Relationship of hepatitis B virus infection to the recurrence of hepatocellular carcinoma after direct acting antivirals

Abstract

Recently, two conflicting articles about recurrence of hepatocellular carcinoma (HCC) after direct acting antivirals (DAA) against hepatitis C virus (HCV) were published. We investigated the relationship between DAA and HCC recurrence. Eligible patients were (1) history of HCC and treated curatively with interventions, and (2) interferon-free DAA therapy was initiated after eradication of HCC. We analyzed contributing factor for HCC recurrence. Ten out of 23 participants (43%) encountered recurrence of HCC. Age, sex, diabetes mellitus, fibrosis score, chemistry, and alpha-fetoprotein did not differ between patients with recurrence and patients without recurrence. The patients with recurrence had significantly higher values of antibody to hepatitis B core antigen (anti-HBc) than the patients without recurrence, 6.06±3.75 vs. 0.91±2.43 (p=0.0019). The relative risk of HCC recurrence comparing anti-HBc positive to negative was 5.2 (95% confidence interval 1.40 to 19.32). Odds ratio was 22.0 (95% confidence interval 2.5 to 191.1). We conclude that anti-HBc positivity was a strong contributing factor for HCC recurrence after DAA therapy.

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

“…Study characteristics were summarised in Tables and . Fifty‐six studies were included, with a total of 5522 patients with HCC, while 27 studies enrolled non‐HCC patients as control groups. Fifty‐three (95%) studies were observational cohorts (45 retrospective and eight prospective) and three studies were clinical trials.…”

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

“…Sixteen papers from 15 study groups (Minami et al published two series), including 17 cohorts of patients, performed a time-to-event analysis of HCC recurrence [6, 9-11, 13-15, 17, 18, 20, 21, 23, 24, 26, 29, 31]. In two papers, this was not explicitly reported in the manuscript, but the data were extrapolated from the figures [24] or the tables [17]. Regarding the paper by Reig and coll.…”

“…Twelve study groups performed a Kaplan-Meyer analysis [6, 9-11, 13-15, 17, 18, 20, 23, 24, 31], and one paper performed a Poisson regression [26]. The time to recurrence was calculated in different ways: from the last HCC treatment in 8 papers [6,9,14,17,18,20,23,29], from the initiation of DAAs therapy in 9 papers [9-11, 13, 15, 17, 20, 26, 31] and from the end of DAAs therapy in one study [24]. In the last two groups, the mean/median time between the last HCC treatment and DAAs start ranged from 8 to 21 months.…”

“…Considering the HCC recurrence rate from the initiation of DAAs treatment, the following figures were reported: 9.6-23.0% at 6 months, 23.1-45.7% at 12 months, and 38.9-54.5% at 24 months. Of note, 4 studies reported the number of patients who developed HCC recurrence during the DAAs treatment [6,11,16,17].…”

“…Twelve studies analyzed the predictors of HCC recurrence in DAAs treated patients [6,7,10,11,13,17,18,20,23,26,29,31]. One additional paper analyzing predictors of recurrence was not considered because it included patients undergoing liver transplantation [16].…”