Keywords
hepatitis B - vaccination - cirrhosis - serology - viral hepatitis
Introduction
All patients with chronic liver disease who are do not have evidence of hepatitis
B virus (HBV) infection (hepatitis B surface antigen [HBsAg-], anti-HBc-, and anti-HBs-negative)
are advised HBV vaccination.[1]
[2] However, this is seldom followed in clinical practice, and data regarding response
rates to vaccination in India is scarce.[3]
[4] Despite the wide availability of the HBV vaccine, a majority of these patients are
not immunized that is usually due to ignorance and fear of side effects associated
with the vaccine. Health-care professionals are often busy managing complications
of cirrhosis and forget about the preventive aspect. We conducted this study to determine
response to HBV vaccination and its determinants in adult patients with cirrhosis.
Methods
This prospective study was conducted over a period of 3 years from 2019 to 2021. Cirrhosis
was diagnosed based on clinical and radiological parameters. Endoscopic screening
was done to confirm the presence of varices. All adult patients (> 18 years) with
cirrhosis of the liver were screened for HBsAg, total anti-HBc, and anti-HBs. Those
who were negative for all three markers were advised vaccination. For vaccine-naïve
patients, a dose of 20 µg intramuscular in the deltoid region was administered at
0, 1, and 6 months. For those with prior history of vaccination but negative anti-HBs
titers, a dose of 40 µg was used at 0, 1, and 6 months.[5] Patients who were known HBsAg positive, on oral antiviral drugs, who did not complete
vaccination schedule, and those who were lost to follow-up were excluded. Anti-HBs
titers were measured 2 months after completion of vaccination. Patients with anti-HBs
titers more than 10 IU/L were considered as responders and those with titers less
than 10 IU/L were labeled as nonresponders. The two groups were compared for demographic
parameters, anthropometry, model of end-stage liver disease (MELD) score, and history
of prior vaccination.
The data were entered in a Microsoft Excel sheet. Analysis was done using Statistical
Package for the Social Sciences version 21 (SPSS, Inc., Chicago, Illinois, United
States) and expressed as numbers, median (interquartile range), or percentages. Chi-squared
test and Mann–Whitney U test were used. p-Values less than 0.05 were considered significant.
Results
A total of 678 patients with cirrhosis were seen over the study period. Seventy-two
patients were newly detected to be HBsAg +/anti-HBc + and 165 were detected to be
anti-HBs + . A total of 277 cases did not complete the vaccination schedule or were
lost to follow-up. The study cohort included 164 patients—median age 43 (18–68) years
and 67% males (110). Patients were followed up at 2 months after completion of vaccination.
One-hundred and three (62.8%) patients had anti-HBs titer more than 10 IU/L. Of these,
54 (52.4%) had titers more than 100 IU/L and 49 (47.6%) had titers ranging from 10
to 99 IU/L. Twelve patients had a history of prior vaccination but low anti-HBs titers.
After double dose vaccination, 10 patients had anti-HBs titers more than 100 IU/L,
while 2 had anti-HBs titer between 10 and 99 IU/L. Therefore, all nonresponders had
a serological response after the double dose of vaccination.
Nonresponders were significantly older than responders (48 vs. 41 years, p = 0.01) ([Table 1]). A majority of the patients had MELD score ranging from 10 to 15. The response
rates for the different MELD groups were as follows: MELD less than 10 (12/24, 50%),
MELD 10 to 15 (82/124, 66%), and MELD more than or equal to 16 (9/16, 56.25%). Response
rates were not significantly different among different MELD groups (p = 0.28).
Table 1
Comparison between responders and nonresponders to hepatitis B vaccination
|
Parameters
|
Nonresponders (n = 61)
|
Responders (n = 103)
|
p-Value
|
|
Age in years (median, range)
|
48 (22–67)
|
41 (18–68)
|
0.01
|
|
Sex (males)
|
32 (52.5%)
|
68 (66%)
|
0.08
|
|
Etiology of cirrhosis
|
|
|
|
|
Alcohol
|
36 (59%)
|
62 (60.2%)
|
|
|
Hepatitis C
|
3 (4.9%)
|
7 (6.7%)
|
|
|
Cryptogenic/nonalcoholic steatohepatitis
|
20 (32.9%)
|
30 (29.1%)
|
0.93
|
|
Others (Wilson's disease 2 cases, Budd Chiari syndrome 1 case, autoimmune hepatitis
3 cases)
|
02 (3.2%)
|
4 (3%)
|
|
|
MELD score (median, range)
|
11 (6–30)
|
12 (7–32)
|
0.15
|
|
Body mass index in kg per sq.m (median, range)
|
24 (17–28)
|
23.4 (16–27)
|
0.12
|
|
Prior history of vaccination
|
17 (27.9%)
|
24 (23.3%)
|
0.51
|
Abbreviation: MELD, model of end-stage liver disease.
Discussion
This study highlights a low response rate (62.8%) in cirrhotics for HBV vaccination.
Nonresponse was likely in older patients. Previous studies have shown that low rates
of anti-HBs seroconversion are related to alcohol use, male gender, nonalcoholic fatty
liver disease, HCV infection, presence of cirrhosis, and older age.[6]
[7]
[8]
[9] Patients with cirrhosis have low anti-HBs seroconversion rates. Despite this, HBV
vaccination is recommended in these patients as it provides protection via clonal
expansion of specific memory cells. Vaccination of all cases waiting for liver transplantation
is likely to prevent de novo HBV infection in pre- and post-transplant periods.[10]
[11]
[12]
This study has a few shortcomings like being a single-center study with a limited
sample size and only patients with end-stage liver disease were included. The waning
of anti-HBs titers is a known phenomenon over the long term. Several patients may
be nonresponders or may have low titers that respond to even a single booster dose
that enhances the antibody titers. We included patients with a history of vaccination
but low anti-HBs titers and administered them a double dose of vaccine as per the
study protocol. However, it is debatable if all these cases were nonresponders to
initial vaccination or lost titers over time. Other factors like malnutrition, hypoalbuminemia,
and sarcopenia may affect the response rates. Unfortunately, these were not evaluated
in this study. More Indian data are needed to ascertain the efficacy of HBV vaccination
in this special patient population.
