Case Report
Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6phosphate dehydrogenase deficiency
Tropical Doctor 2015, Vol. 45(4) 245–246 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475514559959 tdo.sagepub.com
Laxmikant Ramkumarsingh Tomar1, Amitesh Aggarwal2, Piyush Jain3, Surender Rajpal4 and Mukul P Agarwal5
Abstract The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management.
Keywords Acute kidney injury, G6PD, Hepatitis
Introduction Though the impact of G6PD deficiency on patients with hepatitis A virus infection has been associated with a more severe initial clinical presentation,1 in this case the clinical outcome was not affected.2
Case presentation A 15-year-old boy presented with symptoms of high grade fever for 4 days, yellowish discolouration of the eyes and passage of dark coloured urine since 2 days associated with severe nausea, fatigue and decreased appetite. There was decreased urine output over the last one day. There was no history of bleeding from any site, altered behaviour, convulsions, cough, burning micturition, limb swelling, rash or arthralgia. There was no past history of jaundice, blood transfusion, alcohol ingestion, drug addiction or medicinal drug use. Examination revealed fever with severe pallor and deep jaundice. There was tender hepatomegaly without splenomegaly. Examination of the cardiovascular, respiratory and nervous systems was unremarkable. Investigations on admission revealed a haemoglobin of 6.1 g/dl; a peripheral smear suggestive of combined deficiency anaemia, with neutrophilic leucocytosis suggestive of leucoerythroblastic features;
a total leucocyte count 49,700/mm3; a platelet count of 360,000/mm3. The blood urea was 38 mg/dl, serum creatinine 1.3 mg/dl, total bilirubin 38 mg/dl (direct 17 mg/ dl); serum alanine aminotransferase 2,877 U/L; serum aspartate aminotransferase 1,982 U/L; and serum lactate dehydrogenase (LDH) 5,720 U/L (normal range, 200–500 U/L). The prothrombin time was raised by 5 s.
1
Senior Resident, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India 2 Assistant Professor, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH); University of Delhi, Delhi, India 3 Assistant Professor, Department of Medicine, PGIMER; Physician, RML Hospital, New Delhi, India 4 Specialist, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India 5 Professor, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India Corresponding author: Laxmikant Ramkumarsingh Tomar, Senior Resident, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi 110095, India. Email: [email protected]
Downloaded from tdo.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 14, 2015
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Table 1. Haematological and biochemical abnormalities of patient. Parameters
Day 1
Day 3
Day 10
Hb (g/dl) Reticulocyte count (%) TLC (/mm3) PC (/mL) BU (mg/dl) SC (mg/dl) Serum potassium (mEq/dl) Serum bilirubin (mg/dl) (T/D) AST (U/L) ALT (U/L)
6.1 2.48 49,700 360,000 38 1.3 5.0
4.3 3 49,200 567,000 244 3.5 5.9
9.7 1 9,100 288,000 40 1 3.8
38 (T), 17 (D) 2,877 1,982
>20 (T), 15 (D) 290 >500
0.9 (T) 48 112
ALT, alanine transaminase; AST, aspartate aminotransferase; BU, blood urea; Hb, haemoglobin; PC, platelet count; SC, serum creatinine; T/D, total/direct; TLC, total leucocyte count.
Over the next 2 days, the patient became anuric, drowsy, and his haemoglobin level dropped to 4.3 g/ dl, while the urea and creatinine levels increased to 244 and 3.5 mg/dl, respectively. He underwent haemodialysis and was given 2 units of red cell concentrate transfusion. Blood specimens of the patient were assessed for G6PD deficiency before transfusion and retested 9 days after complete recovery. This was performed using the methylene blue reduction test (MRT). The serum was negative for hepatic viral markers except IgM anti-HEV ELISA. Both the peripheral blood smear and the antigen-test were negative for malaria. Direct and indirect Coombs tests were negative. Urine examination revealed haemoglobinuria. Bone marrow aspirate was normocellular for his age. He had normal serum caeruloplasmin levels and no KayserFleischer rings. Peak changes in his haematological and biochemical abnormalities are given in Table 1. His level of consciousness improved with haemodialysis and the haemoglobin level rose to 9.7 g/dl. The bilirubin level fell to 0.9 mg/dl and urea and creatinine reduced to 40 mg/dl and 1.0 mg/dl, respectively. A urine output of 1–1.5 L/day was maintained and his appetite gradually improved. He was discharged on the 10th day of admission.
Discussion With normal liver function, jaundice may result from severe intravascular haemolysis, but is usually modest. Additionally, a decline in haemoglobin levels of more than 1–2 g/dl is rare in viral hepatitis unless there is associated blood loss, severe haemolysis or bone marrow suppression.
