Baseline Viral Load and On-Treatment Hepatocellular Carcinoma Risk in Chronic Hepatitis B: A Multinational Cohort Study.

Hepatocellular carcinoma (HCC) risk persists in patients with chronic hepatitis B (CHB) despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared with those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic patients with CHB. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in patients with CHB.

Choi WM ，Yip TC ，Wong GL ，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 ，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 ... -  《-》

Non-Linear Association Between Liver Fibrosis Scores and Viral Load in Patients with Chronic Hepatitis B.

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

Real-world clinical data-driven modelling on the initiation time of antiviral prophylaxis among pregnant women with chronic hepatitis B infection.

The risk of mother-to-child transmission for pregnant women with chronic hepatitis B (CHB) still exists, especially for those with high HBV DNA levels. The guidelines for initiating prophylaxis for pregnant women with CHB vary across countries. We aimed to explore the latest prophylaxis initiation time for these women. We collected the real-world clinical data of 328 pregnant women aged 20-49 with CHB, who were treated with telbivudine or tenofovir disoproxil fumarate, from July 2010 to December 2020 in China. A mathematical model was developed to describe the viral kinetics of HBV after prophylaxis. We calculated the time required to reduce viral load below the threshold value of 5.3 log10 IU/ml. We derived the prophylaxis initiation time by subtracting the required time to threshold from the childbirth gestational week. The median time for 328 women to reduce HBV DNA levels below the threshold of 5.3 log10 IU/ml was 4.2 (range: 0.2-12.8) weeks, corresponding to a prophylaxis initiation time of no later than 35.1 (25.2-41.4) weeks. Specifically, for women with viral loads >8.0 log10 IU/ml, prophylaxis should be initiated before 33.9 (25.2-39.5) weeks, and even before the lower bound of 25.2 weeks, to maximize clinical safety. For women with viral load >7.0 to ≤8.0 log10 IU/ml, prophylaxis should be initiated before 35.5 (28.6-39.8) weeks, and for women with viral load >5.3 to ≤7.0 log10 IU/ml, prophylaxis should be initiated before 36.2 (28.3-41.4) weeks. Pregnant women with HBV DNA levels >5.3 to ≤8.0 log10 IU/ml can initiate prophylaxis before 28 gestational weeks. However, women with HBV DNA >8.0 log10 IU/ml could consider initiating prophylaxis before 25 weeks. This study investigates how long it takes to decrease maternal viral load below a threshold (5.3 log10 IU/ml) after receiving antiviral prophylaxis in pregnant women with different HBV DNA levels based on real-world clinical data and mathematical modelling, which provides quantitative evidence on the initiation time of antiviral prophylaxis. The results show that pregnant women with CHB infection at high HBV DNA levels (>8 log10 IU/ml) should initiate antiviral prophylaxis earlier to decrease the risk of mother-to-child transmission of HBV. Physicians can determine when to begin antiviral prophylaxis for those women according to their maternal HBV DNA levels. Our findings justify the initiation time of antiviral prophylaxis recommended by the Chinese guidelines and will offer new insights for other international guidelines.

Shen M ，He S ，Yao N ，Li R ，Wang J ，Zhong W ，Wang J ，Wang H ，Xie L ，Zhuang G ，Zhang L ，Chen T ... -  《-》

The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients.

Chronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis. We searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint. We included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P<0.001) and the pooled HR for PFS was 0.54 (95% CI: 0.33-0.89 P=0.014). In individuals with HCC who received ICIs, there was no notable link found between HBV or HCV infection and prognosis. However, HBV infection showed a connection with improved tumor response. A higher initial HBV load is linked to worse survival results in HCC patients undergoing ICIs treatment and antiviral therapy can significantly improve its prognosis.

Ji Z ，Li J ，Zhang S ，Jia Y ，Zhang J ，Guo Z ... -  《Frontiers in Immunology》