Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C

Abstract

Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylated-interferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.

Renal safety after one year of sofosbuvir‐based therapy for chronic hepatitis C: A Brazilian “real‐life” study

“…In Brazil, the administration of second‐generation DAA to treat chronic HCV infection is relatively recent. Acting directly on viral proteases and polymerases, these drugs inhibit polyprotein processing and viral replication, which provides excellent efficacy in HCV eradication . In our study, the rate of treatment success was high (98.9%) and all patients who presented significant renal impairment reached SVR.…”

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

“…Prior to the advent of direct‐acting antivirals (DAAs), chronic HCV was the leading aetiology for liver transplantation (LT) in the United States and population data suggested HCV patient listings were continuing to grow each year . Interferon‐based therapies and ribavirin comprised the backbone of HCV therapy but was poorly tolerated due to side effects . Furthermore, studies suggested that sustained virologic response (SVR) achieved from these therapies was only 30%‐40% in patients with genotype 1 and 70%‐90% for patients with genotype 2 and 3 .…”

“…Furthermore, studies suggested that sustained virologic response (SVR) achieved from these therapies was only 30%‐40% in patients with genotype 1 and 70%‐90% for patients with genotype 2 and 3 . Although protease inhibitors such as boceprevir and telaprevir improved overall SVR rates, use of these medications was limited due to drug‐drug interactions and direct drug toxicity . Sofosbuvir, a second‐generation DAA, targets NS5B and was approved by the FDA in December 2013, and initial clinical trials showed 90% of treatment naïve patients achieved SVR when combined with interferon and ribavirin among patients with genotype 1, and 93%‐100% over genotypes 1‐4 when sofosbuvir was combined with protease inhibitors …”

Longitudinal assessment of hepatic fibrosis in responders to direct‐acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods

“…2 Hepatitis C virus recurrence after LT shows an accelerated evolution to liver cirrhosis that manifests in 20%-40% of the patients within 5 years post-LT. 4 Viral eradication post-LT improves long-term graft and patient survival and reduces the need for retransplantation. Therefore, management of recurrent HCV after LT seems critical for its impact on the outcome of HCV-infected patients after transplantation.…”