In the Journals

HCC rates after interferon-free HCV treatment linked to baseline risk factors

Recently published data suggest that higher hepatocellular carcinoma incidence after sustained virologic response with interferon-free hepatitis C treatment correlates to patient baseline risk factors, such as age, Child-Turcotte Pugh score and prior treatment, rather than IFN-free therapy.

“Recent studies from Europe have warned that the risk of HCC occurrence in cirrhotic individuals may be higher after attaining an IFN-free hepatitis C cure versus an IFN-containing cure,” Hamish Innes, MD, from the Glasgow Caledonian University, and colleagues wrote. “Although this finding could have major implications for the treatment of HCV, the studies on which it was predicated did not carry out multivariate adjustment for confounding factors, and involved small sample sizes only.”

While there are competing theories to explain these results, the researchers focused on the hypothesis that patients treated with IFN-free therapy may have greater preexisting risk factors for HCC compared with patients treated with IFN-containing regimens.

The researchers gathered data on 857 patients from the Scottish HCV clinical database who attained SVR between Jan. 1, 1997, and Apr. 1, 2016, and had a diagnosis of liver cirrhosis prior to therapy. They excluded patients with hepatitis B or HIV coinfection or a diagnosis of HCC prior to treatment.

Patients who received IFN-free therapy (31.7%) were more likely to be older (52.1 vs. 48.1 years; P < .001), white (96% vs. 90.6%; P = .006), have Child-Turcotte-Pugh score B or C (30.4% vs. 9.5%; P < .001), have thrombocytopenia (39.3% vs. 22.1%; P < .001), have a genotype other than genotype 3 (72.8% vs. 35.7%; P < .001), and have been treated for HCV two or more times previously (16.9% vs. 6.7%; P < .001).

Over a median of 1.7 years, 12 patients treated with IFN-containing regimens experienced incident HCC with an event rate of 1.26 per 100 person-years. Thirty-four patients treated with IFN-free regimens experienced incident HCC over a median of 3.5 years with an event rate of 2.53 per 100 person-years. Most cases of HCC comprised a single nodule (61%).

Associated factors

On univariate analysis, the researchers found that patients treated with IFN-free regimens had a significantly higher risk for HCC (HR = 2.48; 95% CI, 1.14-5.37).

Other factors associated with increased HCC risk included age 50 years to 59 years (HR = 2.75; 95% CI, 1.4-5.41) or age 60 years or older (HR = 3.31; 95% CI, 1.37-8.02) compared with 40 years to 49 years; Child-Turcotte-Pugh score B or C (HR = 5.24; 95% CI, 2.63-10.46) compared with A; thrombocytopenia (HR = 3.96; 95% CI, 2.14-7.3); and two or more prior HCV treatments (HR = 3.52; 95% CI, 1.56-7.95).

However, the correlation between IFN-free regimens and an increased risk for HCC was attenuated after multivariate adjustment (HR = 1.15; 95% CI, 0.49-2.71), due particularly to pre-treatment platelet count and Child-Turcotte-Pugh score.

Otherwise, the factors associated with increased risk for HCC remained similar to the univariate analysis for all patients: age 50 years to 59 years (HR = 2.68; 95% CI, 1.33-5.37) or age 60 years or older (HR = 3.62; 95% CI, 1.41-9.3) compared with 40 years to 49 years; Child-Turcotte-Pugh B or C (HR = 2.58; 95% CI, 1.16;5.76); thrombocytopenia (HR = 2.68; 95% CI, 1.32-5.45); and two or more prior HCV treatments (HR = 2.52; 95% CI, 1.04-6.13).

“A major finding from this study therefore, is that upon adjusting for these differences ... the elevated risk of HCC associated with IFN-free regimens was almost entirely attenuated,” Innes and colleagues concluded. “This would tend to indicate that the higher risk of HCC occurrence among individuals receiving IFN-free therapy is a reflection of the shifting patient case mix, as opposed to the pharmacodynamics of IFN-free therapy or any other direct or indirect consequence of IFN-free therapy itself.”

