People with liver cancer who achieved a sustained
virological response (SVR) to direct-acting antiviral (DAA) therapy for
hepatitis C saw a reduction in both liver-related and all-cause mortality over
five years, according to research presented last week at the AASLD Liver Meeting in Boston.
years or decades, chronic hepatitis C virus (HCV) infection can lead to liver
cirrhosis, hepatocellular carcinoma (HCC, the most common type of liver cancer)
and the need for a liver transplant. Prior studies have shown that successful
hepatitis C treatment reduces the risk of developing HCC, and it may also
improve outcomes among those who already have liver cancer.
often detected late and is difficult to treat. Surgery to remove the cancer and
local therapies to destroy tumours may be possible at earlier stages. Systemic
therapies are used at later stages, but this cancer does not respond well to
traditional chemotherapy. A variety of targeted therapies and immunotherapies are
now approved, but survival typically remains short for most people with
- direct-acting antiviral (DAA)
A drug which prevents hepatitis C from reproducing by blocking certain steps in its lifecycle.
"Patients with HCC have such dismal prognosis,
especially those who are not candidates for curative treatment, and
unfortunately, these are the majority of the HCC population," Prof
Mindie Nguyen of Stanford
University in California said in an AASLD press release. "[Patients with SVR] following treatment with
very safe and well-tolerated DAAs could increase their survival rates by a
median of 18 months, [which is] considerable progress compared to other
currently available systemic therapies for HCC."
Prof Nguyen and colleagues compared survival rates among people with HCV-related
liver cancer who either were not treated with DAAs for hepatitis C or were
treated and achieved SVR, defined as continued undetectable HCV RNA (< 25
IU/ml) at three months after completion of treatment, which is considered a
The researchers conducted a
retrospective chart review of medical records from two groups of people with
HCV and HCC in the United States, Japan, South Korea and Taiwan followed between
2005 and 2017. Individuals with hepatitis B or HIV co-infection or other
cancers besides HCC were excluded. This was also the case for people who did not
achieve SVR on HCV treatment, those who were treated and achieved SVR more than
six months prior to liver cancer diagnosis and those never treated for liver
Participants could have
received ether curative or palliative liver cancer treatment. A majority
underwent transarterial chemoembolisation (TACE), a method of
blocking blood flow to liver tumours, according to Prof. Nguyen. Few patients
received the targeted therapy sorafenib (Nexavar)
and none received immunotherapies like nivolumab (Opdivo) or pembrolizumab (Keytruda),
which have only recently been approved for HCC.
After these exclusions, the
remaining study population included 1239 people who were not treated for
hepatitis C and 437 who were successfully treated with interferon-free DAA
The untreated and cured groups were demographically
similar. About 60% were men, about 70% were Asian, the median age was
approximately 66 years and just over 80% had cirrhosis. However, those who were
not treated for hepatitis C had significantly worse liver function and more
advanced HCC than those who achieved SVR (44% vs 27% with Child-Pugh class B or
C; 43% vs 20% with BCLC stage B/C/D; MELD score 8.74 vs 8.19, respectively). Those
not treated for HCV were more likely to receive palliative therapy rather than
curative treatment for HCC, while the opposite was true in the SVR group.
researchers therefore matched the two groups by age, sex, country, cirrhosis
status, HCC severity, type of HCC treatment and other factors, leaving a
propensity-score matched cohort of 321 untreated and 321 cured participants who
were more closely balanced with no significant differences between them.
In the propensity-matched cohort,
those successfully treated for hepatitis C had a higher five-year survival rate
than those who did not receive HCV treatment when assessing only liver-related
mortality, 90.9% vs 68.8%, respectively. The same pattern was observed for
overall survival rates, 87.8% vs 66.0%, respectively. Median survival durations
were 26 months and 44 months – an 18-month improvement.
After adjusting for other factors,
achieving SVR with DAAs was associated with a 66% lower risk of five-year
liver-related mortality and a 63% reduction in five-year all cause mortality,
both of which were statistically significant.
well-matched patients with HCV-related HCC, SVR with interferon-free DAA
therapy was associated with a 60 to 70% improvement in both all-cause and
liver-related five-year survival compared to untreated patients, the
researchers concluded. Thus, "HCV-related HCC patients who are candidates for
HCC therapy should also be considered for DAA therapy," they advised.
"Our results clearly showed that SVR by DAA therapy is associated with
improved overall survival, which is the most important endpoint for patients
with a cancer," said study co-author
Hidenori Toyoda, MD, PhD, of Ogaki Municipal Hospital in Japan. "Next, we should elucidate how SVR by DAA
contributes to improved survival of patients with HCC, whether through the
improvement of liver function which, in turn, provides patients with more hepatic reserve [and] more
opportunities to get HCC treatment, through both initial and repeat treatment, or through more direct effects that suppress the
recurrence and/or progression of HCC."
Speaking at an AASLD press conference, Prof Nguyen
added that DAA therapy should be considered even for those with advanced stages
of liver cancer, as even high-stage patients had a survival benefit, and DAA
therapy has a high cure rate in those with advanced HCC. "I don't think
poor [liver] function should be excluded," she said. "Those patients
could benefit even more."