Fibrosis Stage In Patients Research Articles

Correction: Prospective comparison among transient elastography, supersonic shear imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease.

[This corrects the article DOI: 10.1371/journal.pone.0188321.].

Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B.

Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P<.001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n=219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P<.01) and tended to better than the fibrosis-4 (P=.0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P=.1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P<.05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P=.2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P<.05) models and was comparable with Forn (P=.1649). These results was validated by a validation set (n=198). FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.

Su1507 - Serum Bile Acids Alteration is Associated with the Presence of NAFLD in Twins, and Dose-Dependent Changes with Increase in Fibrosis Stage in Patients with Biopsy-Proven NAFLD

Su1507 - Serum Bile Acids Alteration is Associated with the Presence of NAFLD in Twins, and Dose-Dependent Changes with Increase in Fibrosis Stage in Patients with Biopsy-Proven NAFLD

Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies.

In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.

PS-054 - Serum bile acids alteration is associated with the presence of NAFLD in twins, and dose-dependent changes with increase in fibrosis stage in patients with biopsy-proven NAFLD

PS-054 - Serum bile acids alteration is associated with the presence of NAFLD in twins, and dose-dependent changes with increase in fibrosis stage in patients with biopsy-proven NAFLD

FRI-428 - Comparison of ElastPQ Shear-wave Elastography (ElastPQ-SWE) and FibroScan Transient Elastography (F-TE) for liver fibrosis staging in patients with NAFLD

FRI-428 - Comparison of ElastPQ Shear-wave Elastography (ElastPQ-SWE) and FibroScan Transient Elastography (F-TE) for liver fibrosis staging in patients with NAFLD

Diagnostic accuracy of enhanced liver fibrosis (ELF) test for significant fibrosis in patients with autoimmune hepatitis

Background: Although, liver biopsy is currently the gold standard tool for monitoring fibrosis progression, it is an invasive method and associate with some minor and major complications. Several non-invasive markers have been developed for assessment of liver fibrosis, but their validity has not been well studied in autoimmune hepatitis (AIH). The enhanced liver fibrosis (ELF) test is an alternative, non-invasive method for monitoring fibrosis progression. In this study, we evaluated performance of ELF test for predicting fibrosis stage in patients with AIH. Methods: Serum samples of 46 consecutive patients who were diagnosed with AIH were analyzed, and calculated for ELF scores. All patients underwent a liver biopsy. Patients with ≥F2 were considered to have a significant fibrosis according to the METAVIR scoring system. Diagnostic accuracy of ELF was evaluated with the receiver operator characteristic (ROC) curves analysis. Results: The mean ELF scores were significantly higher in patients with significant fibrosis that those with mild fibrosis (10.60±1.39 vs . 8.62±1.05, P Conclusions: The ELF test differentiates significant from non-significant liver fibrosis. Our results suggest that the ELF test can be a promising non-invasive method for monitoring fibrosis progression in AIH.

Can Elastography Differentiate Isolated Fatty Liver from Nonalcoholic Steatohepatitis?

Ultrasound and magnetic resonance (MR)-based elastography have demonstrated excellent performance for noninvasive staging of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this review, the authors provide background on elastography and review the ability of elastography to discriminate between isolated steatosis and NASH. Studies with available data on the diagnosis of NASH histology are limited to vibration-controlled transient elastography and MR elastography. A wide range of optimal cutoffs for the diagnosis of NASH are reported and likely depend on the prevalence of advanced fibrosis in the study population. MR elastography has good performance characteristics for identifying patients with any fibrosis who are at greatest risk of disease-related morbidity. Currently, neither modality can reliably discriminate NASH from simple steatosis. Novel multiparametric MR imaging and elastography are emerging and may help detect presence of NASH in the future.

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data.