Disclosure: The authors report no relevant financial disclosures.

Recently published data suggest that higher hepatocellular carcinoma incidence after sustained virologic response with interferon-free hepatitis C treatment correlates to patient baseline risk factors, such as age, Child-Turcotte Pugh score and prior treatment, rather than IFN-free therapy.

“Recent studies from Europe have warned that the risk of HCC occurrence in cirrhotic individuals may be higher after attaining an IFN-free hepatitis C cure versus an IFN-containing cure,” Hamish Innes, MD, from the Glasgow Caledonian University, and colleagues wrote. “Although this finding could have major implications for the treatment of HCV, the studies on which it was predicated did not carry out multivariate adjustment for confounding factors, and involved small sample sizes only.”

While there are competing theories to explain these results, the researchers focused on the hypothesis that patients treated with IFN-free therapy may have greater preexisting risk factors for HCC compared with patients treated with IFN-containing regimens.

The researchers gathered data on 857 patients from the Scottish HCV clinical database who attained SVR between Jan. 1, 1997, and Apr. 1, 2016, and had a diagnosis of liver cirrhosis prior to therapy. They excluded patients with hepatitis B or HIV coinfection or a diagnosis of HCC prior to treatment.

Patients who received IFN-free therapy (31.7%) were more likely to be older (52.1 vs. 48.1 years; P < .001), white (96% vs. 90.6%; P = .006), have Child-Turcotte-Pugh score B or C (30.4% vs. 9.5%; P < .001), have thrombocytopenia (39.3% vs. 22.1%; P < .001), have a genotype other than genotype 3 (72.8% vs. 35.7%; P < .001), and have been treated for HCV two or more times previously (16.9% vs. 6.7%; P < .001).

Over a median of 1.7 years, 12 patients treated with IFN-containing regimens experienced incident HCC with an event rate of 1.26 per 100 person-years. Thirty-four patients treated with IFN-free regimens experienced incident HCC over a median of 3.5 years with an event rate of 2.53 per 100 person-years. Most cases of HCC comprised a single nodule (61%).

Associated factors

On univariate analysis, the researchers found that patients treated with IFN-free regimens had a significantly higher risk for HCC (HR = 2.48; 95% CI, 1.14-5.37).

Other factors associated with increased HCC risk included age 50 years to 59 years (HR = 2.75; 95% CI, 1.4-5.41) or age 60 years or older (HR = 3.31; 95% CI, 1.37-8.02) compared with 40 years to 49 years; Child-Turcotte-Pugh score B or C (HR = 5.24; 95% CI, 2.63-10.46) compared with A; thrombocytopenia (HR = 3.96; 95% CI, 2.14-7.3); and two or more prior HCV treatments (HR = 3.52; 95% CI, 1.56-7.95).

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However, the correlation between IFN-free regimens and an increased risk for HCC was attenuated after multivariate adjustment (HR = 1.15; 95% CI, 0.49-2.71), due particularly to pre-treatment platelet count and Child-Turcotte-Pugh score.

Otherwise, the factors associated with increased risk for HCC remained similar to the univariate analysis for all patients: age 50 years to 59 years (HR = 2.68; 95% CI, 1.33-5.37) or age 60 years or older (HR = 3.62; 95% CI, 1.41-9.3) compared with 40 years to 49 years; Child-Turcotte-Pugh B or C (HR = 2.58; 95% CI, 1.16;5.76); thrombocytopenia (HR = 2.68; 95% CI, 1.32-5.45); and two or more prior HCV treatments (HR = 2.52; 95% CI, 1.04-6.13).

“A major finding from this study therefore, is that upon adjusting for these differences ... the elevated risk of HCC associated with IFN-free regimens was almost entirely attenuated,” Innes and colleagues concluded. “This would tend to indicate that the higher risk of HCC occurrence among individuals receiving IFN-free therapy is a reflection of the shifting patient case mix, as opposed to the pharmacodynamics of IFN-free therapy or any other direct or indirect consequence of IFN-free therapy itself.”

Disclosure: The authors report no relevant financial disclosures.