Method for predicting risk of recurrence of autoimmune hepatitis after discontinuation of immunosuppressive therapy

Abstract

FIELD: clinical gastroenterology.SUBSTANCE: intended to predict the risk of relapse of autoimmune hepatitis after discontinuation of immunosuppressive therapy. The patient undergoes a clinical and biochemical examination and the relapse risk probability index is determined using the formula: PI RR = –0.394×(IGA≥ 9) + 1.252×(AT) + 0.915×(a-SLA / LP) + 0.555×(a-LKM1) – 0.692×(IgG norm) + 0.316×(obesity), where PI RR is the prognostic index of recurrence risk; HAI is the histological activity index of more than 9 according to Knodell (binary indicator: HAI ≥ 9 corresponds to the multiplier “1”; HAI < 9 corresponds to the multiplier “0”); AB – the presence of autoantibodies (binary indicator: detection of at least 1 corresponds to the multiplier “1”; absence of autoantibodies corresponds to the multiplier “0”); a-SLA / LP – antibodies to soluble liver / kidney antigen (binary indicator: presence – corresponds to the multiplier “1”; absence – corresponds to the multiplier “0”); a-LKM1 – antibodies to liver and pancreas microsomes (binary indicator: presence corresponds to the multiplier “1”; absence corresponds to the multiplier “0”); IgG – immunoglobulin G (binary indicator: normal Ig G level corresponds to the multiplier “1”; elevated IgG level corresponds to the multiplier “0”); obesity (BMI ≥ 30) – (binary indicator: presence of BMI ≥ 30 corresponds to a multiplier of “1”; BMI < 30 corresponds to the multiplier “0”). With the value of PI RR < 0.93 – low probability of relapse, PI RR > 0.93 – high probability of relapse.EFFECT: increased accuracy in predicting the risk of recurrence of autoimmune hepatitis after discontinuation of immunosuppressive therapy.1 cl, 2 ex

Description

[0001] The invention relates to the field of medicine, namely to clinical gastroenterology, and is intended to predict the risk of relapse of autoimmune hepatitis after discontinuation of immunosuppressive therapy for autoimmune hepatitis.

[0002] A method for determining the risk of relapse (RR) of autoimmune hepatitis (AH) is known by regularly performing a biochemical blood test with measurement of ALT, AST, and immunoglobulin G levels throughout life after the cessation of immunosuppression. This method is accepted as an analogue. Although this method records the fact of relapse, it does not have prognostic value. Its key limitation is the inability to assess the personal risk of AIH relapse before discontinuing immunosuppressive therapy (IST): when deciding on the advisability of discontinuing therapy after achieving a 2-year remission, the physician does not have a tool for assessing the likelihood of an unfavorable outcome, which makes this process purely empirical and increases the risks for the patient [1 - Heneghan, M.A. Update in clinical science: Autoimmune hepatitis / MA Heneghan, AW Lohse / / Journal of Hepatology. - 2025. - Vol. 82. - №5. - P. 926-937].

[0003] Another method, accepted as an alternative, for determining the presence of AIH recurrence is morphological examination of a liver biopsy. This method is used to verify AIH recurrence in cases where increased aminotransferase levels are observed after discontinuation of immunosuppressive therapy, necessitating differential diagnosis between a true relapse of autoimmune hepatitis and other causes of liver damage. However, this method has several fundamental limitations. Firstly, a liver biopsy is an invasive surgical procedure associated with the risk of complications (bleeding, damage to adjacent organs, etc.), which limits its widespread and routine use. Secondly, and this is a key drawback, morphological examination only allows for confirmation of a relapse and has no predictive power.Since biopsy sampling for histological analysis is performed after discontinuation of therapy and against the background of an increase in biochemical markers, this method cannot be used before IST is discontinued as a tool for assessing the individual risk of relapse and, therefore, for making an informed decision on the safety of stopping or the need to prolong treatment [2 - Lohse, AW Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology / AW Lohse, M. Sebode, PS Bhathal [et al.] / / Liver International: Official Journal of the International Association for the Study of the Liver. - 2022. - Vol. 42. - No. 5. - P. 1058-1069].

