Risk factors for recurrence of autoimmune hepatitis after liver transplantation

Abstract

Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty-six patients that underwent liver transplantation because of end-stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5-year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05-13.36; P ϭ 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03-1.14; P ϭ 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03-1.20; P ϭ 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11-1.41; P ϭ 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55-18.79; P ϭ 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52-22.43; P ϭ 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76-26.96; P ϭ 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45-38.45; P ϭ 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation.

Clinical Features of Cirrhosis in Japanese Patients with Type I Autoimmune Hepatitis

“…However, since the relapse rate and the rate of immunosuppressant use were significantly higher in the patients who developed cirrhosis during the follow-up period than in non-cirrhosis patients, it seems that many patients who exhibited relapse from steroid resistance developed cirrhosis. It has been reported that a high IgG level before relapse and a long period to remission are risk factors for relapse (5,19). Regarding the use of immunosuppressants, it appears that the rate of immunosuppressant use was high in this study because many of the cases of relapse were caused by steroid resistance.…”

Autoimmune Hepatitis After Liver Transplantation

“…The severity of the original liver disease may also be a factor in disease recurrence after liver transplantation. Patients with recurrent AIH have higher serum levels of immunoglobulin G and histological findings of plasma cell infiltration and severe inflammatory activity more often immediately prior to transplantation than patients without recurrence (Montano-Loza et al, 2009). These observations suggest that recurrent AIH is a continuum of the original disease or a newly created process in a susceptible host with a propensity for severe immune reactivity (Czaja, 2009).…”

“…These observations suggest that recurrent AIH is a continuum of the original disease or a newly created process in a susceptible host with a propensity for severe immune reactivity (Czaja, 2009). They imply that aggressive disease suppression immediately prior to transplantation might alter the consequences after transplantation (Montano-Loza et al, 2009) or that an vulnerable individual may be identified early who warrants close surveillance after transplantation (Czaja, 2009). Most likely, the intrinsic bases for recurrent AIH interact with the extrinsic factors to define the true risk.…”

“…The serological type of the original disease may affect the need for transplantation (Cattan et al, 2002), but it does not correlate with prognosis after transplantation (Vogel et al, 2004). Similarly, the severity of the disease at transplantation does not predict outcome after the procedure (Montano-Loza et al, 2009). Patients transplanted for fulminant AIH have lower frequencies of recurrence after transplantation and better survivals than patients transplanted for chronic AIH (Reich et al, 2000;Nunez-Martinez et al, 2003), but most patients who develop recurrent AIH do not have fulminant presentations.…”

Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs

“…10,[146][147][148] The implementation of a new nonstandard therapy should not delay or supersede the decision to proceed with liver transplantation in the appropriate candidate. …”