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Objective: The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a noninvasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with HIV type 1 (HIV-1) infections.Design/methods: Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) coinfections that did not exhibit liver fibrosis at the time of sampling.Results: A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 out of the 46 patients developed liver fibrosis (stage F2-4) and 20 remained without signs of liver fibrosis (stage F0-1). We identified a signature of seven miRNAs: 100-5p, 192-5p, 99a-5p, 122-5p, 125b-2-3p, 1246 and 194-5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910-0.806. Two miRNAs, 100-5p and 192-5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression. Conclusion:Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections.

Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC

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