3 years ago

Autoantibodies to cytoplasmic rods and rings in patients with hepatitis C virus infection treated with direct-acting antivirals: The role of prior treatment with interferon plus ribavirin

Mercè Alsius, María José Ferri, Maria Buxó, Carme López, Isabel Serra, Xavier Queralt, Doroteo Acero

Publication date: Available online 13 November 2018

Source: Gastroenterología y Hepatología

Author(s): Mercè Alsius, María José Ferri, Maria Buxó, Carme López, Isabel Serra, Xavier Queralt, Doroteo Acero


The cytoplasmic rods-rings (RR) pattern is found in hepatitis C (HCV) patients treated with interferon-ribavirin when studied with ANA-IIF. Ribavirin aggregates/induces antigenic changes in IMPDH-2, an enzyme necessary for ribavirin action.

Patients and method

Prospective search for anti-RR autoantibodies (HEp-2, INOVA) in patients treated with direct-acting antivirals (DAAs) from October 2015 to June 2017. HCV-negative patients from up to June 2016 acted as controls. Anti-RR was analyzed at baseline and, mainly, during treatment and follow-up. The Chi-square test, Student's t-test and a logistic regression analysis were performed.


Between October 2015 and June 2016, 1258 men and 2389 women who were HCV-negative and 137 men and 112 women who were HCV-positive patients were studied. Approximately 22.9% of HCV-negative and 13.2% of HCV-positive were ANA-IIF-positive (p < 0.05). Three HCV-negative (0.08%) and 23 (9.2%) HCV-positive patients had anti-RR (p < 0.001). A total of 122 patients received DAAs; 30 received DAA + RBV; 46 pre-treated with IFN-RBV received DAA; 31 pre-treated with IFN-RBV received DAA + RBV; 16 received IFNpeg-RBV; and 24 received IFN-RBV-DAA. None of the 122 DAA-treated patients showed anti-RR; anti-RR were identified in 14.8% of those treated with DAA-RBV; in 25.9% of those pre-treated with IFN-RBV receiving DAA; in 22.2% of IFN-RBV-pre-treated patients who received DAA + RBV; in 7.4% of those treated with IFNpeg-RBV and in 29.6% of those treated with IFNpeg-RBV-DAA. The multivariate analysis showed significant associations between anti-RR and “Exposure to IFN” and “Time of exposure to RBV”.


Anti-RR autoantibodies were detected only in patients with current or past treatments with RBV, even in cases in which only DAAs were later administered.


La investigación de ANA-IFI en pacientes con hepatitis C tratados con interferón-ribavirina ha detectado un patrón citoplasmático en bastones y anillos. La ribavirina agregaría e induciría cambios antigénicos en la IMPDH-2, enzima imprescindible para su acción.

Pacientes y método

Investigar las tasas de anti-RR (HEp-2, INOVA) en pacientes tratados con antivirales de acción directa (AAD) entre octubre-2015 y junio-2017. Como controles se han utilizado los pacientes VHC-negativo habidos hasta junio-2016. Los anti-RR se analizaron antes del tratamiento y, mayoritariamente, durante y después del mismo. Se han utilizado las pruebas Chi-cuadrado, T de Student y de regresión logística.


Entre octubre-2015 y junio-2016 hubo 1.258 varones y 2.389 mujeres VHC-negativo y 137 varones y 112 mujeres VHC-positivo. El 22,9% de los VHC-negativo y el 13,2% de los VHC-positivo fueron ANA-IFI-positivo (p < 0,05). Tres pacientes (0,08%) VHC-negativo y 23 (9,2%) VHC-positivo fueron anti-RR+ (p < 0,001). Ciento veintidós pacientes recibieron AAD; 30, AAD + RBV; 46 pretratados con IFN-RBV recibieron AAD; 31, pretratados con IFN-RBV, recibieron AAD + RBV; 16 IFNpeg-RBV; 24 IFN-RBV-AAD. Ningún paciente con AAD mostró anti-RR; tuvieron anti-RR el 14,8% de los tratados con AAD+RBV; 25,9% de los pretratados con IFN-RBV que recibieron AAD; 22,2% de los pretratados con IFN-RBV que recibieron AAD + RBV; 7,4% de los tratados con IFNpeg-RBV; el 29,6% de los tratados con IFNpeg-RBV-AAD. El análisis multivariante asoció significativamente la presencia de anti-RR con «Exposición al IFN» y «Tiempo de exposición a ribavirina».


Los autoanticuerpos anti-RR solo se han detectado en pacientes tratados con ribavirina, incluso cuando después se utilizaron solamente AAD.

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