The presence of high levels of serum bilirubin in patients with viral hepatitis and intravascular haemolysis due to G6PD deficiency has been observed earlier and the levels depend upon the severity of haemolysis and the degree of hepatic involvement.3 The basic mechanism resulting in haemolysis in G6PD deficiency is oxidative stress due to infections or drugs. In acute viral hepatitis, decreased values of reduced glutathione in the red cells have been observed, resulting from accumulation of oxidants due to hepatic dysfunction. The development of ARF in these patients is a serious complication.4 The mechanism of ARF in haemolysis is also related to proximal tubular injury in addition to blockage of tubules by haematin and bilirubin plugs. In our patient we found evidence of severe intravascular haemolysis such as marked anaemia, raised serum LDH and haemoglobinuria. It was associated with high grade fever with chills and neutrophilic leucocytosis, which are rarely observed in uncomplicated viral hepatitis, but are typically associated with acute intravascular haemolysis. This was likely to have been related to G6PD deficiency, which was confirmed by MRT. Intravascular haemolysis in a patient of acute HEV infection with very high bilirubin levels should raise the possibility of G6PD deficiency. By detecting the signs of renal failure early and starting appropriate preventive and therapeutic measures, successful management of such patients can be achieved. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Agarwal RK, Moudgil A, Kishore K, Srivastava RN and Tandon RK. Acute viral hepatitis, intravascular hemolysis, severe hyperbilirubinemia and renal failure in glucose6-phosphate dehydrogenase deficient patients. Postgrad Med J 1985; 61: 971–975. 2. Gotsman I and Muszkat M. Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis A. J Gastroenterol Hepatol 2001; 16: 1239–1243. 3. Clearfield HR, Brody JI and TumenHJ. Acute viral hepatitis, glucose-6-phosphate dehydrogenase deficiency and hemolytic anemia. Arch Int Med 1969; 123: 689. 4. Choudhry VP, Madan N and Sood SK. Intravascular haemolysis and renal insufficiency in children with glucose-6-phosphate dehydrogenase deficiency following antimalarial therapy. IJMR 1980; 71: 561.
Downloaded from tdo.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 14, 2015
Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6phosphate dehydrogenase deficiency
Tropical Doctor 2015, Vol. 45(4) 245–246 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475514559959 tdo.sagepub.com
Laxmikant Ramkumarsingh Tomar1, Amitesh Aggarwal2, Piyush Jain3, Surender Rajpal4 and Mukul P Agarwal5
Abstract The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management.
Keywords Acute kidney injury, G6PD, Hepatitis
Introduction Though the impact of G6PD deficiency on patients with hepatitis A virus infection has been associated with a more severe initial clinical presentation,1 in this case the clinical outcome was not affected.2
Case presentation A 15-year-old boy presented with symptoms of high grade fever for 4 days, yellowish discolouration of the eyes and passage of dark coloured urine since 2 days associated with severe nausea, fatigue and decreased appetite. There was decreased urine output over the last one day. There was no history of bleeding from any site, altered behaviour, convulsions, cough, burning micturition, limb swelling, rash or arthralgia. There was no past history of jaundice, blood transfusion, alcohol ingestion, drug addiction or medicinal drug use. Examination revealed fever with severe pallor and deep jaundice. There was tender hepatomegaly without splenomegaly. Examination of the cardiovascular, respiratory and nervous systems was unremarkable. Investigations on admission revealed a haemoglobin of 6.1 g/dl; a peripheral smear suggestive of combined deficiency anaemia, with neutrophilic leucocytosis suggestive of leucoerythroblastic features;
a total leucocyte count 49,700/mm3; a platelet count of 360,000/mm3. The blood urea was 38 mg/dl, serum creatinine 1.3 mg/dl, total bilirubin 38 mg/dl (direct 17 mg/ dl); serum alanine aminotransferase 2,877 U/L; serum aspartate aminotransferase 1,982 U/L; and serum lactate dehydrogenase (LDH) 5,720 U/L (normal range, 200–500 U/L). The prothrombin time was raised by 5 s.
