title: Adverse effects of peg-Interferon and Ribavirin combined antiviral treatment in a Romanian hepatitis C virus infected cohort.
abstract: BACKGROUND
  Adverse effects appearing during combined peg-Interferon and Ribavirin antiviral treatment against chronic infection with the hepatitis C virus are a major cause for treatment failures and abrupt interruption. In the prospect of the imminent introduction of new direct acting antiviral agents, with demonstrated higher rates of adverse effects, our study aimed to assess the severity and incidence of several types of adverse effects in a cohort of genotype 1 infected Romanian patients.
  
  
  METHODS
  We prospectively included a total of 150 patients (45 men), aged 25 to 64 years, who received combined peg-Interferon and Ribavirin antiviral treatment for chronic hepatitis C. Out of these, 145 patients also had liver biopsies prior to treatment initiation. We recorded their viral loads, hemoglobin values and thrombocyte counts, as well as any dermatological, psychiatric or constitutional adverse effect after twelve doses, eight and twelve months of treatment, with two follow-up examinations at three and six months after treatment completion.
  
  
  RESULTS
  Viral loads significantly decreased after 12 doses of treatment, in the end a total of six patients (two men and four women) being declared non-responders. Hemoglobin values and thrombocyte counts significantly decreased during treatment (p<0.0001), with their values being restored to pre-treatment levels during the follow-up period. We did not find significant differences between the 12-doses, 8 and 12 months values during treatment (p>0.05). We recorded 43 cases (11 men and 32 women) presenting with rashes, drug eruptions and erythema. We only encountered grade 1 and 2 dermatological adverse effects. Psychiatric effects were present in 34 cases (10 men and 24 women, 22.6% of the group) and manifested as mild depressions, which did not require specific medication or antiviral dose adjustment. Patients also presented headaches (80.6%), fatigue (71.3%), nausea (47.3%), arthralgias (35.3%) and fever (30%).
  
  
  CONCLUSIONS
  We did not encounter severe hematological adverse effects that would require Ribavirin dosage adjustments. Cutaneous and psychiatric adverse effects were also present in a significant number of patients; however, their severity did not influence the continuity or outcome of the antiviral treatment. Other constitutional effects were also present with no direct consequence on the course of treatment. Future agents employed in antiviral therapy shall require extensive monitoring of all adverse effects already acknowledged during dual combination therapy.
authors.affiliation: Research Center for Microscopic Morphology and Immunology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
authors.forename: O
authors.initials: O
authors.lastname: Predescu
authors.forename: Letiţia Adela-Maria
authors.initials: LA
authors.lastname: Streba
authors.forename: Eugenia
authors.initials: E
authors.lastname: Irimia
authors.forename: Liliana
authors.initials: L
authors.lastname: Streba
authors.forename: L
authors.initials: L
authors.lastname: Mogoantă
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*; D012383:Romania; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin