Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B.

The association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in CHB patients without cirrhosis. Using a multicentre historical cohort study including 4693 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive, adult CHB patients without cirrhosis who initiated antiviral treatment, HCC risk was estimated by baseline HBV viral load as a categorical variable. During a median of 7.6 years of antiviral treatment, 193 patients developed HCC (0.53 per 100 person- years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a non-linear, parabolic pattern. Patients with moderate baseline viral loads (5.00-7.99 log10 IU/mL) exhibited the highest HCC risk (HR, 2.60; p<0.001), followed by those with low viral loads (3.30-4.99 log10 IU/mL; HR, 1.66; p=0.11). Patients with high viral loads (≥8.00 log10 IU/mL) presented the lowest HCC risk. Particularly, patients with baseline HBV DNA levels 6.00-6.99 log10 IU/mL had the highest on-treatment HCC risk (HR, 3.36; p<0.001) compared with those with baseline HBV DNA levels≥8.00 log10 IU/mL. These findings were more prominent among HBeAg-positive patients, younger patients, or those with less advanced hepatic fibrosis. Patients with moderate baseline viral load, particularly around 6 log10 IU/mL, demonstrated the highest on-treatment HCC risk, despite long-term antiviral treatment. Early initiation of antiviral treatment, tailored to viral load, should be considered to minimise HCC risk in adult CHB patients without cirrhosis.

Choi WM ，Kim GA ，Choi J ，Choi GH ，Lee YB ，Sinn DH ，Lim YS ... -  《-》

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

Choi WM ，Kim GA ，Choi J ，Han S ，Lim YS ... -  《-》

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Choi WM ，Yip TC ，Kim WR ，Yee LJ ，Brooks-Rooney C ，Curteis T ，Clark LJ ，Jafry Z ，Chen CH ，Chen CY ，Huang YH ，Jin YJ ，Jun DW ，Kim JW ，Park NH ，Peng CY ，Shin HP ，Shin JW ，Yang YH ，Wong GL ，Lim YS ... -  《-》

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

Chun HS ，Papatheodoridis GV ，Lee M ，Lee HA ，Kim YH ，Kim SH ，Oh YS ，Park SJ ，Kim J ，Lee HA ，Kim HY ，Kim TH ，Yoon EL ，Jun DW ，Ahn SH ，Sypsa V ，Yurdaydin C ，Lampertico P ，Calleja JL ，Janssen H ，Dalekos GN ，Goulis J ，Berg T ，Buti M ，Kim SU ，Kim YJ ... -  《-》

Moderate levels of serum hepatitis B virus DNA are associated with the highest risk of hepatocellular carcinoma in chronic hepatitis B patients.

Studies have shown a higher risk of hepatocellular carcinoma (HCC) with higher baseline serum hepatitis B virus (HBV) DNA levels in chronic hepatitis B (CHB) patients. However, the association between very high HBV DNA levels (>6 log10 IU/mL) and HCC risk remains unclear, especially in middle-aged and old HBeAg-positive patients. To identify the association between broad-range HBV DNA levels and HCC risk. We conducted a historical cohort study in Korea involving 6949 non-cirrhotic, treatment-naïve CHB patients with alanine aminotransferase (ALT) <2× upper limit of normal for >1 year. HBV DNA was >6 log10 IU/mL in 2029 (29.2%) patients. Follow-up was censored when the antiviral therapy was initiated. The mean age of the patients was 45 years. During 8.0 years of median follow-up, 363 patients (5.2%) developed HCC. By multivariable Cox regression analysis, HCC risk was highest with baseline HBV DNA levels of 6-7 log10 IU/mL (adjusted hazard ratio [aHR] 4.98; P < 0.001), and lowest with >8 log10 IU/mL (aHR 0.90; P = 0.71) and ≤4 log10 IU/mL (aHR 1.00; reference), which was independent of other predictive factors. The similar association between HBV DNA levels and HCC risk was consistently observed in all age subgroups (age <40, 40-49 and ≥ 50 years). HCC risk was highest with moderate serum HBV DNA levels of 6-7 log10 IU/mL in CHB patients without significant ALT elevation. Extending treatment indication to CHB patients with moderate levels of HBV DNA may be considered to further prevent HCC, regardless of ALT levels.

Kim GA ，Han S ，Choi GH ，Choi J ，Lim YS ... -  《-》