Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

Abstract

Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.

Long-Term Hepatocellular Carcinoma Development and Predictive Ability of Non-Invasive Scoring Systems in Patients with HCV-Related Cirrhosis Treated with Direct-Acting Antivirals

“…However, given the high heterogeneity of HCC, a more personalized surveillance strategy based on individual risk assessment is an unmet need. Promising results have been obtained from non-invasive scoring systems (NSS) combining demographic, clinical, and biochemical variables normally collected during standard clinical practice [11,12]. Due to their cost-effectiveness, this approach could be suitable for the surveillance of patients at risk of HCC development.…”

Is it time to refine HCC surveillance strategies in HCV cured patients?

“…The former finding is in line with previous studies that reported portal hypertension being associated with post‐SVR HCC. [ 5 ] Conversely, diabetes was not an independent predictor of HCC in this meta‐analysis, whereas other metabolic factors were not evaluated. The role of metabolic disorders on post‐treatment HCC risk probably needs additional investigations for several reasons.…”

“…[ 3 ] The wide use of DAAs to cure large cohorts of patients with advanced liver disease and/or comorbidities, who were previously contraindicated to IFN‐based therapies, has recently livened up the debate on long‐term surveillance strategies and their cost‐effectiveness. Although the risk of hepatic decompensation remains low, also in patients with severe portal hypertension, before treatment, [ 1,4 ] the residual annual risk of de novo HCC has been estimated to be 2.0%–2.5% in SVR persons with cirrhosis following DAAs, [ 5 ] thus further supporting the need for post‐treatment surveillance in this subgroup of patients. Conversely, data on the residual risk of HCC in patients with F3 fibrosis are controversial, as long as recommendations from scientific societies are not univocal.…”

“…In fact, not all baseline metabolic risk factors have been collected in such studies. Then, not only diabetes, but also surrogate biomarkers of metabolic disorders, such as elevated gamma‐glutamyl transferase, [ 5,8 ] had been previously associated with HCC in some IFN‐ and DAA‐treated cohorts, thus suggesting that the dysmetabolic profile may have a role beyond single comorbidities.…”

Hepatitis C hospitalizations in Spain and impact of new curative antiviral therapies

“…The development of hepatocellular carcinoma in chronic hepatitis C patients with significant or advanced fibrosis or cirrhosis may occur after resolution of HCV infection 28 . The tumour is believed to arise from hepatic areas of residual scar 29 . In this scenario, new curative oral HCV antivirals ameliorate but do not halt the risk of liver cancer in chronic hepatitis C patients 30 .…”