A RARE CASE OF ACUTE LIVER FAILURE, HEPATITIS ASSOCIATED APLASTIC ANEMIA, AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Abstract

SESSION TITLE: Challenging Cases of Hemophagocytic LymphohistiocytosisSESSION TYPE: Rapid Fire Case ReportsPRESENTED ON: 10/19/2022 12:45 pm - 1:45 pmINTRODUCTION: Acute liver failure (ALF) is mostly caused by viral or drug-induced hepatitis, though occasionally, a clear etiology is difficult to find. In rare cases, hemophagocytic lymphohistiocytosis (HLH) can cause ALF. Moreover, ALF can lead to hepatitis associated aplastic anemia (HAAA), which further impedes recovery. We present a fatal case complicated by ALF, HAAA, and HLH.CASE PRESENTATION: A 29-year-old male presented with jaundice and epigastric pain. Labs revealed ALT 3691, AST 2608, Tbili 8.7, WBC 3, platelet 137, ferritin 3657, fibrinogen 123. An extensive hepatitis workup was negative. Liver biopsy showed acute hepatitis with confluent necrosis. Due to cytopenia, he had a bone marrow biopsy which showed hypocellularity with maturing trilineage hematopoeisis. Steroids were started which led to clinical improvement. He was discharged with a prednisone taper and close follow-up.Unfortunately, outpatient labs showed worsening pancytopenia, so he was readmitted. He decompensated with neutropenia and lactic acidosis. Broad-spectrum antibiotics and micafungin were started. CT showed enteritis and blood cultures grew Klebsiella. He was intubated due to worsening hypoxia, shock, and oral bleeding. Repeat bone marrow biopsy showed markedly hypocellular marrow with absent trilineage hematopoiesis consistent with aplastic anemia. Due to HLH suspicion, anakinra, tocilizumab, cyclosporine, anti-thymoglobulin, and neupogen were started. HLH workup was negative for a clear etiology. He then developed VRE bacteremia, Candidemia, and cytomegalovirus viremia. Even with respiratory/hemodynamic support, CRRT, blood transfusions, and IVIG, patient had a cardiac arrest and died despite resuscitative measures. Autopsy showed aggregates of histiocytes including macrophages engulfing red cells, consistent with HLH.DISCUSSION: HLH is a life-threatening syndrome characterized by excess inflammation and tissue destruction due to abnormal immune activation of macrophages and cytotoxic lymphocytes. This leads to profound immunosuppression and cytokine storm. There are familial and sporadic forms, and infection is a frequent trigger, most commonly EBV. Diagnosis is established if 5 of 9 criteria are met. Our patient met 8 of the criteria, but the etiology of HLH was unidentified, which can occur in ~20% of cases. It was presumed that HLH caused ALF, inducing HAAA. HLA treatment can include dexamethasone, etoposide, cyclosporine, anakinra, and IVIG. However, a huge limitation to using these therapies effectively is that diagnosis is usually delayed and the patient is too sick to safely undergo therapy. As for HAAA, most patients die without liver or bone marrow transplantation.CONCLUSIONS: In patients with ALF and HAAA of unknown cause, HLH should be suspected as adult cases are increasingly recognized. Prognosis of HLH is overall very poor, but early diagnosis and treatment could improve the chance of survival.Reference #1: Dong J, Xie F, Jia L, Li J, Hu Z, Zhu Y, Yu H, Zhao Y, Yao Q, Meng Q. Clinical characteristics of liver failure with hemophagocytic lymphohistiocytosis. Sci Rep. 2019 May 31;9(1):8125. PMID: 31148551Reference #2: Lin, S., Li, Y., Long, J., et al. Acute liver failure caused by hemophagocytic lymphohistiocytosis and adults: A case report review of the literature. Medicine. (2016)95:47DISCLOSURES: No relevant relationships by Shawn KimNo relevant relationships by David Stoeckel SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Acute liver failure (ALF) is mostly caused by viral or drug-induced hepatitis, though occasionally, a clear etiology is difficult to find. In rare cases, hemophagocytic lymphohistiocytosis (HLH) can cause ALF. Moreover, ALF can lead to hepatitis associated aplastic anemia (HAAA), which further impedes recovery. We present a fatal case complicated by ALF, HAAA, and HLH. CASE PRESENTATION: A 29-year-old male presented with jaundice and epigastric pain. Labs revealed ALT 3691, AST 2608, Tbili 8.7, WBC 3, platelet 137, ferritin 3657, fibrinogen 123. An extensive hepatitis workup was negative. Liver biopsy showed acute hepatitis with confluent necrosis. Due to cytopenia, he had a bone marrow biopsy which showed hypocellularity with maturing trilineage hematopoeisis. Steroids were started which led to clinical improvement. He was discharged with a prednisone taper and close follow-up. Unfortunately, outpatient labs showed worsening pancytopenia, so he was readmitted. He decompensated with neutropenia and lactic acidosis. Broad-spectrum antibiotics and micafungin were started. CT showed enteritis and blood cultures grew Klebsiella. He was intubated due to worsening hypoxia, shock, and oral bleeding. Repeat bone marrow biopsy showed markedly hypocellular marrow with absent trilineage hematopoiesis consistent with aplastic anemia. Due to HLH suspicion, anakinra, tocilizumab, cyclosporine, anti-thymoglobulin, and neupogen were started. HLH workup was negative for a clear etiology. He then developed VRE bacteremia, Candidemia, and cytomegalovirus viremia. Even with respiratory/hemodynamic support, CRRT, blood transfusions, and IVIG, patient had a cardiac arrest and died despite resuscitative measures. Autopsy showed aggregates of histiocytes including macrophages engulfing red cells, consistent with HLH. DISCUSSION: HLH is a life-threatening syndrome characterized by excess inflammation and tissue destruction due to abnormal immune activation of macrophages and cytotoxic lymphocytes. This leads to profound immunosuppression and cytokine storm. There are familial and sporadic forms, and infection is a frequent trigger, most commonly EBV. Diagnosis is established if 5 of 9 criteria are met. Our patient met 8 of the criteria, but the etiology of HLH was unidentified, which can occur in ~20% of cases. It was presumed that HLH caused ALF, inducing HAAA. HLA treatment can include dexamethasone, etoposide, cyclosporine, anakinra, and IVIG. However, a huge limitation to using these therapies effectively is that diagnosis is usually delayed and the patient is too sick to safely undergo therapy. As for HAAA, most patients die without liver or bone marrow transplantation. CONCLUSIONS: In patients with ALF and HAAA of unknown cause, HLH should be suspected as adult cases are increasingly recognized. Prognosis of HLH is overall very poor, but early diagnosis and treatment could improve the chance of survival. Reference #1: Dong J, Xie F, Jia L, Li J, Hu Z, Zhu Y, Yu H, Zhao Y, Yao Q, Meng Q. Clinical characteristics of liver failure with hemophagocytic lymphohistiocytosis. Sci Rep. 2019 May 31;9(1):8125. PMID: 31148551 Reference #2: Lin, S., Li, Y., Long, J., et al. Acute liver failure caused by hemophagocytic lymphohistiocytosis and adults: A case report review of the literature. Medicine. (2016)95:47 DISCLOSURES: No relevant relationships by Shawn Kim No relevant relationships by David Stoeckel