Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease that follows an erratic course and characterised by elevated transaminases, hypergammaglobulinaemia, the presence of antibodies, and typical histopathological lesions.1 It has an incidence of 1.37 per 100,000 inhabitants and a prevalence of 17.4 per 100,000 inhabitants worldwide.2

Numerous studies performed around the world have evaluated the coexistence of this condition with rheumatological diseases, reporting prevalence rates that vary from 28% to 40%, which speaks to a high degree of variability owing to the heterogeneity of the cohorts studied. Ascertaining the frequency with which rheumatological diseases co-exist in AIH in our setting is pertinent given the impact they have on the natural history of the disease, treatment, and prognosis, bearing in mind that if comorbidities are diagnosed early, they can affect the patient's quality of life.3

The epidemiology of AIH has not been fully elucidated. Depending on the cohort studied, incidences of 1-2 per 100,000 person-years in adult patients and one-off prevalence rates of 11-17 per 100,000 person-years in Norway and Sweden have been reported.4 Alaska reports a particularly high prevalence of the disease (43 per 100,000), with a significant proportion of cases debuting with jaundice.5 One of the obstacles that hinder access to reliable epidemiological data regarding AIH is that some studies include individuals diagnosed without histological confirmation and/ or scoring systems or subjects with other aetiologies of liver disease, such as MAFLD and viral hepatitis with the presence of autoantibodies.6

AIH can debut at any age; however, two peaks of incidence have been documented; specifically, between 10 and 30 years and 40 and 60 years of age.7 It afflicts all ethnicities and Black patients with AIH are reported to be more likely to have an earlier age of onset and liver failure with a greater risk of requiring liver transplantation despite experiencing a comparable response to steroids as non-Black individuals.8

The evidence currently available on the subject is meagre and many questions remain unanswered, which is why this research seeks to identify how often AIH coexists with rheumatological diseases in a fourth-level hospital in Bogota, Colombia. An observational, analytical, retrospective study was carried out by reviewing the medical records of patients with AIH over a 10-year period, in which a cohort of the population with AIH and concomitant autoimmune diseases was obtained. We conducted a sociodemographic characterisation of this population, as well as an analysis of their clinical variables and, more specifically, their immune-serological profile. As for the limitations of this study, of the 616 case histories reviewed, only 66 patients met the inclusion criteria for analysis, and the vast majority of them did not have a complete immune-serological profile.

A total of 616 patients were identified as presenting AIH with ICD-10 diagnosis K75.4 between 2013 and 2023. Out of these 616 cases, only 66 patients met the inclusion criteria for further analysis of the study data (Fig. 1).

Figure 1.

Flow chart of study screening.

Ninety-seven percent of the subjects were female and only two individuals were male. The mean age of the sample was 57 years, with a range of 29 to 82 years at the time of diagnosis of AIH (Table 2).

Cirrhosis was present in 84.8% of the patients examined at the time of diagnosis, with Child-Pugh classification A and B being the primary classification, accounting for 48% and 41%, respectively. In contrast, 8% of the patients presented Child-Pugh C (Table 3). Among the paraclinical parameters, transaminases were observed with mean values of 165 UI/l and 150 UI/l for AST and ALT, respectively, and mean alkaline phosphatase was 312 UI/l, and [mean] GGT was found to be 343 UI/l. The paraclinical indicators of liver function included an albumin of 3.4 mg/dl; prothrombin time was not indicative of INR prolongation, platelet counts were within normal ranges, and direct bilirubin of 2.1 and indirect bilirubin averaged 1.3 (Table 4).

Insofar as the variables considered as part of the simplified diagnostic criteria for AIH are concerned, 63% of the patients analysed had the typical histopathological findings of AIH, while the remaining 36% presented findings that were consistent with AIH (Table 5). As for the immunoserological profile, 89.4% of the subjects tested positive for antinuclear antibodies; 59.1% were found to have anti-smooth muscle antibodies, and 98.1% displayed hypergammaglobulinaemia. Moreover, 42% of cases had no paraclinical tests for liver and kidney microsomal 1 antibodies available, with only 3% presenting these antibodies, and 39.4% of patients with anti-mitochondrial antibodies (Table 5). Finally, 43.9% of the sample displayed overlap syndrome with primary biliary cirrhosis.

