Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Abstract

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization’s goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post–HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post–HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.

Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage

“…High levels of Treg cells, both circulating [ 27 ] and intratumoural [ 7 ], are strongly associated with a poor outcome prognosis, making them potential targets for immunotherapy [ 7 , 28 ]. As HCC occurrence or recurrence happens even after successful DAA treatment [ 29 ], we can assume that DAA therapy does not eliminate the risk of HCC development connected with Treg activity.…”

The Dark Side of the Force: When the Immune System Is the Fuel of Tumor Onset

“…In fact, until now, no evidence of a different HCC occurrence or recurrence has been found in patients treated with DAA and IFN therapy; probably the reduced risk is mainly associated with a sustained virologic response. In this post-HCV era, thanks to DAA therapy, HCC surveillance is currently recommended in all patients with cirrhosis [ 179 ]. HBV is not curable, but it has been almost eradicated after vaccine introduction; however, it remains a problem in those countries in which the vaccine is still not available, such as Eastern Asia.…”

Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target

“…Over the past few decades, liver diseases have mainly been induced by hepatitis viruses and hepatologists have been struggling to treat them [ 1 ]. Chronic infections caused by hepatitis B and C viruses have been linked to chronic hepatitis, fibrosis, and hepatocellular carcinoma (HCC), which has the second worse survival rate and is the fourth leading cause of cancer death worldwide [ 2 , 3 ].…”