Acute myeloid leukaemia following direct acting antiviral drugs in HCV-infected patients: A 10 years' retrospective single-center study.

BACKGROUND: After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. MATERIAL/METHODS: In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM. RESULTS: Over the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA-, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and - was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively). CONCLUSION: AML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results.

Real-Time Shear Wave versus Transient Elastography for Predicting Fibrosis: Applicability, and Impact of Inflammation and Steatosis. A Non-Invasive Comparison.

BACKGROUND AND AIMS: Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. METHODS: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. RESULTS: A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2-90.8), was significantly higher than that of TE, 85.6%(84.0-87.0; P<0.0001). In patients with non-advanced fibrosis (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI) 0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs 0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar results. CONCLUSIONS: Elasticity results including very low minimal signal in the region of interest should be considered not reliable. 2D-SWE had a higher applicability than TE, the reference elastography, with less impact of inflammation and steatosis especially in patients with non-advanced fibrosis, as presumed by blood tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT01927133.

Liver fibrosis evaluation using real-time shear wave elastography: applicability and diagnostic performance using methods without a gold standard.

BACKGROUND & AIMS: Real-time shear wave elastography (SWE) is a new two-dimensional transient elastography which had no assessment of factors associated with reliability, and had limited comparisons with other validated fibrosis biomarkers. The aim was to assess the applicability and performances of SWE for the diagnosis of fibrosis as compared with FibroTest (FT) and liver stiffness measurement (LSM) by transient elastography using two probes (TE-M and TE-XL). METHODS: Without a gold standard, the strength of concordance, discordance analysis and latent class analysis (LCM) were applied. RESULTS: 422 patients were included. The applicability of SWE (90.0%) was significantly lower than that of FT (97.9%; p <0.0001) and did not differ from those of TE-M (90.5%) and TE-XL (90.3%); it was higher though for SWE (86%) in 22 patients with ascites vs. 55% using TE-M (p=0.04). For the diagnosis of all fibrosis stages as presumed by FT, the performance of SWE was highly significant (Obuchowski measure 0.807 ± 0.013 [m ± se]), but lower than those of TE-M (0.852; p=0.0007) and TE-XL (0.834; p=0.046). SWE had a low performance for discrimination between F0 and F1. For the diagnosis of cirrhosis using LCM, SWE specificities were all equal to 99%, and SWE sensitivities ranged from 0.47 to 0.64. For the diagnosis of non-cirrhotic stages, the results were heterogeneous. CONCLUSIONS: The performance of SWE for the diagnosis of cirrhosis was similar to those of FT and TE. SWE applicability was lower than that of FT, but greater than that of TE in patients with ascites.