The new histological criteria for the diagnosis of autoimmune hepatitis

Dear Editor, Recently, Ma et al.1 evaluated the performance of the new autoimmune hepatitis (AIH) histological criteria2 among patients with AIH and drug-induced liver injury (DILI). In their previous study,3 the authors reported that the new histological criteria had good sensitivity and specificity for AIH in a large cohort of patients with liver diseases. Importantly, AIH can be distinguished from most patients with PBC, MASLD and viral hepatitis B/C based only on laboratory findings. Therefore, liver histology is rarely needed for the diagnosis of the AIH component in this group of patients. To better evaluate the performance of the new histological criteria, the authors included a control group of 28 DILI cases.1 In this study, the new histological criteria showed good sensitivity (98%), but the specificity was 29% for likely/possible AIH. Due to the low specificity of the new histological criteria, the authors included low aminotransferase levels and antinuclear antibodies (ANA) ≥1:160 seropositivity as additional discriminative findings for AIH diagnosis. This study provides useful information, but several issues require further clarification. In the first study,3 the authors evaluated the performance of the new histological criteria in 107 DILI cases. The new histological criteria inappropriately upgraded 17 of DILI and showed lower diagnostic performance than the simplified histological criteria. In the current study,1 the new histological criteria efficiently distinguished AIH from DILI, but the authors did not evaluate the performance of the simplified histological criteria. Interface hepatitis and portal inflammation are commonly observed in both DILI and AIH; however, they are more severe in AIH.4 The new histological criteria considered ‘more than mild inflammation’ as an AIH-favouring feature. In the current study,1 the frequency of ‘more than mild inflammation’ was significantly higher in AIH than in DILI (92.7% vs. 53.6%). Serum ALT levels usually indicate inflammatory activity in patients with liver disorders, including AIH. Interestingly, the median ALT levels (U/L) were significantly lower in patients with AIH than in DILI (217 vs. 359). Therefore, the discriminative utility of aminotransferase levels for AIH and DILI may be limited to the current study rather than standard findings that can be used in clinical care. We also evaluated the performance of the new histological criteria.5 In our study, the new histological criteria demonstrate improved performance in diagnosing AIH. Among 35 DILI cases, the new histological criteria downgraded 11 cases, while four DILI cases were upgraded from atypical to possible AIH. These results suggest that the new histological criteria are useful but are still not optimal for discriminating AIH from DILI. We agree with the authors that autoantibody positivity and immunoglobulin (IgG) levels improve the diagnostic accuracy for AIH. The updated immunoserological testing showed that ANA (≥1:160) or smooth muscle antibodies (≥1:160) confer >90% specificity for AIH.6 Also, elevated IgG levels provide additional diagnostic accuracy for AIH. Therefore, we recommend the use of updated serological testing in combination with the new histological criteria for AIH diagnosis. In our experience, liver biopsy may be avoided in some patients with typical laboratory and serological features of AIH.7 Several studies have suggested that the new histological criteria exhibit better diagnostic accuracy than the simplified histological criteria.1, 3, 5 Importantly, both the new and simplified histological criteria were established based on expert opinions rather than large cohort study findings. The current study also showed that moderate inter-observer consistency among expert pathologists renders difficulties in the routine use of the new histological criteria.1 Timing of liver biopsy may also affect the severity of inflammation, which is an AIH-favouring feature according to the new histological criteria. We think that the diagnostic utility of the new histological criteria should be evaluated in prospective studies before they can be incorporated into routine care. Conceptualized the study. C.E., M.P. and K.M. interpreted data and prepared the manuscript. All authors approved the final version of the manuscript. No funding received for this study. None. Patient data were not used. Paperpal 4.4.2 was used to correct grammar errors. The data that support the findings of this study are presented in the manuscript.