Achieving sustained virological response: what’s the impact on further hepatitis C virus-related disease?

Abstract

Continuous hepatic inflammation as a result of chronic infection with the hepatitis C virus may lead to the development of fibrosis and eventually cirrhosis. At the stage of cirrhosis, patients are at elevated risk of liver failure and hepatocellular carcinoma, two complications that shorten their life expectancy. Survival may be further impaired by the extra-hepatic manifestations of chronic hepatitis C virus infection, such as diabetes mellitus and lymphoma. Sustained virological response (SVR) following antiviral therapy has been associated with regression of hepatic fibrosis as well as with a reduction in portal pressure, both important markers of liver disease severity. Long-term follow-up studies indicated that SVR was related not only to a reduced occurrence of solid clinical end points, including liver failure and hepatocellular carcinoma, but also cardiovascular events and malignant lymphomas. Together, these findings may explain the recently observed improved overall survival among patients who attained SVR, even in the case of advanced liver disease.

Keywords:

• all-cause mortality
• antiviral therapy
• chronic HCV infection
• hepatic fibrosis
• hepatocellular carcinoma
• sustained virological response

Financial & competing interests disclosure

AJ van der Meer has received lecture fees from BMS and Gilead. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Chronic infection with the hepatitis C virus (HCV) may impair a patient’s health-related quality of life and can result in liver-related morbidity, such as liver failure and hepatocellular carcinoma, which reduces their life expectancy.

• The reduced overall survival among patients with chronic HCV infection is further explained by the development of extra-hepatic manifestations, such as diabetes mellitus, renal failure, cardiovascular events and malignant lymphoma.

• Antiviral therapy has the potential to result in sustained virological response (SVR), which is defined as HCV RNA negativity 12–24 weeks following cessation of antiviral therapy. Because of its long-term durability, SVR is considered cure of chronic HCV infection.

• The most recent antiviral treatment development success concerns the direct-acting antivirals with excellent virological efficacy and hardly any side effects. Combining multiple classes of direct-acting antivirals showed to result in SVR in around 95% of patients, even in the case of cirrhosis.

• Achievement of SVR has been associated with improvement of patient-reported outcome measures, of which fatigue is probably the most important end point. Indeed, SVR has been related to an increase in the health-related quality of life.

• Regarding the liver, viral clearance was associated with a reduction in hepatic fibrosis and portal pressure, which are two important markers of liver disease severity.

• Long-term followed cohorts of patients with chronic HCV infection and advanced liver disease showed that liver failure, hepatocellular carcinoma and liver-related mortality occurred significantly less often among patients who had attained SVR when compared to those who had not attained SVR. However, in the case of cirrhosis, patients are not free-warded from the complications of their advanced liver disease following SVR.

• Patients with chronic HCV infection who attained SVR were also found to have a lower risk of extra-hepatic complications, which may shorten the life expectancy, including diabetes mellitus, renal failure, cardiovascular events and malignant lymphoma.

• More recent studies have indicated that SVR was associated with a reduced all-cause mortality rate among patients with chronic HCV infection, both among patients with as well as among patients without advanced liver disease.

• Despite effective treatment strategies, antiviral treatment uptake among the HCV-infected population is limited so that the potential beneficial clinical effect of successful therapy remains limited.

• Efforts to increase the number of patients with chronic HCV infection who have been treated are needed to truly reduce HCV-related morbidity and mortality. Increasing awareness amongst a broad spectrum of healthcare workers as well as the implementation of HCV screening programs may be required to fulfill this objective.