[0004] The prototype is a well-known method based on a comprehensive qualitative assessment of clinical, anamnestic, and laboratory data. This approach assumes that the prognosis for RR is formed based on an analysis of factors such as the patient's gender and age, the presence of comorbidities, medical history data (including possible disease triggers), the stage of liver fibrosis before therapy discontinuation, and the dynamics of biochemical parameters during treatment. Predictors of a low risk of relapse traditionally include the presence of an identifiable trigger at the onset of the disease (e.g., drug-induced or viral), rapid achievement and stable maintenance of biochemical remission, and the absence of cirrhotic transformation of the liver at the time of diagnosis.The disadvantages of this method are: the subjective nature of the assessment (the lack of formalized algorithmic data processing leads to the result being dependent on the experience and individual interpretation of the attending physician); the lack of a quantitative assessment of PP, which reduces the accuracy of the method; the lack of validation - this method has not undergone a rigorous statistical validation procedure on independent cohorts of patients, and therefore its prognostic accuracy and reproducibility have not been established [3 - Harrison, L. Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)? / L. Harrison, D. Gleeson / / Liver International: Official Journal of the International Association for the Study of the Liver. - 2019. - Vol. 39. - No. 4. - P. 610-620].

[0005] Thus, the known prototype method does not solve the problem of predicting the risk of AIH recurrence after discontinuation of immunosuppressive therapy and cannot be used as a reliable tool in making a clinical decision to discontinue or continue treatment.

[0006] The aim of the invention is to improve the accuracy of predicting the risk of relapse of autoimmune hepatitis after discontinuation of immunosuppressive therapy.

[0007] The technical result is achieved by the fact that the prognostic index of the probability of the risk of relapse is determined by the formula:

[0008] PI RR = - 0.394 x (IGA ≥ 9) + 1.252 x (AT) + 0.915 (a-SLA / LP) + 0.555 x (a-LKM1) - 0.692 x (IgG norm) + 0.316 x (obesity), where

[0009] PI RR - prognostic index of relapse risk;

[0010] HIA - histological activity index greater than 9 according to Knodell (binary indicator: HAI ≥ 9 corresponds to the multiplier “1”; HAI < 9 corresponds to the multiplier “0”);

[0011] AT - presence of autoantibodies (binary indicator: detection of at least 1 corresponds to the multiplier “1”; absence of autoantibodies corresponds to the multiplier “0”);

[0012] a-SLA / LP - antibodies to soluble liver / kidney antigen (binary indicator: presence - corresponds to the multiplier "1"; absence - corresponds to the multiplier "0");

[0013] a-LKM1 - antibodies to liver and pancreas microsomes (binary indicator: presence corresponds to the multiplier "1"; absence corresponds to the multiplier "0");

[0014] IgG - immunoglobulin G (binary indicator: normal Ig G level corresponds to the multiplier “1”; elevated IgG level corresponds to the multiplier “0”);

[0015] Obesity (BMI ≥ 30) - (binary indicator: having a BMI ≥ 30 corresponds to a multiplier of “1”; BMI < 30 corresponds to a multiplier of “0”),

[0016] and with a value of PI RR < 0.93 - low probability of relapse, PI RR > 0.93 - high probability of relapse.

[0017] The relevance of this method is due to the significant medical and social burden of chronic liver diseases, which remain the leading causes of global mortality, resulting in approximately two million deaths annually [5 - Younossi, ZM The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis / ZM Younossi, P. Golabi, L. de Avila [et al.] / / Journal of Hepatology. - 2019. - Vol. 71. - No. 4. - P. 793-801].

