Viral Load (copies/ml) Differential expression of miRNA-122 as a novel biomarker for HCV infection in genotype 1 and 3 before and during combination therapy (PEG-Interferon-α2a and Ribavirin) Raju Nagarapu, Sandeep K Vishwakarma, Syed Rahamathulla, Avinash Bardia, Shaik Iqbal Ahmed, L. Chandrakala, Mohammed Aejaz Habeeb, Aleem Ahmed Khan Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad-500 058, Telangana, India Background Major aims of the study In recent years, miRNAs are emerging novel therapeutic targets in several infectious and genetic diseases. A variety of miRNAs have been identified to play important role in Hepatitis C Virus (HCV) infection at different levels. But there is need to find more appropriate targets to understand HCV pathogenesis and its treatment response. In present study we screened various sets of miRNAs involved in viral-host interactions and quantified a cascade of 5 major ones before and after standard anti-viral therapy. Differential expression profile of selected miRNAs (miRNA-21, 122, 146a, 155 and 181a) was quantified to understand their kinetic behavior during HCV pathogenesis and treatment response against combination therapy using Pegylated Interferon-α2a with Ribavirin in patients infected with HCV genotypes 1 and 3. Identifying differential expression of selected miRNAs in serum of HCV infected patients of genotype 1 and 3 before and after treatment with Pegylated Interferon-α2a with Ribavirin. Correlation of miRNAs expression with viral load and liver function parameters before and after treatment. Evaluation of most appropriate therapeutic miRNA having most significant response during HCV infection and treatment. Quantification of differential miRNA expression profile miRNA-122 miRNA-21 Flow chart of the study miRNA-146a miRNA-155 miRNA-181a Receiver operating characteristic (ROC) of miRNA -122 (A) Changes in LFT parameters (B) Receiver operating characteristic (ROC) of miRNA-181a Predicted molecular mechanism for miRNA-122 and HCV replication before and after PEG-IFN-α2a and RBA treatment (B) Results Changes in HCV-viral load before and after treatment in genotype 1 and 3 Viral Load (copies/ml) S. No Age/Gender BT 3MT 6MT Genotype P-1 32/M 3,48,150 3a Genotype 3 P-2 55/M 8,48,780 58,490 P-3 49/M 3,18,246 27,409 3b P-4 35/M 17,44,668 5,100 P-5 60/M 1,18,260 5,610 P-6 43/M 3,30,450 P-7 73/M 40,25,780 16,48,620 P-8 43,96,750 12,15,480 P-9 58/F 8,12,560 62,750 P-10 23/M 25,10,840 1,28,650 1a Genotype 1 P-11 57/M 28,45,260 11,04,280 14,750 P-12 45/F 1,29,541 1b P-13 50/M 15,08,170 2,35,460 P-14 60,15,000 8,26,430 44,680 P-15 45/M 12,84,610 1,30,950 50,580 Conclusion Differential expression of miRNA-122 provides a direct measure for HCV quantification in both the genotypes before and during combination therapy and can be used as a prominent diagnostics as well as prognostic marker to develop better therapeutic strategies.