Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy

Abstract

BackgroundThis study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients.MethodsWe enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups.ResultsA total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36–0.91; p<0.05).ConclusionsHBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients.Name of the Trial RegisterHAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC.Clinical Trial Registrationhttps://www.clinicaltrials.gov/, identifier NCT 02436044

Antiviral Treatments Eliminate the Adverse Impacts of High Baseline HBV Loads on the Survival of HBV-Related HCC Patients

“…It has been reported that HBV reactivation had no significant association with OS in HCC receiving HAIC with antiviral treatments. 28 Nucleoside analogs can inhibit hepatitis activity and reverse liver function, which improves patients’ tolerance to anticancer therapy and survival. 29 Second, HBV loads were only measured at baseline, while the changes in viral loads were not regularly monitored.…”

Risk of HBV reactivation during therapies for HCC: A systematic review

“…HBV reactivation was defined as an increase of serum HBV DNA > 1 log or reappearance of HBV DNA in patients with undetectable HBV DNA at baseline in 33 studies, [ 19–21,23–30,32–36,38–43,45–48,50–53,56–58 ] while this definition varied in five studies [ 31,44,49,55,59 ] and was not clearly provided in the remaining three studies. [ 22,37,54 ] A definition of HBV‐related biochemical reactivation was not provided in 18 studies, [ 21–27,30,32–34,37–41,54,59 ] while it varied widely among the remaining 23 studies.…”

“…[ 19,40,42 ] Biochemical reactivation was reported in 144 (10.6%) of 1354 patients from eight studies (pooled estimate, 11%; 95% CI, 6%–20%; heterogeneity, p < 0.01) (Figure 4D). [ 19,20,35–37,42,43,58 ] Biochemical reactivation was diagnosed in only 4/173 (2.3%) patients included in two studies who received prophylactic NA and in 15/70 (21.4%) patients included in the same studies who did not. [ 35,43 ] Eight studies reported biochemical reactivation rates in a total of 795 patients receiving no prophylactic NA (pooled estimate, 16%; 95% CI, 10%–25%; heterogeneity, p < 0.01).…”

“…[ 19,20,35–37,42,43,58 ] Biochemical reactivation was diagnosed in only 4/173 (2.3%) patients included in two studies who received prophylactic NA and in 15/70 (21.4%) patients included in the same studies who did not. [ 35,43 ] Eight studies reported biochemical reactivation rates in a total of 795 patients receiving no prophylactic NA (pooled estimate, 16%; 95% CI, 10%–25%; heterogeneity, p < 0.01). [ 19,20,35–37,42,43,58 ] Five studies reported clinical outcomes including 16/488 (3.3%) patients with liver decompensation [ 19,35,42,43 ] and 7/716 (1.0%) patients with deaths due to HBV reactivation [ 19,35,36,42,43 ] (Table 2).…”

“…Twelve studies including 3474 patients who underwent TACE for HCC provided data for HBV reactivation, which was diagnosed in 517 (14.9%) patients (pooled estimate, 19%, 95% CI, 13%-26%; heterogeneity, p < 0.01) (Table 1 and Figure 4A). [19,20,[35][36][37][38][39][40][41][42][43]58] The pooled rates of HBV reactivation were higher in 2296 patients who received no prophylactic NA (pooled estimate, 23%; 95% CI, 17%-30%; heterogeneity, p < 0.01) (Figure 4B) [19,20,[35][36][37][38][39][40][41][42][43]58] than in 1178 patients who did (pooled estimate, 1%; 95% CI, 0%-10%; heterogeneity, p = 0.13) (Figure 4C). [35,[38][39][40]43,58] The pooled rates of HBV reactivation were 16% (95% CI, 10%-23%; heterogeneity, p < 0.01) in seven studies with mean/ median follow-up ≤6 months [20,35,36,39,41,43,58] and 23% (95% CI, 11%-42%, heterogeneity, p < 0.01) in three studies with mean/median follow-up >6 months.…”