1
Senior Resident, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India 2 Assistant Professor, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH); University of Delhi, Delhi, India 3 Assistant Professor, Department of Medicine, PGIMER; Physician, RML Hospital, New Delhi, India 4 Specialist, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India 5 Professor, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital (UCMS & GTBH), University of Delhi, Delhi, India Corresponding author: Laxmikant Ramkumarsingh Tomar, Senior Resident, Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi 110095, India. Email: [email protected]
Downloaded from tdo.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 14, 2015
246
Tropical Doctor 45(4)
Table 1. Haematological and biochemical abnormalities of patient. Parameters
Day 1
Day 3
Day 10
Hb (g/dl) Reticulocyte count (%) TLC (/mm3) PC (/mL) BU (mg/dl) SC (mg/dl) Serum potassium (mEq/dl) Serum bilirubin (mg/dl) (T/D) AST (U/L) ALT (U/L)
6.1 2.48 49,700 360,000 38 1.3 5.0
4.3 3 49,200 567,000 244 3.5 5.9
9.7 1 9,100 288,000 40 1 3.8
38 (T), 17 (D) 2,877 1,982
>20 (T), 15 (D) 290 >500
0.9 (T) 48 112
ALT, alanine transaminase; AST, aspartate aminotransferase; BU, blood urea; Hb, haemoglobin; PC, platelet count; SC, serum creatinine; T/D, total/direct; TLC, total leucocyte count.
Over the next 2 days, the patient became anuric, drowsy, and his haemoglobin level dropped to 4.3 g/ dl, while the urea and creatinine levels increased to 244 and 3.5 mg/dl, respectively. He underwent haemodialysis and was given 2 units of red cell concentrate transfusion. Blood specimens of the patient were assessed for G6PD deficiency before transfusion and retested 9 days after complete recovery. This was performed using the methylene blue reduction test (MRT). The serum was negative for hepatic viral markers except IgM anti-HEV ELISA. Both the peripheral blood smear and the antigen-test were negative for malaria. Direct and indirect Coombs tests were negative. Urine examination revealed haemoglobinuria. Bone marrow aspirate was normocellular for his age. He had normal serum caeruloplasmin levels and no KayserFleischer rings. Peak changes in his haematological and biochemical abnormalities are given in Table 1. His level of consciousness improved with haemodialysis and the haemoglobin level rose to 9.7 g/dl. The bilirubin level fell to 0.9 mg/dl and urea and creatinine reduced to 40 mg/dl and 1.0 mg/dl, respectively. A urine output of 1–1.5 L/day was maintained and his appetite gradually improved. He was discharged on the 10th day of admission.
Discussion With normal liver function, jaundice may result from severe intravascular haemolysis, but is usually modest. Additionally, a decline in haemoglobin levels of more than 1–2 g/dl is rare in viral hepatitis unless there is associated blood loss, severe haemolysis or bone marrow suppression.
The presence of high levels of serum bilirubin in patients with viral hepatitis and intravascular haemolysis due to G6PD deficiency has been observed earlier and the levels depend upon the severity of haemolysis and the degree of hepatic involvement.3 The basic mechanism resulting in haemolysis in G6PD deficiency is oxidative stress due to infections or drugs. In acute viral hepatitis, decreased values of reduced glutathione in the red cells have been observed, resulting from accumulation of oxidants due to hepatic dysfunction. The development of ARF in these patients is a serious complication.4 The mechanism of ARF in haemolysis is also related to proximal tubular injury in addition to blockage of tubules by haematin and bilirubin plugs. In our patient we found evidence of severe intravascular haemolysis such as marked anaemia, raised serum LDH and haemoglobinuria. It was associated with high grade fever with chills and neutrophilic leucocytosis, which are rarely observed in uncomplicated viral hepatitis, but are typically associated with acute intravascular haemolysis. This was likely to have been related to G6PD deficiency, which was confirmed by MRT. Intravascular haemolysis in a patient of acute HEV infection with very high bilirubin levels should raise the possibility of G6PD deficiency. By detecting the signs of renal failure early and starting appropriate preventive and therapeutic measures, successful management of such patients can be achieved. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Agarwal RK, Moudgil A, Kishore K, Srivastava RN and Tandon RK. Acute viral hepatitis, intravascular hemolysis, severe hyperbilirubinemia and renal failure in glucose6-phosphate dehydrogenase deficient patients. Postgrad Med J 1985; 61: 971–975. 2. Gotsman I and Muszkat M. Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis A. J Gastroenterol Hepatol 2001; 16: 1239–1243. 3. Clearfield HR, Brody JI and TumenHJ. Acute viral hepatitis, glucose-6-phosphate dehydrogenase deficiency and hemolytic anemia. Arch Int Med 1969; 123: 689. 4. Choudhry VP, Madan N and Sood SK. Intravascular haemolysis and renal insufficiency in children with glucose-6-phosphate dehydrogenase deficiency following antimalarial therapy. IJMR 1980; 71: 561.
Downloaded from tdo.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 14, 2015
