Most people with hepatitis B have high hopes for a “hepatitis B surface antigen (HBsAg) reversion”. After all, a “conversion” means a functional cure for hepatitis B, that is, normal liver function and a negative DNA test for the hepatitis B virus, and it also means that the patient no longer has to take medications or injections.
Also, studies have shown that hepatitis B virus infection is a major causative factor for liver cancer worldwide.
If you are “negative” for hepatitis B, do you not have to worry about the threat of liver cancer? A recent study from the Chinese University of Hong Kong has revealed the answer.
The study found that people over the age of 50 still need to be aware of liver cancer after turning negative for hepatitis B. Among people under 50, men need to be more careful, while women are relatively safe.
Functional cure for hepatitis B does not mean complete absence of the virus
Before describing the study, it’s important to explain what a “functional cure” is.
In fact, can a functional cure of hepatitis B be considered a true cure? There is still international controversy. The so-called “functional cure” is not a complete clearance of the virus and there is a possibility of reoccurrence.
When we say “complete clearance”, we mean complete clearance of the hepatitis B virus DNA, but current antiviral therapy is very difficult to clear the DNA completely.
So there are 5 clinical indicators to determine whether a patient has achieved functional cure: normal liver function, negative viral test, no disease progression, less likely to relapse after drug discontinuation, and negative hepatitis B surface antigen.
Tracking more than 4,000 hepatitis B-negative patients across 16 years
From January 2000 to August 2016, Dr. Liyuan Chen’s team at the Chinese University of Hong Kong spanned 16 years and tracked 4568 hepatitis B patients who converted to hepatitis B surface antigen-negative.
During this time, they continuously monitored each patient for serum markers and subsequent development of liver cancer, and analyzed the association between the patient’s gender, age, and other factors with the development of liver cancer.
Of these 4568 patients, 54 later developed liver cancer. the cumulative incidence of liver cancer at 1, 3, and 5 years was 0.9%, 1.3%, and 1.5%, respectively. This suggests that the longer the time after hepatitis B conversion, the higher the risk of developing liver cancer.
Notably, among female patients aged 50 years and younger (545 ), the chance of developing liver cancer within 5 years was 0. That is, younger female patients have little to fear from liver cancer within 5 years of conversion!
And among male patients aged 50 years and younger (769), female patients aged 50 years and older (1149), and male patients aged 50 years and older (2105), the cumulative incidence of liver cancer within 5 years was 0.7%, 1.0%, and 2.5%, respectively.
This suggests that despite a shift to negative hepatitis B surface antigen serology, two groups of patients remain at risk for progression to hepatocellular carcinoma: those older than 50 years of age and those who are male. Old age and males are two independent risk factors. The risk is higher when these two factors are both present.
Why does liver cancer continue to favor men and older patients?
Hepatitis B surface antigen conversion has long been considered the ideal state for the eventual treatment of hepatitis B and has been taken as the end point of antiviral therapy.
Other studies have earlier shown that hepatitis B surface antigen conversion leads to a lower risk of liver cancer. However, this study found that this risk was not completely eliminated in older people older than 50 years or in men.
Why is this the case? One study suggests that it may be due to viral DNA integration into the host genome, resulting in insertional mutations and genomic instability.
There are also studies that say this is due to patients after age 50 tend to have more or less complications, such as lower albumin levels, slightly higher bilirubin levels, or elevated glutaminase levels. This means that patients may have suffered some liver damage before they cleared the antigen themselves (that is, turned negative for hepatitis B), making them more susceptible to the development of liver cancer.
And the preference of liver cancer for male patients may be related to the stimulating effect of androgens and the protective effect of estrogen.
What does it mean for patients?
This study tells us that achieving a “functional cure” for hepatitis B is not the same as a true cure. Especially in older people older than 50 years of age and in all men with hepatitis B, even if the hepatitis B surface antigen is negative to meet the criteria for functional cure, it is still important not to let down your guard against liver cancer.
People in these situations should be screened and monitored for liver cancer in order to increase the early detection rate of liver cancer and to allow the best time for treatment of liver cancer and thus improve the outcome.