Autoantibody Profiling and Diagnostic Performance of Serum and Liver Tissue Markers in Patients with Autoimmune Hepatitis: A Review

Abstract

Autoimmune hepatitis has no single diagnostic test. It is identified by assembling autoantibodies, immunoglobulin G, liver histology and the exclusion of viral disease into a score. Each component behaves differently, and the antibody most people order first is the least specific one available. Objectives: To review the published evidence on serological and histological markers in autoimmune hepatitis: how the individual autoantibodies perform, how the two diagnostic scoring systems compare, what liver biopsy contributes, and where each fails. Material and Methods: Narrative review of diagnostic accuracy studies, scoring system validations, meta-analyses and society guidance indexed in PubMed and the major hepatology and immunology journals. Studies were eligible if they reported the accuracy of an autoantibody or scoring system for diagnosing autoimmune hepatitis in a defined population, or the contribution of histology to that diagnosis. No new patient data were generated; every estimate quoted is one published by the original investigators.
Results: Pooling 29 studies, antinuclear antibodies gave a sensitivity of 65.0 per cent and specificity of 75.1 per cent, smooth muscle antibodies 59.3 and 92.6 per cent, and antibodies to soluble liver antigen 19.4 and 98.9 per cent, with diagnostic odds ratios of 7.38, 31.55 and 16.87 respectively. In 435 patients assessed by both scoring systems, the revised original system was more sensitive (100 against 95 per cent) while the simplified system was more specific (90 against 73 per cent) and more predictive (92 against 82 per cent), and excluded the diagnosis more reliably in diseases with concurrent immune features (83 against 64 per cent). The simplified criteria at a threshold of six reported sensitivity and specificity of 88 and 97 per cent in the derivation cohort, 90 and 95 per cent in a Chinese validation and 96 and 97 per cent in a German one. Conclusion: No autoantibody both identifies and confirms the disease. Antinuclear antibodies are the most frequently positive and the least discriminating; antibodies to soluble liver antigen are close to definitive when present but absent in four patients out of five. The two scoring systems fail in opposite directions and are best used for different purposes rather than as alternatives. Abbreviations: AIH – Autoimmune Hepatitis, ANA – Antinuclear Antibodies, SMA – Smooth Muscle Antibodies, anti-SLA/LP – Antibodies to Soluble Liver Antigen/Liver Pancreas, anti-LKM1 – Anti-Liver Kidney Microsomal Antibody Type 1, anti-LC1 – Anti-Liver Cytosol Antibody Type 1, IgG – Immunoglobulin G, IAIHG – International Autoimmune Hepatitis Group, PBC – Primary Biliary Cholangitis, PSC – Primary Sclerosing Cholangitis, DILI – Drug-Induced Liver Injury, DOR – Diagnostic Odds Ratio.