[0018] Among the variety of liver diseases, AIH occupies a special position as a disease of unknown etiology, developing in individuals with a genetic predisposition and characterized by progressive immune-inflammatory damage to hepatocytes [6 - Sandler, Yu.G. Diagnosis and treatment of patients with autoimmune hepatitis (expert agreement) / Yu.G. Sandler, E.V. Vinnitskaya, K.L. Raikhelson et al. / / Russian Journal of Gastroenterology, Hepatology, Proctology. - 2024. - No. 34 (6). - P. 100-119].

[0019] Global epidemiological data over the past two decades indicate a twofold increase in the incidence of autoimmune pathologies. The results of a large-scale systematic review confirm an increase in the incidence and prevalence of AIH by 3.1 and 2.8 times, respectively, which is accompanied by a significant deterioration in the quality of life of patients, an increase in the level of disability and creates a significant economic burden on healthcare systems [7 - Hahn, JW Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and metaanalysis / JW Hahn, HR Yang, JS Moon [et al.] / / EClinicalMedicine. - 2023. - Vol. 65. - P. 102280].

[0020] The lack of reliable data on the prevalence of AIH in the Russian Federation is due to the limited volume of epidemiological studies. According to published data, the approximate number of patients with AIH in Russia is estimated at between 5,000 and 30,000. At the same time, experts admit a significant underestimation of the actual figures due to the frequent asymptomatic course of the initial stages of the disease and underdiagnosis [8 - Odintsova, A.Kh. Regional clinical and epidemiological features of autoimmune liver diseases / A.Kh. Odintsova, D.I. Abdulganieva, N.A. Cheremina, A.V. Ibragimova / / Practical Medicine. - 2011. - No. 55. - R. 214-215].

[0021] In the absence of therapeutic intervention, autoimmune hepatitis initiates progressive fibrogenesis - pathological remodeling of the liver parenchyma with replacement of functional tissue with connective tissue elements. Disease progression is associated with a deterioration in the quality of life of patients, the development of clinical complications, increased mortality, and an increased risk of hepatocellular carcinoma [9 - Shiffman, ML Autoimmune Hepatitis: Epidemiology, Subtypes, and Presentation / ML Shiffman / / Clinics in Liver Disease. - 2024. - Vol. 28. - No. 1. - P. 1-14].

[0022] The therapeutic strategy for managing patients with AIH is based on the principles of long-term immunosuppression. Glucocorticoid drugs have been the first-line drugs for induction therapy for more than five decades, their clinical efficacy is confirmed by the results of randomized trials and systematic reviews [10 - Dalekos, G. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis / G. Dalekos, N. Gatselis, JP Drenth [et al.] / / Journal of Hepatology. - 2025. - Vol. 83. - №2. - P. 453-501].

[0023] Currently, the timing and criteria for discontinuing immunosuppressive therapy (IST) for autoimmune hepatitis remain unclear. General practice is to consider discontinuing therapy after 2-3 years of sustained biochemical remission, as long-term, especially lifelong, immunosuppression is associated with significant risks for patients, including the development of osteoporosis, metabolic disorders, increased incidence of cancer, and other adverse events.

[0024] After discontinuation of IST, a relapse may develop in some patients - this is the resumption of the immune-inflammatory activity of AIH after achieving clinical, laboratory and histological remission [11 - Pape, S. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group / S. Pape, RJALM Snijders, TJG Gevers [et al.] / / Journal of Hepatology. - 2022. - Vol. 76. - No. 4. - P. 841-849]. The incidence of relapses of autoimmune hepatitis after discontinuation of immunosuppressive therapy, according to large studies, shows a significant range of indicators - from 25% to 100% [47; 170].

[0025] The current diagnostic paradigm allows for the recognition of disease relapse only after its onset, which in clinical practice leads to unjustified discontinuation of therapy in patients with an initially high risk of relapse.

[0026] Relapse is the resumption of the immune-inflammatory activity of autoimmune hepatitis (AIH) after achieving clinical, laboratory and histological remission, confirmed by reducing the dose or completely discontinuing immunosuppressive therapy (IST).

