A.J. van der Meer

Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.

Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma

MicroRNA‐122 (miR‐122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, an anti‐miR‐122 oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA levels in chronic hepatitis C patients.

The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis‐related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis‐related event or death) in one patient was determined with the adjusted (event‐free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2–11.1) years. Fifty‐nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5‐year survival and event‐free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all‐cause mortality (HR 0.15, 95% CI 0.05–0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07–0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937–1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54–101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38–71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271–407), 18 (95% CI 16–24) and 13 (95% CI 11–17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.