Overlap of primary biliary cirrhosis and autoimmune hepatitis: Characteristics, therapy, and long term outcomes

Abstract

Background: Coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is referred to as PBC-AIH overlap. Pathogenesis of PBC-AIH is not well understood and its diagnosis is challenging. We previously reported the clinical characteristics of 10 patients diagnosed with PBC-AIH overlap. Aims: The aim of the study was extend the earlier series and evaluate the diagnostic criteria, biological characteristics, potential therapy, and long-term outcomes of patients with PBC-AIH overlap. Methods and Results:We retrospectively analyzed clinical, biochemical, and histological characteristics of 144 patients diagnosed with PBC and 73 diagnosed with AIH. We identified 16 cases of PBC-AIH overlap, according to criteria established by Chazouillères et al. and other studies. PBC preceded AIH in 6 patients and both diseases occurred simultaneously in the remaining 10 patients. PBC-AIH overlap has clinical, biochemical, and histological characteristics of both PBC and AIH. Thirteen patients treated with both ursodeoxycholic acid (UDCA) and immunosuppressive therapy responded well, with normal alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The remaining three patients treated with either prednisolone (PSL) or UDCA alone developed cirrhosis, varices, ascites, encephalopathy, or died of liver-related causes at the 5, 12, and 14-year follow up. Conclusions: PBC-AIH overlap is not a rare entity; it was observed in 11% of PBC patients in this study. Further studies will be required to investigate whether PBC-AIH overlap is distinct from the two individual diseases in terms of long-term outcomes and therapeutic implications.

Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review

“…10 For patients with overlap syndrome of AIH-PSC or AIH-PBC a combination therapy of immunosuppression with urso deoxy cholic acid (UDCA) is recommended. 1,11 AZA and 6MP are well tolerated in majority, with few adverse effects including nausea, vomiting, rash, arthralgia, fever, pancreatitis, hepatotoxicity and/or cytopenia which require dose modification or discontinuation. There is no established second line therapy for AIH patients who fail, i. e. intolerant or non-responsive to AZA therapy due to lack of randomized controlled trials.…”

A CASE OF OVERLAP SYNDROME OF PRIMARY BILIARY CIRRHOSIS AND AUTOIMMUNE HEPATITIS WITH MARKED ELEVATION OF IgM

“…AIH mouse models have also shown that CpG stimulation results in the breakdown of immune tolerance and induces transient AIH and that inflammation subsides upon the cessation of stimulation. TLR9 stimulation may also be involved in the onset of AIH 13,14) . In addition, hyperimmunoglobulinemia may have been caused by an excessive natural immune response via elevated TLR9 expression due to chronic bacterial stimulation.…”

“…Treatment with a steroid is often effective for PBC -AIH overlap 14,17) . The present case also responded to steroid treatment, resulting in evident improvement in hepatitis and a decrease in IgM level.…”

Review of overlap syndromes of autoimmune liver diseases. Difficulties in the diagnosis and treatment

“…Az overlap gyakorisága nagyban függ az alkalmazott pontrendszertől. Az AIH/PBC overlap gyakorisága 4,8-19% PBC-s betegekben és 5-8,3% AIHbetegekben, Yokokawa és mtsai vizsglatában 11, illetve 12% volt [29], átlagosan 10% körül van [30].…”