Of the 66 individuals studied, 36.4% had an associated extrahepatic autoimmune disease, with Sjögren’s syndrome being the most prevalent, followed by autoimmune thyroid disease and systemic lupus erythematosus (Table 6). The autoimmune profile of the antibodies that were evaluated was positive for anti-DNA, anti-Ro, anti-La, rheumatoid factor, P-ANCA, MPO, and anti-SCL-70; anti-DNA and anti-Ro were the most prevalent (Table 7).

Statistical analyses were carried out to investigate possible associations between histopathological findings and the extrahepatic autoimmune profile; no such associations were detected (Table 7). Similarly, no associations were found between histopathological findings and extrahepatic autoimmune diseases (Table 8). We also found no association between the different types of autoimmune disease and the presence of cirrhosis (Table 9).

A total of 616 patient records with an ICD-10 K75.4 diagnosis of AIH were identified within the 10 year period studied. Of them, though, 62% could not be analysed for the reasons detailed in Fig. 1. It is worth noting that 109 of these records had no liver histology results available, despite the fact that they had a diagnosis of AIH. This suggests that in clinical practice the diagnostic score is not applied to define the presence of this disorder. There were 95 patient records of individuals who were coded with the ICD-10 diagnosis of AIH but who, following extension studies, were found to actually have another condition. In addition, 58 clinical records were located that, following a comprehensive review and after ICD-10 diagnosis, were incompatible in terms of clinical, paraclinical, and histological parameters, and therefore failed to fulfil the criteria for the AIH score; nevertheless, these patients were classified as having AIH, and were therefore not taken into account in the final analysis. This may reveal that while the study was performed with individuals who were evaluated in a referral centre for liver transplantation in Colombia, diagnosing this condition poses a challenge for the specialist.

A higher prevalence of the disorder was detected in women, as well as an average age of 57 years, which is in line with prevalence rates reported around the world.2,4 Five individuals were found who were 75 years old or more, which points to the fact that this diagnosis should not be ruled out at these extremes of age when clinical and paraclinical findings are suggestive of the disease.

Of the cohort that underwent analysis, 84.8% had cirrhosis at diagnosis; 48% exhibited compensated cirrhosis (Child A), and 49% were decompensated (Child B and C). This result contrasts markedly with the observations made by Díaz-Ramírez et al. in their study9 in which only 17% presented cirrhosis at diagnosis and none were Child C. We believe this difference may be due to the facility where the study was carried out inasmuch as it is a referral centre for hepatology, it may receive people whose condition is more advanced than at other institutions.

As regards the histopathological findings, which in this study were classified as typical and consistent on the basis of the simplified AIH score, very similar data were recorded in terms of distribution as those in the work carried out in Cali by Díaz-Ramírez et al.9 This indicates that the histopathological behaviour of the disease is identical in both cohorts under study and may conceivably be extrapolated to the rest of the country.

Based on the results of the autoimmune profile aimed at the diagnosis of AIH using a simplified score, by and large, the diagnosis was made according to ANA positivity, anti-SMA, and hypergammaglobulinaemia. It is important to highlight the scant use of anti-LKM1 in clinical practice, which may be indicative of an underreporting of type 2 AIH in our population.

A 43.9% prevalence rate of overlap with PBC was detected in our cases; although, this diagnosis was not confirmed when the Paris criteria were considered. In comparison to international works, this could potentially reflect overdiagnosis, given that the prevalence rates reported in the literature ranged from 2 to 19%.10

With respect to concomitant autoimmune disease, 24 of our 66 subjects evidenced some autoimmune disease, primarily Sjögren’s syndrome (25%), systemic lupus erythematosus (20.8%), and autoimmune thyroid disease (20.8%). Only a single case of Sjögren’s syndrome with systemic lupus erythematosus is reported in a patient with AIH. These findings are in line with other studies in Latin America, such as the one by Paredes Millán et al.11 in Lima, Peru, as well as the one performed by Díaz-Ramírez et al.9 in Cali, Colombia.9

