Persistent Hepatitis C Viremia Predicts Late Relapse after Sustained Response to Interferon-α in Chronic Hepatitis C

  1. Liliana Chemello, MD, PhD;
  2. Luisa Cavalletto, MD;
  3. Carla Casarin, MD;
  4. Paola Bonetti, MD;
  5. Elisabetta Bernardinello, MD;
  6. Patrizia Pontisso, MD;
  7. Carlo Donada, MD;
  8. Fabio Belussi, MD;
  9. Silio Martinelli, MD; and
  10. Alfredo Alberti, MD
  1. The TriVeneto Viral Hepatitis Group From the University of Padova, Padova, Italy; O.C. Pordenone, Pordenone, Italy; O. Le Grazie, Venezia, Italy; and O.C. Cittadella, Cittadella, Italy. Grant Support: In part by grant 407/01/94 from Ricerca Sanitaria Finalizzata-Regione Veneto. Requests for Reprints: Alfredo Alberti, MD, Clinica Medica 2, via Giustiniani 2, 35100 Padova, Italy. Current Author Addresses: Drs. Chemello, Cavalletto, Casarin, Bonetti, Bernadinello, Pontisso, and Alberti: Clinica Medica 2, University of Padova, via Giustiniani 2, 35100 Padova, Italy. Dr. Donada: III Divisione Medica, O.C. Pordenone, via Monteverde, 33170 Pordenone, Italy.

    Abstract

    Objective: To define long-term outcome in patients with chronic hepatitis C who remain viremic after sustained biochemical response to interferon-α therapy.

    Design: Prospective evaluation of an outpatient cohort.

    Setting: University hospital.

    Patients: 107 patients with chronic hepatitis C who maintained normal aminotransferase levels as long as 12 months after interferon-α therapy. Patients were followed prospectively for an additional 6 to 36 months.

    Measurements: Aminotransferase levels were monitored at 3-month intervals. Serum hepatitis C virus (HCV) RNA was tested by polymerase chain reaction before therapy, at the end of therapy, and 12 months after therapy. The HCV genotype was defined by spot hybridization using serum specimens obtained before treatment.

    Results: Hepatitis C virus RNA was detected in 27 (25%) patients with sustained biochemical response; 80 (75%) patients were negative for HCV RNA. Patients positive for HCV RNA were older (P < 0.001), had received a smaller interferon-α dose (P = 0.02), and were more frequently infected with HCV genotype 2 (P < 0.01). Liver histologic findings were active in 57% of patients positive for HCV RNA, despite normal alanine aminotransferase levels, compared with only 12% of patients who were negative for HCV RNA (P = 0.01). The estimated probability of hepatitis relapse by 4 years after therapy was 53% in viremic patients and 0% in patients negative for HCV RNA (P < 0.001).

    Conclusion: Patients with chronic hepatitis C should be tested for serum HCV RNA 1 year after a sustained biochemical response to interferon-α therapy to determine whether the response is complete and permanent.

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