[0027] Relapse in this category of patients requires repeated administration of immunosuppressive therapy at induction doses, which is associated with an increased risk of adverse events, worsens the course of the underlying disease, and promotes the progression of liver fibrosis. Therefore, assessing the individual risk of relapse in each individual patient is of great clinical importance, to avoid unnecessary discontinuation of IST in high-risk groups.

[0028] A critical limitation of current clinical practice is the lack of validated tools for the early identification of patients at high risk of relapse, which would allow individualizing the decision to continue maintenance therapy in this category of patients [12 - Pape, S. Clinical management of autoimmune hepatitis / S. Pape, C. Schramm, TJ Gevers / / United European Gastroenterology Journal. - 2019. - Vol. 7. - No. 9. - P. 1156-1163].

[0029] For patients with AIH, the implementation of a personalized approach allows for optimizing treatment efficacy and reducing the incidence of adverse events. A key aspect of this approach is determining the optimal duration of therapy, including justifying the need for lifelong maintenance IST in patients at high risk of relapse, based on predicting the individual likelihood of disease relapse. Addressing this clinical challenge forms the basis of the proposed invention.

[0030] The method is as follows.

[0031] The patient undergoes a comprehensive examination, standard for autoimmune hepatitis: clinical and anamnestic data are collected, laboratory examination and a liver puncture biopsy with morphological examination of the biopsy material and assessment using the Knodell and METAVIR scales are performed.

[0032] The following prognostic parameters are determined: the initial level of immunoglobulin G, the presence of autoantibodies characteristic of AIH in the peripheral blood, an assessment of the histological activity index according to Knodell; the presence or absence of obesity is recorded.

[0033] Then the prognostic index of the probability of relapse (PI RR) is determined by the formula:

[0034] PI RR = - 0.394 x (IGA ≥ 9) + 1.252 x (AT) + 0.915 (a-SLA / LP) + 0.555 x (a-LKM1) - 0.692 x (IgG norm) + 0.316 x (obesity), where

[0035] PI RR - prognostic index of relapse risk;

[0036] HIA - histological activity index greater than 9 according to Knodell (binary indicator: HAI ≥ 9 corresponds to the multiplier “1”; HAI < 9 corresponds to the multiplier “0”);

[0037] AT - presence of autoantibodies (binary indicator: detection of at least 1 corresponds to the multiplier “1”; absence of autoantibodies corresponds to the multiplier “0”);

[0038] a-SLA / LP - antibodies to soluble liver / kidney antigen (binary indicator: presence - corresponds to the multiplier "1"; absence - corresponds to the multiplier "0");

[0039] a-LKM1 - antibodies to liver and pancreas microsomes (binary indicator: presence corresponds to the multiplier "1"; absence corresponds to the multiplier "0");

[0040] IgG - immunoglobulin G (binary indicator: normal Ig G level corresponds to the multiplier “1”; elevated IgG level corresponds to the multiplier “0”);

[0041] Obesity (BMI ≥ 30) - (binary indicator: having a BMI ≥ 30 corresponds to a multiplier of "1"; BMI < 30 corresponds to a multiplier of "0"); and

[0042] if the PI RR value is < 0.93 - low probability of relapse;

[0043] if the PI RR value is > 0.93, there is a high probability of relapse.

[0044] Based on the results, a decision is made to discontinue or prolong immunosuppressive therapy: if the likelihood of AIH recurrence is low after 2 years of stable biochemical remission, IST can be discontinued; if the likelihood of recurrence is high, continuation of IST is recommended (in the absence of contraindications).

[0045] The proposed method can be used in patients who seek medical help from a gastroenterologist or hepatologist with an established diagnosis of AIH, receiving IST for at least 2 years with stable biochemical remission.

[0046] The method is confirmed by the following examples.

[0047] Example 1. Patient K., 38, consulted a hepatologist. Her complaints included severe general weakness, increased fatigue, heaviness in the right hypochondrium, and occasional nausea.

