Letter: hepatocellular carcinoma negatively affects sustained virological response of direct-acting anti-viral treatment in decompensated cirrhosis

We read with interest the article by Mecci et al regarding the interaction between direct-acting anti-virals (DAA) for chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC).1 Their study is in line with a previous study suggesting that DAA treatment does not increase but significantly decreases the risk of HCC.2 However, they showed that patients with decompensated cirrhosis who developed HCC achieved a lower sustained virological response (SVR) rate than patients without HCC (68% vs 87%, P < .001, odds ratio: 3.13, 95%CI: 1.64-5.99).1 We have several comments on the latter.

Our previous studies showed that Asian patients infected with genotype 1 HCV and a history of HCC achieved a lower SVR than patients without HCC treated with ledipasvir (LDV)/sofosbuvir (SOF) (94.1% vs 98.7%, P = .001).3, 4 In Beste and colleagues’ study, only 74.4% patients with HCC achieved SVR, compared to 91.1% in those without HCC.5 Prenner et al also showed that cirrhotic patients with active HCC (viable tumour on imaging) were almost eight times more likely to fail HCV treatment than those without active HCC.6 These results were consistent with our recent systematic review and meta-analysis demonstrating that HCC was associated with a significantly higher risk of treatment failure. In paticular, patients with active HCC (n = 277) at the time of DAA treatment had significantly lower SVRs than those with inactive HCC (n = 2304) (73.1% vs 92.6%, P = .002) (See fig. S14 in Ref.7), corresponding to an 18.8% (95% CI 7.3-31.8) reduction in SVR rate.7 However, most of the patients in those studies had either compensated cirrhosis or no cirrhosis. There was insufficient data to evaluate the effect of HCC on SVR rates in patients with decompensated cirrhosis. However, a few studies showed that patients with decompensated cirrhosis with baseline HCC achieved a lower SVR (62.1%, 95% CI 44-77.3, n = 29) than patients without HCC (79.3%, 95% CI 74.9-83.1, n = 377).8 Furthermore, a study from Spain showed that in HCV-infected patients awaiting for liver transplantation, low SVR rate was not associated with HCC, but mainly with poor liver function in patients with end-stage liver disease.9

A recent study described five patients with cirrhosis who developed HCC within 6 months of therapy and who experienced virological relapse compared to 8% patients without HCC (P < .0001).10 Together with the present study, this supports the possible effect of HCC emerging during treatment in hindering SVR.10 Thus, we presume that early HCC and a significantly higher risk of developing HCC were associated with treatment failure in patients with decompensated cirrhosis in this study.1

In summary, this study indicates that HCC negatively affects SVR with DAA treatment in patients with decompensated cirrhosis, and adds further evidence that HCC reduces the anti-viral efficacy of DAA in HCV-infected patients with different severity of liver disease. More importantly, for patients with compensated or decompensated cirrhosis who fail DAA treatment, the diagnosis of HCC should be considered. Thus, a shortened surveillance interval for early HCC screening would be crucial in patients with advanced disease who fail DAA treatment.

FUNDING INFORMATION

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