HCC risk remains even after achieving positive HBV outcomes
medwireNews: Two meta-analyses published in the Journal of Viral Hepatitis confirm that patients with hepatitis B virus (HBV) infection remain at risk for hepatocellular carcinoma (HCC) even after achieving positive virologic outcomes, and identify factors associated with the risk.
The virologic outcomes in question were hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) seroclearance, both of which are in general associated with favorable clinical outcomes.
In the first analysis, which included 16 studies with 4910 patients who achieved HBeAg seroconversion, the pooled incidence of HCC was 3.33%.
Although HBeAg seroconversion was associated with a significantly reduced risk for HCC development compared with persistent positivity, with a relative risk (RR) of 0.60 (p=0.02), HCC can still occur, note Jia Wei (Second People’s Hospital of Yunnan Province, Kunming, China) and co-researchers.
Specifically, patients with active disease had a significantly higher risk for HCC development than those in sustained remission (RR=4.47, p=0.01), as did patients with versus without cirrhosis (RR=26.33, p<0.0001) and those older than 40 years of age at the time of seroconversion versus younger patients (RR=2.64, p=0.04).
The investigators did not observe a significant difference in the rate of HCC occurrence between participants who achieved HBeAg seroconversion spontaneously or following treatment. But they note that “patients with earlier HBeAg seroconversion (children or adults younger than 40 years) had a better prognosis, which implies that it may be a good choice to achieve HBeAg seroconversion as early as possible with the use of treatment.”
The second analysis – by Jian-Hong Zhong (Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China) and team – involved 28 studies with more than 105,000 participants in total.
The rate of HCC development was 1.86% among patients who achieved HBsAg seroclearance, which was significantly lower than the 6.56% rate for those who remained positive for the antigen (p<0.001).
“While HCC occurrence after seroclearance is relatively infrequent, it should be considered a potential late complication,” say the study authors.
As in the Wei et al study, cirrhosis was associated with a significantly increased HCC risk, with an RR of 6.43 (p<0.001) versus no cirrhosis, as was age at seroclearance, such that patients aged at least 50 years were a significant 3.71 times more likely to develop HCC than their younger counterparts (p<0.001).
The third significant factor identified in the analysis was sex, with male patients having a significant 2.72-fold higher risk for HCC than females (p<0.001).
“These findings indicate that HBsAg seroclearance does not necessarily imply HBV eradication and suggest that HBsAg loss may not be an adequate endpoint of antiviral therapy for patients with chronic hepatitis B,” the researchers comment.
“The fact that most asymptomatic HBV carriers do not consult their doctor after HBsAg seroclearance is an even stronger argument for the importance of HCC surveillance and perhaps even antiviral therapy for patients with chronic hepatitis B who have experienced seroclearance.”
They conclude: “To maximize cost-effectiveness [of HCC surveillance], we suggest monitoring patients with none of these risk factors at longer follow-up intervals and monitoring patients with any of the risk factors at shorter intervals.”
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