Hepatitis C patients in the Kaiser Permanente Southern
California health maintenance organisation had significantly increased cancer
rates compared to members without HCV infection, researchers reported at the
European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna, Austria. This remained the case even
after accounting for liver cancer, which showed the greatest excess risk.
Over years or decades, chronic hepatitis C virus (HCV)
infection can lead to advanced liver disease including cirrhosis and
hepatocellular carcinoma (HCC), a type of liver cancer. But the effects of HCV infection
elsewhere in the body are not fully understood. Chronic hepatitis C has been
linked to cardiovascular disease, diabetes and several other conditions
including non-Hodgkin's
lymphoma; its association with other kinds of cancer is unknown.
Anders
Nyberg of Kaiser Permanente San Diego and colleagues conducted a retrospective
analysis comparing cancer rates among people with hepatitis C in their cohort and
health plan participants without hepatitis C.
Glossary
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
- lymphoma
A
type of tumour affecting the lymph nodes.
Kaiser
Permanente Southern California (KPSC) is a large health maintenance
organisation with more than 3 million members. The KPSC cancer registry
(affiliated with the US National Cancer Institute's SEER registry) maintains a
complete profile of all cancer diagnoses among Kaiser Permanente members.
This analysis
looked at all cancer diagnoses among adult patients with or without hepatitis C
between January 2008 and December 2012. During this period, the analysis
included 35,712 people in the HCV cohort and 5,297,191 people the non-HCV
cohort. People with HIV and people with a history of solid organ or bone
marrow transplants were excluded.
The HCV
cohort was younger (approximately 60 vs 72 years) and included a higher
proportion of men (about 60% vs about 50%) than the non-HCV cohort. Compared to
the non-HCV cohort, people with hepatitis C were more likely to have other
cancer risk factors including tobacco smoking (about 70% vs 30%), heavy alcohol
use/abuse (about 15% vs 2%), diabetes (about 25% vs 8%) and higher body mass
index. Seventy-two per cent of HCV patients diagnosed with cancer, 35% of HCV patients without
cancer and 7% of people in the non-HCV cohort had liver cirrhosis.
According
to the published study abstract, cancer diagnosis rates were 1524 per 100,000
person-years in the HCV cohort compared to 605 per 100,000 person-years in the
non-HCV cohort. When liver cancer was excluded, the corresponding cancer rates
were 1139 and 601 per 100,000 person-years, respectively. Liver cancer
accounted for 25% of all cancers in the HCV cohort but only 7% in the non-HCV
group.
People in
the HCV cohort had significantly higher rates of several types of cancer,
typically with a two-fold to four-fold increased risk:
- Colon-rectum: relative risk (RR) 1.88
- Prostate: RR 2.05
- Lung: RR 2.44
- Oesophagus: RR 2.51
- Head-neck: RR 2.56
- Pancreas: RR 2.79
- Stomach: RR 3.03
- Kidney: RR 3.05
- Myeloma: RR 3.41
- Non-Hodgkin's lymphoma: RR 3.59.
Not
surprisingly, liver cancer showed the greatest excess risk in the HCV cohort,
with a nearly a 68-fold increased risk (RR 68.67). For all sites including
liver cancer, the relative risk was 2.33, falling to 1.84 for all sites except
the liver.
People
with HCV had an increased risk for many cancers even in the absence of smoking,
heavy alcohol use and diabetes. The differences were smaller after stratifying
for these other risk factors, but remained significant for overall cancer,
liver cancer and non-Hodgkin's lymphoma.
"In
our cohort of hepatitis C infected patients, cancer rates were significantly
increased compared to the non-HCV cohort," the researchers concluded.
"This suggests that another extra-hepatic manifestation of HCV may be an
increased risk of cancer."
Regarding the mechanisms
by which HCV infection contributes to cancers beyond the liver, Nyberg
suggested at an EASL press conference that this may be related to chronic
inflammation or the virus' effects on oncogenes (cancer-causing genes) and tumour-suppression
genes.
However, noting the
influence of other risk factors, he stressed that we cannot assume that HCV is
actually the cause of cancers other than HCC. In the presence of confounding
factors, HCV may have only a moderate effect, he explained. "Adding
HCV to smoking doesn't add to the risk much, but for a non-smoker HCV has a
larger effect," he said.
"Increased cancer
rates are likely multifactorial," Nyberg continued. "The
take-home message is that we can take HCV out of the equation by treating it
for three months, then we can work on lifestyle factors that may take more
time."
He added that Kaiser Permanente currently has no
restrictions on which hepatitis C patients are eligible for antiviral therapy
and he recommends treatment for everyone.
"We can wait for studies showing whether HCV
treatment reduces cancers, including HCC, but my preference is to treat
now," he concluded.