| Invited Lecture (JSH) |
| Thu. November 1st 9:00 - 9:40 Room 4: Portopia Hotel South Wing Portopia Hall |
| HCV and HCC risk post-SVR: We’re not done yet | |||
| Raymond T Chung | |||
| Massachusetts General Hospital | |||
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| Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer death in developed countries. Chronic infection with hepatitis C virus (HCV) is a major driver of HCC. Recently developed direct-acting antivirals (DAAs) now achieve exceptional rates of sustained virologic response (SVR). Initial reports from Europe suggested unexpectedly high frequencies of incident HCC in the first year post-SVR with DAAs, raising concerns about possible provocation of hepatocarcinogenesis in the context of DAAs. However, many subsequent studies have demonstrated that the rates of HCC were not in excess of expected when duration of disease and underlying HCC risk was taken into account. Moreover, with longer term followup there has been an observed overall decrease in HCC post-SVR at rates comparable to those observed in persons following SVR accomplished with interferon (IFN) based regimens. Importantly, however, the risk of HCC development, while substantially diminished, still does persist post-SVR even beyond a decade. Thus, precise prediction of post-SVR HCC risk is urgently needed to identify a subset of patients who will require regular monitoring and prevention. Although clinical studies have suggested several risk factors such as older age, advanced fibrosis, and diabetes, none has been clinically adopted to guide post-SVR HCC screening. What are the mechanisms underlying this persistent risk for HCC development? While the inflammatory milieu that promotes hepatic fibrosis largely recedes with elimination of viral infection, emerging data suggest that there are genetic and epigenetic “scars” of the chronic infection and fibrotic state that in some cases persist beyond viral cure. Practically, this has the effect of altering gene expression patterns unfavorably toward a pro-growth and proliferation state. Together with our colleagues, we have observed persistence of an abnormal gene signature in the liver tissue of patients after SVR that predicted subsequent HCC development. These findings support the clinical utility of use of such a signature as a biomarker to identify persons who should undergo continued HCC screening. However, given the lack of appeal of dependence on liver biopsy as a prognostic tool, particularly after accomplishment of SVR, there is still a strong need to develop a simple prognostic tool that can be blood-test or imaging based. We will discuss several possible avenues in this area, including protein markers, as well as circulating cell-based and cell-free assays. |
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