A session
on hepatitis C post-SVR management featured several other studies of HCC among
people treated with DAAs.  Massimo
Colombo of Universita degli Studi in Milan gave an overview of these
presentations at an EASL press conference.

Maria
Reig and colleagues of Hospital Clinic Barcelona updated their 2016 Journal of Hepatology report, confirming
a high rate of liver cancer recurrence among people treated with DAAs. Over a
12-month period, 31% saw their HCC return, and nearly a third of those treated
for liver cancer nonetheless experienced HCC progression within six months.

“Our study offers further support to previous findings
that there is an unexpected high recurrence rate of hepatocellular carcinoma
associated with DAAs, and that this association may result in a more aggressive
pattern of recurrence and faster tumor progression,” Reig stated in an EASL press release.

However, Reig’s group was alone in reporting increased
liver cancer risk associated with DAA treatment.

Etienne Audureau of Henri Mondor University Hospital
in Créteil, France, reported that among hepatitis C patients with compensated
cirrhosis, lack of SVR was the strongest predictor of liver cancer. Among
people who achieved SVR, age over 50 years, heavy alcohol use and biomarkers of
impaired liver function also predicted HCC.

Hamish Innes of Glasgow Caledonian University in
Scotland and colleagues found that the risk of HCC following SVR was associated
with baseline patient risk factors, but not use of DAAs. In a multivariate
analysis, HCC risk was similar for patients treated with DAAs or interferon.

A Chinese study presented by George Lau of the Hong
Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre in Beijing
saw no increased HCC incidence among people cured with DAAs compared to
interferon. And Vincenza Calvaruso of the University of Palermo in Sicily
likewise reported similar HCC risk in people treated with DAAs or interferon. Finally,
a Japanese study by Masaaki Korenaga of Kohnodai Hospital in Chiba, Japan, and
colleagues found a lower incidence of liver cancer among people treated with
DAAs.

These new studies were not part of Dore’s
meta-analysis, and their inclusion would likely strengthen his conclusion that
the risk of HCC does not increase after treatment with DAAs.

Turning to the mechanisms underlying the development
of liver cancer, Thomas Baumert of the University of Strasbourg in France reported
findings from a laboratory study showing that epigenetic and transcriptional
changes that occur in the liver during HCV infection are only partially
reversed by DAAs and persist after SVR.

Colombo explained that histone proteins act as a kind of ‘glue’ that holds
molecules together and protects genetic material during cell replication. HCV
appears to disrupt the histones, making DNA more susceptible to changes that
can trigger development of cancer.

Taken
together, these study findings underscore the need for on-going liver cancer
monitoring for people who had cirrhosis before starting hepatitis C treatment –
even after they are cured – and supports early DAA treatment before people develop
advanced liver disease.

“The best HCC prevention
strategy and best way to reduce mortality is to scale-up DAA therapy as broadly
and rapidly as you can,” Dore concluded.