Acute Hepatitis in Malaria

Background

Malaria is endemic in 91 countries and approximately 40% of the world population is at risk of acquiring the infection. However, malaria is not a common cause of acute hepatitis.¹ We describe a case of malaria and acute hepatitis in a patient who presented to our institution complaining of abdominal pain and fever.

Case

A 42-year-old man presented to the emergency department with a 5-day history of fever, chills, and epigastric pain and a 1-day history of vomiting. The patient had no comorbid conditions. He had come from Haiti 5 days prior to presentation and described a history of possible mosquito bites.

The patient denied alcohol abuse, previous blood transfusions, and unprotected sex. A physical examination was notable for low-grade fever, icteric sclerae, and epigastric tenderness. The laboratory tests were relevant for bandemia, thrombocytopenia, and a raised serum creatinine level of 1.6 mg/dL (Table 1). His liver profile was consistent with hepatitis and hyperbilirubinemia (Table 2). The possibility of malaria was considered based on the clinical presentation and the fact that the patient had come from an area in which malaria is endemic. The diagnosis of malaria was confirmed on a Wright stained peripheral smear, which revealed bodies within some erythrocytes consistent with Plasmodium falciparum. Treatment was started with an initial dose of 600 mg of oral chloroquine followed by 300 mg 6 hours later and on days 2 and 3 of treatment in the hospital. Autoimmune, viral, and metabolic causes of acute hepatitis were excluded by confirming negative antinuclear and antismooth-muscle antibodies, negative hepatitis A and B serologies, negative hepatitis C virus RNA, and normal ceruloplasmin. Alpha-1-antitrypsin and ferritin and iron saturation were within normal limits. The hospital course was notable for further increase in the activity of transaminases; however, the patient experienced symptomatic improvement and was discharged 5 days after admission in stable condition. His laboratory tests indicated a downward trend of the activity of the transaminases as well as serum bilirubin and creatinine concentrations. One week after discharge, follow-up laboratory tests revealed decreased transaminase activity and normal serum bilirubin level (see Table 2).

Table 1.

Complete Blood Count

	WBC, 103/mL	Bands, %	Hb, g/dL	HCT, %	Platelets, 105/mL
Day 1	5.59	45	15.2	47.4	46
Day 2	9.29	35	15	44.9	43
Day 3	10.6	13	14.3	43.2	72
Day 4	11.1	0	13.7	40.9	72
Day 5	12.80	0	13.2	40.2	119
Day 12	6.98	0	12.9	41.5	521

WBC = white blood cells; Hb = hemoglobin; HCT = hematocrit.

Table 2.

Liver Profile

	AST, IU/mL	ALT, IU/mL	Alkaline Phosphatase, IU/mL	Total Bilirubin, mg/dL
Day 1	196	129	84	5
Day 2	350	211	110	5.4
Day 3	406	284	108	4.2
Day 4	305	241	150	4.8
Day 5	292	238	166	4.1
Day 12	40	80	88	1

ALT = alanine aminotransferase; AST = asparate aminotransferase.

Discussion

Malaria is an uncommon cause of acute hepatitis. According to the World Health Organization (WHO), other than jaundice, signs of hepatic dysfunction are unusual and clinical signs of liver failure are rarely seen unless there is concomitant viral hepatitis including B and E.¹ In our patient, viral markers for hepatitis A, B, and C infections were negative.

Jaundice and renal failure are the most common systemic manifestations of malaria. Jaundice is mostly due to unconjugated hyperbilirubinemia secondary to intravenous hemolysis¹; however, there are reports from Asia of hepatitis with evidence of hepatic encephalopathy and conjugated hyperbilirubinemia.^2,3 Liver histology reveals hepatocyte necrosis, cholestasis, and granulomatous lesions with malarial nodules.² The liver function abnormalities are not reported to be related to the grade of parasitemia, fever, duration of illness, nutritional status, or associated medical problems. The term malarial hepatitis has been used to describe this condition.

Patients with severe malarial hepatitis usually have a poor prognosis, characterized by a high incidence of renal failure, acute respiratory distress syndrome, and septicemia, with a mortality rate as high as 40%.⁴ The mechanism suggested to explain liver insult is ischemia, resulting from an alteration in blood flow through the liver as infected red blood cells (RBCs) adhere to endothelial cells, blocking the sinusoids.⁵ Early recognition, as exhibited in this patient, and treatment of malaria should lead to quick reversal of liver abnormalities.

To our knowledge, this is the first reported case of malarial hepatitis treated in the United States. With the increase in travel between the United States and areas where malaria is endemic, recognizing malaria as a cause of acute hepatitis should lead to expeditious diagnosis and treatment.