Acute Myeloid Leukaemia following Direct Acting Antiviral drugs in HCV-infected patients: a 10 years' retrospective single-center study

International audienceBackground: 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.

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.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.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.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.ClinicalTrials.gov NCT01927133

Elasticity values according to inflammation, or steatosis, among patients with or without severe fibrosis (F3F4).

<p>(A) 2D-SWE elasticity according to inflammation. (B) TE-M elasticity according to inflammation. (C) TE-XL elasticity according to inflammation. (D) 2D-SWE elasticity according to steatosis. (E) TE-M elasticity according to steatosis. (F) TE-XL elasticity according to steatosis. If not impacted by inflammation or steatosis the curves should be flat. 2D-SWE was less impacted than TE-M.</p

Distribution of elasticity values according to different standardizations.

<p>Upper circles corresponded to severe outliers for whom elasticity values were outside boundaries defined as three times the inter-quartile range. (A) No transformation. (B) Log¹⁰ Transformation. (C) Log-transformation plus standardized according to the range of values (0-75kPa), from 0.00 to 1.00. (n = 1,588 for all tests except for ActiTest n = 1,270).</p

Quantitative concordance between elasticity values and severity of fibrosis, adjusted by inflammation, and steatosis.

<p>The strength of concordance was assessed by the Lin concordance correlation coefficient. Fibrosis, Steatosis and Inflammation were assessed by FibroTest, ActiTest and SteatoTest respectively.</p

Applicability of fibrosis tests in investigated patients.

<p>Applicability of fibrosis tests in investigated patients.</p

Subjects Flow chart.

<p>¹ As FibroTest (FT) was taken as the reference, the not-reliable FTs were excluded of the "intention to diagnose population". ² Several failures or not-reliable results were possible in the same patient explaining why the total failures or not reliable results were greater than the number of patients excluded of the 2D-SWE reliability population and of the concordance population. ³ 132 patients had not-reliable SWE, but reliable TE-M and TE-XL and FT.</p

Comparison of SWE minimal elasticity value cut-offs according to elasticity concordance with the 3 other reliable tests' results (FibroTest, TE-M, TE-XL), in the "Reliability population" (n = 1,720).

<p>Comparison of SWE minimal elasticity value cut-offs according to elasticity concordance with the 3 other reliable tests' results (FibroTest, TE-M, TE-XL), in the "Reliability population" (n = 1,720).</p

Similar 5-year HCC occurrence in Tenofovir- and Entecavir-treated HBV chronic infection in the French AFEF/ANRS CO22 Hepather cohort.

International audienceBackground: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications.Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort.Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co-infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW).Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow-up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir- (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person-years) and entecavir-treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person-years, respectively.Conclusion: The risk of liver-related events or death was not different between tenofovir- and entecavir-treated patients in this large prospective cohort of predominantly non-cirrhotic French patients.Trial registration number: NCT019553458