What is the management of autoimmune hepatitis type 2?

Autoimmune Hepatitis Type 2: Clinical Overview and Management

Definition and Epidemiology

Autoimmune hepatitis type 2 (AIH-2) is a rare, aggressive variant of autoimmune hepatitis characterized by anti-liver kidney microsomal-1 (anti-LKM1) and/or anti-liver cytosol-1 (anti-LC1) antibodies, typically affecting children and young adults with a more severe clinical course than type 1 AIH. 1

Key Distinguishing Features:

• Accounts for less than 10% of AIH cases in North America and northern Europe, but more common in southern Europe 1
• Extremely rare in East Asian populations (1-3% of adult AIH patients in Korea, essentially absent in Japanese and Taiwanese cohorts) 1
• More prevalent in South Asian countries, the United States, and Europe (13.2-16% of pediatric AIH cases in Malaysia and Canada) 1
• Primary age of onset: children under 14 years or young adults 1

Clinical Presentation

AIH-2 presents more aggressively than type 1, with acute onset in 31-40% of cases and up to 25% developing acute liver failure. 1

Characteristic Features:

• Higher rates of treatment resistance compared to type 1 AIH 1
• Associated with worse prognosis: type 2 AIH is specifically identified as a risk factor for liver-related death or transplantation 1
• IgG levels may be normal or even lower than in type 1 AIH, particularly in early disease stages 1
• Commonly associated with type 1 diabetes, autoimmune thyroid disease, and autoimmune skin conditions (vitiligo, leukocytoclastic vasculitis, urticaria, alopecia areata) 1

Diagnostic Approach

Serological Markers:

• Anti-LKM1 antibodies target cytochrome P-450 2D6 epitopes 1
• Anti-LC1 antibodies may be present 1
• ANA and smooth muscle antibodies are typically absent 1
• Cross-reactivity with hepatitis C virus has been demonstrated, suggesting molecular mimicry mechanisms 1

Histological Features:

• Interface hepatitis with lymphoplasmacytic infiltration 1
• Portal tract plasma cell infiltration 1
• Confluent necrosis (associated with worse prognosis) 1

Treatment Strategy

Immediate immunosuppressive therapy with prednisolone plus azathioprine is the standard first-line treatment, though AIH-2 shows higher rates of treatment failure than type 1. 1

First-Line Therapy:

• Prednisolone combined with azathioprine 1 mg/kg/day 1
• In non-responding patients, increase azathioprine to 2 mg/kg/day with higher steroid doses (including methylprednisolone) 1
• Treatment duration: minimum 2 years and at least 12 months after transaminase normalization 1

Second-Line Options for Treatment Failure:

• Cyclosporine has demonstrated efficacy in pediatric type 2 AIH, with normalization of ALT within 6 months and minimal side effects 2
• In children with acute liver failure progressing despite steroids and azathioprine, addition of cyclosporine normalized prothrombin time 2
• Tacrolimus (expert consultation recommended) 1
• Mycophenolate mofetil with prednisone (78.7% mean aminotransferase reduction, 88.6% histological remission rate) 3

Critical Management Points:

• Patients with liver failure, bridging necrosis, or jaundiced patients whose MELD score doesn't rapidly improve require immediate liver transplant center contact 1
• Vaccination against hepatitis A and B should be performed early in susceptible patients 1
• Calcium and vitamin D supplementation mandatory; DEXA scanning at 1-2 yearly intervals while on steroids 1

Monitoring and Prognosis

Poor Prognostic Indicators:

• Type 2 AIH designation itself is an independent risk factor for liver-related death or transplantation 1
• Cirrhosis at presentation 1
• Confluent necrosis on biopsy 1
• Failure of AST to halve within 6 months 1
• Persistent inflammation on liver biopsy despite treatment 1

Long-Term Outcomes:

• Relapse rate after treatment withdrawal: 50-90% within 12 months 1
• Liver-related death or transplantation: 10-20% overall 1
• Lifelong clinical and biochemical monitoring is mandatory 1

Special Considerations

Liver biopsy to confirm histological remission is valuable for planning further management, particularly given the higher treatment resistance in type 2 AIH. 1

In pediatric patients with type 2 AIH who have risk factors for poor steroid tolerance, cyclosporin as primary immunosuppression is a validated alternative with minimal side effects and no relapses in 10 patients followed for 1-6 years. 2