Viral hepatitis — chronic hepatitis B with immunosuppression flare, HBV reactivation and stepwise management

Diagnosis: hepatitis B reactivation in an immunosuppressed patient, progressing to acute-on-chronic liver failure. The combination of HBsAg positivity, IgM anti-HBc NEGATIVE (so this is NOT acute HBV — IgM anti-HBc would be positive in true acute infection), total anti-HBc positive, HBeAg positive, and a very high HBV DNA in a patient on R-CHOP (rituximab plus high-dose corticosteroids) is the classical serological picture of HBV REACTIVATION. The INR above 1.5 with confusion defines ACUTE LIVER FAILURE on a background of chronic HBV. The HBeAg positivity and very high viral load reflect uncontrolled HBV replication in the setting of profound T-cell suppression.^[1][4]

Pathophysiology of HBV reactivation^[1] — HBV replication is normally held in check by a cytotoxic CD8-positive T-cell response. Immunosuppression (rituximab depletes B cells and secondarily disrupts T-cell help; high-dose corticosteroids suppress T-cell function directly) allows uncontrolled HBV replication (the increase phase). On immune reconstitution or partial recovery, the returning T-cell response attacks the large population of infected hepatocytes, producing massive immune-mediated hepatocyte necrosis (the flare phase) — hence the precipitous ALT rise and acute liver failure. The cccDNA minichromosome in the hepatocyte nucleus is never eliminated, which is why chronic HBV (and even past infection — anti-HBc positivity) carries a lifelong reactivation risk on immunosuppression.

Immediate management (ABCDE):^[8][9]

1. Airway/Breathing — he is confused (encephalopathy grade II-III); intubate early if consciousness deteriorates, for airway protection and intracranial pressure control. High-flow oxygen.
2. Circulation — two large-bore cannulae, group and save, IV access; treat hypotension with albumin; noradrenaline for vasoplegic shock.
3. Disability — check and treat hypoglycaemia (10% or 50% dextrose); head of bed 30 degrees; monitor for cerebral oedema; consider hypertonic saline to sodium 145-155 mmol/L and mannitol 0.5 g/kg for rising intracranial pressure.
4. Coagulopathy — give vitamin K 5-10 mg; do NOT prophylactically correct the INR with fresh frozen plasma (it erases the key prognostic and transplant marker); correct only if bleeding or before a procedure. Platelets if needed for procedures.
5. Renal — he has an acute kidney injury (creatinine 160); stop nephrotoxins, give albumin, consider continuous renal replacement therapy if he develops hepatorenal syndrome.

Specific antiviral therapy:^[1]

• Start tenofovir 300 mg orally once daily IMMEDIATELY (or entecavir 1 mg daily if dose-adjusted for renal function). A high-genetic-barrier nucleos(t)ide analogue is mandatory — it suppresses HBV replication and reduces the substrate for the immune-mediated flare. Continue indefinitely.
• Discuss with the haematology team whether rituximab/chemotherapy can be held or modified; ideally interrupt immunosuppression to allow immune recovery without catastrophic injury — but each case is individualised.
• Do NOT use lamivudine (low genetic barrier, resistance) or pegylated interferon (contra-indicated in acute liver failure and decompensated cirrhosis).

Transplant evaluation:^[8][9]

• Apply the non-paracetamol King's College Criteria: INR over 6.5 alone, OR any three of age under 10 or over 40, unfavourable cause (drug-induced is unfavourable), interval from jaundice to encephalopathy over 7 days, INR over 3.5, bilirubin over 300 micromol/L.
• He meets several criteria (age over 40, drug-triggered unfavourable cause, INR over 3.5 at 2.6 and rising, bilirubin approaching 300) — refer urgently to a liver transplant centre for consideration of emergency liver transplantation. Do not wait for multi-organ failure.
• Admit to ICU; treat sepsis (broad-spectrum antibiotics after cultures); monitor lactate, INR, ammonia.

Prevention — what should have been done:^[1][4]

• Every patient should be screened for HBV (HBsAg, anti-HBc, anti-HBs) before any immunosuppressive therapy — chemotherapy, biological therapy (especially anti-CD20 such as rituximab and ofatumumab), high-dose corticosteroids, haematopoietic stem cell or solid organ transplant, TNF inhibitors.
• An HBsAg-positive patient starting a HIGH-RISK regimen (rituximab is one of the highest-risk drugs) should have received prophylactic tenofovir or entecavir for the entire duration of immunosuppression plus 12 to 18 months afterwards.
• Even an HBsAg-negative, anti-HBc-positive patient (past infection) on rituximab carries a reactivation risk and requires prophylaxis per AASLD guidance.
• The National Viral Hepatitis Control Programme and AASLD endorse universal pre-immunosuppression HBV screening. The catastrophic, often fatal, outcome in this case was entirely preventable.