A 65-year-old Chinese man was diagnosed with stage IIA diffuse, large B-cell lymphoma in April 2011 after presenting with cervical lymphadenopathy. His past medical history was significant for hypertension, thyroidectomy in 2008 for papillary cancer, thalassemia trait, and right inguinal hernia. He was known to have chronic HBV infection but had been told he was an "inactive carrier" and did not receive regular followup and had never received antiviral therapy. He was taking levothyroxine 0.112 mg, valsartan 160 mg, and hydrochlorothiazide 12.5 mg daily. He was also found to have latent TB during screening before R-CHOP chemotherapy. He received the first cycle of R-CHOP on June 2, 2011. He was evaluated by the hepatology service the same week, and lamivudine 100 mg daily was started immediately, on June 10, 2011. Isoniazid 300 mg daily and pyridoxine 25 mg daily were started for latent TB on July 24, 2011, at the recommendation of the infectious disease consultant. Chemotherapy was complicated by febrile neutropenia after the second cycle of R-CHOP, treated with piperacillin-tazobactam (Tazocin) and filgrastim (neupogen), and he subsequently received levofloxacin prophylaxis for the fifth and sixth cycles of chemotherapy. Metformin was also started after the fifth cycle for hyperglycemia. He finished a total of 6 cycles of R-CHOP on September 16, 2011.
Evaluation of the hepatitis B status prechemotherapy showed that he was HBeAg negative and anti-HBe positive with an HBV DNA of 6.65E5 IU/mL and ALT of 43 IU/L. Fibroscan was 4.4 KPa, suggesting F0 (no) liver fibrosis. There was a good initial response to lamivudine, as HBV DNA fell to 2.18E1 IU/mL after 2 months of therapy. His ALT was 36 IU/L after two months, 22 IU/L after three months, and 23 IU/L after 4 months (October 2011) of treatment.
On January 18, 2012, ALT was found to be increased to 79 IU/L on routine bloodwork. Repeated bloodwork on February 2, 2012, 4 months after completing chemotherapy, showed ALT 877 IU/L, AST 1188 IU/L, ALP 118 IU/L, total bilirubin 226 mmol/L, INR 3.21, and HBV DNA 1.34E7 IU/mL (Figure 1). The patient was notably jaundiced but otherwise asymptomatic. He and his family confirmed adherence to lamivudine during and after completing chemotherapy. He was admitted to hospital, despite feeling well, and ALT peaked at ALT 1019 IU/L. INH was also discontinued; however the marked rise in HBV DNA was strongly suggestive of HBV-reactivation-associated hepatitis rather than INH hepatotoxicity. HBeAg remained negative, and genotyping with the INNO-LIPA assay confirmed L80I and M204I mutations, conferring lamivudine resistance. Tenofovir was started on presentation; however there was continued deterioration with investigations showing ALT 578 IU/L, AST 619 IU/L, ALP 121 IU/L, total bilirubin 534 mmol/L, INR 7.05, and HBV DNA 1.94E5 IU/mL. With the continued deterioration despite potent antiviral therapy, a decision was made to add prednisone therapy for a possible anti-inflammatory effect with continuation of tenofovir. Unfortunately there was no clinical response to prednisone, and the patient died on February 17, 2012, from progressive liver failure.