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SVR is determined with measurement of HCV RNA using a highly sensitive assay 24 weeks following the end of treatment. SVR12 has been adopted by drug approval bodies as a surrogate for SVR24. Earlier response at 4 weeks after treatment (SVR4) is often reported by trial investigators as it is predictive of later response. These markers are undergoing validation in clinical trials. For patients treated with protease inhibitor–containing regimens, SVR has been specifically defined as HCV RNA < 25 IU/mL at Week 24 posttreatment.
For patients who obtain an SVR and do not have advanced fibrosis or cirrhosis (ie, Metavir stage F3 or F4), no long-term monitoring is necessary. In some centers, such patients undergo HCV RNA testing 1 year after completion of treatment to confirm that HCV RNA remains undetectable. It is important to be aware of the potential for reinfection,[184,185] and to counsel patients with ongoing risk behavior on risk reduction strategies.
For patients who obtain an SVR and have advanced fibrosis or cirrhosis, long-term follow-up is required. Provided these individuals do not develop further liver injury, the risk of hepatic decompensation after achieving SVR is very low. Specifically, patients without esophageal varices before treatment will not develop them after SVR, and therefore endoscopic surveillance can be discontinued once SVR has been achieved. In contrast to liver failure, liver cancer may still occur after SVR, albeit much less frequently. Therefore, patients with advanced fibrosis or cirrhosis (Metavir stage F3-F4) require ongoing ultrasound surveillance for hepatocellular carcinoma every 6 months.[5,54]
Strategies to Reduce the Risk of Reinfection
Long-term follow-up is advisable for members of specific populations at an elevated risk of reinfection with HCV after obtaining a SVR following the end of treatment. Some cases of reinfection following successful HCV treatment should be anticipated among persons who inject drugs (PWIDs), either currently or previously; HIV-coinfected men who have sex with men (MSM); and individuals in correctional settings. Presently, the AASLD and the IDSA guidance recommends follow-up testing for HCV reinfection among individuals with ongoing risk factors (ie, PWID and HIV-coinfected MSM engaging in unprotected sex with men).
HCV reinfection rates are higher in these groups than the general population. A 2016 meta-analysis of 59 studies estimated the 5-year risk of HCV recurrence following SVR and reported that the lowest risk was observed in patients with no recognized risk factors for HCV reinfection (5-year recurrence rate: 0.95%); intermediate risk in individuals with ≥ 1 recognized risk factor, defined as current or former injection drug use, incarceration, or MSM status (rate: 10.67%); and highest risk in individuals coinfected with HCV and HIV, independent of other risk factors (rate: 15.02%). Among individuals receiving substance abuse treatment while still using drugs, the risk is greater among those using injection drugs. In a 3-year follow-up analysis of patients who received elbasvir/grazoprevir through the phase III C-EDGE CO-STAR trial while also receiving opioid agonist therapy and continuing to use drugs, the overall reinfection rate after successful HCV treatment was low: 2.3 cases per 100 person-years (Capsule Summary). However, the reinfection rate was nearly double among those who self-reported using injection drugs (4.2 cases per 100 person-years). Among MSM, a recent retrospective study of HIV-infected MSM in Europe reported that among 606 men who cleared HCV infection, 25% later presented with HCV reinfection, yielding a reinfection rate of 7.3 per 100 person-years. This rate was still higher among those presenting with a second reinfection (18.8 per 100 person-years)—suggesting a pattern of ongoing high-risk behaviors.
Given the risks of reinfection, some experts recommend extending the HCV care continuum past the point of SVR, in order to maintain the benefits of HCV cure. Guidance from the AASLD/IDSA recommends annual HCV testing for PWID and HIV-coinfected MSM engaging in unprotected sex with men. Given that the HCV antibody test is anticipated to be positive, HCV RNA testing is recommended among those at risk of reinfection. In addition to monitoring for reinfection, constructive strategies that address and prevent HCV reinfection include education and counseling, harm reduction interventions, effective addiction treatment in settings of injection drug use, scaling up treatment provision (including targeting participants of injecting networks), and rapid retreatment of infection.[190,191] However, evidence is lacking on the efficacy of these strategies to prevent HCV reinfection; nonetheless, it is anticipated that interventions intended to prevent HIV transmission (ie, avoiding fluid exchange and equipment sharing among PWID, condom use among MSM) may offer efficacy against HCV reinfection.