We thank Dr. Westin and his colleagues for their letter regarding our original paper.1 Westin et al. previously presented data from a European HCV multicenter treatment study2 and herein examined the impact of liver histology and platelet count on rates of sustained virologic response (SVR) in this group of treatment-naïve patients. In the European cohort of 270 patients, 80 had either bridging fibrosis or cirrhosis; 32 of these 80 patients (40%) had cirrhosis defined by Ishak fibrosis scores of 5 or 6. The proportion with cirrhosis was identical to the proportion with cirrhosis in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C). However, in the European cohort, only 22% of patients with cirrhosis and 8% of patients with bridging fibrosis had ≤125,000 platelets/μl. In contrast, in the HALT-C cohort 50% of patients with cirrhosis and 15% of patients with bridging fibrosis had ≤125,000 platelets/μl. Nonetheless, the pattern of results in patients with genotype 1 infection is consistent between the 2 reports; worsening severity of liver disease defined by liver histology and platelet count may be a reliable predictor of response to peginterferon/ribavirin therapy.
Due to the relatively small sample size, the impact of other predictors of response can not be adequately examined in the European cohort. However, in the large HALT-C Trial cohort (n = 1,046) we were able to adjust or control for the impact of other predictors of response, such as body weight, homeostasis model assessment (HOMA) score, HCV genotype or level, race, prior treatment, and dose reduction or discontinuation. In the HALT-C cohort, patients with either thrombocytopenia or cirrhosis were more likely to experience discontinuation or dose reductions of treatment. By multiple logistic regression, cirrhosis (P < 0.001) and dose reduction (P < 0.04), but not platelet count, were significant independent predictors of virologic response. The negative impact of thrombocytopenia on virologic response was related, at least in part, to higher rates of cytopenias requiring dose reduction or discontinuation.
Patients with chronic hepatitis C who have thrombocytopenia or cirrhosis represent a group of patients in critical need of effective antiviral therapy. Unfortunately, these patients are “difficult to treat” and “difficult to cure”. Inadequate response to interferon-based treatment may also represent an Achilles' heel to development of regimens using interferon with HCV protease or polymerase inhibitors. Understanding mechanisms of viral resistance may be crucial to development of effective new strategies of treatment to improve virologic responses.