[0048] Patient's medical history: She considers herself ill for the past three years, when she first noticed the onset of unexplained weakness. During inpatient treatment, she underwent a comprehensive examination, including a liver biopsy with morphological examination of the biopsy specimen. The morphologist's conclusion was: "Histological examination reveals a moderate lymphoplasmacytic infiltrate in the portal tracts, with isolated stepwise necrosis, consistent with autoimmune hepatitis. Fibrosis stage is F1 according to the METAVIR scale. IHA according to Knodell is 10."

[0049] During examination:

[0050] Immunoglobulin G level - 12.1 g / l (normal 7.0-16.0 g / l).

[0051] Gamma globulins: 22% (normal up to 21%).

[0052] Autoantibodies: Antibodies to soluble liver antigen / liver and pancreas antigens (anti-SLA / LP) were detected at a titer of 1:320.

[0053] Based on examination, the patient was diagnosed with high-activity autoimmune hepatitis and was started on immunosuppressive therapy, which included prednisolone, followed by azathioprine after two weeks, and then gradually tapered to a maintenance dose. Biochemical remission was achieved and has been maintained for two years.

[0054] The patient is currently receiving prednisolone 5 mg + azathioprine 50 mg. She sought medical advice on further treatment.

[0055] Objective status: satisfactory. BMI 24. Skin and visible mucous membranes are normal in color. The liver does not protrude beyond the costal margin upon palpation. The spleen is not palpable. Other organs and systems are normal.

[0056] Results of laboratory and instrumental examination:

[0057] Clinical blood test:

[0058] Hemoglobin 14.8 (13.0-16.0) g / dL; Erythrocytes 4.85 (4.00-5.00)×10 6 / μl; Average corpuscular hemoglobin content 30.5 (27.0-31.0) pg; Average corpuscular volume 88.2 (80.0-100.0) fl; Average corpuscular hemoglobin concentration 34.6 (30.0-38.0) g / dl; Hematocrit 42.8 (40.0-48.0)%; Platelets 245 (180-320)×10 3 / μl; Average platelet volume 9.20 (7.40-12.00) fl; Leukocytes 7.35 (4.00-9.00)×10 9 / l; Neutrophils 65.40 (48.00-78.00)%; Eosinophils 1.8 (0.5-5.0)%; Monocytes 8.2 (3.0-11.0)%; Lymphocytes 24.10 (19.00-37.00)%; Basophils 0.5 (0.0-1.0)%; Neutrophils abs. 4.81 (2.00-7.50)×10 9 / l; Eosinophils abs. 0.13 (0.02-0.30)×10 9 / l; Monocytes abs. 0.60 (0.09-0.60)×10 9 / l; Lymphocytes abs. 1.77 (1.20-3.00)×10 9 / l; Basophils abs. 0.04 (0.00-0.07)×10 9 / l; Erythrocyte sedimentation rate according to Westergren 18 (0-30) mm / h;

[0059] Biochemical blood test:

[0060] Total protein 72.4 (64.0-83.0) g / L; Albumin 42.8 (34.0-48.0) g / L; ALT 28.3 (10.0-40.0) U / L; AST 26.7 (15.0-40.0) U / L; Total bilirubin 12.8 (5.0-21.0) μmol / L; Direct bilirubin 2.2 (0.0-3.4) μmol / L; Indirect bilirubin 10.4 (0.0-15.9) μmol / L; Glucose 5.15 (4.10-5.90) ​​mmol / L; Creatinine 84 (80-115) μmol / L; Iron 19.6 (11.6-31.3) μmol / L; Total cholesterol 4.65 (0.00-5.18) mmol / L; Alpha-amylase 78 (28-100) U / L; Gamma-Glutamyltransferase 32 (0-55) U / L; Alkaline phosphatase 94.8 (30.0-120.0) U / L; Ferritin 68.5 (10.0-120.0) μg / L;

[0061] Immunoglobulin G level - 6.8 g / l (normal 7.0-16.0 g / l).

[0062] Gamma globulins: 16% (normal value up to 21%).

