and tobacco are all independent risk
factors for hepatocellular carcinoma
(HCC), according to a case-control
study presented at the 54th Annual
Meeting of the American Association
for the Study of Liver Diseases
(AASLD abstract 253).
Jorge A. Marrero, MD, of the University
of Michigan Health System,
Ann Arbor, found lifetime smokers
were most vulnerable, and suggested
lifetime exposure to more than one
risk factor would significantly raise a
person's risk of liver cancer. "Tobacco,
alcohol, and obesity interact synergistically
to increase the risk of hepatocellular
carcinoma," he said.
The study matched 65 consecutive
HCC patients with two control groups:
65 patients with cirrhosis but no signs
of HCC, and 65 healthy persons with
normal liver tests and no history of
liver disease. Each group had an aver
age age in the mid-50s and more men
The investigators used validated
questionnaires to gather information
on lifetime tobacco and alcohol use,
which were measured in pack-years
and kilogram-years, respectively. Body
mass index (BMI) was recorded when
the patients were interviewed.
Lifetime exposure to alcohol and
tobacco was significantly higher in
HCC patients and in cirrhotic patients:
73% of the cancer group and 83% of
the cirrhotic patients, but only 5% of
the healthy controls, were former
drinkers; 12% of the cancer patients
and 6% percent of the controls, but
none of the cirrhotic patients, were
Only 2% of those with healthy livers
reported being current smokers;
the same percentage identified themselves
as former smokers. Among HCC
patients, however, 63% said they used
to smoke and 18% were current smokers.
In the cirrhotic group, 37% were
former smokers and 29% continued
Significant Predictors for HCC
Dr. Marrero and his colleagues calculated
that alcohol intake greater than
6 kilogram-years of ethanol (defined
as 20 g/d for 15 years) and tobacco use
greater than 15 pack-years were significant
predictors of HCC. The average
total alcohol consumption was 34
kilogram-years for the cancer patients,
24 for the cirrhosis patients, and 5 for
the healthy controls.
Cancer patients had double the lifetime
tobacco exposure of cirrhotic patients-
31 pack-years vs 15. In contrast,
the healthy group's exposure was
2 pack- years on average. The HCC
patients also smoked longer than the
cirrhotic patients (22 years vs 17) and
drank longer (29 years vs 22). Both
groups had much longer exposures
than the healthy people.
HCC risk increased 2.6-fold with
moderate exposure to tobacco, but
shot up 8.2-fold with heavy exposure,
Dr. Marrero said. Similarly, the risk
increased almost 3-fold with moderate
alcohol consumption, but almost
4.5-fold with heavy consumption.
Average BMI was 32 for the HCC
patients and 28 for the cirrhosis patients.
Among heavy smokers, Dr.
Marrero said, HCC risk increased almost
5-fold in people with a BMI greater
than 30. Yet obesity increased risk
only 1.5-fold in people who did not
smoke. While smoking and drinking
tripled risk for lean patients, no significant
interaction was found between
alcohol by itself and BMI.
Dr. Marrero called for prospective
studies toward developing a method
to stratify cirrhotic patients into highand
low-risk groups for HCC.