AIMTo investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD).METHODSTwo individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant.RESULTSA total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies.CONCLUSIONLow vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

Transient elastography for noninvasive assessment of liver fibrosis in patients with primary biliary cirrhosis

Backgrund/Aim. In recent decades noninvasive methods for the assessment and monitoring of liver fibrosis have been developed and evaluated in numerous chronic liver diseases. The aim of this study was to evaluate the diagnostic accuracy of noninvasive markers for fibrosis assessment transient elastography (TE) and biochemical markers using liver biopsy as reference in patients with primary biliary cirrhosis (PBC). Methods. One hundred and twenty-two patients underwent both liver biopsy and blood tests on the same day and TE in a month following the biopsy and the tests. Liver biopsies were reviewed by a single pathologist using the METAVIR scoring system for assessment of liver fibrosis. Aspartate aminotransferase (AST), platelet ratio index (APRI), Forns scores, AST and alanine transaminase (ALT) ratio and TE were compared with liver fibrosis stage in order to determine the best noninvasive marker of liver fibrosis. Results. There was a statistically significant difference (p &lt; 0.05) for the APRI score, Forns index and TE according to stages of liver fibrosis. TE showed superior diagnostic performance when compared to other surrogate markers of liver fibrosis that were investigated. Optimal cut-off for TE were 4.25 and 5.9 kPa for diagnosing the presence of fibrosis and distinguishing mild/moderate and advanced stages of fibrosis respectively. The areas under the receiver operating characteristic (AUROC) of TE were 0.963 and 0.865, respectively. Conclusion. Based on our investigation the APRI score, Forns index and TE adequately predict fibrosis stage in patients with primary biliary cirrhosis, but the most sensitive and specific parameter appears to be TE. Using noninvasive markers and methods in the evaluation of patients in daily clinical practice may reduce, but not eliminate, the need for invasive diagnostic procedures.

Diagnostic Accuracy of 2-D Shear Wave Elastography for the Non-Invasive Staging of Liver Fibrosis in Patients with Elevated Alanine Aminotransferase Levels

This study assessed the diagnostic accuracy of 2-D shear wave elastography (2-D-SWE) for the non-invasive staging of liver fibrosis and compared the findings with those for biochemical markers (the aspartate aminotransferase-to-platelet index and fibrosis-4 index) of liver fibrosis in patients with elevated alanine aminotransferase (ALT) levels (>5 × the upper limit of normal). Patients with chronic liver diseases and elevated ALT levels who underwent liver biopsy were consecutively included. Receiver operating characteristic (ROC) curves were constructed to assess overall accuracy and to identify optimal cutoff values. After exclusions, data from 105 patients were analyzed. The areas under the ROC curves (AUROCs) for significant fibrosis, severe fibrosis and cirrhosis were 0.83, 0.86 and 0.91, respectively. The optimal cutoff values for predicting significant fibrosis, severe fibrosis and cirrhosis were 10.6, 13.2 and 17.6 kPa, respectively. The AUROCs of 2-D-SWE were significantly higher than those of biochemical markers for predicting significant fibrosis, severe fibrosis and cirrhosis (all p values < 0.05). Therefore, the diagnostic performance of 2-D-SWE in assessing liver fibrosis stages in patients with elevated ALT levels was promising. The optimal cutoff values were increased but appropriate for this cohort because the baseline levels of liver stiffness measurements were increased in these patients, even in the absence of fibrosis.

Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection

Serum Golgi protein 73 (GP73) is a potential biomarker for fibrosis assessment. We aimed to develop an algorithm based on GP73 and liver stiffness (LS) for further improvement of accuracy for significant fibrosis in patients with antiviral-naïve chronic hepatitis B virus (HBV) infection. Diagnostic accuracy evaluation of GP73 and development of GP73-LS algorithm was performed in training cohort (n=267) with an independent cohort (n=133) for validation. A stepwise increasing pattern of serum GP73 was observed across fibrosis stages in patients with antiviral-naïve chronic HBV infection. Serum GP73 significantly correlated (rho=0.48, P<.001) with fibrosis stage and was an independent predictor for the presence of significant fibrosis (OR, 95%CI: 1.02, 1.01-1.03, per increase in 1ng/mL, P<.001). Both LS (AUROC, 95%CI: 0.82, 0.77-0.87, accuracy: 74.7%) and GP73 (AUROC, 95%CI: 0.76, 0.71-0.82, accuracy: 71.5%) well-predicted significant fibrosis and outperformed APRI (AUROC, 95%CI: 0.69, 0.63-0.76, accuracy: 66%) and FIB-4 (AUROC, 95%CI: 0.66, 0.60-0.73, accuracy: 63.6%). Using GP73-LS algorithm, GP73<63 in agreement with LS<8.5 provided accuracy of 81.7% to excluded significant fibrosis. GP73≥63 in agreement with LS≥8.5 provided accuracy of 93.3% to confirm significant fibrosis. Almost 64% or 68% of patients in the training or validation cohort could be accurately classified. Serum GP73 is a robust biomarker for significant fibrosis diagnosis. GP73-LS algorithm provided better diagnostic accuracy than currently available approaches. More than 60% antiviral naïve CHB patients could use this algorithm without resorting to liver biopsy.

