Failure to achieve SVR after DAA treatment linked to HCC

New data suggest that failure to achieve sustained virologic response after treatment with direct-acting antivirals for hepatitis C was a strong predictor for development of hepatocellular carcinoma.

Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità in Rome, discussed the findings during an oral presentation at The Liver Meeting Digital Experience.

In the prospective, real-life, multicenter Italian PITER cohort study, Kondili and colleagues assessed the medium- and long-term risk for HCC among patients with HCV-induced cirrhosis who were treated with DAAs at 30 hepatology, infectious disease and internal medicine centers in Italy.

Of 2,214 patients who were treated with DAAs for HCV, 6.7% developed de novo HCC during a median follow-up of 30 months after the conclusion of treatment, with an incidence rate of 2.8 per 100 person-years. Of those treated, 93% achieved SVR and of those who achieved SVR, 5.8% developed de novo HCC. Of the 150 patients who did not achieve SVR, 20% developed HCV.

According to Cox regression analysis, the likelihood of developing de novo HCC was sevenfold higher among those who did achieve SVR compared with those who did achieve SVR (adjusted HR = 7.38; 95% CI, 4.27-12.78). Kondili noted that this finding was confirmed by a Kaplan-Meier HCC-free survival analysis in which 2-year HCC-free survival was higher in patients who achieved SVR vs. those who did not (98% vs. 81%; P < .001).

Certain baseline characteristics were also associated with an increased risk for developing de novo HCC after DAA treatment. Specifically, independent predictors of HCC included older age (aHR = 1.06; 95% CI, 1.04-1.09), HCV genotype 3 (aHR = 3.51; 95% CI, 1.79-6.86), platelet levels lower than 150,000 µ/L (aHR = 2.43; 95% CI, 1.28-4.61) and albumin levels lower than 3.5 g/dL (aHR = 2.36; 95% CI, 1.52-3.67), according to Kondili.

Interestingly, Kondili noted, in patients with vs. without de novo HCC, levels of liver stiffness were not only higher at baseline but were also significantly higher in patient with de novo HCC during follow-up.

“These data showed that liver stiffness measurement is an important predictor in occurrence of de novo HCC,” Kondili said.

Moreover, Kondili noted that high baseline liver stiffness, ranging from 17 kPa to 31 kPa, was the sole independent predictor of death by HCC (aHR = 1.05; 95% CI, 1.01-1.09).

In terms of other outcomes, 80% of the 119 patients who developed de novo HCC were diagnosed as having Barcelona Clinic Liver Cancer (BCLC) stage B or C, 26% died during follow-up, 7.6% underwent liver transplantation and 38% of the patients who were still alive at the end of follow-up had an active status of HCC, according to Kondili.

“A significant proportion of patients who developed de novo HCC after eradication had an advanced BCLC stage,” Kondili said. “Accurate patient monitoring over time, possibly with the aid of prognostic predictors, is necessary in order to promptly address them in appropriate therapeutic regimens.”