Acute Leukaemia Presenting as Acute Liver Failure with Stage 1 Hepatic Encephalopathy

Le résumé fourni par la source

INTRODUCTION Acute lymphoblastic leukaemia (ALL) is the most common malignancy encountered in the paediatric age group. The most common age of presentation of ALL is 5–9 years with a male preponderance. ALL has a good prognosis when it occurs in the 1–10 year age group. Less than 1 year and >10 years of age at presentation are associated with bad prognosis.[1] Acute liver failure is loss of liver function occurring within days to weeks and can occur due to a variety of causes such as infection, obstruction and malignancies. Acute liver failure at presentation in acute leukaemia is a rare occurrence and is hence almost never a differential in cases with deranged liver function. Here, we report the case of a 12-year-old child presenting with signs and symptoms of acute liver failure and hepatic encephalopathy and then diagnosed with ALL on bone marrow aspirate examination and on flow cytometry. CASE REPORT A 12-year-old male presented to the paediatric outpatient department with complaints of fever for 15 days, vomiting (non-projectile) for 4 days and yellowish discoloration of eyes and foot with dark-coloured urine. The patient lost about 20 kg from the initial weight of 68 kg to the present weight of 48 kg in about a year. On examination, the patient had icterus. On ultrasound, an enlarged liver (13.5 cm) with increased hepatic echogenicity was found. Erythrocyte sedimentation rate and C-reactive protein were raised (85–110 and 34.5, respectively). Liver function test was deranged [Table 1].Table 1: Liver function test details of the patientKidney function test: urea: 51.3 mg/dL (20–40) and Ca: 3.5 (8–10). The coagulation profile was deranged, prothrombin time: 27.6 s (11–14) and INR: 2.0. Blood culture was positive for Staphylococcus hominis. Complete blood count: haemoglobin: 7.8 g/dL, total leucocyte count: 1500/mm3 and Plt: 99,000/mm3. Viral markers (HIV, hepatitis C virus [HCV] and hepatitis B surface antigen [HBsAg]) were negative. Investigations for leptospirosis were negative. Clinically, the patient was diagnosed with acute-on-chronic liver failure with stage 1 hepatic encephalopathy and pancytopenia. Peripheral smear revealed 14% blasts. The blasts were 1.5–2 times the size of small mature lymphocytes having a high N:C ratio. Nuclei have irregular margins, with few showing cleaving. Chromatin is opened up with 0–1 prominent nucleoli. The cytoplasm is scant-to-moderate agranular [Figure 1a]. Red blood cells were predominantly microcytic hypochromic with many polychromatophils. Platelets were adequate on the smear.Figure 1: (a) Blast in peripheral blood, (b) Blasts in bone marrow aspirate with erythroid cells and lymphocytes. Red arrow points to a blastBone marrow aspirate was performed, and the smears showed >80% blasts. These blasts had similar morphology as in peripheral smear [Figure 1b]. The rest of the cellularity comprised lymphoid cells and erythroid series cells, and only occasional cells of myeloid series were seen. No megakaryocyte was identified. The blasts were approximately 2 times the size of nucleus of small mature lymphocyte with high N:C ratio. Chromatin is opened up with 0–1 prominent nucleoli. The cytoplasm is scant-to-moderate agranular. On flow cytometry, 71% of blasts were gated on forward scatter (FSC) versus side scatter (SSC) as dim-to-moderate positive. These blasts were positive for CD 19, CD 10, CD 20, CD 34, CD 38 and HLA-DR. These cells were negative for CD3, CD8, CD4, CD33, CD 13, CD14, CD14, CD79a, CD 117, MPO and tdt [Figure 2a-c].Figure 2: (a) Blasts positive for CD19, (b) Blasts positive for CD20, (c) Blasts positive for CD34A diagnosis of B-ALL (CALL-A positive) was rendered. A liver biopsy could not be done owing to the deranged coagulation profile of the patient. DISCUSSION Eighty per cent of all ALL cases occur in children. Common symptoms of ALL at presentation are lymphadenopathy and systemic symptoms such as fever, infection, loss of appetite, weight loss and fatigue. ALL in the age group of 2–5 has an excellent prognosis with an overall survival rate approaching 90%. However, ALL in >10 years of age has considerably less overall survival of 20%–40%.[1,2] Hepatomegaly and splenomegaly are common at clinical presentation in acute leukaemia, and hepatitis is a well-documented complication of treatment in ALL patients; however, acute liver failure in acute leukaemia at initial presentation is largely unknown. Our case had jaundice at presentation along with deranged liver function test and hepatomegaly when investigated. Clinically, the differentials considered were hepatitis secondary to an infectious cause. Multiple tests done to find out the infectious agent came out to be negative (HIV, HCV, HBsAg, Staphylococcus and leptospirosis). Obstructive causes of jaundice were ruled out on ultrasonography. Based on urea levels and clinical signs and symptoms, there was a diagnosis of acute-on-chronic liver failure with stage 1 hepatic encephalopathy and pancytopenia. Hepatomegaly in acute leukaemia occurs as a result of extramedullary haematopoiesis. CD34-positive cells migrate from bone marrow to other solid organs such as the liver, spleen and lymph nodes and lead to extramedullary haematopoiesis. However, the pathogenesis of acute liver failure in acute leukaemia is different and has been theorised to be because of leukaemic cell infiltration of the hepatic sinusoids, leading to obstruction, hepatocyte injury and subsequent development of liver failure. It can also occur as a complication resulting from infection due to the neutropenic status of the patient.[2,3] In our case, the entire workup in an attempt to identify any infectious cause came out to be negative. This forced the clinician to look for an alternative cause, and bone marrow aspiration was done which revealed infiltration by blast cells. Liver dysfunction in patients with ALL has mostly been described in the paediatric population. Asymptomatic hepatomegaly is often present at the time of diagnosis in ALL patients along with deranged liver enzymes. This presentation in ALL patients remains to be fully understood but is likely to be secondary to infection, obstruction or ischaemia. In one retrospective paediatric study by Segal et al. which examined hepatitis at the time of ALL diagnosis, approximately one-third of patients had increased aminotransferase levels, with normal bilirubin and alkaline phosphatase and no evidence of viral hepatitis. They found ALL-induced hepatitis to be more common in patients with T-cell ALL and also associated with higher white blood cell, uric acid and lactate dehydrogenase levels, suggesting leukaemic cell infiltration as the underlying aetiology.[4] Hepatic encephalopathy in association with acute liver failure is even rarer. Kader et al. described the case of a 4-year-old girl presenting with grade 3 hepatic encephalopathy with acute liver failure and later diagnosed with acute leukaemia.[5] Our case had grade 1 hepatic encephalopathy. This finding may be associated with the leukaemic disease burden; however, it needs to be studied further. There is a role of adding hepatoprotective drugs and steroids to the chemotherapy regimen in these patients.[4] The drugs that are metabolised in the liver are contraindicated in these patients. ALL is the most common haematological malignancy of children. Acute liver failure is quite rare at presentation in acute leukaemia having a poor prognosis with only a few case reports documented in literature until now. Therefore, ALL should be kept as a differential in solid organ dysfunction as leukaemic cell infiltration can occur in any organ at any stage of the disease. Declaration of generative AI and AI-assisted technologies in the writing process None of the authors used any AI tools. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other c

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.