Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile

Abstract

Cholestatic complications, important causes of morbidity and mortality after orthotopic liver transplantation (OLT), often have an unclear etiology. Human cytomegalovirus (CMV) infections occur in immunosuppressed patients and can be detected in blood samples. However, CMV analyses of body fluids and biopsies are more sensitive. Here we evaluated whether a CMV analysis of bile could reveal occult CMV cholangitis. We evaluated OLT patients undergoing endoscopic retrograde cholangiography (ERC) for suspected biliary complications after OLT at a tertiary care center. Biliary CMV DNA levels were measured with real-time polymerase chain reaction. A nonanastomotic biliary lesion (NABL) group consisted of patients with nonanastomotic strictures (NASs) at the time of ERC (n 5 59) and patients with normal ERC findings but microscopic biliary lesions in biopsy samples (n 5 12). The anastomotic stricture (AS) group comprised patients with ASs only (n 5 53). In all, 124 OLT patients underwent 240 ERC procedures. Biliary CMV DNA was detected in 14 of the 124 patients and was more frequently found in the NABL group (12/71 for the NABL group versus 2/53 for the AS group, P 5 0.02). Concurrent sampling of CMV DNA in blood yielded negative results. Biliary CMV was more frequently detected in patients with a positive recipient status (13/73 or 17.8% versus 1/44 or 2.3%, P < 0.05). There was no significant difference in the incidence of biliary CMV between patients with a high-risk CMV status and patients with a low-risk CMV status. The median interval between OLT and biliary CMV detection was 8.4 months (range 5 0.4-212.8 months). In conclusion, biliary CMV was detected in a substantial number of patients after OLT and was significantly associated with NASs or microscopic biliary lesions. A potential occult CMV infection could, therefore, be considered as a contributory etiological factor in the development of biliary complications.

Cytomegalovirus and posttransplant biliary complications: Elusive offender or innocent bystander?

“…This study by Gotthardt et al advances our understanding of the role of CMV in the development of biliary strictures after liver transplantation by demonstrating (1) the presence of CMV in the biliary fluid of posttransplant patients with biliary complications and (2) a higher frequency of biliary CMV in patients with an NABL. As a result, our approach to the treatment and diagnosis of posttransplant nonanastomotic biliary complications may need to shift if these findings are confirmed in larger studies.…”

“…None directly identified CMV in the biliary tract of living humans, and this would be a necessary step in making the leap from association to cause and effect . Therefore, the study reported by Gotthardt et al is exciting because it is the first to isolate CMV DNA in the biliary tract of living humans, and it offers a more direct link between CMV infection and posttransplant biliary complications.…”

“…However, when they were stratified by macroscopic lesions versus microscopic lesions, the proportion with biliary CMV was higher only for those with microscopic biliary lesions [33.3% (4/12) versus 13.6% (8/59)]. The presence of biliary CMV, however, was not associated with an increased risk of graft failure [28.6% (4/14) versus 29.1% (32/110), P = 0.97] …”

Endoscopic management of biliary strictures after living donor liver transplantation

“…Immunological factors (e.g., ABO blood type incompatibility [37,38] and cytomegalovirus infection [39]) are also associated with non-BAS formation. Because cholangiocytes play an important role in mucosal immunity in the biliary system [40,41], they are the primary targets of immune attack, which leads to stricture formation.…”

Clinical Significance of Cytomegalovirus Infection in Pediatric Liver Transplant Recipients

“…ЦМВ-ретинит является редким осложнением те-чения ЦМВИ, может протекать без клинических проявлений, особенно если поражение затрагива-ет периферическую область сетчатки, в некоторых случаях поздней диагностики и неэффективности лечения может приводить к ухудшению зрения [22]. Исследование D. Gotthardt (Германия) продемонс-трировало, что ЦМВ может поражать желчные про-токи и приводить первично к развитию холангита, а впоследствии к клинически значимым сужениям протоков вне зоны анастомоза и микроповреждени-ям желчных протоков после трансплантации пече-ни [23].…”