Impact of disease severity on outcome of antiviral therapy in treatment-naïve patients with chronic hepatitis C


  • Potential conflict of interest: Dr. Hellstrand is a consultant, advises, owns stock in, and have intellectual property rights with Epicepty Corp. Dr. Newmann is a consultant and is on the speakers' bureau of HGS and Schering. He is also on the speakers' bureau of Roche. Dr. Pawlotsky is a consultant for, advises, is on the speakers' bureau, and received grants from Roche. Dr. Zeuzem is a consultant for, advises, and is on the speakers' bureau of Roche and Schering-Plough. Dr. Lagging advises for Schering-Plough.

Impact of Disease Severity on Outcome of Antiviral Therapy in Treatment-Naïve Patients with Chronic Hepatitis C

To the Editor:

We read with interest the article by Everson et al.1 The authors convincingly demonstrate that disease severity, as measured by both degree of liver fibrosis and platelet count, has a major impact on the rate of sustained viral response (SVR) following therapy with peginterferon α-2a and ribavirin among patients with advanced chronic HCV infection who have formerly not responded to interferon therapy. Previous reports indicate SVR rates of 43%–75% among treatment-naïve patients with cirrhosis and/or bridging fibrosis after combination therapy with peginterferon and ribavirin,2–4 with the highest response rates noted among patients infected with genotypes 2 or 3.3 The impact of portal hypertension with splenomegaly as reflected by the platelet count was, however, not reported in these studies.

In a European HCV multicenter treatment study,5 we treated 270 treatment-naïve HCV-infected patients with peginterferon α-2a and ribavirin. Eighty of these patients had either bridging fibrosis (Ishak stage 3–4) or cirrhosis (Ishak stage 5–6) in their pretreatment liver biopsies. Their SVR rates with regards to genotype and baseline platelet counts and fibrosis stage are summarized in Table 1.

Table 1. SVR Rates Among Patients with Significant Fibrosis Stratified According to Pretreatment Fibrosis Stage, Platelet Count, and Genotype
Disease SeverityAll PatientsGenotype 1Genotype 2 or 3
Bridging fibrosis (Ishak 3–4) and platelet count >125,000/mm357% (25/44)41% (12/29)87% (13/15)
Bridging fibrosis (Ishak 3–4) and platelet count ≤125,000/mm375% (3/4)100% (2/2)50% (1/2)
Cirrhosis (Ishak 5–6) and platelet count >125,000/mm357% (14/25)31% (5/16)100% (9/9)
Cirrhosis (Ishak 5–6) and platelet count ≤125,000/mm314% (1/7)0% (0/5)50% (1/2)

Interestingly, patients infected with genotype 1 who had both bridging fibrosis and platelet count ≤125,000/mm3 achieved SVR, compared to none of 5 patients infected with genotype 1 who had cirrhosis and low platelet count (P = 0.0476, Fisher's exact test). Disease severity, however, had less impact on SVR among patients infected with genotypes 2 or 3.

In conclusion, these findings support the results presented by Everson et al. that disease severity as measured by both fibrosis stage and platelet count is a major determinant of treatment outcome in patients with advanced chronic hepatitis C, especially those infected with genotype 1, even in patients previously naïve to treatment.

Johan Westin*, Kristoffer Hellstrand*, Åsa Alsiö*, Magdalena Ydreborg*, Carlo Ferrari†, Avidan U. Neumann‡, Jean-Michel Pawlotsky?, Solko W. Schalm?, Stefan Zeuzem**, Elke Verhey-Hart?, Martin Lagging*, * Department of Infectious Diseases, University of Göteborg, Sweden, † Azienda Ospedaliera di Parma, Parma, Italy, ‡ Bar-Ilan University, Ramat-Gan, Israel, ? Hôpital Henri Mondor—Université Paris XII, Creteil, France, ? University Hospital Rotterdam Dijkzigt, Rotterdam, The Netherlands, ** Saarland University Hospital, Homburg/Saar, Germany.