infectious Hepatitis with Excessive Hyperbilirubinemia and a Hemolytic Crisis in an 8-Year-Old Boy His G6PD Deficiency Was
an
Aggravating Factor
Daniel Fried, M.D., Abraham Gotlieb, M.D., Abraham Roitman, M.D.
HEMOLYTIC of acute viral but only rarely does
course
ANEMIA hepatitis is
during not
the
unusual
a severe hemolytic crisis develop.2 Underlying the hemolysis in many infectious hepatitis patients is G6PD deficiency.3
Case The
History patient
8-year-old Jewish boy of Iraqui parentage. The only sibling was a healthy I 1-year-old sister. There was nothing remarkable in his past medical history. was an
mixed Moroccan and His illness started 5
days prior
to
admission with
fever, asthenia, loss of appetite, soon followed by weakness, darkly colored urine, and the appearance of jaundice. On the day prior to admission,
diffuse abdominal pain, and severe in, and the jaundice became more pronounced. During that same period, several of his classmates also fell ill with jaundice. Before his illness he received no medications, and his diet did not contain fava beans.
vomiting,
weakness
set
On hospitalization he was thin and markedly jaundiced, with pale lips and coated tongue. His pulse was rapid. The liver edge was 3 cm below the coastal margin and the tip of the spleen was palpable.
Department of Pediatrics, Zahalon GovernHospital, Jaffa, and Tel-Aviv University Medical School, Israel. From the
ment
Laboratory Finding. Hemoglobin
10.1i gm%, 2.5 per cent, hematocrit 28 per cent with anisocytosis, a few spherocytes, and 3 erythroblasts per 100 leukocytes. Serum bilirubin was 44 mg% (direct 23 mg%). The urine contained protein and bilirubin. Treatment on the first day included intravenous fluids with ACTH. On the second day the bilirubin rose to 60 mg% while hemoglobin fell abruptly to 7.3 gm% with hematocrit 20 per cent; and hemoglobin appeared in the urine. Other findings at this time: blood urea 78 ing%a, serum electrolytes and proteins normal, SGOT 300 units, SGPT 240 U, prothrombin time 100 per cent. Direct and indirect Coombs tests negative, G6PD content of the erythrocytes was 0 botch in the patient and his mother (normal values 3-6 U).4 The diagnosis was made of severe infectious hepatitis accompanied by acute hemolysis, which was apparently related to G6PD deficiency. That evening the hemoglobin level was still 7.2 gm%, but next day it was 6 gxn% with 4.4 per cent reticiulocytes and a leucocytosis of 24,000. Prothrombin time was 60 per cent. The bilirubin
reticulocytes
reached 71 (38.5 direct). Even at this stage there
clinical signs of such as reduction of liver size, alteration of consciousness or hypoglycemia. Nevertheless, exchange transfusion was decided upon; 2,300 ml of blood were exchanged (the body weight was 26 kg) by means of infusion through a catheter in one arm and extraction of blood from the other by vacuum bottles. The pro-
impending hepatic
were no
coma,
482
Downloaded from cpj.sagepub.com at CARLETON UNIV on June 16, 2015
cedure lasted about 4 hours, without any untoward incident. After the exchange total bilirubin was 41 mg% (26 ing% direct) and the hemoglobin was 12 ~rrr~l~: After this, the course was one of rapid recovery. Next day the bilirubin level was still 39 mg%, but two days later it was 15 nig%, and steadily returned to normal. The free and conjugated glttctiroiiic acid levels in the urine, which reflect the conjugative activity of the liver, indicated disturbed liver function during the acute stage of the disease, with good recovery thereafter.&dquo; The boy was discharged after I I days. Six months following his illness, he was symptomless and had normal liver function tests, hemoglobin and reticulocyte counts.
Discussion
our
transfusion
was correct.
References
Hemolysis in G6PD-deficient individuals may be precipitated by a diversity of infections.6 ln nitro studies have demonstrated increased autohemolysis of G6PD-deficient erythrocytes when incubated in the presence of influenza-A virus, related to their inability to activate the hexose monophosphate shunt.’ In infectious hepatitis, low levels of reduced red cell glutathione have been found during the acute stage, with a return to normal upon recovery.&dquo; This would indicate that the impaired liver function, led to an accumulation of metabolites capable of oxidizing red cell SH groups. Erythrocytes containing adequate G6PD can protect themselves from such oxidative insult through the reduction of additional glutathione, whereas G6PD-deficient erythrocytes are more readily destrc~yed.~ Hence, oxidant drugs should be avoided with G6PD-deficient patients, especially those who have or may have viral
hepatitis.9 The high prevalence of G6PD deficiency in Israel would warrant a more frequent occurrence of severe hemolysis during infectious hepatitis; but, such a situation seems quite uncommon.10
patient, the bilirubin rose to unusually high levels.71 mg%. The hemolytic process most probably enhanced the production of bilirubin at a stage of deranged clearance and disturbed excretion by the liver. The rise of blood urea in our patient, apparently reflected impairment of renal function by. the hemc~~lobinuria.;~ Our patient might have recovered with conservative treatment only, but because of the potential danger of bilirubin encephalopathy (indirect bilirubin 32.5 mg%) and more renal damage from ongoing hemolysis, we feel that the decision to perform exchange In
Conrad, M. E., Schwartz, F. D., and Young, A. A.: Infectious hepatitis: A generalized disease. A study of renal, gastrointestinal and hematologic abnormalities. Am. J. Med. 37: 789, 1964. 2. Salen, G., Goldstein, F., Haurani, F., and Wirts, 1.
