Hepatic CMV-IE expression and distribution further defines the aetiological and prognostic subtypes of biliary atresia.

BACKGROUNDS AND AIMS: Cytomegalovirus (CMV) is involved in the pathogenesis and progression of biliary atresia (BA). The immediate-early (IE) protein, the earliest and abundantly expressed viral protein following CMV infection, serves as an indicator of active viral replication when upregulated. This study aimed to investigate the expression and distribution of CMV-IE in liver tissues of BA and to evaluate their impact on postoperative prognosis following Kasai portoenterostomy (KPE).

METHODS

This was a retrospective study in which clinical data from BA patients who underwent KPE were collected and analyzed. Preoperative variables included baseline demographics, serum biochemical indices, serologic CMV-IgM, blood and urine CMV-DNA, and liver fibrosis score. Prognostic endpoints included the jaundice clearance (CJ) rate within 3 months postoperatively, episode of cholangitis within 6 months postoperatively, and native liver survival (NLS) at 2 years postoperatively. Immunohistochemical staining of liver tissues was performed to assess the expression of CMV-IE and cytokeratin 19 (CK19). According to whether CMV-IE was detectable within CK19-positive areas, patients were categorized into three groups: bile duct involved group, bile duct non-involved group, and CMV-IE negative group. We compared liver function at the time of KPE and prognosis after KPE among the three groups.

RESULTS

Among 102 BA patients, 63 were CMV-IE negative and 39 were CMV-IE positive. 89 patients underwent both serologic CMV antibody testing and hepatic CMV-IE detection. Among the 28 patients with serum CMV-IgM+, 18 patients (64.3 %) showed positive expression of CMV-IE in liver tissue. Among the 61 patients with serum CMV-IgM-, 19 cases (31.1 %) had positive CMV-IE expression in liver tissue. 75 patients had both hepatic CMV-IE expression and CMV-DNA testing (serum or urine) results, of 17 patients with CMV-DNA+, 8 (47.1 %) had hepatic CMV-IE expression, among 58 patients with CMV-DNA-, 20 (34.5 %) were positive for hepatic CMV-IE expression. Based on CMV-IE expression within CK19 positive regions or not, the 39 CMV-IE positive cases were further subdivided into bile duct involved group (n = 9) and bile duct non-involved group (n = 30). Compared with the bile duct non-involved group and the CMV-IE negative group, patients in the bile duct involved group had significantly older age at surgery, more referral times, higher preoperative alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and higher aspartate aminotransferase-to-platelet ratio index (APRi) (all P < 0.05). In addition, the bile duct involved group exhibited more severe liver fibrosis at KPE, lower jaundice clearance rate at 3 months post-KPE, higher incidence of postoperative cholangitis, and reduced native liver survival rates after KPE (all P < 0.05).

CONCLUSION

Immunohistochemical detection of hepatic CMV-IE provides a more direct reflection of CMV infection in liver tissue. CMV-IE expression in cholangiocytes was significantly associated with older age at surgery, more severe hepatic injury, and poorer prognosis.