Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C

Garcı́a-Buey, Luisa; García‐Monzón, Carmelo; Rodríguez, Santiago; Borque, M.J.; Garcı́a-Sánchez, Asunción; Rodríguez, Iglesias; Decastro, Mar; Mateos, F. González; Jl, Vicario; Balas, A.; Moreno–Otero, Ricardo

doi:10.1016/0016-5085(95)90139-6

Cited by 166 publications

(85 citation statements)

References 34 publications

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“…67,68 For these reasons, a pre-existing autoimmune disease or diathesis is considered a relative contraindication to interferon therapy. This limitation is particularly true for systemic and potentially life-threatening autoimmune conditions, such as autoimmune hepatitis and lupus erythematosus.…”

Section: Treatment Of Hepatitis C In Understudied Populationsmentioning

confidence: 99%

Understudied populations with hepatitis C

Strader

2002

Hepatology

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Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR).Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus ( H epatitis C is an important cause of acute and chronic liver disease worldwide and the most common indication for liver transplantation in adults in the United States. Since the discovery of the hepatitis C virus (HCV) in 1989 and its linkage to non-A, non-B hepatitis, there have been major advances in knowledge of the incidence and prevalence of this infection, its clinical manifestations, natural history, molecular virology, histopathology, and treatment. At present, the management of patients with hepatitis C focuses largely on combination antiviral treatment using a 24-or 48-week course of peginterferon and ribavirin. Two large trials evaluating the safety and efficacy of this combination therapy have demonstrated sustained virological responses (SVR) in slightly more than 50% of patients. 1,2 It is important to stress, however, that response rates of 50% in randomized, controlled trials of therapy do not guarantee that 50% of all patients with chronic hepatitis C can be or will be successfully treated. Patients enrolled in the registration trials of combination therapy were highly selected and not fully representative of the broader population of patients with chronic HCV infection. The strict inclusion and exclusion criteria used in registration trials often exclude populations that have high rates of hepatitis C. Furthermore, chronic hepatitis C is common in populations that are not reached by clinical trials of new and investigational therapies. Because patients enrolled in registration trials of new antiviral treatments are a selected group, the applicability of results of these trials to the general population is problematic.

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Section: Treatment Of Hepatitis C In Understudied Populationsmentioning

confidence: 99%

Understudied populations with hepatitis C

Strader

2002

Hepatology

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“…The difference in autoantibody prevalence between the various studies may derive from technical reasons and/or differences in the populations investigated. Moreover, some studies [10][11][12] have suggested that interferon-alpha (IFN-a) treatment induces the appearance of serological markers of autoimmunity or even triggers the clinical manifestations of autoimmune hepatitis in patients with chronic HCV infection. Others [7,8] have suggested that IFN-a treatment does not induce clinically overt autoimmune disease even in the presence of autoimmune serum markers.…”

Section: Introductionmentioning

confidence: 99%

Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection

Gregorio

Pensati

Iorio

et al. 1998

Clinical and Experimental Immunology

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SUMMARYHCV infection and interferon-alpha (IFN-a) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-a cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-a, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P ¼ 0·12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-a had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-a; and (iii) IFN-a should be used cautiously in the treatment of LKM-1/HCV-positive patients.

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“…El tratamiento tuvo que suspenderse prematuramente a las 12 semanas por el desarrollo de una hepatitis autoinmune asociada a la administración de interferón. El interferón alfa puede inducir autoanticuerpos hasta en el 50% de los pacientes, pero sólo en el 1-2% desencadena una enfermedad autoinmune, siendo las más comunes la disfunción tiroidea y la diabetes mellitus, y más infrecuentes la hepatitis autoinmune, el lupus, y la anemia y trombopenia autoinmunes (8). La presencia de anticuerpos no órgano-específicos en la hepatitis C crónica puede favorecer la aparición de hepatitis autoinmune con la administración de interferón, pero no constituye una contraindicación absoluta para este tratamiento (9).…”

Section: Discussionunclassified