Antihistamines used for relief of allergies and hay fever
halved the risk of developing hepatocellular carcinoma (HCC; liver cancer) in people
with viral hepatitis during a ten-year follow-up period, a review of people
with viral hepatitis in Taiwan has concluded.
The findings, published in the Journal of Clinical
Oncology, showed that greater use of H-1 antihistamines – the type used for
allergy relief – reduced the risk of liver cancer by 60% in people with
hepatitis B who used them on at least 120 days in the follow-up period.
People with hepatitis B who took fewer antihistamine doses
had a smaller reduction in risk, although those with the lowest exposure (28-42
daily doses) still had a 40% reduction in the risk of liver cancer. Similar
dose-response relationships were seen in people with hepatitis C and in people
with both hepatitis B and C.
Antihistamines come in two forms, the H-1 class that treat
allergy symptoms and the H-2 class that treat gastrointestinal conditions such
as acid reflux, indigestion and stomach ulcers. Some recent laboratory studies
have suggested that H-1 antihistamines may have anti-cancer effects by unknown
Several small studies have shown that the addition of the
H-1 antihistamine cyproheptadine to treatment regimens for HCC improved outcomes at advanced stages of disease.
In view of the unsatisfactory outcomes of people with
advanced HCC receiving current treatment, researchers in Taiwan looked into
whether population-based evidence supports further investigation of H-1
antihistamine use as an adjunctive therapy for HCC in a group at high risk of
developing HCC, people with viral hepatitis.
The study used the Taiwan National Health Insurance Research
Database to identify people with viral hepatitis, assess their H-1
antihistamine exposure and calculate their risk of HCC.
The researchers identified 521,071 people with hepatitis B,
169,159 people with hepatitis C and 39,016 people with both viruses who
received health care in Taiwan between 2006 and 2015. The study excluded people
diagnosed with HCC less than a year after a diagnosis of viral hepatitis or
with missing data.
People with viral hepatitis using H-1 antihistamines were
individually matched with non-users, leaving 127,398 people with hepatitis B
using H-1 antihistamines and a matched non-using control group; 40,428 people
with hepatitis C using H-1 antihistamines and a matched non-using control
group, and 8661 people with both hepatitis B and C using H-1 antihistamines
and a matched non-using control group.
In all groups, the risk of HCC was greater in men and in
people with cirrhosis, type 2 diabetes and hypertension. Alcoholic liver
disease raised the risk of HCC in people with hepatitis B or dual infection but
not in the hepatitis C cohort. Older age increased risk of HCC in people with hepatitis B
but not hepatitis C or dual infection.
The cumulative incidence rate of HCC was significantly lower in
H1-antihistamine users in each group after ten years of follow-up. After adjusting for age, sex and
co-morbidities, the risk of HCC was 51% lower in people with hepatitis B who
used antihistamines (adjusted hazard ratio 0.489, 95% confidence interval
0.455-0.524). In people with hepatitis C using antihistamines, the risk was 52%
lower (aHR 0.484, 0.45-0.52) and 53% lower in people with both hepatitis B and
C who used antihistamines (aHR 0.469, 0.416-0.529).
People with viral hepatitis were significantly less likely
to develop HCC if they had been prescribed non-steroidal anti-inflammatory
drugs (NSAIDS), aspirin or statins. The researchers say that the relationship between
aspirin, NSAIDS and HCC risk needs to be clarified by further research, but
they point out that their finding regarding statins and reduced HCC risk
confirms separate cohort studies in people with hepatitis B and C.
The Taiwanese research group say that their findings suggest
that further research is needed to understand the mechanism by which
H1-antihistamines might reduce the risk of HCC and to clarify whether they
could serve as an adjuvant treatment.