Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon‐alpha 2a plus ribavirin

• Published in: Alimentary pharmacology & therapeutics Vol. 27; no. 9; pp. 810 - 819
• Main Authors: TANG, K. H., HERRMANN, E., PACHIADAKIS, I., PAULON, E., TATMAN, N., ZEUZEM, S., NAOUMOV, N. V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008; Blackwell
• Subjects: Adult; Antiviral Agents - therapeutic use; Biological and medical sciences; Digestive system; Drug Therapy, Combination; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Humans; Interferon-alpha - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Ribavirin - therapeutic use; Statistics as Topic; Viremia - blood; Antineoplastic agent; Human; Cytokine; Genotype; Ribavirin; Virus; Immunomodulator; Interferon alpha 2a; Peginterferon alfa-2a; Treatment; Nucleoside analog; Antiviral; Clinical trial; Flaviviridae; Pegylated form; Inosine monophosphate dehydrogenase inhibitor; Hepatitis C virus; Hepacivirus
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2008.03628.x

Summary Background  Individualized treatment regimens, taking into account the heterogeneity of patients with chronic hepatitis C, are needed to improve treatment outcomes. Aim  To investigate prospectively the period of undetectable viraemia required for a high rate of sustained virological response in patients with chronic hepatitis C genotype 1 and the relationship to early viral kinetics. Methods  Forty‐five chronic hepatitis C genotype 1 patients were given peginterferon‐alpha 2a plus ribavirin. Viraemia and hepatocyte HCV‐RNA levels were quantified using a TaqMan assay. Beyond the first time point of undetectable viraemia (<20 IU/mL) between baseline and treatment week 12, 32 of 45 (71%) patients were randomized to additional 12 weeks (G12); 24 weeks (G24) or 36 weeks therapy (G36). The remaining 13 patients received 48 weeks’ treatment (G48). Results  The sustained virological response rates were: G12 – five of 11 (45%); G24 – eight of 10 (80%); G36 – eight of 11 (73%); G48 – four of 13 (31%). The anti‐viral efficacy (ε) and treatment‐induced loss of infected hepatocytes (Mδ), were significantly higher in patients with early viral clearance. In G12, patients with sustained virological response had lower baseline viraemia than those who relapsed. Conclusions  Early viraemia clearance is a better marker than baseline viral load and differentiates chronic hepatitis C genotype 1 with high or low probability of sustained virological response. In patients with viraemia clearance within 12 weeks of starting peg‐interferon/ribavirin therapy, an additional period of undetectable viraemia of minimum 24 weeks is required for high sustained virological response.