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

Abstract

Background and aims

The objective was to describe the dynamics of noninvasive tests (NITs) in cirrhotic patients following sustained virological response (SVR) and to assess their correlation with hepatocellular carcinoma (HCC) risk.

Methods

The dynamics of NITs (Fib4, APRI and LSM) were described in patients with cirrhosis after SVR included between 2006 and 2015 in two prospective French multicentre cohorts (ANRS CO22 Hepather and CO12 CirVir). 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 taking into account competing risks of death.

Results

3067 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 contrasted changes were observed during the follow-up of patients who ultimately developed HCC. Joint model analyses showed that current values of Fib4, APRI and platelet count at any time impacted HCC risk. Only Fib4 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 cirrhotic patients who could be safely excluded from surveillance programmes. NIT current value is more informative than slope which would necessitate to regularly re-assess HCC risk to design individualized surveillance strategies.

Impact and implications

It has been postulated that that monitoring noninvasive tests (NIT) dynamics following HCV cure may inform on HCC residual risk 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 cirrhotic patients who did not develop HCC, those who eventually developed liver cancer showed more contrasted changes in these tests. Specifically, the current values of tests like Fib4 and APRI 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 NIT 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.