Increased response rate to interferon therapy after a second course in hepatitis C patients who show relapse after the initial course

Abstract

Some patients with chronic hepatitis C become HCV-RNA seronegative during interferon (IFN) therapy. However, about one-half of these patients show a relapse, evident by high serum alanine aminotransferase (ALT) level. In some patients with biochemical relapse, the serum HCV-RNA level becomes low immediately after the ALT relapse. Here, we assessed the changes in serum HCV-RNA level in patients with ALT relapse after IFN therapy, and evaluated the efficacy of a second course of IFN, started at the recovery stage after ALT relapse. Two hundred and seventy-seven patients who showed HCV-RNA seronegativity by reverse transcription nested-polymerase chain reaction (RT nested-PCR) and normalization of ALT during the initial IFN therapy, and had positive HCV-RNA with ALT relapse (> 100 IU/l) within 3 months after completion of the initial IFN course were enrolled in this retrospective study. Two hundred and sixty patients were followed-up without further IFN retreatment after the ALT relapse (group 1), and 17 patients received another 6-month course of IFN after the ALT relapse (group 2). The median level of serum HCV-RNA, determined with a branched DNA probe assay (version 1; Chiron-Dai-ichi Kagaku Tokyo, Japan), in group 1 was 3.1 Meq/ml before IFN therapy, 1.3 Meq/ml at the time point of the ALT peak after the completion of IFN therapy, and 0.7 and 2.6 Meq/ml at 2-4 and 6-8 weeks after the ALT peak, respectively. The serum HCV-RNA level at 2-4 weeks after the ALT peak was lower than that before IFN therapy. The eradication rate of HCV-RNA (complete response; CR) in group 2 (47.1%; 8/17) was significantly higher than that in group 1 (1.5%; 4/260; P < 0.001). In conclusion, our data suggested that: (1) patients who showed biochemical relapse after initial IFN therapy had a significantly lower serum HCV-RNA level at recovery after ALT relapse compared with that before initial IFN therapy. (2) A high response rate was noted after a second course of IFN administered at the recovery stage of the ALT relapse, compared with patients without IFN retreatment.

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

“…22 Moreover, we reported that HCV-RNA levels dropped dramatically following this "rebound phenomenon" in patients who exhibited "rebound" of ALT after completion of IFN therapy; we also reported that an increased response rate to IFN therapy was achieved after a second course in hepatitis patients who relapsed after the initial course of IFN therapy. 23 All three patients reported in this article exhibited an "autoimmune phenomenon," and the autoimmune reactions were activated by the administration of a low dose of IFN, resulting in acute exacerbation of hepatocellular impairment and elevation of total bilirubin. As a result, HCV-RNA levels dropped strikingly.…”

Efficacy of early retreatment with interferon β for relapse in patients with genotype Ib chronic hepatitis C

“…In the determination of predictive factors for IFN retreatment efficacy, simple logistic regression analysis was performed. Logistic analysis was performed for age (21-49 years versus 50-69 years), gender (male versus female), time of starting retreatment (Group A versus Group B), HCV-RNA level (<100 kcopies/ml versus ≥100 kcopies/ml), liver histology (HAI score 2-10 versus [11][12][13][14][15][16][17][18][19][20][21][22], and serum ALT value (< 2 × ULN versus ≥ 2 × ULN). Probability values of <0.05 stands for statistically significant.…”

“…Our data supports that retreatment should be started after HCV recurrence as soon as possible for patients with low viral load. HCV load may rise from 4 to 8 weeks after completing treatment with IFN but then decrease [19]. Retreatment in Group A was probably started at a time of decreased HCV load, thus resulting in a high SR rate.…”

Postpartum acute exacerbation of chronic hepatitis C with complete response to interferon-α

“…The patient's low pretreatment HCV RNA concentration was probably a consequence of this CTL response. Arase et al 31 reported an increased response rate to a second course of IFN therapy that was started immediately after relapses following completion of the initial course of IFN. In their report, the serum HCV RNA concentration showed a decrease 2 to 4 weeks after the ALT peak.…”