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Does DAA Therapy Up Risk for Liver Cancer? It's Debatable


Eight studies at the 2017 International Liver Congress illuminate the question but the answer is open to interpretation.

Is there an increased risk of hepatocellular carcinoma after treatment of hepatitis C? A short review of studies presented at the International Liver Congress 2017 may help answer the question.

Direct acting antiviral (DAA) therapy for hepatitis C (HCV) has revolutionized treatment by improving patient outcomes with fewer side effects and is associated with an extremely high (~90%) cure rate. But there is significant debate in the infectious disease community based on studies that suggest HCV cure does not eliminate risk for hepatocellular carcinoma (HCC); other research has found a high rate of HCC recurrence in patients successfully treated with DAAs.  At the International Liver Congress 2017, held April 19-23, 2017 in Amsterdam, eight studies were presented that provide evidence both pro and con and compared DAA treatment with interferon-based therapy.

A prognostic tool that was developed by Dr Etienne Audureau and colleagues (Henri Mondor University Hospital) showed that among those patients with compensated cirrhosis, failure to achieve sustained virologic response (SVR) was the most influential factor in predicting HCC. They also recommended that treatment of HCV with compensated cirrhosis should be initiated prior to evidence of impaird liver function. Another recommendation from the team was that those with compensated cirrhosis who have achieved SVR should be monitored for liver cancer after 50 years of age.

[[{"type":"media","view_mode":"media_crop","fid":"59065","attributes":{"alt":"","class":"media-image media-image-right","height":"268","id":"media_crop_7093807865577","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7486","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Tenofovir molecule ","typeof":"foaf:Image","width":"273"}}]]Dr Thomas Baumert and colleagues at the University of Strasbourg, France investigated the mechanism behind the development of HCC following HCV cure. They found that HCV infections produce epigenetic and transcriptional changes in the liver that were only partially reversed by DAAs and that they persist after HCV cure. They suggest the  aforementioned changes play an important role in HCC even after HCV cure.

Contrary to the prior findings, Professor Gregory Dore, Dr. Reem Waziry, and colleagues from The Kirby Institute, UNSW Sydney did not find any evidence of HCC occurrence or recurrence post-treatment with DAA. They assessed 41 studies (total 13,875 patients) and concluded that incidence of  HCC was higher among those who had shorter follow- up. Incidence of HCC was lower in those of younger age and where follow-up was longer. When adjusted for follow- up and age, no evidence of HCC occurrence or recurrence was found between DAA- and interferon-based regimens.

Another study led Dr. Hamish Innes at the Glasgow Caledoninan University in Scotland found no difference in HCC risk between DAA-containing regimens versus DAA-free regimens. They concluded that instead of the regimens used to treat HCC, it is the underlying risk factors that place patients at risk of HCC after HCV treatment.

A Japanese study led by Dr Masaaki Korenga at Kohnodai Hospital in Chiba, Japan, found a reduced incidence of liver cancer among those treated with interferon-free regimens and those treated with interferon-containing regimens after SVR at 12 weeks. This study was similar to a Chinese study that was led by Dr George Lau from Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center in Beijing, China, who found no increase in the incidence of HCC among those treated with DAA- compared to peginterferon-based regimen after SVR at 12 weeks.

A Sicilian study that was led by Dr Vincenza Calvaruso at the University of Palermo, Italy, found that those who achieved SVR with DAAs had a lower risk of developing liver cancer than those patients whose HCV was not cured. Also, the incidence of HCC among those treated with DAA- compared to peginterferon-based regimen after SVR at 12 weeks were similar.

In the setting of ongoing debate regarding whether or not DAA increases risk of HCC, all physicians who care for patients with HCV should be mindful of continued screening post-DAA treatment--particularly of those who have liver cirrhosis prior to DAA treatment who may be at increased risk for HCC.


ILC 2017: Is direct-acting antiviral therapy for Hepatitis C associated with an increased risk of liver cancer? The debate continues [press release]. Amsterdam: European Association for the Study of the Liver; April 20, 2017.


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