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Hepatitis B infection is causally associated with extrahepatic cancers: A Mendelian randomization study (lay summary)

This is a lay summary of the article published under the DOI: 10.1016/j.ebiom.2022.104003

Published onMay 02, 2023
Hepatitis B infection is causally associated with extrahepatic cancers: A Mendelian randomization study (lay summary)

Hepatitis B virus can lead to cancers throughout the body, not just in the liver

Researchers from South Africa, Uganda, the UK and Taiwan said prolonged Hepatitis B virus (HBV) infection can cause several cancer types that occur outside the liver. This knowledge encourages doctors to test HBV infected patients for various cancers and to manage the disease better.

Doctors know that a microorganism called Hepatitis B virus (HBV) can cause liver cancer. They have also observed that it is common for people who have been infected by HBV for a long time, to also suffer from many other cancers.

In this study, the researchers investigated whether prolonged HBV infection caused these other cancers outside the liver.

They studied patient samples previously collected from hospitals throughout Japan. They focused on people originating from East Asia.

The researchers used genetic information to predict whether HBV infection could also cause cancers outside the liver, for example, in the cervix, bile duct (the tube that connects the liver to the small intestine), lungs, throat or intestines.

Their results confirmed that prolonged HBV infection caused liver cancer, as well as other cancers outside the liver, such as cervical or stomach cancers. People with HBV infection were also more likely to suffer from cancers of the bile duct, womb (uterus), colon, rectum, throat and pancreas.

They however found that people with HBV infections had reduced chances of ovarian cancer. Ovarian cancer affects the ovaries, and therefore fertility, as they are part of the female sex organs that release eggs.

They said they found 4 genetic variations that were more likely to favour HBV infection in people originating from East Asia.

The researchers said they did not find much difference between Korean and Japanese patients in their results.

This was the first study to show that HBV infection could cause other cancers other than liver cancer.

The researchers however said that their results did not show very strong relationships, and that might have been because of the small number of cases for some cancer types in the samples they studied.

They also said their study only included people from East Asia, and other communities might show different results.  

The study was done by researchers based in universities in South Africa, Uganda, the UK and Taiwan.


Evidence from observational studies suggests that chronic hepatitis B virus (HBV) infection is associated with extrahepatic cancers. However, the causal association between chronic HBV infection and extrahepatic cancers remains to be determined. We performed two-sample Mendelian randomization (MR) to investigate whether chronic HBV infection is causally associated with extrahepatic cancers. We identified four independent genetic variants strongly associated (P-value < 5 × 10−8) with the exposure, chronic HBV infection in 1371 cases and 2938 controls of East Asian ancestry in Korea, which were used as instrumental variables. Genome-wide association summary level data for outcome variables, that included cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, hepatocellular carcinoma, lung, ovary and pancreas were obtained from Biobank Japan.

Using the multivariable inverse variance weighted method, we found genetic liability to chronic HBV infection causally associated with extrahepatic cancers including cervical cancer (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.29–1.91, P-value = 0.0001) and gastric cancer (OR = 1.12, 95% CI = 1.05–1.19, P-value = 0.0001). Moreover, chronic HBV infection (OR = 1.20, 95% CI = 1.07–1.34, P-value = 0.0021) was causally associated with hepatocellular carcinoma, supporting a well-established association between chronic HBV infection and hepatocellular carcinoma.

Our MR analysis revealed that chronic HBV infection is causally associated with extrahepatic cancers including cervical and gastric cancers.


This summary is a free resource intended to make African research and research that affects Africa, more accessible to non-expert global audiences. It was compiled by ScienceLink's team of professional African science communicators as part of the Masakhane MT: Decolonise Science project. ScienceLink has taken every precaution possible during the writing, editing, and fact-checking process to ensure that this summary is easy to read and understand, while accurately reporting on the facts presented in the original research paper. Note, however, that this summary has not been fact-checked or approved by the authors of the original research paper, so this summary should be used as a secondary resource. Therefore, before using, citing or republishing this summary, please verify the information presented with the original authors of the research paper, or email [email protected] for more information.

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