Hepatitis C: 5 Things to Know

Nancy S. Reau, MD


July 05, 2019

In a mere 30 years since it was identified, hepatitis C (HCV) is now a curable disease when treated with short-duration, well-tolerated finite therapy. Despite these advances, however, HCV continues to be a public health threat that requires better identification and linkage to care. Here are five issues about HCV that clinicians should know.

1. HCV is now a bimodal disease.

Until recently, baby boomers made up the biggest group of people infected with HCV, defined by the Centers for Disease Control and Prevention as those born between 1945 and 1965. But now there is a new peak in those aged 20-35 years, driven largely by the opioid epidemic and injection drug use.[1] This new cohort defies preconceptions of HCV, in that patients are more rural, nearly equally divided between women and men, and less likely to be predominantly from minority populations. This bimodal distribution has significant implications for screening guidelines and could lead to a recommendation for universal screening.[2] Until then, it is vital that we ask our patients about risk factors.

With these demographics, HCV is also affecting women of reproductive age. The rates of HCV diagnosed during pregnancy have increased more than 100% in some locations.[3] Legislation mandating HCV testing in all pregnant women was approved in Kentucky.[4] Although medical society guidelines differ, the HCV guidance document from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America recommends universal screening in all pregnant women, irrespective of risk factors.

2. HCV is more than a liver disease.

HCV is a well-recognized cause of liver-related morbidity and mortality, but as a proinflammatory and immune modulatory virus, it is also associated with several extrahepatic manifestations. Retrospective and prospective studies are building the case that this infection is a systemic insult.[5,6,7] Large patient databases confirm higher rates of multiple conditions across all organ systems in those with HCV, including type 2 diabetes, cardiovascular disease, chronic kidney disease, extrahepatic malignancies, and immune conditions such as celiac disease.[8] Vasculitis, glomerulonephritis, and cryoglobulinemia have also been associated with HCV.

Extrahepatic manifestations of HCV were underrecognized until 2012, when an international study that followed 530 patients with HCV and advanced fibrosis found not only the expected decrease in risk for liver-related morbidity and mortality in those who cleared the virus with therapy but also an association with lower all-cause mortality, suggesting that the cure affected more than just liver health.[9] HCV cannot be defined only by the degree of fibrosis, as that monumentally underestimates the overall impact of this virus.

Providing effective therapy for our patients should be a priority. Virologic cure improves patient-reported outcomes, with patients free of viral replication and without risk for relapse, and extends benefits well beyond the liver.[8]

3. Fibrosis is reversible.

Reversing fibrosis was not previously considered possible, but now, fibrosis regression is increasingly recognized after eradication of HCV, with well-documented examples of histologic improvement, and even reversal, of cirrhosis.[10]

This is a cautionary tale, however. Liver disease can continue to progress in patients, even after being cured, if they have other coexisting diseases or conditions, such as hepatitis B virus, steatosis, diabetes, or iron overload; are obese; or use alcohol. These patients will still require appropriate follow-up and management.

Limitations in technology are an equally important consideration. Some noninvasive assessments of fibrosis will overestimate regression, with improved scores because of inflammation resolution that occurs as a result of therapy.[10] Thus, improvements in "fibrosis" on assessment may reflect more than just the regression of scar tissue. You cannot "restage" patients after cure to guide postcure management. If your patients are diagnosed with cirrhosis before treatment, they need to be monitored post-treatment with standard screening for cirrhosis, along with liver cancer surveillance, at 6-month intervals.


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