The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers

Abstract

Central perivenulitis (CP) in the allograft liver can be associated with portal-based acute cellular rejection and autoimmune hepatitis or can occur in isolation (isolated CP). Although several studies have demonstrated the significance of CP, the prevalence and natural history of untreated isolated CP have not been well studied. We examined 100 adult allograft liver recipients who had long-term follow-up, had routine protocol biopsies, and received no treatment for isolated CP. Isolated CP was identified in 28 (28%) patients. It occurred late at a mean of 658 days. Interestingly, patients with late isolated CP (defined as Ͼ3 months posttransplant) usually manifested only mildly to modestly elevated liver function tests. However, late isolated CP was associated with prior and subsequent allograft complications. Nearly all (94%) cases of late isolated CP occurred in patients who had early episodes of CP and/or acute cellular rejection. Of 13 patients who developed adverse outcomes in their allografts (zone 3 fibrosis in 10, de novo autoimmune hepatitis in 3, and ductopenia in 3), all experienced episodes of prior CP, and 12 (92%) had late CP; 1 patient required retransplant for chronic rejection, but all were alive within the last year. In summary, "transplant-associated" isolated CP occurs in 28% of adult patients, early CP is predictive of late CP, and late CP (often present as isolated CP) is associated with long-term liver injury in some patients.

Current views on rejection pathology in liver transplantation

“…Late AR can be portal and central, but the central component is more common and prominent and more frequently occurs as ICP [8,9] (Fig. 2).…”

“…ICP is generally preceded by at least one episode of CP occurring in conjunction with portal features of rejection [8,9,14,15], occurs in around 30% of protocol biopsies [8,9,16] and is more commonly seen more than 1 year post-transplant [9,17], often with no or mild abnormalities in liver function tests [9]. A grading system for CP proposed by the Banff group [7] appears to correlate with adverse outcomes [9]. Rejection is the usual cause of ICP, but other causes of centrilobular injury such as ischaemia, drug toxicity, viral hepatitis (recurrent or acquired) and AIH (recurrent or acquired) should also be considered [18].…”

Infiltrative (sinusoidal) and hepatitic patterns of injury in acute cellular rejection in liver allograft with clinical implications

“…1,[5][6][7] One such pattern is plasma cell hepatitis variant, variably referred to as de novo autoimmune hepatitis, hepatitic/atypical late-onset acute cellular rejection, or isolated central perivenulitis. 6,8,9 This variant in our and others' experience typically occurs www.modernpathology.org beyond the first year of transplant, and is characterized by a hepatitic, plasma cell-rich, perivenularaccentuated histologic picture and relative steroid resistance, when seen in adult population. 5,8,9 Two other features of acute cellular rejection have been recognized but are rarely reported or studied to determine their clinical relevance.…”

“…6,8,9 This variant in our and others' experience typically occurs www.modernpathology.org beyond the first year of transplant, and is characterized by a hepatitic, plasma cell-rich, perivenularaccentuated histologic picture and relative steroid resistance, when seen in adult population. 5,8,9 Two other features of acute cellular rejection have been recognized but are rarely reported or studied to determine their clinical relevance. These patterns either demonstrate active sinusoidal infiltration or hepatitic component, different from plasma cell hepatitis both in histopathological and clinical features.…”

Autoimmune Hepatitis After Liver Transplantation

“…Plasma cell hepatitis does not improve with corticosteroid treatment; it may develop as immunosuppressive therapy is reduced; and it improves as the immunosuppressive regimen is intensified (Demetris & Sebagh, 2008;Fiel et al, 2008). Isolated central perivenulitis can be found in 28% of allografts, and it can lead to de novo autoimmune hepatitis or chronic liver injury, especially if it occurs late after transplantation (Krasinskas et al, 2008). Typically, perivenulitis is untreated, but this approach is debated and anti-rejection therapy has been proposed.…”