six patients, respectively) and infection (eight vs. one patients, respectively). Importantly, the rate of depression was similar in the two groups [four vs. five patients in the PEG-IFN ��-2a (40KD) 180 ��g week?1 Ruxolitinib structure and PEG-IFN ��-2a (40KD) 270 ��g week?1 groups, respectively], and the rate of neutropenia was low in both groups [three vs. no patients in the PEG-IFN ��-2a (40KD) 180 ��g week?1 and PEG-IFN ��-2a (40KD) 270 ��g week?1 groups, respectively]. Three patients in the PEG-IFN ��-2a (40KD) 180 ��g week?1 plus ribavirin and no patients in the PEG-IFN ��-2a (40KD) 270 ��g week?1 plus ribavirin group required reduction or omission of one or more dose of PEG-IFN ��-2a (40KD) for a clinical or a laboratory abnormality. Four serious adverse events were recorded, two in each treatment group.

One patient in the PEG-IFN ��-2a (40KD) 180 ��g week?1 plus ribavirin group had a myocardial infarction, and another patient had pneumonia. The patient who had a myocardial infarction had a reduction in haemoglobin from a baseline of 14.2 g dl?1 to 10.8 g dl?1, which required dose reduction of ribavirin. The myocardial infarction occurred when haemoglobin was 10.8 g dl?1. This occurred at week 20. Treatment was discontinued after this event. This patient was classified as a relapser because their HCV RNA was undetectable at week 12, but became detectable again on subsequent assessments. The patient with pneumonia had a low absolute neutrophil count (0.7 �� 109 cells l?1) at week 16 (dose was not reduced). By week 20 their absolute neutrophil count was within normal range.

The patient was hospitalized for pneumonia at week 38, and by this time their neutrophil count had been >1.0 �� 109 cells l?1 for the preceding 5 months prior to admission. Treatment continued in this patient. In the PEG-IFN ��-2a (40KD) 270 ��g week?1 plus ribavirin treatment group, one patient was diagnosed with appendicitis and another patient had reported severe irritability. Treatment continued in the patient who had appendicitis. The patient with severe irritability was only 6 weeks into treatment, and was then lost to follow up; data from this patient were therefore not included in either the efficacy or PK analyses. No patient received erythropoietin during the trial. Overall, only one of the patients received <80% PEG-IFN ��-2a (40KD), 80% ribavirin, 80% of the time.

Discussion The reasons underlying the influence of obesity on a poor response rate to antiviral therapy in patients with CHC is unknown. It has been suggested that the poor response rate in obese patients may be a consequence of inadequate drug doses resulting in lower serum PEG-IFN-�� levels [11]. This current open-labelled, randomized, single-centre study has suggested that PEG-IFN ��-2a (40KD) 270 ��g week?1 increases PEG-IFN ��-2a (40KD) AV-951 levels in obese patients with CHC compared with the standard dose of 180 ��g week?1.