Sustained Virologic Response (SVR): A sustained virologic response (SVR) is an undetectable HCV RNA level using a sensitive assay (typically with a lower limit of 25 IU/ml) 12 weeks after completion of therapy for hepatitis C (Figure 1). This is typically referred to as the SVR12 and achieving an SVR12 is the goal of therapy. Among persons who achieve an SVR12, more than 99% go on to achieve an SVR24. More recently, many research studies have used shorter duration SVR time frames (SVR8, and SVR4) in an effort to expedite conclusions from these trials, but SVR4 and SVR8 are not the standard in clinical practice.
Durability of SVR: Long-term follow-up of patients who achieve an SVR24 has shown that more than 90 to 100% remain HCV RNA negative years after therapy. The largest studies have shown a minimal relapse rate, between 0 to 1%. Thus, a negative HCV RNA 24 weeks after antiviral therapy can be considered a virologic cure.
Impact of SVR on Liver Histology: Patients who achieve an SVR are more likely to have an improvement in liver inflammation and fibrosis. In a retrospective study of patients treated with standard interferon, those patients who had an SVR were twice as likely to have lower inflammation scores after treatment, compared to patients who relapsed (87% versus 36%). In the same study, fibrosis levels decreased in 44% of patients with SVR versus 14% in patients who relapsed. In some cases, there was complete regression of liver fibrosis. Multiple studies have confirmed this long-term histologic benefit.
Impact of SVR on Survival and Natural History: In a study that compared U.S. veterans with chronic hepatitis C with age-matched controls without hepatitis C, investigators demonstrated that hepatitis C infection increased the risk of death by approximately 37%. However, veterans with chronic hepatitis C infection who received at least 48 weeks of peginterferon and ribavirin had a 60% reduction in mortality compared with untreated veterans (Figure 2). In a study involving the general population, patients with advanced fibrosis who underwent antiviral therapy and achieved an SVR had reduction in overall mortality, liver-related death, liver failure, and hepatocellular carcinoma when compared with those who did not achieve an SVR (Figure 3). Most of this survival benefit resulted from the marked reduction in liver failure. In a recent meta-analysis of 35 studies, investigators showed a clear 5-year survival benefit with HCV treatment, including patients with cirrhosis and with HIV coinfection (Figure 4).
Impact of SVR on Other Medical Conditions: Hepatitis C can cause a myriad of extrahepatic complications, including membranoproliferative glomerulonephritis and Non Hodgkin's lymphoma. Chronic hepatitis C infection is associated with a higher prevalence of insulin resistance and diabetes mellitus. In some patients, successful treatment of hepatitis C is associated with remission of these underlying conditions. In addition, achieving an SVR has been shown to reduce the chance of impaired fasting glucose and diabetes development by 50%, an effect that is independent of other established risk factors for diabetes, such as age and body mass index.