The burden of liver cancer and cirrhosis caused by hepatitis
C is likely to continue to grow in the United States despite curative treatment
for hepatitis C, and people who have cirrhosis at the time they are cured of
hepatitis C will require long-term monitoring for liver cancer, studies
presented this week at the 2015 AASLD Liver Meeting in San Francisco show.
However, curing hepatitis C results in a two-thirds
reduction in the subsequent risk of liver cancer for people who have cirrhosis
at the time they are cured. People aged 55 or over and those with diabetes or a
high body mass index are likely to be at higher risk of liver cancer after a
Sustained virologic response after treatment for hepatitis C
has been defined as a cure, and is now the outcome of direct-acting antiviral
treatment for the vast majority of people who receive the newest
interferon-free treatment combinations.
However, many people who are being treated have suffered
many years of liver damage as a result of hepatitis C and remain at elevated
risk of hepatocellular carcinoma (liver cancer). What impact is curative treatment
having on the incidence of liver cancer?
Until now most of the available data has come from small
cohort studies, and in order to give a more precise estimate of the risk,
researchers used the VA Hospitals Database to look at the risk of developing
liver cancer in all VA patients cured of hepatitis C between 1999 and 2009 – a population
of 10,817 people. (These people were treated with pegylated interferon or
interferon and ribavirin, prior to the introduction of direct-acting
antivirals, but there is no evidence that the type of treatment used to cure
hepatitis C affects the subsequent likelihood of liver cancer.)
This population was compared to 11,380 people who underwent
hepatitis C treatment but who did not achieve a sustained virologic response.
10,738 of those cured were defined as being free of HCC at
the end of treatment and eligible for analysis, and of these 100 developed
The investigators found an incidence of liver cancer of 3.27
cases per 1000 person-years of follow-up in those who achieved SVR12, compared
to an incidence of 13.2 per 1000 person-years of follow-up in those who were
not cured, a risk reduction of 64.2%.
Liver cancer occurred much more frequently in people who had
cirrhosis at the time of cure: there was an annual incidence of 1.54 cases per
1000 patient-years in people with cirrhosis, compared to 0.28 per 1000
patient-years in those without cirrhosis. Multivariable analysis showed that
people with cirrhosis had around four-and-a-half times the risk of developing
liver cancer, regardless of other risk factors, when compared to those without
cirrhosis at the time of cure (hazard ratio 4.45, 95% confidence interval 2.53-7.82,
p < 0.0001).
Diabetes was also associated with an elevated incidence of
liver cancer, as was genotype 3 hepatitis C infection. The incidence of liver
cancer was greatly elevated in those aged 65 and over, particularly when
compared to under-45s and those aged 45-54 (0.95 cases per 1000 py compared to
0.07 and 0.21 cases per 1000 py respectively). People aged 65 and over were
four-and-a-half times more likely to develop liver cancer than those under 55,
a multivariable analysis showed (hazard ratio 4.69, 95% confidence interval
2.03 – 10.78, p = 0.0003).
AASLD President Gyongyi Szabo, speaking at an opening press
conference, warned that although “we can eradicate virus, which makes patients
clinically more stable, we haven't eliminated cirrhosis, [so patients with
cirrhosis] should be candidates for screening [for HCC]. Direct-acting
antivirals will reduce HCC risk, and the way they will do that is by treating patients
before end-stage cirrhosis, before getting cirrhotic. If we treat patients who
already have cirrhosis, we can make the liver a little better, but the risk of
liver cancer will remain.”