Screening for HCC in HCV-related cirrhosis patients likely to be cost effective, even after HCV is cured

Screening patients with hepatitis C-related cirrhosis for hepatocellular carcinoma (HCC) is known to be cost effective before treatment. Now Canadian researchers have shown that ultrasound screening for HCC is likely to be cost effective even after patients with hepatitis C virus (HCV) have achieved a sustained virologic response (SVR).

In study data presented in April at the International Liver Congress 2018, in Paris, France, the incremental cost-effectiveness ratio (ICER) of biannual ultrasound screening in patients with HCV-related cirrhosis after direct-acting antiviral agent (DAA) therapy was found to be $40,803 per quality-adjusted life-year (QALY), which falls within an accepted willingness-to-pay threshold of $50,000/QALY.

The investigators concluded that this finding supports biannual ultrasound screening as cost effective in post-SVR patients if the annual HCC incidence is above 1.1%, which is lower than the recommended 1.5% threshold.

They also found that HCC screening was unlikely to be cost effective in patients who have advanced liver fibrosis but no evidence of cirrhosis—a finding that challenges current clinical practice guidelines.

“This study is important because it emphasizes the importance of HCC surveillance by ultrasound in patients with cirrhosis, even if HCV has been eliminated,” said Markus Cornberg, MD, who was not involved in the study but is a governing board member of the European Association for the Study of the Liver (EASL), which hosts the International Liver Congress.

Surveillance for HCC among HCV-infected individuals has been considered cost effective if the risk of HCC exceeds 1.5% per year prior to SVR. But the cost-effectiveness values may differ after achieving SVR because of the substantially reduced risk of liver failure.

Therefore, Hooman Farhang Zangneh, MD, MSc, postdoctoral research fellow, Toronto Centre for Liver Disease, University of Toronto, Canada, and colleagues evaluated the cost effectiveness of ultrasound screening for HCC in HCV-infected patients who had achieved SVR after completing DAA therapy. They developed a Markov model to evaluate the cost effectiveness of biannual or annual ultrasound screening versus no screening in 50-year-old cirrhotic patients post-SVR. Costs and QALYs were discounted at 5% per year.

The base case was all patients with advanced fibrosis (F3/F4) in whom the risk of HCC post-SVR was estimated to be 0.5% per year. With this low incidence of HCC, biannual screening post-SVR provided an additional 0.16 QALYs (ICER $84,242/QALY) and annual screening resulted in an additional 0.15 QALYs (ICER $53,756/QALY).

When using recent data suggesting that the annual incidence of HCC in patients with HCV-related cirrhosis following SVR is as high as 1.82%, the researchers found that biannual HCC screening was likely to be cost effective (ICER $40,803/QALY).

Acknowledging that cirrhosis may be difficult to diagnose, the researchers then sought to estimate cost effectiveness stratified by the aspartate aminotransferase to platelet ratio index (APRI) and FIB4 to assess fibrosis. In contrast to their first finding, they determined that biannual screening strategy for those with a pretreatment APRI of less than 2 and a corresponding annual HCC incidence of 0.093% was not cost effective (ICER of $1,024,982/QALY), supporting the use of this test to help select patients for surveillance.

With a pretreatment APRI greater than 2, even without documented cirrhosis, the annual incidence of HCC was 0.89%, leading to an ICER of $55,916/QALY for biannual screening.

“The results of our study challenge current clinical practice guidelines by suggesting that ultrasound surveillance is very unlikely to be cost effective in patients without cirrhosis,” Dr. Zangneh said.
For patients with cirrhosis, even if diagnosed using only pretreatment APRI/FIB4, biannual or annual ultrasound surveillance after an SVR induced by DAAs is likely to be cost effective, particularly if the risk of HCC is found to increase with age.

Additional long-term follow-up data will allow for improved risk stratification to guide optimal screening strategies, according to the investigators.