Fatal HBV-related liver failure during lamivudine therapy in a patient with non-Hodgkin's lymphoma.

.Wereportthecaseofa59-year-oldmanadmittedtoourdepartmenton2August2006withfever,fatigueandjaundice.InDecember2005thepatientwasfirstdiagno -sedwithstageIIBbulkydiffuselargeBcelllymphoma,CD20+withanaaIPIof1.Atthetimeofdiagnosis,hehadsplenomegalyandhepatomegaly;laparoscopicspleenandliverbiopsyresultedinahistologicaldiagnosisofsplenicinfiltrationofnon-Hodgkin’slymphoma(NHL)inacontextofchronichepatitis(withmildactivity,gradeG2),suggestiveofviralinfection.Stagingwascompletedwiththoracicandabdomi-nalCTthatevidencedaspleniclesionof13x14x16cmalongwithliverinvolvementwithsmallnodulesinthefourthsegmentandseveralmesenteric,hepatichilumandparaaorticinvolvedlymphnodes.SerologyrevealedthepatienttobeachronicHBVcarrier(HbsAgpositive).ThepatientwasHbeAgnegativeandanti-HBcpositivewithahighHBVDNAtiterof5,017,954IU/mL.CoexistinghepatitisCorhepatitisDviruswasexcludedbeforechemotherapy.Thelevelofaspartateaminotransferase(AST)was60U/L(normal10-45U/L),alanineaminotransferase(ALT)was50U/L(normal10-50U/L),whiletheremainingroutinebiochemicalexaminationsincludingbiliru -bin,albumin,plateletandWBCcountswerewithinnormalranges.ViralsequencingoftheHBVstraindidnotrevealthepresenceofmutationsassociatedwithresistanceto lamivudine. Lamivudine treatment 100 mg/day was started together with achemotherapyregimenconsistingofcyclophosphamide,doxorubicin,vincristine,prednisoneandrituximab(CHOP-R)givenfor8cycles.PETCTafterchemotherapyshowedremissionoftheneoplasticdiseasebutasplenicresidual,sothepatientwasgivenadditionalradiotherapytothesplenicarea(lastcourseon7July2006).Athisadmissiontoourdepartment,thepatient’shematologicalpanelwasnormalbutliverbiochemistryrevealedserumASTtobe3,878U/L,ALT4,364U/L,totalbilirubin137.1 mol/L,alkalinephosphatase138U/L,andalbumin35.5g/L.Othernonviralcausesofacutehepatitiswereexcluded.HBVDNAwas95,528IU/mL.Thepatientwasstillonlamivudinetreatment.ViralsequencingoftheHBVstrainrevealedthepresenceofacombinedL180MandM204Imutation,whichisassociatedwithre -si tan ce o lmv ud