If we look at the extrahepatic autoimmune serological profile, we find that the vast majority of these individuals do not have this type of study available to them, which indicates that they were requested when a particular condition was suspected, not as a screening tool for any other autoimmune disease. While a higher prevalence of anti-DNA and anti-Ro positivity is evidenced, the statistical analysis for associations with histopathological findings found no correlation between these variables, which would imply that the current practice of requesting these studies when rheumatological disease is suspected should be maintained. Likewise, we sought out associations between the type of extrahepatic autoimmune disease and histopathological findings; this yielded a p-value of 0.307, indicating no statistically significant association. This implies that histopathological findings do not depend on whether there is a greater or lesser burden of systemic autoimmunity. In the same way, no relationship was apparent between the type of autoimmune disease and the presence of cirrhosis at the time of AIH diagnosis. It is unclear whether concomitant autoimmune disease results in worse outcomes for AIH in terms of progression to fibrosis and complications from portal hypertension. Nonetheless, having rheumatological comorbidity increases morbidity and diminishes the patient's quality of life.3 In this study, we did not examine whether concomitance increased the risk of progression to cirrhosis and its complications or if it entailed any prognostic implications. Further studies will be needed to answer these questions.

Methodologically speaking, given the nature of the study conducted and for one reason or another, some people who have a diagnosis of AIH were not coded with the ICD-10 code K75.4 during the study period and were therefore excluded from consideration. Moreover, the simplified score was chosen as the diagnostic criterion for AIH, which, though it has greater specificity and accuracy than the revised IAIHG score, the latter is more sensitive for cases with unusual or more complex presentations, which may have resulted in patients being excluded who would, in fact, have met the diagnostic criteria as per the revised score.6,12 Furthermore, there is a percentage of patients who may be seronegative for AIH depending on how they present (<7% who debut in acute forms and between 1% and 34% in chronic forms12) and who, because of our inclusion criteria, were not included in the study. Another limitation derives from information bias, in view of the retrospective nature of the study and the review of medical records, i.e., 103 individuals with missing data that might have represented a larger sample to be analysed in the study were excluded because of the meticulous review of the medical records.

It is still worth noting the previously mentioned overlap syndrome with PBC, in which the Paris criteria to confirm the diagnosis of overlap syndrome were not verified, which may point to possible overdiagnosis compared to reports in the literature.

It should also be mentioned that despite the fact that this is a single-centre study, it is a referral centre for liver disease in Colombia, and the results previously mentioned are very much in line with what has been found in the literature, which lends some measure of external validity to the study.

One of the strengths of the study is that, to the best of our knowledge, this is only the second study in Colombia to characterise patients with AIH, which is important because it contributes to what is known about this condition in our region. Furthermore, this is the first time that the extrahepatic autoimmune profile of these people has been described in Colombia. More specifically, this is the first study in the literature to explore the association between histopathological findings and the presence of cirrhosis at diagnosis in individuals who present AIH and concomitant extrahepatic autoimmune diseases.

In summary, the frequency with which AIH coexists with rheumatological diseases in adult patients is 36.4% for the cohort studied, which is in the range of previously reported global prevalence rates of 14-44%.13 Of the sociodemographic characteristics studied, the predominant sex and average age at presentation are similar to reports in the literature from around the world. Nevertheless, unlike other cohorts, a higher prevalence of cirrhosis was detected at the time of presentation, in more advanced stages of decompensation, which is probably related to the fact that our work was performed in a referral centre for hepatology. On the other hand, in spite of not finding any connection between the type of extrahepatic autoimmune diseases and the immunoserological profile with the presence of cirrhosis or histopathological findings, this is the first time this type of association has been examined, which therefore provides novel information and confirms that an immunoserological study should not be routinely performed in all cases of AIH unless a particular rheumatological entity is suspected. We encourage further efforts to search for other possible associations that may have an impact on the prognosis and survival of patients with AIH.