Parvovirus B19 infection and fulminant hepatitis

Abstract

Etienne Sokal and colleagues (Nov 28, 1998, p 1739)1Sokal EM Melchoir M Cornu C et al.Acute parvovirus B19 infection associated with fulminant hepatitis of favourable prognosis in young children.Lancet. 1998; 352: 173941Summary Full Text Full Text PDF Scopus (124) Google Scholar report the cases of four children with fulminant hepatitis associated with acute human parvovirus (HPV) B19 infection. Their diagnosis was based on the detection of the HPV B19 genome in serum. The diagnosis of acute viral hepatitis cannot be ascertained since liver tissue was not available, and these workers concede that acute HPV B19 infection could not be regarded as the actual cause of the acute liver disease in their four patients. HPV B19 has been proposed as the cause of fulminant hepatic failure in American patients with or without aplastic anaemia,2Langnas AN Markin RS Cattral MS Naides SJ Parvovirus B19 as a possible causative agent of fulminant liver failure and associated aplastic anemia.Hepatology. 1995; 22: 166165Google Scholar on the basis of HPV B19 DNA in liver specimens. However, as emphasised by Sokal et al, such a finding is poorly specific for actual HPV B19 liver infection. Moreover, the mechanisms of liver damage associated with HPV B19 remain conjectural.2Langnas AN Markin RS Cattral MS Naides SJ Parvovirus B19 as a possible causative agent of fulminant liver failure and associated aplastic anemia.Hepatology. 1995; 22: 166165Google Scholar, 3Yoto Y Kudoh T Haseyama K Suzuki N Chiba S Human parvovirus B19 infection associated with acute hepatitis.Lancet. 1996; 347: 86869Crossref Scopus (151) Google Scholar Since HPV B19 has not been detected in non-fetal hepatocytes, a direct cytopathic effect of the virus on these cells is unlikely, as Sokal et al emphasise. An immunologically-mediated mechanism of HPV B19-induced hepatocyte destruction has been postulated, but not documented.3Yoto Y Kudoh T Haseyama K Suzuki N Chiba S Human parvovirus B19 infection associated with acute hepatitis.Lancet. 1996; 347: 86869Crossref Scopus (151) Google Scholar Thus, there could be an unsuspected cofactor that is associated with HPV B19 infection and deleterious to the liver. Sokal and colleagues emphasise the distinctive profile of life-threatening hepatitis in children with HPV B19 infection-namely, serum amino-transferase activity more than 100 times higher than normal, lack of jaundice together with serum bilirubin lower than 90 μmol/L, and spontaneous recovery after transient low-grade encephalopathy. However, these characteristics, especially the first, are shared by herpes simplex hepatitis, ischaemic hepatitis (two rare conditions not missed by highly experienced paediatricians), and acetaminophen-induced hepatitis. Acetaminophen is generally given to patients, including children, with fever whether or not acute viral infection is the cause. Retrospectively, the ingestion, even repeated, of therapeutic doses of acetaminophen may be missed because patients or mothers of sick children do not mention it, and the drug might be undetected by routine blood tests of toxicology on admission. Acetaminophen hepatotoxicity has been recorded in benign infectious diseases,4Ackerman Z Flugelman MY Wax Y Shouval D Levy M Hepatitis during measles in young adults: possible role of antipyretic drugs.Hepatology. 1989; 10: 20306Crossref Scopus (20) Google Scholar and wrong calculation of dose ingested and no or irregular feeding, may result in severe, sometimes fatal, hepatotoxicity in young children.5Alonso EM Sokol RJ Hart J Tyson RW Narkewicz MR Whitington PF Fulminant hepatitis associated with centrilobular hepatic necrosis in young children.J Pediatr. 1995; 127: 888894Summary Full Text Full Text PDF Scopus (65) Google Scholar Thus, one could postulate that recent acetaminophen ingestion was a crucial causal factor of hepatic injury in the four children with HPV-B19-associated fulminant hepatitis reported by Sokal et al. A detailed history of ingestion of acetaminophen and diminished feeding in the days before admission by interview of the parents and whether the children were given intravenous N-acetylcysteine, which prevents the aggravation of acetaminophen-induced liver lesions, would be useful information. Our hypothesis could also explain why a case of fulminant hepatitis clinically similar to that associated with, but developed in a child without, HPV B19 infection was seen.