Recurrent and De Novo Liver Disease, Histopathology, and Long-Term Outcomes
Recurrence, pathology, and the long view
Recurrent disease is the leading cause of late graft loss for several indications. Hepatitis C recurred universally before direct-acting antivirals; treatment is now highly effective and should be given post-transplant. Hepatitis B is prevented with HBIG plus a nucleos(t)ide analogue. Primary sclerosing cholangitis recurs in 10-20%, PBC in up to a third, autoimmune hepatitis in 20-30%, and recurrent HCC in roughly 10-20% at 5 years. Alcohol-associated liver disease can recur; sustained abstinence predicts better outcomes.
Histopathology. Biopsy distinguishes recurrent disease from rejection. Recurrent PSC shows fibrous cholangitis and biliary-type fibrosis; chronic rejection shows ductopenia with foam-cell arteriopathy. Recurrent AIH shows interface hepatitis with plasma cells; de novo autoimmune hepatitis can appear in patients transplanted for other diseases. Fibrosis staging matters - recurrent disease often progresses faster than in the native liver.
Long-term outcomes. Five-year patient survival is about 75-80% and graft survival slightly lower. Late mortality is driven by cardiovascular disease, renal failure, malignancy, infection, and recurrent disease; adherence to immunosuppression is the strongest modifiable factor. De novo NAFLD and metabolic syndrome are increasingly common as patients survive longer on tacrolimus and steroids.
Rule of thumb: a cholestatic enzyme rise in a patient transplanted for PSC is recurrent PSC versus ductopenic rejection versus biliary stricture - get a biopsy, imaging, and medication levels before changing immunosuppression.
Trap: assuming allograft dysfunction is rejection; biopsy first, especially after the first year.