Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis

Abstract

Background & aims: Whether the dynamics of non-invasive tests (NITs) correlate with hepatocellular carcinoma (HCC) risk in patients with cirrhosis following sustained virological response (SVR) remains unknown. Thus, we aimed to describe NIT dynamics and assess their correlation with HCC risk.

Methods: The dynamics of NITs (fibrosis-4 index [FIB-4], aspartate aminotransferase-to-platelet ratio index [APRI] and liver stiffness measurement) were described in patients with cirrhosis after SVR included in two prospective French multicenter cohorts (ANRS CO22 Hepather and CO12 CirVir) between 2006 and 2015. To assess their relationship with the risk of HCC, a joint modeling approach was employed using both standard and flexible models adjusted for age and sex. The impacts of NIT current value and slope during follow-up on HCC risk were assessed, considering competing risks of death.

Results: A total of 3,067 patients with cirrhosis who achieved SVR were analyzed, among whom 228 (7.4%) developed HCC and 210 (6.9%) died during a 26-month follow-up. All NITs were increased at baseline in patients who ultimately developed HCC, whereas platelet counts were lower. All NITs improved in patients who did not develop HCC. More varied changes were observed during the follow-up of patients who ultimately developed HCC. Joint model analyses showed that current values of FIB-4, APRI and platelet count at any time impacted HCC risk. Only FIB-4 and APRI slopes influenced the same outcome. When considering NIT current value and slope simultaneously, only the current value of NITs impacted HCC risk while the slopes were not informative.

Conclusions: The dynamics of NITs following SVR do not identify patients with cirrhosis who could be safely excluded from surveillance programs. NIT current value is more informative than slope, which will necessitate regularly re-assessment of HCC risk to design individualized surveillance strategies.

Impact and implications: It has been postulated that monitoring non-invasive test (NIT) dynamics following HCV cure may provide information on the residual risk of hepatocellular carcinoma (HCC) in patients with cirrhosis and may allow for the discontinuation of surveillance in certain patient subsets. We analyzed data from over 3,000 patients and found that while all NITs improved in patients with cirrhosis who did not develop HCC, those who eventually developed liver cancer showed more varied changes in these tests. Specifically, the current values of tests like FIB-4 (fibrosis-4 index) and APRI (aspartate aminotransferase-to-platelet ratio index) were linked to an increased risk of HCC, while their slopes did not provide additional useful information, suggesting that dedicated prospective studies are warranted to define how repeated measurement of NITs could be combined with other variables into HCC risk stratification algorithms. Until then, HCC surveillance should be maintained in all patients with cirrhosis following HCV eradication, even in case of decreased NIT values.

Keywords: HCC; HCV; SVR; noninvasive tests; risk stratification; surveillance.