Direct-Acting Antivirals for HCV-Associated Rheumatic Diseases

Not only is the hepatitis C virus (HCV) the cause of liver diseases in up to 170 million people worldwide, it also has many extrahepatic disease manifestations. These include rheumatic, hematologic, cardiovascular diseases.

In a review article published in Rheumatic Disease Clinics of North America, Patrice Cacoub, MD, from the Pitié-Salpêtrière University Hospital, Paris, France, and colleagues discuss the main rheumatologic diseases associated with chronic HCV infection, and how direct-acting antiviral agents (DAAs) have affected these extrahepatic manifestations.

According to the authors, HCV infection is frequently associated with clinical and biological rheumatologic manifestations, including arthralgia, myalgia, cryoglobulinemia vasculitis, sicca syndrome, and autoantibody production.

Several mechanisms underlie the development of rheumatologic manifestations in patients with HCV infection. These include immune mechanisms that result from chronic stimulation of B cells by the virus, as well as factors related to HCV infection of mononuclear cells in the peripheral blood.

The authors note that recent data also show that HCV infection leads to increased cardiometabolic-related morbidity and mortality. “Patients with HCV chronic infection have an increased prevalence of carotid atherosclerosis and increased intima-media thickness,” they say. Active chronic HCV infection also seems to be an independent risk factor for ischemic cerebrovascular accidents and ischemic heart disease. It has also been associated with higher rates of diabetes mellitus and insulin resistance when compared to healthy individuals.

Treatment of HCV Infection

Although patients with HCV infection have typically received interferon (IFN)-based treatment, this was found to be poorly effective and was also contraindicated in individuals with rheumatic disease, in particular because of the risk of exacerbation of autoimmune and rheumatic disorders.

However, the emergence of DAAs has changed the treatment landscape for patients with HCV, providing them with IFN-free regimens of short treatment duration that are highly effective and well-tolerated with minimal side effects.

Most recently, all-oral, IFN-free, and ribavirin-free treatment regimens have been approved that can lead to cure rates of 90% to 100% in all HCV genotypes. Several, large clinical studies have investigated different DAA combinations, including simeprevir plus sofosbuvir, sofosbuvir plus daclatasvir (with or without ribavirin), or sofosbuvir plus ledipasvir. These regimens are costly, but the authors emphasize that they offer significant benefit to patients with HCV infection, particularly those with rheumatic manifestations in whom IFN-based treatment has failed or was not tolerated.

In particular, Dr Cacoub and colleagues highlighted data from the recent VASCUVALDIC study which investigated the efficacy and safety of sofosbuvir plus ribavirin in patients with HCV-associated cryoglobulinemia vasculitis. This treatment combination was associated with a high rate of complete clinical response. “Of note, the complete clinical response was very rapid because it was noted at on-treatment week 12 in two-thirds of patients,” they say. “Kidney involvement with membranoproliferative glomerulonephritis improved in 4 out of 5 patients.” And only two serious adverse events were reported.

The authors concluded, “The emergence of new oral interferon-free combinations now offers an opportunity for patients infected with hepatitis C virus with extrahepatic manifestations, including autoimmune/inflammatory disorders, to be cured with a short treatment duration and a low risk of side effects.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.