Diagnosis: Fibrosing Cholestatic Hepatitis
• Marked parenchymal cholestasis with prominent ductular reaction after liver transplantation warrants clinical and radiologic exclusion of biliary tract obstruction (e.g., anastomotic stricture, biloma). If obstruction is excluded in any patient who underwent liver transplantation for chronic hepatitis B or C, the leading diagnosis would be fibrosing cholestatic hepatitis, a severe complication of overimmunosuppression.
• A patient with chronic hepatitis C may develop fibrosing cholestatic hepatitis, in which severe exacerbation of intrahepatocellular hepatitis C virus (HCV) growth results in defective bile secretion and marked cholestasis, along with a prominent ductular reaction. Fibrosing cholestatic hepatitis C may affect patients after liver transplantation whose native livers showed cirrhosis secondary to chronic hepatitis C. In other transplant recipients, posttransplant immunosuppression may also trigger fibrosing cholestatic hepatitis.
• There is virtually universal recurrence of viral infection months to years after liver transplantation for chronic hepatitis C with cirrhosis. The histologic manifestations may closely resemble the type and histologic course of chronic HCV infection in the nontransplant setting, consisting predominantly of portal and periportal lymphocytic or lymphoplasmacytic portal and periportal inflammation. In certain cases, there are superimposed changes of acute rejection, which may be difficult to discern histologically from underlying recurrent chronic hepatitis. Fibrosing cholestatic hepatitis is an unusual but histologically distinctive complication that warrants direct action from the clinical care team.
• Marked cholestasis many months after liver transplantation for chronic hepatitis C with cirrhosis is an unusual histologic finding and should raise suspicion of possible fibrosing cholestatic hepatitis.
• Fibrosing cholestatic hepatitis was originally described in individuals with chronic hepatitis B–related cirrhosis who underwent liver transplantation and, under the influence of immunosuppression, developed diffuse ground-glass change (and corresponding extensive hepatocellular recurrent hepatitis B virus (HBV) reinfection with hepatitis B surface antigen production), marked cholestasis, and a distinctive portal and periportal fibrosis that demonstrated marked periportal fibrosis (with strands of periportal and perisinusoidal collagen) in tandem with marked proliferation of bile ductular structures (termed ductular reaction).