[0063] Autoantibodies: Antibodies to soluble liver antigen / liver and pancreas antigens (anti-SLA / LP) were detected at a titer of 1:160.

[0064] Abdominal ultrasound: diffuse heterogeneity of the liver parenchyma, without focal lesions. The spleen is normal in size.

[0065] Liver fibroelastometry: The liver stiffness index corresponds to the fibrosis stage F=1 according to the METAVIR scale.

[0066] Esophagogastroduodenoscopy (EGDS): no pathological changes.

[0067] Diagnosis:

[0068] Autoimmune hepatitis (stage F1 fibrosis according to the METAVIR scale based on liver morphological examination, in the process of IST (prednisolone + azathioprine) since 2022).

[0069] Based on the examination results, the patient was in biochemical remission for more than 2 years, which required consideration of the issue of discontinuing IST.

[0070] When calculating the PI RR according to the claimed method, the parameters for patient K. will be as follows: IGA more than 9 points (1), AT - at least 1 detected (1), a-SLA detected (1), LKM1 not detected (0), IgG - normal level initially (1), no obesity (0).

[0071] PI RR = -0.394 x 1 + 1.252 x 1 + 0.915 x 1 + 0.555 x 0 - 0.692 x 1 + 0.316 x 0 = 1.081, which is greater than 0.93, therefore, corresponds to a high probability of AIH relapse upon discontinuation of IST. In this regard, the patient continued maintenance IST therapy.

[0072] Example 2. Patient H., 52 years old, was hospitalized in the hepatology department.

[0073] Complaints upon admission: severe general weakness, a feeling of discomfort and heaviness in the right hypochondrium.

[0074] Patient History: Patient considers himself ill for approximately 4.5 years, when he first noticed unexplained fatigue. At 3.5 years of age, he first sought medical attention from a gastroenterologist and was referred for inpatient treatment to the hepatology department. A comprehensive examination was performed, the results are presented below. A liver biopsy with morphological examination of the biopsy specimen was performed. The morphologist's conclusion was: "Histological examination reveals a picture of moderate lymphoplasmacytic infiltrate in the portal tracts, stepwise necrosis, which may be consistent with autoimmune hepatitis. Fibrosis stage is F2 according to the METAVIR scale. IHA according to Knodell is 11."

[0075] During examination:

[0076] Immunoglobulin G level - 22.1 g / l (normal 7.0-16.0 g / l).

[0077] Gamma globulins: 27% (normal up to 21%).

[0078] Autoantibodies: not detected.

[0079] Based on examination, the patient was diagnosed with high-activity autoimmune hepatitis and was started on immunosuppressive therapy, which included prednisolone, followed by azathioprine after 2 weeks, and then gradually tapered to maintenance doses. Biochemical remission was achieved and has been maintained for 3 years.

[0080] The patient is currently receiving prednisolone 5 mg + azathioprine 50 mg. The patient sought advice on the possibility of discontinuing IST.

[0081] Objective status: satisfactory. BMI 34.2. Skin and visible mucous membranes are normal in color. The liver protrudes 3 cm from the costal margin upon palpation. The spleen is not palpable. Other organs and systems are normal.

[0082] Results of laboratory and instrumental examination:

[0083] Clinical blood test:

[0084] Hemoglobin 14.2 (13.0-16.0) g / dL; Erythrocytes 4.72 (4.00-5.00)×10 6 / μl; Average corpuscular hemoglobin content 29.8 (27.0-31.0) pg; Average corpuscular volume 87.4 (80.0-100.0) fl; Average corpuscular hemoglobin concentration 34.2 (30.0-38.0) g / dl; Hematocrit 41.5 (40.0-48.0)%; Platelets 251 (180-320)×10 3 μl; Average platelet volume 9.6 (7.40-12.00) fl; Leukocytes 6.9 (4.00-9.00)×10 9 / l; Neutrophils 59.2 (48.00-78.00)%; Eosinophils 2.3 (0.5-5.0)%; Monocytes 7.8 (3.0-11.0)%; Lymphocytes 28.4 (19.00-37.00)%; Basophils 0.3 (0.0-1.0)%; Neutrophils abs. 4.08 (2.00-7.50)×10 9 l; Eosinophils abs. 0.16 (0.02-0.30)×10 9 l; Monocytes abs. 0.54 (0.09-0.60)×10 9 l; Lymphocytes abs. 1.96 (1.20-3.00)×10 9 l; Basophils abs. 0.02 (0.00-0.07)×10 9 l; Erythrocyte sedimentation rate according to Westergren 11 (0-30) mm / h.