Assessment of liver fibrosis stage influence on clinical course of periodontal diseases in patients with chronic hepatitis C

The aim. To assess the influence of liver fibrosis stage on the clinical course of periodontal diseases in patients with chronic hepatitis C. Material and Methods. 122 patients with chronic hepatitis C, treated at the 7 th department ofLvivRegionalInfectiousDiseasesHospital during 2013 – 2015 were included into dental investigation. The periodontal disease was diagnosed in accordance with the classification of M. F. Danilevsky (1994). The clinical condition of periodontium was assessed by the papillary marginal alveolar index (PMA) in the modification ofParma, by the periodontal index – PI (AL Russel, 1956), by the Muhlemann and Son index – the degree of bleeding in the region of the gingival papilla (PBI). The stage of liver fibrosis was determined according to the medical history. The significance of the difference between two or more relative indicators was calculated using the Fisher test with the Metropolis algorithm. The correlation dependence between the clinical condition of periodontal tissues and the stage of liver fibrosis in patients with viral hepatitis C was studied using the Spearman rank correlation coefficient. Results. The highest percentage of patients with stage of liver fibrosis F 0 (70.00 ± 15.28 %) was registered in patients with healthy periodont, the lowest - in patients with generalized periodontitis of the third stage (7.89 ± 4.37 %). The highest frequency of patients with the stage of liver fibrosis F 3 (73.68 ± 7.14 %) was also observed in persons suffering from generalized periodontitis stage III (73.68 ± 7.14 %). Conclusions. The distribution of periodontal lesion severity statistically significant (p < 0.001) depended on the stage of liver fibrosis in patients with chronic hepatitis C. Direct (R = 0.70; p < 0.001) strong correlation between the clinical state of periodontal tissues and the stage of liver fibrosis in patients with chronic hepatitis C (using the Spearman rank correlation coefficient) has been determined

Application of the combined FibroMeter vibration-controlled transient elastography algorithm in Chinese patients with non-alcoholic fatty liver disease.

The FibroMeter vibration-controlled transient elastography (FM VCTE) is a new formula combining the serum test FM and liver stiffness measurement (LSM) by VCTE. We tested the accuracy and utility of FM VCTE for fibrosis staging in patients with non-alcoholic fatty liver disease (NAFLD). Two hundred fifteen NAFLD patients with LSM, FM NAFLD, FM VCTE, and other serum tests (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, BARD score, NAFLD fibrosis score, and aspartate aminotransferase-to-alanine aminotransferase ratio) performed 1day before liver biopsy were evaluated. Sixty-nine (32.1%) and 43 (20.0%) patients had F2-4 and F3-4, respectively. LSM had higher diagnostic accuracy (area under receiver-operating characteristics curves [AUROC] 0.851 for F2-4, 0.940 for F3-4; Obuchowski index 0.937±0.007) than all evaluated serum tests, while FM NAFLD was the most accurate serum test (AUROC 0.775 and 0.774; Obuchowski index 0.891±0.013). FM VCTE had similar accuracy to LSM (AUROC 0.855 and 0.901; Obuchowski index 0.927±0.009). LSM had excellent negative predictive values of 92.4% and 99.2% to exclude F2-4 and F3-4, but the positive predictive values (PPV) were only 71.4% and 61.0%, respectively. In patients with high LSM, the use of FM VCTE improved the PPV from 71.4% to 84.4% for F2-4 and from 61.0% to 88.9% for F3-4. Liver biopsy could be spared in around 50-65% of patients. Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4.

