Introduction

Autoimmune hepatitis (AIH) and its variants are uncommon causes of chronic liver disease (CLD) in India [1]. Concomitant metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with autoimmune hepatitis (AIH) is a distinct entity [2]. We aimed to explore the frequency and impact of concomitant MASLD in patients with AIH [3].

Aims & Methods

This is a retrospective study conducted at Sanjay Gandhi Post Graduate Institute of Medical Sciences and King George Medical University, Lucknow, India. Data of patients with AIH who underwent treatment between 2013-2022 were collected from a prospectively filled-up electronic database. Standard criteria were used to diagnose AIH and MASLD [3][4]. Patients presenting with acute severe-AIH, acute-on-chronic-liver-failure, simple steatosis without any metabolic dysfunction, and hepatocellular carcinoma HCC) were excluded.Criteria to diagnose MASLD were applied to patients with AIH. Their demographic, clinical, biochemical, serological parameters, treatment response and long-term outcomes were measured and compared.

Results

Of 175 patients with AIH, 51 were excluded. A total of 122 patients [median age: 46 (34-54) years; 69.6% female] were included in the final analysis. The median follow-up period was 61 (50-76) months. Of the 122 patients, 38 (31%) had concomitant MASLD (AIH-MASLD). Patients withAIH-MASLD had higher baseline liver enzymes [aspertate aminotranferase 226 (121-278) vs 174 (113-225); p= 0.033, alanine aminotranferase: 115 (113-189) vs 97 (47-169); p=0.041]. A higher number of patients with AIH-MASLD presented with advanced fibrosis and decompensation (20.4% vs 10.7%; p=<0.001,30.3% vs 25%; p=0.030, respectively). Following immunosuppression, Patients with MASLD-AIH had attenuated remission rates compared to AIH alone (34.2% vs 77.4%; p=<0.001) [table: 1].

Table: 1
Outcome of patients with AIH and MASLD-AIH

Outcome	Overall	AIH	MASLD-AIH	p-value
Biochemical Remission at six months	82 (67.2%)	62 (74%)	20 (52.6%)	0.016
Non-response to steroid after two weeks	32 (26.2%)	12 (14.2%)	20 (52.6%)	0.001
Advanced fibrosis	25 (20.4%)	9 (10.7%)	16 (42.1%)	<0.001
Steatohepatitis	13 (10.6%)	5 (5.9%)	8 (21%)	0.012
Adverse events to steroid	44 (44.2%)	34 (47.6%)	21 (55.2%)	0.068
Presentation with Decompensation	37 (30.3%)	21 (25%)	16 (42.1%)	0.030
New Decompensation among patients with c-ACLD	26 (30.5%)	14 (16.7%)	12 (31.5%)	0.002
HCC	2 (1.6%)	0	2 (5.2%)	0.034
Mortality	25 (20.4%)	13 (15.4%)	12 (31.5%)	0.012

On multivariate analysis, liver biopsy suggestive of concomitant Metabolic dysfunction-associated steatohepatitis (MASH) [OR 5.25 (95% CI 2.27 - 12.16); p<0.001), concomitant MASLD [OR: 3.07 (95% CI1.02 - 9.24); p=0.045], advanced fibrosis [ OR: 2.69 (95% CI1.07 - 6.59); p=0.035], and presentation with decompensation [OR: 2.66 (95% CI:1.07 - 6.59); p=0.035] were associated with non-responsiveness to steroid.

Conclusion

About a third of patients with biopsy-proven AIH have concomitant MASLD. A significant number of patients with AIH-MASLD present with higher liver enzymes, advanced fibrosis, and decompensation compared to AIH alone. Patients with AIH-MASLD respond poorly to steroids and have a lower remission rate. Proper work-up is necessary in patients with steroid non-responsive-AIH to rule out concomitant MASLD.

