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Liver cancer risk reduced after hepatitis C treatment, but vigilance needed for aggressive cancers in months after treatment
Keith Alcorn, 2016-11-14 03:00:00
People who are cured of hepatitis C after a course of
direct-acting antiviral treatment do not have a higher risk of developing liver
cancer (hepatocellular carcinoma), and probably have a reduced risk, studies
from Italy and Canada presented at The Liver Meeting this week in Boston have
However, Italian researchers also found that those people
who did develop liver cancer during or shortly after antiviral treatment were
more likely to develop an aggressive form of liver cancer, perhaps because of
changes in immune surveillance in the liver as a result of treatment.
Hepatitis C infection can be cured with a course of
direct-acting antiviral treatment, but eliminating the infection may not heal
the liver sufficiently to prevent the development of liver cancer. Furthermore,
there is evidence that people with cirrhosis previously treated for liver
cancer have a high rate of recurrence of liver cancer. Two studies, conducted
in Italy and Spain, both found that around 30% of people previously treated for
liver cancer experienced a recurrence of liver cancer within a median of six
months of completing hepatitis C treatment. Both research groups considered the
rate of recurrence in their patients to be unusual and warned doctors to be on
the lookout for liver cancer recurrence.
To investigate whether these findings hold true in a larger
population, researchers at hospitals in the Veneto region of northern Italy
analysed the incidence of hepatocellular carcinoma in a prospective study of
3075 consecutive patients with F3 or F4 fibrosis treated with direct-acting
antivirals between January 2015 and June 2016. People previously diagnosed with
liver cancer were excluded from the analysis, as were people who had undergone
liver transplant prior to DAA treatment.
Seventy-two per cent had cirrhosis, in the vast majority of
cases less advanced (Child-Pugh stage A, 65.3%). The population was almost
two-thirds (63%) male, 62% had genotype 1 infection, 12.7% genotype 2, 17%
genotype 3 and 7.7% genotype 4.
After average follow up of approximately ten months from the
time of beginning treatment (300 days), 41 people had developed liver cancer,
an incidence of 1.64 cases per 100 patient years. Incidence ranged from 0.23
per 100 person years in people without cirrhosis to 1.93 per 100 patient years
in those with cirrhosis. Incidence was higher in those with Child-Pugh stage B cirrhosis
(2.92) than in those with Child Pugh stage A (1.64) but this difference was not
These incidence rates compare to observed incidence rates of
2.8 per 100 person years in untreated patients in the same region of Italy
previously reported by the same research network.
Incidence was higher in people with genotype 3 or 4
infection but genotype was not significantly associated with the development of
HCC. Multivariate analysis showed that the only factors associated with
development of HCC were baseline AST and platelet counts. The baseline APRI
score – indicating the degree of liver scarring - was the strongest predictor
of the development of liver cancer, with each 1-point increase in APRI score
being associated with a 10% increase in the risk of liver cancer.
Although the study found a reduced risk of liver cancer in
those who were cured of HCV infection, it also found an unusually high
proportion of the cases of liver cancer that did occur were more aggressive,
manifesting as multiple HCC nodules or infiltrative HCC. Sixteen of 41 cases
took this form (39%), and these aggressive cases of HCC were more frequently
seen in the first six months after the initiation of DAA treatment.
Single-nodule cases of HCC were more likely to occur at least six months after
the initiation of DAA treatment.
Speaking at a press conference, Alfredo Alberti, Professor
of gastroenterology at the University of Padova said that changes in the
immunological and tumour-suppressive environment in the liver as a result of
the rapid elimination of viral replication might permit more rapid growth of
tumours already present in the liver. Participants in the study were screened
for the presence of tumours by ultrasound three months before initiating
treatment, so the presence of tumours at the time of treatment initiation
cannot be ruled out definitively.
A larger study, of the entire population of people treated
for hepatitis C in British Columbia province between 1990 and 2013, Canada,
found that the risk of liver cancer was reduced by 80% in people cured of
hepatitis C compared to those who were not cured. This study did not look at
the relationship between exposure to DAAs and liver cancer risk.
The study identified 8147 people treated with
interferon-based regimens, 57% of whom were cured. Treated individuals were
followed for a median of 5.6 years.
Liver cancer incidence was highest among those with
cirrhosis who did not achieve a sustained virologic response (21 cases per 1000
patient-years of follow up). In comparison liver cancer incidence was 6.4 per
1000 patient-years in those with cirrhosis who achieved SVR, 7.2 in those who
without cirrhosis who did not achieve SVR12 and 1.1 per 1000 patient-years in
those without cirrhosis who achieved SVR12.
In a multivariable analysis liver cancer was associated with
cirrhosis, age over 50 years, genotype 3 infection versus genotype 1, alcohol
consumption and being male in those who were not cured. In those who were cured
of hepatitis C, only cirrhosis, age over 50 and being male were associated with
an increased risk of liver cancer.
The British Columbia researchers concluded that although
curing hepatitis C infection greatly reduces the risk of developing liver
cancer, it does not eliminate the risk entirely. Older people and those with
cirrhosis are at higher risk than others, underlining the importance of early
diagnosis and treatment.