Treatment of chronic viral hepatitis C (HCV) infection with direct-acting antiviral agents (DAAs) results in cure, or sustained viral response (SVR), in more than 90% of patients. However, there are subsets of patients who have persistent liver inflammation and fibrosis and develop hepatocellular carcinoma (HCC) despite achieving SVR. A possible reason for these phenomena may be the presence of virus particles in liver tissue but not blood, otherwise defined as occult infection.


To describe liver histologic findings following successful DAA therapy, test HCV RNA by (liver) tissue polymerase chain reaction in treated cases, and identify predictive markers for HCC development in treated cases.


A total of 96 identified patients were divided into 4 groups, each differentiated by the presence or absence of SVR and HCC. Groups were compared for several clinicopathologic variables, including degree of inflammation and fibrosis, and the ‘directionality' of fibrosis in cirrhotic livers using the novel progressive-indeterminate-regressive scoring system.


Overall, we found a significant decrease in inflammation in SVR patients. None of the patients showed regression of their cirrhosis following treatment. No evidence of occult HCV infection was seen in 40 livers tested, including 21 with HCC. The number of patients who developed HCC was similar in the SVR and non-SVR groups, and increased inflammation and fibrosis were associated with HCC development.


Following DAA-SVR there appears to be an overall decrease in inflammation, but the fibrosis tends to persist, at least in the short term (median follow-up of 20.2 months).

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.

Presented in part at the United States and Canadian Academy of Pathology (USCAP) National Meeting; March 17–23, 2018; Vancouver, Canada; and at the American Association for the Study of Liver Diseases (AASLD) National Meeting; October 20–24, 2017; Washington, DC.