Incidence and recurrence of autoimmune/alloimmune hepatitis in liver transplant recipients

Abstract

We prospectively collected data on 1,429 liver transplant recipients between December 1984 and December 1998. A utoimmune hepatitis (AIH) is a recognized pathological process first described in the 1950s. However, diagnostic criteria have been clearly defined only recently. 1 AIH affects predominantly middle-aged women and often responds to immunosuppressive therapy. When it leads to chronic liver failure, it constitutes an indication for orthotopic liver transplantation (OLT). 1 Because of post-OLT immunosuppressive therapy, recurrence in liver allografts has been believed to be relatively low. 2,3 This has been supported by reports from both American and European centers 4 dating back to the mid-1980s. Although these studies made use of histological and biochemical parameters for their diagnosis of recurrence, precise patterns of histopathologic findings were not described. In addition, hepatitis C virus infection was not completely excluded because a marker of viremia was not yet available. 5 In this study, we reviewed our experience using OLT for the treatment of AIH. We analyzed the incidence of recurrence and possible risk factors associated with recurrence. We also studied the impact of AIH recurrence on patient and graft survival, HLA typing, episodes of rejection, liver function test (LFT) results, and other biochemical and histological parameters. Materials and MethodsData were collected prospectively between December 1984 and December 1998 on a total of 1,429 patients who underwent OLT at Baylor University Medical Center (Dallas, TX). There were 753 men and 676 women. Mean age at OLT was 48 Ϯ 12 (SD) years. The initial diagnosis of AIH was based on: (1) detection of antinuclear antibodies, anti-smooth muscle antibodies, or antiliver/kidney microsomal type 1 antibodies in titers greater than 1:80; (2) total gamma globulin or immunoglobulin G (IgG) levels greater than 1.5 times the upper limit of normal; (3) absence of IgM antibodies to hepatitis A virus; (4) absence of hepatitis B virus surface antigen and antibodies to hepatitis B virus core antigen; (5) absence of antibodies to hepatitis C virus and hepatitis C virus RNA by polymerase chain reaction assay; (6) laboratory findings of abnormal LFT results (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]); (7) absence of liver disease attributable to alcohol or hepatotoxic drugs; and (8) presence of histological findings consistent with interface hepatitis or piecemeal necrosis, concurrent lobular hepatitis, and no biliary lesions or other changes.Biochemical and clinical data were collected preoperatively and at various times after OLT. All transplant recipients

Liver biopsy interpretation for causes of late liver allograft dysfunction

“…Criteria used to distinguish rejection from AIH can be melded into generalized criteria applicable to other causes of late liver allograft dysfunction, [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] including: (1) histopathological evidence of liver injury showing a pattern compatible with the diagnosis (liver tests are usually elevated in a pattern consistent with the diagnosis); (2) positive serological, molecular biological, immunological, or radiographic evidence of pathogen or possible cause of injury; and (3) other causes of similar histopathological changes and elevated liver tests, if present, have been reasonably excluded. Table 1 shows approximate incidences, risk factors, and clinical, immunological, and radiological observations for common causes of late dysfunction.…”

Alloimmune hepatitis following peripheral stem cell transplantation

“…1 Occasional examples of de novo autoimmune-like hepatitis have been reported following liver, bone marrow or stem cell transplantation. [3][4][5][6][7][8] Other etiologies including viral hepatitis, non-alcoholic steatohepatitis and metabolic liver disease were excluded. The diagnosis was distinguished from chronic GVHD as liver histopathology did not reveal any changes consistent with GVHD (Table 2).…”

Autoimmune Hepatitis After Liver Transplantation

“…Alternatively, rejection may be the basis for releasing hepatic antigens that sensitize the susceptible individual and trigger the recurrence (Czaja, 2009). Patients with recurrent AIH have a higher frequency of rejection during the first 3, 6 and 12 months after transplantation than patients without recurrent disease, but previous rejection is not a requisite for recurrence (Molmenti et al, 2002). Another factor that has been implicated in recurrence has been the calcineurin inhibitors used in the immunosuppressive regimen after transplantation (Schreuder et al, 2009;Gautam et al, 2006).…”

“…Transplant recipients with AIH are younger and more commonly women than other transplant recipients (Molmenti et al, 2002), and they have HLA DRB1*03 more frequently (Sanchez-Urdazpal et al, 1992;Gonzalez-Koch et al, 2001). HLA DRB1*03 and DRB1*04 are the principal susceptibility factors for AIH in white North American and northern European www.intechopen.com patients (Donaldson et al, 1991), and HLA DRB1*03 has been associated with early age of disease onset and a higher frequency of treatment failure than patients with other HLA (Czaja et al, 1993(Czaja et al, , 1997Czaja & Carpenter, 2006).…”

“…Environmental agents like viruses, toxins or drugs (Krawitt, 2006, Czaja, 1999a may trigger a cascade of T-cell mediated events against liver antigens in a context of genetic predisposition (Czaja & Manns, 1995;Alvarez, 1999, Molmenti et al, 2002Sanchez-Urdazpal et al, 1992), leading to a progressive necroinflammatory liver disease.…”