Moving toward noninvasive tests
While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.
Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.
Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.
Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
The last frontier
Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.
Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
A disease pegged for elimination
In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.
Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.
Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
References
Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.
Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.
Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.
Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.
Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.
This article first appeared on Medscape.com.