Serum microRNA-122 levels in different groups of patients with chronic hepatitis B virus infection O. Waidmann, 1 V. Bihrer, 1 T. Pleli, 1 H. Farnik, 1 A. Berger, 2 S. Zeuzem, 1 B. Kronenberger 1 * and A. Piiper 1 * 1 Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie; and 2 Institut fu ¨r Medizinische Virologie, Klinikum der Goethe-Universita ¨t, Frankfurt/Main, Germany Received June 2011; accepted for publication July 2011 SUMMARY. miR-122 is a liver-specific microRNA, which also circulates in the blood. The levels of miR-122 in serum and plasma correlate with hepatic necroinflammation in patients with hepatitis B virus (HBV) infection. Here, we investigated whether miR-122 levels correlate with surrogate markers for viral replication and translation. Furthermore, we examined whether miR-122 levels differ in the different groups of HBV- infected patients and whether miR-122 levels may be useful to identify patients with higher or lower risk for liver disease progression. Therefore, RNA was extracted from sera of therapy-naı ¨ve patients with HBV infection (n = 89) and from healthy volunteers (n = 19). The concentration of miR- 122 was assessed by quantitative real-time reverse-tran- scription PCR. HBs antigen and HBV DNA levels were quantified as surrogate parameters for HBV replication and translation. Liver biopsies were examined according to the histological activity index and the degree of fibrosis was assessed. We found that the miR-122 serum concentration correlated with the level of ALT, HBV DNA and HBs antigen (r = 0.259, P < 0.05; r = 0.225, P < 0.05; r = 0.508, P < 0.001, respectively). The miR-122 serum levels dis- criminated the different patient groups infected with HBV from healthy subjects (P < 0.001), and inactive carrier patients with high (>3500 IU/mL) or low (<3500 IU/mL) levels of HBs antigen could be differentiated by the miR-122 serum concentration (P < 0.05). As serum miR-122 levels strongly correlated with HBs antigen, it might be an indi- cator for viral translation. Furthermore, serum miR-122 levels discriminated HBV carrier patients with high or low risk for disease progression and may, thus, be an additional marker for risk stratification. Keywords: HBs antigen, HBV carrier, HBV DNA, hepatitis B, microRNA-122. INTRODUCTION Chronic infection with the hepatitis B virus (HBV) accounts for 350–400 millions of patients worldwide [1]. If the infection becomes chronic, which occurs in about 20% of cases, then the patients are at high risk to develop liver cirrhosis and hepatocellular carcinoma (HCC). The risk of cirrhosis and HCC is associated with the level of HBV DNA and the persistence of HBe antigen [2]. On the molecular level, after hepatocyte infection, the double-stranded HBV DNA is converted into covalently closed circular DNA (cccDNA). The cccDNA not only serves as a pool for replication of viral DNA but also for the pro- duction of mRNA for the translation of viral proteins, including HBs antigen [1]. HBs antigen in the blood of therapy-naı ¨ve patients is secreted by infected cells as subviral particles as well as infectious viruses, reflects the viral per- sistence in hepatocytes and correlates with the amount of infected cells and intrahepatic HBs antigen, but does not correlate with intrahepatic HBV DNA or cccDNA [3]. The main goal of anti-viral therapy is inhibition of liver disease progression. Treatment should be considered with regard to the following three criteria: high HBV DNA levels (>2000 IU/mL), elevated liver enzymes and advanced fibrosis [4]. If treatment is indicated, nucleotide and nucleoside analogues or pegylated interferon are potential options with different profiles of effects and side effects [4]. Inactive HBV carriers have low levels of HBV DNA and normal serum aminotransferases and are at low risk to develop liver cirrhosis and HCC. However, some patients with low-replicative hepatitis B develop viral flares with consecutive disease progression. Recently, an HBs antigen level-based risk stratification has been suggested for these patients. It has been shown that subjects with low levels of Abbreviations: HAI, histological activity index; HBV, hepatitis B virus; HCC, hepatocellular carcinoma. Correspondence: Oliver Waidmann, MD, Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universita ¨t, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. E-mail: waidmann@biochem2.uni-frankfurt.de *Equal contribution. Journal of Viral Hepatitis, 2012, 19, e58–e65 doi:10.1111/j.1365-2893.2011.01536.x Ó 2011 Blackwell Publishing Ltd