Liver transplantation for autoimmune hepatitis

Abstract

Publications about liver transplantation (LTX) for autoimmune hepatitis (AIH) have started to emerge, but many issues remain unresolved. We reviewed data on 32 patients transplanted for AIH to determine how pretransplantation and posttransplantation characteristics correlate with recipient outcome, including disease recurrence. Recipients were 37؎ 14 years old; 30 of 32 were women. Most had chronic disease (8 ؎ 6 years); 25% had fulminant failure. The majority had ascites (91%), jaundice (88%), elevated prothrombin time (18 ؎ 3 seconds), and hypoalbuminemia (2.7 ؎ 0.6 g/dL). All had hypergammaglobulinemia (3.0 ؎ 1.0 g/dL) and autoantibodies (72% antinuclear, 74% smooth muscle). Only one was HLA A1-B8-DR3 positive. Other autoimmune disorders affected 25% of patients; half improved after transplantation. Actuarial survival was 81% at 1 and 2 years posttransplantation. There was a high frequency of rejection (75% of recipients had 1.7 ؎ 0.8 episodes), and 39% of rejections required OKT3. Among 24 recipients with long-term follow-up (27 ؎ 14 months), histologically proven recurrent AIH occurred in 25%, 15 ؎ 2 months posttransplantation; half (3 patients) required retransplantation 11 ؎ 3 months after diagnosis. After retransplantation 2 of 3 patients had re-recurrence within 3 months; 1 received a third LTx. Recurrence occurred in 6 of 18 patients transplanted for chronic disease vs. 0 of 6 transplanted as fulminants (P ‫؍‬ not significant [NS] Until a short time ago the literature on LTX for AIH was sparse, including one publication that addressed the role of LTX for AIH, 2 and some reports about recurrence of AIH after LTX. [4][5][6][7] Recently, several retrospective reviews on LTX for AIH have emerged from various transplantation programs [8][9][10][11][12] as well as a few publications about rejection and immunosuppression after LTX for AIH. [13][14][15] In general there is consensus about the demographics of AIH patients that come to LTX. However, there are unresolved issues regarding the posttransplantation course of these patients. For example, there is controversy about the prevalence, risk factors, and outcome of recurrent AIH, and about appropriate posttransplantation immunosuppression strategies that take into account the increased immunoreactivity of these patients.To address some of these issues, we reviewed our data on 32 patients who underwent LTX for a primary indication of AIH and we sought to determine whether specific pretransplantation characteristics or various aspects of the postoperative course could be used to predict posttransplantation outcome, including disease recurrence. PATIENTS AND METHODSWe retrospectively reviewed our data on patients in whom a clinical and pathologic diagnosis of AIH had been made on the basis of the diagnostic criteria of the International Autoimmune Hepatitis Group 16 and who underwent transplantation at The Mount Sinai Medical Center (New York, NY) between September 1988 and January 1995. Patients with coexisting causes of hepatitis, such as viral or alcohol-ind...

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.…”

Recurrent autoimmune hepatitis after orthotopic liver transplantation

“…The inclusion of patients with acute lobular hepatitis, acidophilic bodies, steatosis, severe cholestasis, and paucity of bile ducts may have resulted in greater estimates of recurrence in other studies than in our own. 12,13,16 The diagnostic criteria for recurrent autoimmune hepatitis have not been codified, and our findings may reflect a minimum occurrence of the disease.…”

“…3,4 Furthermore, autoantibodies and hypergammaglobulinemia disappear in most patients within 2 years. 1,2 Despite these successes, recurrent disease is possible, 2,3,[5][6][7][8][9][10][11][12][13] and recent reports have indicated that it may lead to cirrhosis and graft failure. 2,8,12 Furthermore, the immunoreactive propensity of the recipient may contribute to greater frequencies of acute rejection, steroid-resistant rejection, and chronic rejection, especially if corticosteroids are withdrawn in the posttransplantation period.…”

Relationship between autoimmune hepatitis and HLA-DR4 and DR®allelic sequences in the third hypervariable region in Chinese

“…Novel drugs with potent immunosuppressive and cytoprotetive functions must be evaluated [31,32] . Liver transplanta tion has been an extremely successful treatment option for the decompensated patients [33] , but better drug regimens are needed to conserve this limited resource.…”