Introduction

Patients with ulcerative colitis (UC) are at an increased risk of cytomegalovirus (CMV) infection. CMV infection in acute severe ulcerative colitis (ASUC) may worsen disease severity and clinical outcomes. Current guidelines recommend colonic biopsies for the exclusion of CMV in all patients with ASUC. One study found that CMV positivity in ASUC was associated with greater need for rescue therapy, longer hospital length of stay (LOS) and higher readmission rates but found no difference in rate of colectomy.¹ We aimed to investigate the impact of positive CMV result on clinical outcomes in patients presenting with ASUC.

Aims & Methods

A retrospective review included all ASUC presentations to a quaternary hospital over a 10-year period based on modified Truelove and Witts’ criteria. ASUC presentations were grouped based on CMV positivity as determined by colonic biopsy. Data on pre-admission medications was collected. Data was collected on rates of rescue therapy, referral to colorectal surgery, colectomy, total parenteral nutrition (TPN). Outcomes assessed included intensive care unit (ICU) admission, 30- and 90-day readmission rates, 30- and 90-day mortality rates and mean LOS.

Results

A total of 172 ASUC presentations were identified. Of these, 133 had available colonic biopsy CMV results. 11 patients (8%) had positive CMV. Positive CMV result was significantly associated with increased need for TPN (36% vs 11%, p=0.02), ICU admission (27% vs 5%, p=0.004) and referral to colorectal surgery (82% vs 43%, p=0.01). Patients with CMV had longer LOS (27.1±14.0 vs 11.0±7.4, p=0.003). There were no significant differences in rates of rescue therapy, inpatient colectomy, readmission or mortality rates. 9 of the patients (82%) were treated with ganciclovir or valganciclovir. Patients on maintenance advanced UC therapies, including biologics and small molecule inhibitors, had significantly higher rate of CMV (22% vs 5%, p=0.01). Biologic therapy alone was associated with higher rate of CMV (24% vs 7%, p=0.02), whereas small molecule inhibitor alone was not (p=0.6). Pre-admission use of 5-aminosalicylates, high dose steroids, thiopurines or combination therapies were not associated with CMV positivity.

Table 1: Comparison data of clinical outcomes in ASUC between patients with and without CMV positivity on colonic biopsy

	CMV on biopsy		p-value
	Positive	Negative
Rescue therapy (n)	7 (64%)	44 (36%)	p=0.07
TPN (n)	4 (36%)	14 (11%)	p=0.02*
Referral to colorectal surgery (n)	9 (82%)	52 (43%)	p=0.01*
Inpatient colectomy (n)	3 (27%)	14 (11%)	p=0.13
ICU admission (n)	3 (27%)	6 (5%)	p=0.004*
Readmission at 90 days (n)	4 (40%)	23 (19%)	p=0.11
Mortality at 90 days (n)	1 (9%)	2 (2%)	p=0.11
Length of stay (days)	27.1 ± 14.0	11.0 ± 7.4	p=0.003*

Conclusion

Patients with CMV positive colonic biopsies tend to require more inpatient interventions, including increased need for TPN, ICU admission, referral to colorectal surgery and longer hospital length of stay. Despite more complex admission course of ASUC patients with concurrent CMV infection, these patients were not observed to have worse outcomes than those without CMV diagnosis. Maintenance biologic and small molecule inhibitor use was associated with higher rates of CMV, reflecting the immunosuppressant effects of advanced UC therapies. CMV detection needs to be considered as a potential exacerbating factor in disease severity.

References

1. Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis. 2024 Mar 28;15:20406223241233203. doi: 10.1177/20406223241233203. PMID: 38560721; PMCID: PMC10981253.

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

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Data are presented as % (n/N). N, number of patients having clinical response/remission/endoscopic remission data. n, number of patients achieving clinical response/remission and endoscopic remission data.
	Moderate UC			Severe UC
	Clinical response	Clinical remission	Endoscopic remission	Clinical response	Clinical remission	Endoscopic remission
Week 14	89.8 (79/88)	65.9 (58/88)	57.1 (12/21)	90.0 (72/80)	63.8 (51/80)	56.3 (9/16)
Week 30	87.7 (64/73)	69.9 (51/73)	30.8 (4/13)	91.2 (62/68)	66.2 (45/68)	90.9 (10/11)
Week 54	92.2 (59/64)	81.3 (52/64)	62.5 (5/8)	88.5 (46/52)	73.1 (38/52)	60.0 (3/5)
	Biologic-exposed UC: 10.9% (41/376)			Biologic-naïve UC: 89.1% (335/376)
Week 14	69.0 (20/29)	66.7 (20/30)	16.7 (1/6)	77.8 (200/257)	71.7 (187/261)	69.4 (34/49)
Week 30	74.2 (23/31)	71.0 (22/31)	83.3 (5/6)	78.7 (170/216)	77.1 (168/218)	60.5 (23/38)
Week 54	60.0 (15/25)	81.5 (22/27)	83.3 (5/6)	83.3 (140/168)	83.6 (143/171)	68.2 (15/22)

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.