[0085] Blood chemistry test:

[0086] Total protein 73.5 (64.0-83.0) g / L; Albumin 42.1 (34.0-48.0) g / L; ALT 32.8 (10.0-40.0) U / L; AST 29.3 (15.0-40.0) U / L; Total bilirubin 14.8 (5.0-21.0) μmol / L; Direct bilirubin 2.6 (0.0-3.4) μmol / L; Indirect bilirubin 12.2 (0.0-15.9) μmol / L; Glucose 5.2 (4.10-5.90) ​​mmol / L; Creatinine 87 (80-115) μmol / L; Iron 23.7 (11.6-31.3) μmol / L; Total cholesterol 4.85 (0.00-5.18) mmol / L; Alpha-amylase 76 (28-100) U / L; Gamma-Glutamyltransferase 41 (0-55) U / L; Alkaline phosphatase 98.6 (30.0-120.0) U / L; Ferritin 89.4 (10.0-120.0) μg / L.

[0087] Immunoglobulin G level - 9.1 g / l (normal 7.0-16.0 g / l).

[0088] Gamma globulins: 11% (normal value up to 21%).

[0089] Autoantibodies: not detected.

[0090] Abdominal ultrasound: moderate hepatomegaly, diffuse heterogeneity of the liver parenchyma. The spleen is not enlarged.

[0091] Liver fibroelastometry: the liver stiffness index corresponds to the fibrosis stage F=2 according to the METAVIR scale.

[0092] Esophagogastroduodenoscopy (EGDS): signs of chronic hepatitis.

[0093] Diagnosis:

[0094] Autoimmune hepatitis, stable biochemical remission (fibrosis stage F2 on the METAVIR scale according to morphological examination of the liver, in the process of IST (prednisolone + azathioprine) since 2022).

[0095] Based on the examination results, the patient was in biochemical remission for more than 2 years, which required consideration of discontinuing IST.

[0096] When calculating the PI RR according to the claimed method, the parameters for patient H. will be as follows: IGA more than 9 points (1), AT - not detected (0), a-SLA not detected (0), LKM1 not detected (0), IgG - normal level initially - no, the level was elevated (0), obesity is present (1).

[0097] PI RR = -0.394 x 1 + 1.252 x 0 + 0.915 x 0 + 0.555 x 0 - 0.692 x 0 + 0.316 x 1 = 0.0078, which is less than 0.93, and therefore corresponds to a low probability of AIH relapse when IST is discontinued. In this regard, the patient's IST was gradually discontinued; after 24 months of observation, biochemical remission was maintained.

[0098] The invention provides a significant clinical effect by preventing premature discontinuation of immunosuppressive therapy in patients with a high predicted risk of relapse of autoimmune hepatitis. This avoids the negative clinical consequences associated with disease recurrence, in particular the need for repeated high induction doses of immunosuppressants and the development of adverse drug reactions associated with such therapy.

[0099] Sources of information

[0100] 1. Heneghan, М.А. Update in clinical science: Autoimmune hepatitis / M.A. Heneghan, A.W. Lohse / / Journal of Hepatology. - 2025. - Vol. 82. - №5. - P. 926-937.

[0101] 2. Lohse, A.W. Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology / A.W. Lohse, M. Sebode, P.S. Bhathal [et al.] / / Liver International: Official Journal of the International Association for the Study of the Liver. - 2022. - Vol. 42. - №5. - P. 1058-1069].