References

1. Choudhuri G, Somani SK, Baba CS, et al. Autoimmune hepatitis in India: profile of an uncommon disease. BMC Gastroenterol. 2005 Aug 15;5:27. doi: 10.1186/1471-230X-5-27. PMID: 16098234; PMCID: PMC1236920.
2. Zachou K, Azariadis K, Lytvyak E, et al; International Autoimmune Hepatitis Group (IAIHG). Treatment responses and outcomes in patients with autoimmune hepatitis and concomitant features of non-alcoholic fatty liver disease. JHEP Rep. 2023 Apr 22;5(8):100778. doi: 10.1016/j.jhepr.2023.100778. PMID: 37456672; PMCID: PMC10339258.
3. Wang G, Tanaka A, Zhao H, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatol Int. 2021 Apr;15(2):223-257. doi: 10.1007/s12072-021-10170-1. Epub 2021 May 4. PMID: 33942203; PMCID: PMC8144150.
4. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020 Jul;73(1):202-209. doi: 10.1016/j.jhep.2020.03.039. Epub 2020 Apr 8. PMID: 32278004.

Introduction

Immune checkpoint inhibitors (ICI) are widely used in the management of numerous solid tumors and act by enhancing T-cell–mediated anti-tumour responses. While this activation boosts the immune response against cancer cells, it may also result in immune-related side effects (irAEs). Gastrointestinal symptoms, mainly colitis and diarrhea, are among the most common irAEs.¹ We have recently (February 2025) opened a dedicated clinic, within our Gastroenterology outpatient service, to manage patients who experience gastrointestinal irAEs during ICI therapy for epithelial cancers.

Aims & Methods

Our aim was to evaluate characteristics and outcomes of patients referred to our dedicated clinic for the management of gastrointestinal irAEs associated with ICI therapy since its start (February 2025). All patients were clinically evaluated and were treated with standard-of-care therapy in accordance to European Guidelines². Patients were followed up for at least 8 weeks following initiation of therapy. We collected data on patient demographics (gender and age), patient’s overall health status as assessed by the Charlson Comorbidity Index (CCI)³, cancer type, oncological therapy, diarrhea severity (graded via CTCAE)⁴, time to onset of diarrhea following the initiation of oncological therapy, interruption of ICI, outcomes of colonscopy (if performed), treatment modality for ICI-related gastrointestinal toxicity, time to resolution of diarrhea (in weeks), and whether ICI therapy was subsequently resumed.

Results

We included 14 patients affected by ICI-related diarrhea or colitis (grade 1: n=2 , grade 2: n=9 , grade 3: n=2; grade 4: n=1). Four patients were affected by endometrial cancer, 3 patients melanoma, 3 lung cancer, 2 breast cancer, 1 ovarian cancer, 1 cervical cancer. Thirteen patients were treated with PD1/PDL1- inhibitors (Pembrolizumab: n=9 , Dostarlimab: n=2, Nivolumab: n=2) and one patient was treated with CTLA-4 (Ipilimumab: n=1). Ten patients interrupted immunotherapy due to ICI-related diarrhea after 17 weeks of therapy on average. As indicated by the European Guidelines², all patients with diarrhea grade G2 or higher (6 patients) underwent colonoscopy, which revealed signs consistent with ICI-induced colitis. After standard-of-care treatment,12 patients experienced diarrhea grade 1 or lower. Mean time to resolution of diarrhea was 4.2 weeks. Among the 10 patients who had to interrupt ICI due to gastrointestinal adverse events, 5 patients (50%) resumed ICI after a mean of 4 weeks. No patients experienced any adverse events related to the standard-of-care treatment as defined by CTCAE.⁴

Conclusion

Despite being preliminary, our experience shows that patients managed in a dedicated clinic for gastrointestinal irAEs associated with ICI therapy experience acceptable outcomes. Future studies, aimed at comparing whether this approach is more effective than a non-dedicated management, are warranted.

References

1. Chan KK, Bass AR. Autoimmune complications of immunotherapy: pathophysiology and management. BMJ. Published online April 6, 2020:m736. doi:10.1136/bmj.m736
2. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217-1238. doi:10.1016/j.annonc.2022.10.001
3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
4. Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr. 2021;112(1):90-92. doi:10.1016/j.ad.2019.05.009

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.