OC 52.2 - Residual burden of liver disease after HCV-clearance in hemophilia: a word of caution in the era of gene therapy.

Tuesday, June 27, 2023

11:00 – 11:15 ET

Room: 710B

Session Available As: On-Demand

Presenting Author(s)

Vincenzo La Mura, MD PhD

Associate Professor
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Milan, Lombardia, Italy

Co-Author(s)

NB

Niccolò Bitto

Medical Doctor
Foundation I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi and Thrombosis center, Milan, Italy
Milan, Lombardia, Italy
CC

Cecilia Capelli

Medical Doctor
Foundation I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi and Thrombosis center, Milan, Italy
Milan, Lombardia, Italy
CC

Camilla Caputo

Medical Doctor - Resident
Foundation I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi and Thrombosis center, Milan, Italy
Milan, Lombardia, Italy
SS

Simona Siboni

MD
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
Sara Arcudi, MD

Academic researcher, MD, PhD
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
Alessandro Ciavarella, MD (he/him/his)

Specialized Doctor
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
Roberta Gualtierotti, MD, PhD

Associate Professor
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
AF

Anna Ludovica Fracanzani

Associate Professor
Department of Pathophysiology and Traplantation, University of Milan, Milan, Italy.
Milan, Lombardia, Italy
AS

Angelo Sangiovanni

Medical Doctor
Foundation I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, Gastroenterology and Hepatology, Milan, Italy.
Milan, Lombardia, Italy
Flora Peyvandi, MD, PhD (she/her/hers)

Director
IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
Milano, Lombardia, Italy

Background: Ruling out advanced fibrosis/cirrhosis is mandatory to candidate people with hemophilia (PWH) to gene therapy. Clinical presentation and non-invasive techniques may be combined to pursue this aim, however, a non-negligible proportion of HCV-patients after virus clearance can be misdiagnosed.

Aims: We conducted a prospective hepatological screening to detect any relevant risk-factor of liver-complication in PWH after HCV-clearance.

Methods: We evaluated 119 patients (median age: 54 years; range:36-87) with previous history of HCV-infection: 108/11 hemophilia A/B. Any active factor of chronic liver damage was registered along with biochemistry, liver stiffness measurement (LSM) and ultrasound (US) to diagnose advanced fibrosis/cirrhosis. A pre/post HCV-clearance sub-analysis was conducted in 57 patients with simultaneous measurement of LSM, US, non-invasive tests of fibrosis (NITs) (e.g.: FIB-4, APRI).

Results: Ninety-six patients (81%) presented at least one active risk-factor of chronic liver damage, metabolic factors were the most prevalent (77%). Ten patients (8%) were HIV and 4(4%) HBV. After our evaluation, 51 patients (43%) had US-steatosis. Twenty-one patients (18%) had clinical, biochemical, liver-morphology and/or LSM suggestive of advanced fibrosis/cirrhosis. Furthermore, 10 patients (8%) had esophageal varices, 3(3%) hepatocellular carcinoma (HCC). One HCC was detected in a non-cirrhotic liver but associated with metabolic comorbidities, 2 HCC were out of Milan criteria for transplantation and were addressed to a down-staging approach. Finally, all HCC were transplanted. In the sub-analysis, LSM and NITs were reduced after HCV-clearance (p < 0.05), while morphological US-signs specific of cirrhosis did not change. Overall, after HCV-clearance, 12/66 patients (18%) with LSM < 8KPa had at least one US-sign suggestive of advanced fibrosis/cirrhosis.

Conclusion(s): Residual risk-factors of chronic liver damage after HCV-clearance are frequent. LSM and NITs significantly change after HCV-clearance and could be inaccurate to rule-out advanced fibrosis/cirrhosis. A specific diagnostic work-up is warranted to optimize the screening for liver-health in hemophilia in the era of gene-therapy.

Learning Objectives:

Detect the most common residual risk-factors of liver damage after HCV-clearance
Use non-.invasive markers and/or ultrasound signs of advanced fibrosis/cirrhosis in agreement with the specificity and sensitivity of these tests after HCV-clearance
Address patients to advanced lines of therapy if affected by severe liver-related complications