C. W.: Acute Hemolytic anemia complicating viral hepatitis in patients with G6PD deficiency. Ann. Intern. Med. 65: 1210, 1966. 3. Burka, E. R., Weaver, Z., and Marks, P. A.: Clinical spectrum of hemolytic anemia associated with
Ann. 817, Intern. 1966. Med. G6PD deficiency. 64:
4.
Kornberg, A., and Horecker, B. L.: in S. P. Colowick and N. O.
Kaplan, eds., Methods in Enzymology,
Vol. I, New York and London, Academic Press, 1955, p. 323. 5. Gotlieb, A., Nir, I., and Pesach, J.: Urinary excretion of free and conjugated glucuronic acid in jaundiced newborn. Acta. Paediatr. Scand. 60: 6.
437, 1971. Beutler, E.: G6PD deficiency (Annotation). Haematol. 18: 117, 1970.
Br.
J.
7. Necheles, T. F., and Gorshein, D.: Virus-induced hemolysis in erythrocytes deficient in G6PD. Science 160: 535, 1968. 8. Pitcher, G. S., and Williams, R.: Reduced red cell survival in jaundice and its relation to abnormal 24: 239, 1963. glutathione metabolism. Clin. Sci. 9. Chah, T. K., and Todd, D.: Haemolysis complicating viral hepatitis in patients with G6PD deficiency. Br. Med. J. 1: 131, 1975. 10. Levy, N., and Chajani, A.: Viral hepatitis and G6PD
357, 1970. deficiency. Harefuah 79:
S. M., and Silvers, N. P.: G6PD deficiency, infectious hepatitis, acute hemolysis and renal
11. Phillips,
failure. Ann. Intern. Med. 70: 99, 1969.
483
Downloaded from cpj.sagepub.com at CARLETON UNIV on June 16, 2015
an
Aggravating Factor
Daniel Fried, M.D., Abraham Gotlieb, M.D., Abraham Roitman, M.D.
HEMOLYTIC of acute viral but only rarely does
course
ANEMIA hepatitis is
during not
the
unusual
a severe hemolytic crisis develop.2 Underlying the hemolysis in many infectious hepatitis patients is G6PD deficiency.3
Case The
History patient
8-year-old Jewish boy of Iraqui parentage. The only sibling was a healthy I 1-year-old sister. There was nothing remarkable in his past medical history. was an
mixed Moroccan and His illness started 5
days prior
to
admission with
fever, asthenia, loss of appetite, soon followed by weakness, darkly colored urine, and the appearance of jaundice. On the day prior to admission,
diffuse abdominal pain, and severe in, and the jaundice became more pronounced. During that same period, several of his classmates also fell ill with jaundice. Before his illness he received no medications, and his diet did not contain fava beans.
vomiting,
weakness
set
On hospitalization he was thin and markedly jaundiced, with pale lips and coated tongue. His pulse was rapid. The liver edge was 3 cm below the coastal margin and the tip of the spleen was palpable.
