Case Report of Acute Liver Failure Secondary to Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH), an aggressive and life threatening syndrome of excessive immune activation, most commonly affects infants Symbol < 18 months old, but can occur in older children and adults. An extremely rare case is reported of HLH presenting as acute liver failure in an adult. A 47-year-old Caucasian man with a past medical history of diabetes type II was treated with a 10 day course of trimethoprim-sulfamethoxazole for an upper respiratory infection three weeks prior to admission, and developed a pruritic rash several days later. He then presented with fatigue, pyrexia, and profound jaundice. Physical examination on admission revealed temperature=103.1 0C, blood pressure=89/48 mmHg, profound jaundice, and no hepatomegaly or stigmata of chronic liver disease. Laboratory examination revealed severe neutropenia (absolute neutrophil count=100 cells/mm3), leukocyte count=700 cells/mm3, and hemoglobin=8.6 mg/dl. The sodium=116 mmol/L and creatinine=1.67 mg/dl. Total bilirubin=45.1 mg/dl, direct bilirubin=26.4 mg/dl, alkaline phosphatase=490 U/L, AST=70 U/L, ALT=167 U/L, GGT=730 U/L, albumin=2.4 g/dl, INR=1.9, and ferritin=3100 ng/ml. The acetaminophen level was normal and an acute viral hepatitis panel was negative. Abdominal ultrasound and CT scan revealed normal hepatobiliary findings. MRCP revealed a normal biliary tree, multiple small pancreatic cysts up to 11 mm in diameter, and mild diffuse iron deposition in liver and spleen. The patient was treated empirically with doxycycline for possible leptospirosis because he works as a sewer inspector. He was treated with IV aztreonam and vancomycin after Pseudomonas and group A streptococcus were isolated from blood cultures. Serum IgG level was normal. Anti-smooth muscle antibody, and antimitochondrial antibody were absent in serum. Leptospiral antibodies were negative. Genotyping was negative for C282Y, and was heterozygous for H63D mutation for hemochromatosis. Pathologic examination of a bone marrow biopsy revealed HLH. CD25 and IL-2 receptor levels were elevated, consistent with HLH. Patient was treated with prednisone 100 mg daily. He was not a candidate for etoposide (VP16) because of his profoundly elevated bilirubin and transaminase levels. He underwent transjugular liver biopsy which revealed centrilobular hepatocellular necrosis. He developed massive hematemesis, EGD revealed deep elongated lower esophageal ulcers and esophagitis, typical for CMV/viral esophagitis. He became hypotensive, was intubated, and developed disseminated intravascular coagulopathy with intra-abdominal bleeding and perihepatic hematoma. He was transfused multiple blood products and underwent two arteriograms with embolizations of two major hepatic arteries that successfully controlled the hemorrhage. He was treated with micafungin for candidemia, and ganciclovir for possible CMV esophagitis. Repeat viral cultures and serologies were negative for CMV, VZV, EBV, HSV, and HIV. Hence ganciclovir was discontinued. During the ensuing 10 days his ferritin became >33000 ng/ml, but the bilirubin and transaminase levels significantly declined. He became more clinically stable. A case of acute liver failure is reported secondary to HLH, a rare syndrome in adults. Although DILI from Bactrim was a confounding factor, the prompt diagnosis and initiation of treatment with corticosteroids was crucial. He was unable to receive chemotherapy with etoposide or cyclosporine because he had elevated bilirubin and transaminase levels. HLH can occur as a familial or sporadic disorder, which can be triggered by various events that disrupt immune homeostasis, such as infection. Given the rarity of this syndrome, prompt diagnosis and treatment is crucial for patient survival.SymbolFigure: Medium power photomicrograph of Diff-Quik stain of bone marrow smear showing foamy macrophages engulfing mature and precursor erythrocytes (arrow).Figure: High power photomicrograph of Diff-Quik stain of bone marrow smear showing a foamy macrophage engulfing precursor erythrocytes (arrow).Figure: Medium power photomicrograph of liver showing centrilobular hepatocellular necrosis with cholestasis (asterisk).