Comparison of 2-D Shear Wave Elastography and Transient Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B

This study compared 2-D shear wave elastography (SWE) and transient elastography (TE) for liver fibrosis staging in patients with chronic hepatitis B (CHB) infection using liver biopsy as the reference standard. Patients with CHB infection who underwent liver biopsy were consecutively included. After exclusions, 257 patients were analyzed. Two-dimensional SWE resulted in a significantly higher rate of reliable measurements (98.1%, 252/257) than TE (93.0%, 239/257) (p = 0.011). Liver stiffness measurements of the two examinations exhibited a strong correlation (r = 0.835, p < 0.001). In patients given a confirmed histologic diagnosis, Spearman's rank coefficients were 0.520 in stage F0 (p < 0.001), 0.684 in stage F1 (p < 0.001), 0.777 in stage F2 (p < 0.001), 0.672 in stage F3 (p < 0.001) and 0.755 in stage F4 (p < 0.001). There were no significant differences between the areas under the receiver operating characteristic (ROC) curves of 2-D SWE and TE for liver fibrosis staging (all p values > 0.05). Two-dimensional SWE had diagnostic accuracy comparable to that of TE for liver fibrosis staging. The measurements that the two techniques provide are not interchangeable.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis

Background and rationaleMany different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. Material and methodsA systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. ResultsEight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastogra-phy and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. ConclusionIn conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease.

Latest data suggest that placental growth factor (PLGF), growth differentiation factor-15 (GDF-15) and hepatic growth factor (HGF) are involved in hepatic fibrogenesis. Diagnostic performance of these markers for non-invasive liver fibrosis prediction was evaluated based on liver histology and stiffness. In total 834 patients were recruited. Receiver-operating-characteristics were used to define cut-offs for markers correlating to fibrosis stages. Odds-ratios were calculated for the presence/absence of fibrosis/cirrhosis and confirmed in the sub-group of patients phenotyped by elastography only. Logistic and uni- and multivariate regression analyses were used to test for association of markers with liver fibrosis stages and for independent prediction of liver histology and stiffness. Marker concentrations correlated significantly (P<0.001) with histology and stiffness. Cut-offs for liver fibrosis (≥F2) were PLGF = 20.20 pg/ml, GDF15 = 1582.76 pg/ml and HGF = 2598.00 pg/ml. Logistic regression confirmed an increase of ORs from 3.6 over 33.0 to 108.4 with incremental (1–3) markers positive for increased liver stiffness (≥12.8kPa; all P<0.05). Subgroup analysis revealed associations with advanced fibrosis for HCV (three markers positive: OR = 59.9, CI 23.4–153.4, P<0.001) and non-HCV patients (three markers positive: OR = 144, CI 59–3383, P<0.001). Overall, serum markers identified additional 50% of patients at risk for advanced fibrosis presenting with low elastography results. In conclusion, this novel combination of markers reflects the presence of significant liver fibrosis detected by elastography and histology and may also identify patients at risk presenting with low elastography values.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis.

Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease.

Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.

Evaluation of Mir-224, Mir-215 and Mir-143 as Serum Biomarkers for HCV Associated Hepatocellular Carcinoma

HCV induced hepatitis and hepatocellular carcinoma as its sequel are major health problems world-wide and especially in Egypt. For diagnosis and during treatment of liver diseases, liver functions are monitored through determination of serum levels of liver enzymes and α-fetoprotein although the obtained information is generally not sufficient for either early detection of hepatic insult or effective follow up of therapeutic effects. More sensitive biomarkers may help to achieve these goals. MiRNAs are small non-coding RNAs that have an important role in gene expression and regulation. Many, such as miR-224, miR-215, miR-143 are correlated with tumor appearance and with the degree of fibrosis in lung, breast and colon cancer. This study was performed to estimate the level of these miRNAs in serum of patients with HCV-associated hepatitis and HCC in relation to grade of hepatitis, stage of fibrosis and differentiation of tumor tissue. In addition, correlations between serological and tissue levels were assessed. A total of 80 patients were examined, out of which 50 were included in the study. Blood samples and tissue specimens from malignant tumor and corresponding non-tumor tissue of HCV hepatitis patients were collected. Blood samples from 20 healthy volunteers were also obtained as controls. It was found that miRNAs profiles differed in HCC patients compared to controls and HCV-associated hepatitis cases. Distinction of tumor grade and fibrosis stage of patients as well as between different grades of tumor differentiation proved possible, making miRNAs promising biomarkers for diagnosis and assessment of treatment response of HCC patients.