Despite Antiviral Treatment, Liver Cancer Risk Persists
Researchers have hoped that treating hepatitis B patients with antivirals would reduce both their viral loads and their liver cancer risk. However, a new study that followed 1,378 treated and 1,014 untreated patients over five years found antivirals did not reduce liver cancer rates as hoped.
The study tracked new liver cancer cases among patients infected with the hepatitis B virus (HBV) (average age 47, 65% male) who had been treated primarily with entecavir (Baraclude) for their high viral loads and liver damage. They compared that group's liver cancer occurrence to those of patients whose "inactive" HBV infection did not require treatment.
Among the treated group, 70 patients (6.2%) developed liver cancer during the study period compared to only 11 (1.1%) in the untreated group. Notwithstanding the ability of antivirals to reduce viral load, a life-long history of HBV infection and liver damage appeared to increase cancer risk, despite the reduction in viral load later in life.
What is especially disappointing is that liver cancer developed even in treated patients who had no history of cirrhosis (severe liver scarring) which increases cancer risk. Among the antiviral-treated patients:
20 of 223 HBeAg-negative patients who had cirrhosis at the start of treatment developed liver cancer.
15 of 316 HBeAg-negative patients who had no cirrhosis also developed liver cancer.
Among the treated patients who developed liver cancer, 30 were positive for the hepatitis B "e" antigen (HBeAg) and 30 were HBeAg-negative.
How well the antiviral worked in patients also determined who remained cancer-free. Of the 246 patients who failed to achieve low or undetectable viral loads as a result of treatment, 36 (18.8%) patients developed liver cancer over the five-year study.
The risk of cancer was increased overall by male gender, underlying cirrhosis and older age in the treated group. Curiously, having high viral loads (HBV DNA) at the start of treatment did not appear to increase liver cancer risk.
The key message for doctors is that liver cancer risk remains despite a dramatic reduction in viral load, researchers noted. "...Patients on (antiviral) treatment that effectively suppressed viral replication are still at higher risk of liver cancer compared with patients with inactive stage chronic hepatitis B," they concluded in the study published in the March issue of the journal Gut.
Persistent liver damage before the start of antiviral treatment, evidenced by elevated alanine aminotransferase (ALT) levels, may predispose patients to liver cancer, they also noted.
"The inactive group may have more intact immune response to HBV and therefore may also have entered the inactive stage early in life, with a shorter period of high viral replication and active hepatitis," they wrote.
there are studies already with direct correlation hbsag level and liver cancer risk with lowest cancer risk on hbsag less than 1000iu/ml.
since inactive carriers have hbsag less than 1000iu/ml they should make this research on hbsag levels and liver cancer risk.it would be good to check also nagalase and liver cancer risk but i dont think they will never check this, they had decades to check it and never did
Can you explain why age matters that much that seems there is no point to clear hbsag after 50 yo ? If in future myrrcludex or replicor hit the market these drugs will be of no use for hcc lowering in patients over 50 yo also ?
no i think it is more correlated with immune function decline, after 50yo the immune system is much much weaker and even acute hbv has a very high death rate in very old people
also the increase of hcc on cirrhosis might be due to weak immune system, cirrhotics are severely immune suppressed with even bacteria superinfections
i experienced this immune suppression myself with never ending flu infections, candida and so on
but all this is just a guess we have no data to confirm this....my idea is we have it since birth so i dont think the 50yo limit can be due to more or less hbv integration
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