HCC Risk Comparable in Hepatitis C Patients Treated With DAA or Interferon

Gregory J. Dore, MBBS, PhD

A meta-analysis found that patients were at no elevated risk of developing hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) following treatment with direct-acting antiviral therapy (DAA) for hepatitis C compared to interferon therapy, researchers reported here at the 2017 International Liver Congress (ILC).

The data reflected that there was no difference in liver cancer risk following cure with either therapy. However, achieving SVR does lower the risk of HCC.

“The best HCC prevention is to scale up hepatitis treatment to achieve SVR and to stop patients from progressing to cirrhosis,” said Gregory J. Dore, MBBS, PhD, head of the Hepatitis Viral Clinical Research Program at the Kirby institute, UNSW Sydney, Australia.

In meta-regression analysis that adjusted for patient characteristics, such as age and the length of follow-up, DAA therapy was not associated with higher HCC occurrence (relative risk [RR], 0.7; 95% CI, 0.2-2.6; P = .62), or with higher HCC recurrence (RR, 1.4; 95% CI, 0.5-4.1; P = .56).

By random effects meta-analyses, the incidence rates per 100/person years (py) for HCC occurrence was 1.1/100 py (95% CI, 0.8-1.5) in interferon studies compared to 3.1/100 py (95% CI, 1.9-4.9) in studies using DAA-based therapy. HCC recurrence was 9.2/100 py (95% CI, 7.1-11.8) versus 11.8/100 py (95%, 4.8-28.7) in interferon versus DAA studies.

The 2017 ILC provided a forum to resolve the emerging issue of whether treatment with DAA may put patients at higher risk for HCC than interferon-based treatments. Unexpectedly high rates of HCC occurrence and recurrence have been reported in patients who previously underwent successful tumor treatment and had also received DAAs. However, other studies have found that patient characteristics were more often associated with HCC recurrence.

“Recent studies have reported contradicting evidence on the risk of hepatocellular carcinoma following direct-acting antiviral therapy; our aim was to bring some clarity to this,” commented Dore.

Dore and colleagues conducted a systematic review, meta-analyses, and meta-regression study comprising 41 studies and 13,875 patients—including 26 on HCC occurrence and 15 on HCC recurrence—using Embase, Medline, Web of science, CINHAL, Cochrane, and DARE. They included studies published between January 2000 and February 2017 relative to HCC outcomes by response to HCV therapy in patients with HCV-related cirrhosis or patients with curative HCC treatment.

“The data show the higher incidence of HCC observed following DAA therapy can be explained by the shorter duration of follow-up and older age of participants, rather than the DAA treatment regimen,” Dore said. The investigators found that the incidence of HCC occurrence and recurrence was lower with longer follow-up and younger age, irrespective of treatment modality.

The analysis evaluated the occurrence or recurrence of HCC following sustained SVR to Hepatitis C. In studies assessing HCC occurrence, 17 studies used interferon to reach SVR and DAA were used in 9 studies. Substantial differences emerged in patient age and the time of follow-up in these studies: The average follow-up was 5.5 years in the interferon-based studies compared to 1.0 year in the DAA studies, and the average patient age was 52 years compared to 60 years in interferon and DAA studies, respectively. The RR for the association between HCC occurrence and patient age was 1.06, (P = 0.08), and was 0.77 (P = .03) for the association between HCC occurrence and average follow-up.

In the studies assessing HCC recurrence, 7 involved interferon and 8 involved DAA. The average follow-up was 5.0 years compared to 1.3 years, and the average age was 66 years versus 64 years in the interferon and DAA studies, respectively. The adjusted RR was 1.11 (P = 0.14) for the association of HCC recurrence and age, and was 0.79 (P = 0.19) for the association between HCC recurrence and follow-up.

“The higher incidence of HCC occurrence and recurrence following DAA therapy can be explained by a shorter duration of follow-up or cohort effect, and older aged patients with a higher base-line risk in this group,” said Dore. “The interferon and DAA studies were not addressing the same patient population—there is a classic cohort effect with the DAA cohort including higher risk patients who had been untreatable with interferon.”

Waziry R, Hajarizadeh B, Grebely J, et al. No evidence for higher risk of hepatocellular carcinoma occurrence or recurrence following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression. Presented at: International Liver Congress; April 19-23, 2017. Amsterdam, The Netherlands. Abstract PS160.

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Disparities were also noted in patient Child-Pugh stage, which was B/C in 0% of patients versus 10% of patients in the interferon versus DAA studies, respectively.