Antihistamine use halved the risk of liver cancer in people with viral hepatitis

Keith Alcorn
Published:
08 February 2022
Alina Kuptsova/Pixabay

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 mechanisms.

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.