Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B

Abstract

BACKGROUND It is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen–positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB). METHODS We conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log 10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels. RESULTS During a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log 10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00–5.99 log 10 IU/mL ( P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log 10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00–7.99 log 10 IU/mL, 6.00–6.99 log 10 IU/mL, or 5.00–5.99 log 10 IU/mL were 2.48 ( P = 0.03), 3.69 ( P = 0.002), and 6.10 ( P < 0.001), respectively. CONCLUSION On-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log 10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log 10 IU/mL) may maintain the lowest risk of HCC for those patients. FUNDING Patient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.

Impact of expanding hepatitis B treatment guidelines: A modelling and economic impact analysis

“…Although the expansion of treatment criteria in CHB patients is highly controversial, 37 many Korean studies have suggested that expanding treatment indications may significantly reduce the incidence of HCC and mortality among those with CHB infection not currently eligible for treatment. [13][14][15][16][17][18]38 In fact, the results of this study are consistent with those of the previous global modelling studies, which suggested that scaling up the coverage of treatment to 80% of eligible individuals with CHB infection is essential to achieve a target of a 65% reduction in mortality by HBV. 39 While the risk of treatment-emergent adverse events is low, as the number of individuals treated increases, the absolute number of individuals experiencing treatment-emergent adverse events will also increase.…”

“…These data suggest that the complexity and strictness of current guidelines in defining treatment eligibility is a serious challenge in accomplishing the WHO's target to eliminate HBV by 2030. Although the expansion of treatment criteria in CHB patients is highly controversial, 37 many Korean studies have suggested that expanding treatment indications may significantly reduce the incidence of HCC and mortality among those with CHB infection not currently eligible for treatment 13–18,38 . In fact, the results of this study are consistent with those of the previous global modelling studies, which suggested that scaling up the coverage of treatment to 80% of eligible individuals with CHB infection is essential to achieve a target of a 65% reduction in mortality by HBV 39 …”

Early Treatment Consideration in Patients with Hepatitis B ‘e’ Antigen-Positive Chronic Infection: Is It Time for a Paradigm Shift?

“…The authors hypothesize that a decreasing but considerable viral load (e.g., 5–8 log10 IU/mL) may indicate the progressive damage of hepatocytes, clonal hepatocyte repopulation, and subsequent increased risk of HCC, compared to their peers that received early treatment with the same range of HBV DNA levels. They concluded that early initiation of antiviral treatment with a high viral load (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC in those patients [ 44 ].…”

Concerns about the inverse relationship between baseline HBV DNA and on-treatment hepatocellular carcinoma risk

“…We read with great interest the article by Choi et al, which concluded that baseline HBV DNA level was inversely associated with on-treatment hepatocellular carcinoma (HCC) risk in HBeAg-positive, noncirrhotic, chronic hepatitis B (CHB) patients ( 1 ). Their findings are novel, but several issues deserve discussion.…”