Incidence of hepatotropic viruses in biliary atresia

Abstract

Biliary atresia (BA) is the most frequent indication for paediatric liver transplantation. We tested the hypothesis of a viral aetiology of this disease by screening liver samples of a large number of BA patients for the common human hepatotropic viruses. Moreover, we correlated our findings to the expression of Mx protein, which has been shown to be significantly up-regulated during viral infections. Seventy-four liver biopsies (taken during Kasai portoenterostomy) were tested by polymerase chain reaction (PCR) for DNA viruses (herpes simplex virus [HSV], Epstein-Barr virus [EBV], varicella zoster virus [VZV], cytomegalovirus [CMV], adenovirus, parvovirus B19 and polyoma BK) and RNA viruses (enteroviruses, rotavirus and reovirus 3). Mx protein expression was assessed by immunohistochemistry. Virus DNA/RNA was found in less than half of the biopsies (8/74 CMV, 1/74 adenovirus; 21/64 reovirus, 1/64 enterovirus). A limited number presented with double infection. Patients that had detectable viral RNA/DNA in their liver biopsies were significantly older than virus-free patients (P = 0.037). The majority (54/59) of the liver biopsies showed expression of Mx proteins in hepatocytes, bile ducts and epithelium. Our data suggest that the known hepatotropic viruses do not play a major role in the aetiology and progression of BA. Their incidence appears to be, rather, a secondary phenomenon. Nonetheless, the inflammatory response in the livers of BA patients mimics that observed during viral infections.

Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome

“…A wide range of enteric viruses has been implicated including REOvirus and cytomegalovirus (CMV) but clinical evidence of exposure and its relevance is conflicting whether derived from serological studies (7,8,9) or more directly from PCR studies on liver biopsies to detect viral nucleic acids (10).…”

Analysis of prognostic factors for infantile rotavirus infection

“…The results showed that age, feeding pattern, and CNS damage were significant independent risk factors for the prognosis of infantile RV enteritis. Although RV enteritis is often complicated by hepatic functional damage (Rauschenfels et al, 2009;Kawashima et al, 2012;Akelma et al, 2013), multivariate logistic analysis revealed no correlation between hepatic functional damage and the prognosis of RV enteritis. This may be because myocardial and hepatic damages are temporary rather than irreversible in most infants with RV enteritis.…”

Role of Rotavirus Enterotoxin NSP4 in the Inflammatory Response in Murine Macrophage RAW 264.7 Cells

“…It was also noted that NSP4 elicits systemic and intestinal antibody responses in gnotobiotic pig and rabbit models (17,21) and induces diarrhea in newborn mice (17,22). Recently, biliary atresia (BA), a fibroinflammatory pediatric liver disease that is the primary indication for liver transplantation in children, has been demonstrated to occur in rotavirus infection (3,23,24). Osteopontin (OPN), a glycoprotein with inflammatory and fibrogenic activity, may play a pathogenic role in BA (25).…”