Auxiliary Partial Orthotopic Liver Transplantation with De Novo Autoimmune Hepatitis in the Allograft and Leftover Primary Biliary Cirrhosis in the Native Liver

CASE REPORT

A 40-year-old woman, who presented with abnormal liver enzymes on routine check-up, was diagnosed to have primary biliary cirrhosis (PBC) on further laboratory tests and liver biopsy findings. The laboratory data included aspartate aminotransferase (AST) of 39 U/L, alanine aminotransferase (ALT) 32 U/L, alkaline phosphatase (ALP) 51 King-Armstrong U/L (normal, 2.7 to 10.0 King-Armstrong U/L), gamma-glutamyltranspeptidase (GGTP) 121 U/L, immunoglobin M (IgM) 748 mg/dL (upper limit of normal [ULN] 148 mg/dL), and antimitochondrial antibody (AMA) titer of 1:160. Antinuclear antibody (ANA) and anti-smooth muscle antibody (SMA) were undetected. The serum IgG was normal at 1422 mg/dL (ULN, 1774 mg/dL). The disease progressed during the following 8 years with the development of jaundice and esophageal varices despite ursodeoxycholic acid administration.

Needle liver biopsies were performed 7, 5, and 1 year prior to liver transplantation (LT). The first and second biopsy specimens showed fibrous portal enlargement with ductopenia and focal deposition of copper binding proteins in periportal hepatocytes. The third biopsy showed extensive bile duct loss with portal and septal fibrosis, with scattered bile plugs and feathery degeneration of hepatocytes, and extensive deposition of copper-binding proteins in the parenchyma (Fig. [1]A), compatible with stage III PBC. One remaining interlobular bile duct showed mild chronic cholangitis (Fig. [1]B). Lobular and periportal hepatitis were not evident in all three biopsy specimens, and portal inflammatory reaction was minimal. This case was regarded as the cholestatic type of PBC.[1] [2]

Figure 1 (A) There are no bile ducts in a fibrously enlarged portal tract with fibrous septa. Arrow denotes hepatic arterial branch. There is no interface hepatitis or lobular hepatitis (hematoxylin and eosin [H&E], ×200). (B) One interlobular bile duct (B) shows chronic cholangitis with moderate lymphoid cell infiltration and biliary epithelial damage. (Liver biopsy 1 year before liver transplantation; H&E, ×240.)

The patient underwent an auxiliary orthotopic liver transplantation (APOLT)[1] in May 1997. APOLT was elected to support the small-for-size graft from the living donor. The lateral segment of recipient liver was removed, and the left lobe of her ABO-compatible sister was transplanted. The patient's body weight was 54.1 kg and the weight of the liver graft was 213 g. Ratio of the graft to body weight was 0.39%. The recipient's serological histocompatibility leukocyte antigen (HLA) type was A2, A24, B46, B60, DR4, DR8, and the donor had identical HLA compatibility. The explanted liver was fibrotic and severely cholestatic, and histologically showed transition to cirrhosis with marked ductopenia and many bile plugs compatible with PBC stage III. As in the biopsy specimens, the hepatitic features in the portal tracts, in the parenchyma, and at the interface were minimal. A wedge biopsy of the donor liver was unremarkable. The initial immunosuppressive regimens included tacrolimus, azathioprine (AZA), and prednisolone (PSL). In the immediate postoperative period, the patient converted from tacrolimus to cyclosporine A (CyA) because of acute pancreatitis and neurological symptoms such as nausea and headache. Acute cellular rejection proven by biopsy occurred, and the transaminase levels decreased to the normal range by steroid pulse therapy. AZA was reduced and withdrawn because of neutropenia on postoperative day 98. On day 158, the patient was discharged.

At 11 months post-LT, protocol biopsies showed minimum inflammatory cell infiltration in the portal tracts of the allograft, and PBC stage III in the native liver. Bile plugs, however, disappeared and deposition of copper-binding proteins significantly decreased. Because transaminase levels were normal, PSL was tapered and was withdrawn entirely at 13 months post-LT (Fig. [2]). Thereafter, the target CyA serum trough level was approximately 50 ng/mL. The native liver became atrophic and the graft was enlarged on computed tomography. The technetium-99m galactosyl serum albumin scintigram, which was used to monitor allograft and native liver functions in patients who had undergone APOLT,[3] suggested that the allograft exhibited 85% of total liver function. Her monthly ALT and AST values were less than the ULN.

Figure 2 Changes in alkaline phosphatase (ALP; solid line) and immunoglobulin G (IgG; dotted line) level. Bars represent therapy of tacrolimus (FK), Cyclosporine A (CyA), and prednisolone (PSL). The titers of autoantibodies are indicated: antimitochondrial antibody (AMA), antinuclear antibody (ANA), anti-liver-kidney microsomal type 1 antibody (LKM-1). In the immediate postoperative period, she converted tacrolimus to cyclosporine A.

At 22 months post-LT, the pertinent laboratory data included: AST of 40 U/L, ALT of 26 U/L, ALP of 576 U/L, GGTP of 67 U/L, IgG of 1840 mg/dL, IgM of 525 mg/dL, AMA negative status (less than 1:20), ANA strongly positive status (1:1280), and positive anti-liver-kidney microsomal type 1 (LKM-1) antibody. Clinically, she had no jaundice or abdominal pain. Needle liver biopsies from the allograft and the native liver were obtained.

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