Revaccination for HBV With Additional Doses Improves Response Rates in Cirrhosis

Among patients with cirrhosis who do not respond to the initial 3 doses of the standard vaccination for hepatitis B virus (HBV), treatment with a second round of 3 doses improves response rates compared with a single additional booster dose, according to a study in Gut.

The open phase 3 randomized clinical trial (ClinicalTrials.gov Identifier: NCT01884415) compared the efficacy of 2 HBV vaccination regimens using 40-µg doses in patients with cirrhosis who were nonresponders to the 3 first double doses using either a fourth dose administered as a booster at month 6 or a repeat round of vaccination with 3 additional doses.

Participants aged at least 18 years who were hepatitis B surface antigen (HBsAg) negative with cirrhosis, positive and negative for antibody to hepatitis B core antigen (anti-HBc), were enrolled in the study.

Patients in the classical regimen (arm A) received the fourth booster, delayed as normal to day 90 (control treatment group), similar to the responder patients’ protocol. Those in the experimental regimen (arm B) received a new round of three 40-µg doses, 1 per month, administered immediately and followed by vaccine doses at days 30 and 60.

Postvaccinal anti-HBs levels ≥10 mIU/mL were defined as a final positive response.

A total of 120 participants (mean [SD] age, 56.7[7.7] years; men, 75%) were in the intention-to-treat (ITT) population, of which 60 patients were assigned to each treatment arm.

The response rate was 25% in arm A, vs 46.7% in arm B (odds ratio [OR], 2.63; 95% CI, 1.21-5.69; P =.013). The experimental arm had an increase in response rates vs the classical arm, from 31% to 68% in Child A patients (P =.007), from 24.4% to 50% in patients who had a Model for End-Stage Liver Disease (MELD) score less than 15 points (P =.012), and from 24.4% to 53.8% in patients with a MELD-sodium (Na) score less than 15 points (P =.007).

In a post hoc analysis that assessed response rates among negative anti-HBc patients, among final responders the overall median anti-HBs levels (mIU/mL) were 63 (22-145) and lower for the control group vs the experimental treatment group (27 [22-92]) vs 98 [24-326], P =.041).

In multivariable logistic regression analysis, cirrhosis severity assessed in 3 models was associated with poorer response rates when experimental treatment was included.

A total of 93 adverse events (AEs) occurred (55 in arm A and 38 in arm B) among 47 patients (39.2%): 26 (43.3%) in arm A vs 21 (35%) in arm B (P =.349). For participants in arm A, 46.7% (vs 33.3% of arm B) were considered serious AEs (P =.136).

The main limitation was that actual patient losses were greater than initial estimates. Also, protocol breaches resulted from noncompliance with trial-specified procedures.

“We have demonstrated a substantially greater benefit from the administration of a new complete round of vaccination,” the study authors wrote. “Clinical practice guidelines should revise their proposals in the light of this new evidence, and consider recommending a vaccination scheme such as the one tested in this study of cirrhotic patients.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Gastroenterology Advisor