[0102] 3. Harrison, L. Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)? / L. Harrison, D. Gleeson / / Liver International: Official Journal of the International Association for the Study of the Liver. - 2019. - Vol. 39. - №4. - P. 610-620].

[0103] 4. Wang, L. Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases / L. Wang, Y. - F. Hu, A. - Y. Yang [et al.] / / Scandinavian Journal of Gastroenterology. - 2024. - Vol. 59. - №1. - P. 62-69].

[0104] 5. Younossi, Z.M. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis / Z.M. Younossi, P. Golabi, L. de Avila [et al.] / / Journal of Hepatology. - 2019. - Vol. 71. - №4. - P. 793-801].

[0105] 6. Sandler, Yu.G. Diagnostics and treatment of patients with autoimmune hepatitis (expert agreement) / Yu.G. Sandler, E.V. Vinnitskaya, K.L. Raikhelson, et al. / / Russian journal of gastroenterology, hepatology, proctology. - 2024. - No. 34 (6). - P. 100-119].

[0106] 7. Hahn, JW Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis / JW Hahn, HR Yang, JS Moon [et al.] / / EClinicalMedicine. - 2023. - Vol. 65. - P. 102280].

[0107] 8. Odintsova, A.Kh. Regional clinical and epidemiological features of autoimmune liver diseases / A.Kh. Odintsova, D.I. Abdulganieva, N.A. Cheremina, A.V. Ibragimova / / Practical medicine. - 2011. - No. 55. - R. 214-215].

[0108] 9. Shiffman, ML Autoimmune Hepatitis: Epidemiology, Subtypes, and Presentation / ML Shiffman / / Clinics in Liver Disease. - 2024. - Vol. 28. - No. 1. - P. 1-14].

[0109] 10. Dalekos, G. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis / G. Dalekos, N. Gatselis, J.P. Drenth [et al.] / / Journal of Hepatology. - 2025. - Vol. 83. - №2. - P. 453-501].

[0110] 11. Pape, S. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group / S. Pape, R.J.A.L.M. Snijders, T.J.G. Gevers [et al.] / / Journal of Hepatology. - 2022. - Vol. 76. - №4. - P. 841-849].

[0111] 12. Pape, S. Clinical management of autoimmune hepatitis / S. Pape, C. Schramm, T.J. Gevers.

Claims

A method for predicting the risk of relapse of autoimmune hepatitis after discontinuation of immunosuppressive therapy, including a clinical and biochemical study, characterized in that the prognostic index of the probability of relapse risk is determined by the formula: PI RR = - 0.394 × (IGA ≥ 9) + 1.252 × (AT) + 0.915 × (a-SLA / LP) + 0.555 × (a-LKM1) - 0.692 × (IgG norm) + 0.316 × (obesity), where PI RR - prognostic index of relapse risk; IHA - histological activity index greater than 9 according to Knodell (binary indicator: IHA ≥ 9 corresponds to the multiplier “1”; IHA < 9 corresponds to the multiplier “0”); AT - presence of autoantibodies (binary indicator: detection of at least 1 corresponds to the multiplier “1”; absence of autoantibodies corresponds to the multiplier “0”); a-SLA / LP - antibodies to soluble liver / kidney antigen (binary indicator: presence - corresponds to the multiplier "1"; absence - corresponds to the multiplier "0"); a-LKM1 - antibodies to liver and pancreas microsomes (binary indicator: presence corresponds to the multiplier "1"; absence corresponds to the multiplier "0"); IgG - immunoglobulin G (binary indicator: normal IgG level corresponds to the multiplier “1”; elevated IgG level corresponds to the multiplier “0”); obesity (BMI ≥ 30) - (binary indicator: having a BMI ≥ 30 corresponds to the multiplier “1”; BMI < 30 corresponds to the multiplier “0”), and with a value of PI RR < 0.93 - low probability of relapse, PI RR > 0.93 - high probability of relapse.