High-dose interferon-α2b treatment prevents chronicity in acute hepatitis C

Abstract

Acute hepatitis C takes a chronic course in 50-80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-alpha2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested using PCR prior to treatment, three times weekly during the first two weeks of treatment, and then once weekly until the end of therapy. During the 15-month follow-up, HCV-RNA tests were performed monthly up to month 6 and every two to three months thereafter. Twenty-four patients were enrolled at the time of writing; age ranged from 18 to 76 years (mean = 32), and nine patients were men. All patients presented with cholestatic hepatitis; 19 were actively abusing intravenous drugs, four had no known parenteral exposure, and one was a medical laboratory technician. All patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five patients were infected with genotype 3, five with genotype 1a, five with genotype 1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized serum transaminase concentrations within 18-43 days; HCV-RNA became negative in all patients within 4-12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up period, which ranged from six to 29 months (mean = 19.5 +/- 10.4), serum ALT concentrations remained normal and HCV-RNA remained negative in all patients except two dropouts and two patients who developed relapsing disease after having been HCV-RNA negative for three and eight months, respectively. In both patients, the same HCV genotype 3 reemerged. Serum ALT concentrations ranged from 531 to 1940 IU/liter (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryville, California) were < 3.5 x 10(5) eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4 x 10(5) eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed between HCV-RNA concentrations and serum ALT concentrations at presentation (r = 0.331; P = 0.67) and total dose of interferon-alpha2b administered until normalization of ALT (r = -0.088; P = 0.74). Twenty-two of 24 patients completed treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) remained HCV-RNA negative for 18.65 (+/-9.7) months. These findings suggest that high-dose interferon-alpha2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.

Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load

“…Only one study using 10 MU of IFN-2b until normalization of transaminase levels reported an 82% sustained virologic response. 16 A recent study 17 using 5 MU IFN alfa-2b for 6 months showed a 98% HCV eradication in patients who received the full course of treatment. Based on these findings, the investigators concluded that early treatment with IFN-2b should be given to all patients with acute HCV infection.…”

“…Only one study using 10 MU of IFN-2b until normalization of transaminase levels reported an 82% sustained virologic response. 16 A recent study 17 using 5 MU IFN alfa-2b for 6 months showed a 98% HCV eradication in Abbreviations: HCV, hepatitis C virus; IFN, interferon; ALT, alanine transaminase. From the…”

Risk and Management of Blood-Borne Infections in Health Care Workers

“…Several studies have suggested that early therapy with alpha interferon may be effective in preventing progression from acute to chronic disease (36,200,270). However, there are no data indicating that treatment begun early in the course of chronic infection is less effective than treatment begun in the acute phase of infection.…”

Acute Hepatitis C

“…Several trials exist, both controlled [61][62][63][64][65][66] and uncontrolled, [67][68][69][70] using IFN in the setting of acute HCV infection. Nearly all are problematic because of small numbers of patients and insufficient data on important parameters such as time following exposure and other inclusion criteria, type of IFN and dose used, definition of response, and follow-up periods.…”

“…In an uncontrolled trial by Vogel et al, 69 patients with symptomatic acute hepatitis and detectable HCV RNA were treated with high dose IFN-␣. Twenty-two subjects received 10 MU daily until aminotransferase levels normalized (3 to 6 weeks).…”