Utility of laboratory monitoring during hepatitis C treatment with ribavirin‐free direct‐acting antiviral regimens

Abstract

| INTRODUC TI ONWidespread implementation of safe and effective oral direct-acting antiviral (DAA) regimens has led to a revolution in the treatment of chronic hepatitis C virus (HCV) infection, a major cause of cirrhosis and hepatocellular carcinoma. Before the advent of DAA regimens, the standard of care for HCV treatment was subcutaneous polyethylene-conjugated interferon alpha (peginterferon) in combination with oral ribavirin, administered for up to 48 weeks. Incomplete on-treatment virological suppression or virological relapse resulted in rates of sustained virological response (SVR) of approximately 50% overall, 1 defined (in the peginterferon era) as the absence of detectable serum HCV RNA 24 weeks after treatment completion. Frequent laboratory monitoring was necessary throughout the treatment course due to the risk of haematologic toxicities of peginterferon and ribavirin. Furthermore, the kinetics of reduction in serum HCV RNA during treatment were used to guide the duration of antiviral therapy, which required measurement of serum HCV RNA at multiple time points during and after treatment. 2With the high SVR rates (greater than 90% overall) and absence of haematological toxicities associated with ribavirin-free DAA regimens, the need for frequent laboratory monitoring, and in particular, determination of on-treatment kinetics of virological suppression, is less clear. With DAA treatment, confirmation of SVR can be achieved by measurement of serum HCV RNA only 12 weeks after treatment completion; thus current monitoring recommendations, codified in joint guidelines from the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA), include determination of serum HCV RNA at week 4 of DAA-based treatment and at 12 weeks after treatment completion. 3 However, the guidelines leave open decision making about serum HCV RNA determination at the end of treatment. 3 Many centres, including our own, have continued to test at end-treatment in this interferon-free era, but the utility of this practice has not been established. To address this unresolved issue, we sought to determine the extent to which testing at week 4 and the end of ribavirin-free DAA treatment predicted SVR and whether it identified unexpected drug toxicity that would alter post-treatment management. completed all laboratory follow-up. Baseline data included demographic information, HCV genotype, previous antiviral treatment if applicable, and DAA regimen used. Cirrhosis was defined by (a) abdominal imaging, (b) liver stiffness of at least 12.5 kPa, measured by transient elastography, or of at least 4.81 kPa, measured by magnetic resonance elastography, or (c) biopsy. 4 Exclusion criteria included the following: (a) concomitant hepatitis B infection (defined as the presence of detectable serum hepatitis B surface antigen), (b) Abbreviations: AASLD, American Association for the Study of Liver Diseases; ALT, serum alanine aminotransferase; AST, aspartate aminotransferase; DAA, direct-acting an...

Simplification of Care for Chronic Hepatitis C Virus Infection

“…In a retrospective review of 208 patients infected with HCV receiving DAAs, no difference was reported in SVR12 rates between patients with detectable and undetectable HCV RNA at week 4 (96.5 vs. 97.5%; p ¼ 0.69). 79 These results have been replicated irrespective of treatment regimen or duration. 80,81 AASLD/IDSA guidelines have recently been updated to dispense with 4-week HCV RNA viral load assessment, now recommending testing only at 12 or more weeks posttreatment completion.…”