Rejection-independent cholangitis and cirrhosis following orthotopic liver transplantation

The histologic diagnosis of extrahepatic biliary obstruction in the setting of orthotopic liver transplantation (OLT) may be complicated by nonobstructive factors, such as rejection, preservation injury, drug effects, and infection. Indeed, biopsy specimens from OLT patients frequently exhibit early posttransplant cholestasis, which is likely the result of several of these factors acting in concert. We reviewed the clinicopathologic features of 14 OLT patients whose biopsy specimens displayed prominent cholangitis with "obstructive"-type features. Cholangiograms, Doppler ultrasound examinations, and bacterial cultures were obtained in conjunction with all biopsy specimens. Despite histologic evidence of biliary obstruction, cholangiography revealed obstruction in only one case, leaks in four cases, and nine normal studies. Ten patients had severe systemic bacterial or cytomegalovirus infections. Biliary infection was documented in two cases. Hepatic artery occlusion was diagnosed in one case. The cholangitic pattern persisted in patients with unremitting infections, and two patients developed secondary biliary cirrhosis despite having consistently normal cholangiograms. Features of acute rejection or viral hepatitis were not observed on any biopsy specimen. The presence of this clinicopathologic spectrum was associated with a poor prognosis. Nine patients died and only four patients who responded to antibiotics survived. These findings demonstrate a striking cholangitic response to systemic infections in OLT grafts. The diagnosis of biliary obstruction in OLT liver biopsy specimens cannot be rendered without cholangiographic verification.