https://orcid.org/0000-0001-5139-0449
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Abstract
Hepatitis B virus (HBV) reactivation is a condition marked by the return of HBV particles in patients whose HBV has previously cured or by an increase in HBV viremia in individuals whose HBV was previously chronic (CHB). Immunosuppressive treatments are more frequently the cause of reactivation; however, it can happen on its own. Reactivation can result in severe morbidity and death, but it can be avoided if screening identifies those who are at-risk and initiates antiviral prophylaxis, if necessary.
In patients with chronic hepatitis B infection and those who have previously been exposed to HBV, HBV reactivation (HBVr) has been found to be a side effect of immunosuppressive medications, namely cytotoxic chemotherapy.
In people with previous exposure to HBV, the loss of HBV immunological control is the main early event in HBVr that results in a rise in HBV DNA.
Patients with HBVr may experience a hepatitis flare-up if they have elevated levels of the enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
HBVr with hepatitis flare-ups can present as asymptomatic hepatitis to acute hepatitis with potentially lethal liver damage.
Definition
Elevation in HBV DNA compared with baseline or absolute increase if baseline is unavailable.
Seroconversion to HBsAg positive for HBsAg-negative, HBcAb-positive patients.
Pathophysiology
Many infected patients during pregnancy go on to develop chronic hepatitis B (CHB) later in life because of persistent viral replication.
Hepatocytes that have already experienced HBV infection are unfortunately susceptible to HBVr because HBV DNA might persist as covalently closed circular DNA (cccDNA) in these cells.
Adult acute HBV infection usually goes away without causing CHB, chronic cccDNA still increases the chance of reactivation.
Diagnosis
Diagnostic criteria include the detection of HBsAg, elevations in ALT levels and elevations in baseline HBV DNA levels.
Furthermore, HBVr has been defined as HBsAg reverse seroconversion with or without increased ALT levels.
Stages of hepatitis B reactivation
Stages of HB reactivation are as follows:
Silent reactivation, which is characterized by an elevated viral load without overt hepatitis; HBV-associated hepatitis, which is characterized by an elevated viral load and evidence of histological, biochemical or clinical hepatitis.
Fulminant liver failure, which is characterized by an elevated viral load along with hepatic synthetic dysfunction, encephalopathy and coagulopathy.
Screening & risk stratification
Any patient scheduled for cytotoxic chemotherapy or long-term immunosuppression should undergo screening for HBsAg and anti-HBc.
Risk categorization based on virological status and IS regimen comes after HBV screening. Compared with patients with cured HBV, those with CHB are at a greater risk.
The largest risk is associated with IS regimens in patients receiving hematopoietic stem cell transplant (HSCT) and B cell-depleting medications (e.g., rituximab).
Risk factors
Host factors- male sex, older age (50 y or above), presence of cirrhosis and hematologic malignancy.
Virologic factors- high HBV DNA, HBsAg and HBeAg levels +ve, absence of anti-HBs, co-infection with HCV, HDV or HIV.
IS regimen- its potency, dose and duration.
Early studies shows that HBIg should be given in the perioperative period with aim to maintain high HBsAb titers (100–500 U/l) in the first few months following LT had beneficial effects.
Management
In patients listed for liver transplant: - start antivirals in patients with cirrhosis with detectable HBV-DNA.
Post liver transplant patients: give HBIG+ Antivirals or Antivirals after evaluating risk factors. HBIG can be stopped once HBsAG-ve/ HBV DNA becomes undetectable.
In non liver solid organ transplant patients, management depends on anti-HB core Ab and HBsAg status.
Conclusion
Reactivation of HBV is a dangerous illness that has a high risk of morbidity and death. If at-risk individuals are properly identified by screening and triaged to a suitable treatment regimen, reactivation can be prevented.
According to current guidelines, patients who are most at risk, such as those with CHB undergoing cytotoxic regimens and B-cell-depleting medications, or recipients of stem cell transplants, should begin getting PPX prior to the initiation of immunosuppression and continue receiving it well after immunosuppression has ended.
Future perspective
Numerous screening approaches, such as risk-adaptive, risk-factor-based and universal screening, have been put forth.
Tenofovir and entecavir generally have less evidence supporting their use in HBV prevention, but there is considerable evidence supporting their use in the treatment of CHB.
There is a need for more well planned clinical studies to investigate these knowledge gaps.
Author contributions
JS Kumar - conceptualization, formal analysis, writing; D Khanna - formal analysis; P Kar - formal analysis.
Financial disclosure
The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.