Comparison of acoustic radiation force impulse imaging with transient elastography for the detection of complications in patients with cirrhosis.

BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a new non-invasive, ultrasound-based method for the evaluation of liver fibrosis and cirrhosis. AIM: To determine the diagnostic accuracy of ARFI imaging, transient elastography (TE) and Fibrotest for the evaluation of complications in patients with cirrhosis. METHODS: A total of 166 patients (109 male, mean age: 54 ± 11 years) with chronic liver disease and established cirrhosis were included in this study. ARFI-imaging of the liver and spleen, TE and Fibrotest were performed in all patients. In addition, clinical, laboratory and morphological parameters, including MELD/Child-Pugh scores, presence of oesophageal varices and hepatocellular carcinoma, history of variceal bleeding and history of hepatic encephalopathy were recorded. RESULTS: Acoustic radiation force impulse liver was significantly correlated with ARFI spleen (r = 0.48, P < 0.001), TE (r = 0.75, P < 0.001) and Fibrotest (r = 0.21, P = 0.006). The diagnostic accuracy (AUROC) for the diagnosis of large oesophageal varices was 0.58 (95% CI: 0.48-0.67), 0.58 (0.49-0.67), 0.53 (0.44-0.63) and 0.50 (0.41-0.59) for ARFI liver, spleen, TE and Fibrotest respectively (P > 0.20). The AUROC for the detection of hepatocellular carcinoma (HCC) was 0.54 (0.39-0.70), 0.58 (0.44-0.73), 0.56 (0.40-0.73) and 0.72 (0.60-0.84) respectively (P > 0.20). Multiple logistic regression analysis showed that ARFI spleen better predicted the presence of large oesophageal varices and HCC compared with ARFI liver. CONCLUSIONS: The diagnostic accuracy of ARFI liver and spleen was comparable to TE and Fibrotest for the detection of complications in patients with cirrhosis.

Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma.

BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC. METHODOLOGY/PRINCIPAL FINDINGS: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = -0.494, P = 0.00002), alanine aminotransferase (ALT) (r = -0.309, P = 0.007), aspartate aminotransferase (r = -0.495, P = 0.000007), bilirubin (r = -0.362, P = 0.002), international normalized ratio (r = -0.338, P = 0.034) and γ-glutamyltransferase (r = -0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dC(T) of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%. CONCLUSIONS/SIGNIFICANCE: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.

Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy.

BACKGROUND AND AIMS: Addition of ribavirin to interferon alfa treatment has substantially increased sustained virologic response rates in patients with chronic hepatitis C (CHC). Ribavirin acts as an RNA virus mutagen in vitro, thereby leading to error catastrophe. However, data in CHC are controversial. METHODS: The nonstructural (NS) 5B quasi-species heterogeneity was analyzed in Huh7 cells harboring a subgenomic hepatitis C virus (HCV) replicon system treated with ribavirin or levovirin. Accordingly, NS5B quasi-species were studied in 14 patients with CHC who received ribavirin alone or combined with pegylated interferon alfa both at baseline and during the first weeks of therapy. Analysis of NS3 quasi-species served as control. RESULTS: Cultivation of HCV replicon cells with ribavirin led to higher NS5B mutational frequencies compared with levovirin-treated or untreated cells (P < .05). Patients receiving ribavirin monotherapy showed higher overall mutational frequencies within NS3 and NS5B during therapy as compared with baseline (P < .01). Proportions of ribavirin-specific G-to-A and C-to-T transitions increased (P < .01). Paired analysis confirmed significant mean increases of mutational frequencies of approximately 5%. Ribavirin serum concentrations were positively correlated with mutational frequency changes (P < .05). In patients receiving combination therapy, a decrease of NS5B mutational frequencies ( approximately 10%) and lower proportions of G-to-A and T-to-C mutations (P < .01) were detectable. CONCLUSIONS: Ribavirin, but not its L-enantiomer levovirin, is a mutagen in HCV replicon cells. In patients with CHC, ribavirin monotherapy exhibits a moderate mutagenic effect early during therapy that is not detectable in combination with pegylated interferon alfa.