The breakthrough phenomenon during ??-interferon therapy of chronic hepatitis C: incidence, management, and outcome

Lebovics, Edward; Lantin, J.; Chaurushia, Gaurang; Dworkin, B.; Casellas, Ana; Rosenthal, WR

doi:10.1097/00042737-199510000-00025

Cited by 4 publications

(5 citation statements)

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“…16 Other investigators have suggested that continued IFN treatment, even at a higher dose, does not induce a response in chronic HCV. 15 Our data suggest that patients with breakthroughs should be retreated, because they have a reasonable chance of responding to retreatment.…”

Section: Discussionmentioning

confidence: 70%

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Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

et al. 1999

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The treatment of chronic hepatitis C has been a challenge to most hepatologists and gastroenterologists. Approximately half of the patients demonstrate a response at the end of treatment with standard interferon (IFN) therapy. Of these responders, only half will eventually have sustained responses 6 months after the end of treatment. 1-3 There appear to be 2 challenges to achieving responses to IFN therapy in hepatitis C virus (HCV). The first is to initiate an antiviral response, and the second is to maintain the response after therapy and prevent a relapse. Longer IFN treatment durations, i.e., 12 to 18 months rather than 6 months, increases the chance of a sustained response. 4 However, the former issue of how to increase the initial response rate has not been resolved, although ''induction'' therapy may enhance initial IFN responsiveness. The issue of initial response rate is further complicated by the phenomenon of breakthroughs. A breakthrough occurs when a patient achieves a response while on IFN therapy and then loses the response despite continued IFN therapy. Breakthroughs have largely been defined by a transient normalization of alanine transaminase (ALT) values, because ALT has been the primary measure of efficacy in most HCV clinical trials. However, sensitive assays to measure HCV RNA have now become the standard in assessment of efficacy. Thus, patients could have either an ALT breakthrough or an HCV-RNA breakthrough. The latter would be a transient undetectable serum HCV-RNA value that returns to detectable levels during continued IFN Abbreviations: IFN, interferon; HCV, hepatitis C virus; ALT, alanine transaminase; CIFN, consensus interferon.From the

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Section: Discussionmentioning

confidence: 70%

“…Lebovics et al reported achieving a 50% ALT response after breakthrough, 15 but only a 10% sustained ALT response. They did not see an advantage to increasing the dose of IFN.…”

Section: Discussionmentioning

confidence: 99%

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

et al. 1999

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“…[13][14][15][16][17][18][19] In addition, several investigators have reported that autoimmune reactions were induced or aggravated by the administration of IFN. 11,13,19,20 Furthermore, IFN therapy is contraindicated for patients with autoimmune hepatitis. There is no established therapy available at present to indicate whether we should prescribe IFN or an immunosuppressant for chronic hepatitis C patients who present with AIH-like manifestations.…”

Section: Discussionmentioning

confidence: 99%

Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy

Sezaki

Arase

Tsubota

et al. 2003

Journal of Gastroenterology

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Of a total of 2342 patients with type-C chronic hepatitis treated with interferon (IFN) at this hospital, 3 patients developed jaundice during the course of IFN therapy, but all 3 of them exhibited negative conversion of hepatitis C virus (HCV)-RNA following readministration of IFN. All 3 patients were assessed as having "probable autoimmune hepatitis (AIH)" in accordance with the AIH scoring system, indicating association with an "autoimmune phenomenon". Readministration of IFN at a low-dose induced activation of the autoimmune phenomenon, leading to fulminant hepatocellular impairment. As a result, HCV-RNA content dropped dramatically, possibly contributing to the negative conversion of HCV-RNA noted following the readministration of IFN. At present, no adequate therapy has been established for type-C chronic hepatitis with autoimmune manifestations. However, in conclusion, our findings suggested that: IFN should be a frontline regiment: (1). if autoantibody titers are low or patients are rated as having "probable AIH" or lower in accordance with the AIH scoring system, indicating a strong link to chronic hepatitis or (2). if IFN is expected to be efficacious on the basis of genotype of HCV-RNA level; even if there is acute exacerbation of type-C chronic hepatitis, IFN should be re-administered in the HCV-RNA level has dropped subsequently.

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“…About 10% of patients treated with IFN alone and 5% treated with IFN in combination with ribavirin experience a viral breakthrough during treatment [8,9]. Three main hypotheses have been proposed to explain viral breakthrough during IFN treatment: (1) the development of anti-IFN antibodies, (2) the down-regulation of IFN receptors (3) the emergence of resistant viral strains.…”

Section: Introductionmentioning

confidence: 99%

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Zekri

El-Din

Bahnassy

et al. 2007

Virol J

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The breakthrough phenomenon during ??-interferon therapy of chronic hepatitis C: incidence, management, and outcome

Cited by 4 publications

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Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy

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