Impact of pretransplant antinuclear antibody and antismooth muscle antibody titers on disease recurrence and graft survival following liver transplantation in autoimmune hepatitis patients

Abstract

Background and Aims Disease recurrence following transplant occurs in 20-45% of patients with autoimmune hepatitis. Factors associated with an increased risk of recurrence include HLA DR3 and HLA DR4 positivity, inadequate immunosuppression and severity of inflammation in the native liver. Titers of several auto antibodies can be elevated in patients with autoimmune hepatitis including ANA and SMA however it is unclear whether or not the degree of elevation influences the risk of disease recurrence following transplant. Methods We conducted a retrospective study to evaluate the potential impact of pre transplant titers on post transplant outcomes for patients with autoimmune hepatitis. Sixty three patients with autoimmune hepatitis who underwent 72 liver transplants between January 1, 1989 and January 1, 2009 were included with a median follow up of 104 months. Patients were divided into group A (ANA or SMA ≥ 1:160) and group B (titers ≤ 1:160). Results There was no significant difference in recurrence rates or death between patients in group A and B respectively. Only race appeared to impact outcomes with African American patients having a higher incidence of death and recurrent disease post transplant compared to other ethnicities. Conclusions Based on our findings, pre transplant ANA and ASMA levels do not appear to impact recurrence rates or outcomes following liver transplantation for autoimmune hepatitis.

Autoimmune hepatitis

“…AIH can recur in the transplanted donor allograft, despite the absence of intentional HLA matching between donor and recipient in OLT [4,211,212]. The occurrence of AIH in a recipient mismatched for the HLA alleles of the donor allograft appears to violate the dictum that autoreactive T cells are restricted to autoantigens presented by self-HLA molecules on hepatocytes [213,214].…”

“…Successful treatments have been reported using intensified dosing or reintroduction of steroids and optimizing dosages of calcineurin or mTOR inhibitors [4,211,212]. Refractory patients may benefit from the addition of azathioprine (1-2 mg/(kg$d)) or MMF.…”

“…Arbitrary, diagnostic criteria have been proposed for recurrent AIH [4,211,212]. These criteria include: (1) OLT performed for either AIH or cryptogenic cirrhosis;…”

Autoimmune Hepatitis and Overlap Syndromes: Diagnosis and Management

“…AIH recurs in donor allografts, despite the absence of intentional HLA matching between donor and recipient in OLT 16,200,201 . Since autoreactive T cells are restricted to recognition of autoantigens presented by self-HLA molecules 202,203 , putative recurrent AIH may be a different disease involving distinct pathogenic mechanisms 202 .…”

“…Based on arbitrary, diagnostic criteria for recurrent AIH 16,200,201 , reported rates varied from 12% to 50% after 8-10 years with a median time to diagnosis of 2 years [205][206][207][208] . After corrections for biases, the true weighted recurrence rate appears to be 22% 209 , and the rate of AIH recurrence was similar for TAC or CSA immunosuppression.…”