Chapter 12 Liver Transplantation 1 Orthotopic liver transplant, consistent with recurrent primary biliary cirrhosis Case 12.7

Clinical Presentation 12 Liver Transplantation 2 Clinical Presentation A 58-year-old man with cirrhosis of probable alcoholic etiology was transplanted in 2006. He had done well post-transplant but abnormal liver tests developed including a high alkaline phosphatase and a liver biopsy was performed in 2007.

12 Liver Transplantation 3 Pathology The portal tracts exhibited a prominent lymphocytic infiltrate with increased numbers of plasma cells. Bile ducts showed non-suppurative damage with portal epithelioid granuloma formation (a, b). Figure 12.7(a) Figure 12.7(b)

12 Liver Transplantation 4 Pathology The parenchyma showed occasional small epithelioid granulomas (c). Figure 12.7(c)

12 Liver Transplantation 5 Diagnosis Orthotopic liver transplant (OLT), chronic hepatitis with non-suppurative duct injury and portal and lobular granulomas, etiology uncertain (approximately 1 year post-transplant)

Clinical Presentation 12 Liver Transplantation 6 Clinical Presentation A diagnosis of possible acute rejection was entertained but no cause of the granulomas was determined, with special stains for micro-organisms negative and further workup showing no definite infectious cause. An additional biopsy was performed in 2010 due to persistently abnormal liver tests.

12 Liver Transplantation 7 Pathology The portal tracts showed prominent lymphocytic and plasma cell infiltrates with occasional histiocytes; no interlobular bile ducts were present (d). Figure 12.7(d)

12 Liver Transplantation 8 Diagnosis OLT, chronic hepatitis with duct loss suggestive of a developing chronic rejection (approximately 4 years post-transplant) Note: At this time further laboratory values showed a serum IgM of 1022 (normal 48−271), AMA of 1:1280, and SMA of 80 (>30 high positive) with ANA negative. In conjunction with the two biopsies and these laboratory tests, these features are most suggestive of primary biliary cirrhosis (PBC) or autoimmune hepatitis–PBC overlap syndrome with progression to duct loss, the diagnosis of PBC confirmed on review of the original explant that showed a decrease in interlobular bile ducts

12 Liver Transplantation 9 Comment Recurrent primary biliary cirrhosis (PBC) may develop in up to 20% of patients by 5 years post-transplant with the percentages even higher (up to 35%) in longer-term followup. Almost ½ of these patients develop a positive anti-mitochondrial antibody although its presence is not an indicator of definite disease recurrence. Because the non-suppurative duct injury seen in PBC is also a feature of acute cellular rejection, distinguishing between the two on biopsy can at times be extremely difficult.

12 Liver Transplantation 10 Comment The presence of epithelioid granulomas can help support recurrent PBC while endothelial inflammation leans towards a diagnosis of acute rejection, although coexisting processes cannot totally be excluded at times. In this case the positive SMA also was initially suggestive of a possible coexisting autoimmune hepatitis although no definite periportal interface inflammatory activity or significant lobular inflammation was present on either biopsy, and the explant did not show autoimmune hepatitis features either.