their corresponding nearby nontumorous liver tissues	NR	HBx-mediated downregulation of miR-205 through the induction of miR-205 promoter hypermethylation	HBx is able to inhibit tumor suppressor miR-205. miR-205 may be useful in the treatment of HCC
Zhang ZZ, WJG, 2011 China Period: NR	miRNA expression profiles obtained from 78 HCC patients from Gene Expression Omnibus study	8/ 10 differentially expressed miRNAs common to the AHB infection and HCC datasets were inversely changed, only 3/8 differentially expressed miRNAs common to the chronic HBV infection and HCC datasets exhibited opposite alterations	8/ 10 differentially expressed miRNAs common to the AHB infection and HCC datasets were inversely changed, only 3/8 differentially expressed miRNAs common to the chronic HBV infection and HCC datasets exhibited opposite alterations	miRNA level is correlated in HBV infection and HCC
Zhao Q, PLoS One, 2014 China Period: February 2012 - January 2013	Serum and cancerous and non-tumors tissue samples obtained from: -66 patients with HBV-related HCC patients -11 hepatic hemangioma Patients	Up-regulation of miR-545/374a cluster in HBV-HCC tissue	NR	The overexpression of miR-545/374a cluster is partially responsible for a poor prognosis, and monitoring sera levels of miR-545/374a may be a useful diagnostic marker for HCC
Zhou J, J Clin Oncol, 2011 China Period: August 2008 - June 2010	934 blood samples, from healthy subjects patients with CHB, cirrhosis or HCC	High expression levels of miR-192, miR-21, and miR-801 in patients with HCC compared with those in the control group	Low expression levels of miR-122, miR-223, miR-26a, and miR-27a observed in patients with HCC compared with those in the control group	miR panel with considerable clinical value in diagnosing early-stage of HBV-related HCC
Zhu HT, PLoS One, 2012 China Period: January 2004 - December 2008	Tissue obtained from:	Up-regulation in microdissected HCC tissue with early recurrence: miR-29a-5p, miR-27b*, miR-204, miR-29c, miR-10b, miR-	Down-regulation in microdissected HCC tissue with early recurrence:	In the multivariate analyses, miR-29a-5p was identified as an independent factor for tumor recurrence. miR-29a-5p might be a useful marker for the prediction of early tumor recurrence after HCC resection, especially in BCLC 0/A stage HCCs
	266 patients, undergoing curative liver resection for HCC 48 patients subdivided into: -group with early recurrence (24) -group without early recurrence (24) 218 patients enrolled into: training (106) and validation (112) cohort	196b, miR-216a, miR-217, miR-517a, miR-518e, miR-518f, miR-518b, miR-519a, miR-519d, miR-522, miR-486-5p, miR-181c, miR-210, miR-215 Up-regulation in microdissected non-tumorous liver tissue with early recurrence: miR-486-5p, miR-181c, miR-193b*, miR-643, miR-409-3p, miR-424*, miR-139-3p, miR-766	miR-193b*, miR-643, miR-22, miR-15b, miR-505, miR-107, miR-142-5p, miR-135a, miR-34c-5p, miR-98, miR-483-5p Down-regulation in microdissected non-tumorous liver tissue with early recurrence: miR-210, miR-215, miR-22, miR-409-5p, miR-200a*, miR-10b*

ABH: Acute B hepatitis; ASCs: Asymptomatic HBsAg carriers; BCLC: Barcelona clinic liver cancer staging system; CHB: Chronic hepatitis B; CLD: Chronic liver disease; ER-α: Estrogen receptor-α; FNH: Focal nodular hyperplasia; HCC: Hepatocellular carcinoma; HC: Healthy controls; HCA: Hepatocellular adenoma; LC: Liver cirrhosis; LT: Liver transplantation; NR: Not reported; OS: Overall survival; RFS: Recurrence-free survival; SR: Spontaneously recovered.