Simple Stratification of Hepatocellular Carcinoma Surveillance after Direct-acting Antiviral Therapy for Chronic Hepatitis C

Reports on surveillance systems useful for determining the risk of developing hepatocellular carcinoma （HCC） after direct-acting antiviral （DAA） treatment for hepatitis C have been published. Liver cirrhosis （LC） is a high-risk factor for HCC, but the evaluation frequency necessary for patients with chronic hepatitis （CH） remains unknown. Here, we aimed to identify how frequent CH patients should be evaluated for HCC, with particular emphasis on patients achieving a sustained virological response （SVR） with DAA treatment. Data were collected pre-treatment （Pre） and at the time of SVR for 141 patients with hepatitis C receiving DAA treatment. We defined LC by a platelet （PLT） count ≤10×104/µl, and CH was defined by a PLT count of ＞10×104/µl. The incidence of HCC in patients with CH after achieving SVR was retrospectively evaluated. In total, 128 patients （CH, n＝102; LC, n＝26） achieved SVR, and 13 developed HCC after SVR during the follow-up period （mean, 748 days）. Although fibrosis-4 （FIB-4） index, the presence of α-fetoprotein, and prothrombin time were significant risk factors for HCC in patients with CH in the univariate analysis, only the Pre-FIB-4 index was an independent predictive factor for HCC development in the multivariate analysis （p＝0.04）. An FIB-4 index ≥3 was a significant risk factor for HCC （p＝0.005）. The cumulative risk for HCC at 1000 days was 2.6％ and 24.2％ in the FIB-4 index ＜3 and FIB-4 index ≥3 groups, respectively （p＝0.004）. Frequent HCC examination is recommended for FIB-4 index ≥3 CH patients who obtain SVR after DAA treatment

Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer

International audienceBackground: To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC. Methods: Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration-time curve of regorafenib, M2 and M5. Results: Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045). Conclusions: MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment