In this issue, Fiel et al. 1 use the phrase "plasma cell hepatitis (de novo autoimmune hepatitis)" to describe what they eventually conclude to be a variant of acute rejection. This study was likely prompted by curiosity about the significance of plasma cell-rich infiltrates in liver allograft biopsies. Patients were first chosen for study with a free-text search of pathology reports for the key words "liver allograft," "lymphoplasmacytic," and "plasma cell(s)." These results were then cross-referenced with all patients undergoing liver transplantation for hepatitis C virus (HCV)-induced cirrhosis. "Hepatitis" was not included in the search.
Twenty-eight (42%) initially selected patients were excluded because they had histological and/or clinical evidence of concomitant acute cellular rejection, chronic rejection, mechanical bile duct obstruction, hepatic artery thrombosis/stenosis, cytomegalovirus or other nonhepatotropic viral infection, or medicationinduced hepatotoxicity. Additional patients were excluded because their biopsies contained ี
30% plasma cells.
The outcome of these highly selected patients was not good. Twenty-three of 38 (60%) died (n ฯญ 10) or developed graft failure and portal hypertension. Neither detailed descriptions of the causes of death and allograft failures nor the treatment approaches before these endpoints were included. One might assume that portal hypertension developed because of plasma cell hepatitis (PCH)-induced classical cirrhosis, but silently developing veno-occlusive disease due to centrilobularbased rejection can lead to the same endpoint. 2 Also, lowering immunosuppression after widespread perive-nular inflammation is found on biopsy might lead to an adverse outcome.
The authors concluded that PCH represents a form of acute rejection because this cohort (1) frequently developed PCH in association with suboptimal immunosuppression, (2) had a high incidence of acute rejection before the development of PCH that signaled a propensity toward rejection, and (3) had a better outcome when they were treated with increased immunosuppression.
Fiel et al. 1 address 3 distinct but related questions in this article: (1) how does one distinguish between rejection and recurrent HCV, (2) how does one distinguish between HCV and autoimmune hepatitis (AIH), and, most importantly, (3) how does one distinguish between rejection and AIH? The Mt. Sinai group is to be congratulated on tackling some of these very difficult issues.
The authors appear to have distinguished recurrent HCV from acute rejection by examining the centrilobular areas for necroinflammatory activity involving a majority of perivenular regions. They stated the following:
We did not examine the significance of portal inflammation, interface hepatitis or lobular activity on clinical outcome or histological resolution because we could not reliably differentiate PCH from recurrent HCV based solely on these features. However, 25 patients (76%) had some degree of plasma cell infiltration pre-PCH with over half (14/25) already manifesting focal centrilobular necrosis (severe plasma cell infiltrate was found in two other patients but they also had ACR). Indeed, centrilobular necroinflammatory activity was present in the index biopsy, which established the diagnosis of PCH, in all selected patients (100%).