Department of Pediatrics, Zahalon GovernHospital, Jaffa, and Tel-Aviv University Medical School, Israel. From the
ment
Laboratory Finding. Hemoglobin
10.1i gm%, 2.5 per cent, hematocrit 28 per cent with anisocytosis, a few spherocytes, and 3 erythroblasts per 100 leukocytes. Serum bilirubin was 44 mg% (direct 23 mg%). The urine contained protein and bilirubin. Treatment on the first day included intravenous fluids with ACTH. On the second day the bilirubin rose to 60 mg% while hemoglobin fell abruptly to 7.3 gm% with hematocrit 20 per cent; and hemoglobin appeared in the urine. Other findings at this time: blood urea 78 ing%a, serum electrolytes and proteins normal, SGOT 300 units, SGPT 240 U, prothrombin time 100 per cent. Direct and indirect Coombs tests negative, G6PD content of the erythrocytes was 0 botch in the patient and his mother (normal values 3-6 U).4 The diagnosis was made of severe infectious hepatitis accompanied by acute hemolysis, which was apparently related to G6PD deficiency. That evening the hemoglobin level was still 7.2 gm%, but next day it was 6 gxn% with 4.4 per cent reticiulocytes and a leucocytosis of 24,000. Prothrombin time was 60 per cent. The bilirubin
reticulocytes
reached 71 (38.5 direct). Even at this stage there
clinical signs of such as reduction of liver size, alteration of consciousness or hypoglycemia. Nevertheless, exchange transfusion was decided upon; 2,300 ml of blood were exchanged (the body weight was 26 kg) by means of infusion through a catheter in one arm and extraction of blood from the other by vacuum bottles. The pro-
impending hepatic
were no
coma,
482
Downloaded from cpj.sagepub.com at CARLETON UNIV on June 16, 2015
cedure lasted about 4 hours, without any untoward incident. After the exchange total bilirubin was 41 mg% (26 ing% direct) and the hemoglobin was 12 ~rrr~l~: After this, the course was one of rapid recovery. Next day the bilirubin level was still 39 mg%, but two days later it was 15 nig%, and steadily returned to normal. The free and conjugated glttctiroiiic acid levels in the urine, which reflect the conjugative activity of the liver, indicated disturbed liver function during the acute stage of the disease, with good recovery thereafter.&dquo; The boy was discharged after I I days. Six months following his illness, he was symptomless and had normal liver function tests, hemoglobin and reticulocyte counts.
Discussion
our
transfusion
was correct.
References
Hemolysis in G6PD-deficient individuals may be precipitated by a diversity of infections.6 ln nitro studies have demonstrated increased autohemolysis of G6PD-deficient erythrocytes when incubated in the presence of influenza-A virus, related to their inability to activate the hexose monophosphate shunt.’ In infectious hepatitis, low levels of reduced red cell glutathione have been found during the acute stage, with a return to normal upon recovery.&dquo; This would indicate that the impaired liver function, led to an accumulation of metabolites capable of oxidizing red cell SH groups. Erythrocytes containing adequate G6PD can protect themselves from such oxidative insult through the reduction of additional glutathione, whereas G6PD-deficient erythrocytes are more readily destrc~yed.~ Hence, oxidant drugs should be avoided with G6PD-deficient patients, especially those who have or may have viral
hepatitis.9 The high prevalence of G6PD deficiency in Israel would warrant a more frequent occurrence of severe hemolysis during infectious hepatitis; but, such a situation seems quite uncommon.10
patient, the bilirubin rose to unusually high levels.71 mg%. The hemolytic process most probably enhanced the production of bilirubin at a stage of deranged clearance and disturbed excretion by the liver. The rise of blood urea in our patient, apparently reflected impairment of renal function by. the hemc~~lobinuria.;~ Our patient might have recovered with conservative treatment only, but because of the potential danger of bilirubin encephalopathy (indirect bilirubin 32.5 mg%) and more renal damage from ongoing hemolysis, we feel that the decision to perform exchange In
Conrad, M. E., Schwartz, F. D., and Young, A. A.: Infectious hepatitis: A generalized disease. A study of renal, gastrointestinal and hematologic abnormalities. Am. J. Med. 37: 789, 1964. 2. Salen, G., Goldstein, F., Haurani, F., and Wirts, 1.
C. W.: Acute Hemolytic anemia complicating viral hepatitis in patients with G6PD deficiency. Ann. Intern. Med. 65: 1210, 1966. 3. Burka, E. R., Weaver, Z., and Marks, P. A.: Clinical spectrum of hemolytic anemia associated with
Ann. 817, Intern. 1966. Med. G6PD deficiency. 64:
4.
Kornberg, A., and Horecker, B. L.: in S. P. Colowick and N. O.
Kaplan, eds., Methods in Enzymology,
Vol. I, New York and London, Academic Press, 1955, p. 323. 5. Gotlieb, A., Nir, I., and Pesach, J.: Urinary excretion of free and conjugated glucuronic acid in jaundiced newborn. Acta. Paediatr. Scand. 60: 6.
437, 1971. Beutler, E.: G6PD deficiency (Annotation). Haematol. 18: 117, 1970.
Br.
J.
7. Necheles, T. F., and Gorshein, D.: Virus-induced hemolysis in erythrocytes deficient in G6PD. Science 160: 535, 1968. 8. Pitcher, G. S., and Williams, R.: Reduced red cell survival in jaundice and its relation to abnormal 24: 239, 1963. glutathione metabolism. Clin. Sci. 9. Chah, T. K., and Todd, D.: Haemolysis complicating viral hepatitis in patients with G6PD deficiency. Br. Med. J. 1: 131, 1975. 10. Levy, N., and Chajani, A.: Viral hepatitis and G6PD
357, 1970. deficiency. Harefuah 79:
S. M., and Silvers, N. P.: G6PD deficiency, infectious hepatitis, acute hemolysis and renal
11. Phillips,
failure. Ann. Intern. Med. 70: 99, 1969.
483
Downloaded from cpj.sagepub.com at CARLETON UNIV on June 16, 2015
