Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Abstract

Background & aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria.

Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC.

Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9-95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation - not receiving immunosuppression - compared to those with AIH-PBC (65%; 95% CI 52.2-77.8% vs. 87%; 95% CI 83.2-90.8%; hazard ratio 0.52; p = 0.043).

Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy.

Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.

Keywords: Autoimmune Hepatitis; Primary Biliary Cholangitis; Variant syndrome; glucocorticoids; immunosuppression; ursodeoxycholic acid.

Graphical abstract

Fig. 1

Flowchart of included patients with AIH-PBC under combination therapy. AIH-PBC, autoimmune hepatitis – primary biliary cholangitis variant syndrome.

Fig. 2

Histology scores. (A) Interface hepatitis, portal infiltrate, lobular infiltrate, biliary damage and (B) fibrosis in available histopathology of patients with AIH-PBC under combination therapy. AIH-PBC, autoimmune hepatitis – primary biliary cholangitis variant syndrome.

Fig. 3

Liver transplantation-free survival of patients with AIH-PBC under combination therapy. Compared to patients with (A) AIH and (B) PBC. AIH, autoimmune hepatitis; AIH-PBC, autoimmune hepatitis – primary biliary cholangitis variant syndrome; PBC, primary biliary cholangitis.

Fig. 4

Liver transplantation-free survival of patients with AIH-PBC under combination therapy is better than for patients with PBC and hepatic inflammation (logrank p = 0.045) and comparable to other patients with PBC. Patients with PBC and hepatic inflammation defined as those with elevated IgG and AST and/or ALT >2.5x ULN at diagnosis. AIH-PBC, autoimmune hepatitis – primary biliary cholangitis variant syndrome; ALT, alanine aminotransferase; AST, aspartate aminotransferase; PBC, primary biliary cholangitis; ULN, upper limit of normal.