HCC, mortality risk remains for untreated immune tolerant-phase HBV patients
medwireNews: Being in the immune tolerant phase of chronic hepatitis B virus (HBV) infection is no assurance against the risk for developing hepatocellular carcinoma (HCC), requiring liver transplantation, or dying, say South Korean investigators.
They evaluated 1910 noncirrhotic, hepatitis B e antigen-positive patients with serum HBV DNA levels of at least 20,000 IU/mL, of whom 413 were classified as immune tolerant as their serum alanine aminotransferase (ALT) levels were below the upper limit of normal, while 1497 were categorized as immune active, defined by ALT levels higher than twice the upper limit of normal.
The immune tolerant patients were untreated, as international guidelines generally recommend against treating such patients due to “the notion that the histological activity is dormant and the risk of disease progression is low in [this] phase,” whereas all patients in the immune active phase had received nucleos(t)ide analog therapy, the researchers report.
The estimated 5- and 10-year cumulative incidence of HCC was significantly higher in the immune tolerant than the immune active group, at 4.2% versus 1.6% and 12.7% versus 6.1%, respectively (p=0.001). And the same was true for the cumulative incidence of death or transplantation, with 5-year rates of 1.9% versus 0.8% and 10-year rates of 9.7% versus 3.4% (p<0.001).
In a multivariate analysis adjusting for factors such as patient group, age, sex, and serum HBV levels, the immune tolerant phase was associated with a significant 2.54-fold increased HCC risk (p<0.001) and a 3.38-fold higher risk for death or transplantation (p<0.001).
These findings remained consistent in inverse probability treatment weighting, propensity score-matched, and competing risks analyses, Young-Suk Lim (University of Ulsan College of Medicine, Seoul) and team report in Gut.
They point out that patients in the immune tolerant group were significantly younger than those in the immune active group (p=0.04), and had significantly higher albumin levels and platelet counts (p<0.001 for both), all factors that favor a lower HCC risk, but nevertheless their risk was higher.
Lim et al write: “Given the lack of evidence that antiviral therapy is beneficial for reducing clinical events in [immune tolerant]-phase patients, it has been considered that the potential harms of long-term therapy, including cost, drug adverse effects and development of resistance, outweigh its benefits.”
But these data could provide the impetus for earlier treatment initiation in select immune tolerant-phase patients, which could prevent many unnecessary deaths, they believe.
The team adds that “[r]andomised controlled trials evaluating the long-term clinical outcomes of the [immune tolerant]-phase patients with or without antiviral treatment may be worthwhile.”
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