Associations between irritable bowel syndrome and non-alcoholic fatty liver disease: A systematic review

Table 1 Search terms used

Database
PubMed	(Irritable bowel syndrome[Mesh] OR "Irritable bowel syndrome"[tiab] OR "irritable colon*"[tiab] OR IBS[tiab]) AND (Fatty Liver[Mesh] OR (fatty[tiab] AND (liver*[tiab] OR hepat*[tiab]) OR steatohepat*[tiab] OR NAFL*[tiab] OR NASH*[tiab]))
EMBASE	('irritable colon'/exp OR 'irritable bowel syndrome':ab,ti OR ‘irritable colon’:ab,ti OR ‘IBS’:ab,ti) AND (‘Fatty Liver’/exp OR (fatty:ab,ti AND (liver*:ab,ti OR hepat*:ab,ti) OR steatohepat*:ab,ti OR NAFL*:ab,ti OR NASH*:ab,ti))
CENTRAL	#1 MeSH descriptor: [Irritable Bowel Syndrome] explode all trees
	#2 ('irritable bowel syndrome' OR ‘irritable colon’ OR ‘IBS’):ti,ab,kw
	#3 MeSH descriptor: [Fatty Liver] explode all trees
	#4 fatty:ab,ti AND (liver*:ab,ti OR hepat*:ab,ti) OR steatohepat*:ab,ti OR NAFL*:ab,ti OR NASH*:ab,ti
	#5 (#1 or #2) and (#3 or #4)

CENTRAL: Cochrane Central Register of Controlled Trials.

Table 2 Summary of study findings

Ref.	Location	Sample characteristics	Study design	IBS diagnosis	NAFLD diagnosis	IBS and NAFLD overlap	Associated risk factors
Ke et al[20], 2013	China	No. of patients: 945. NAFLD population: 470 (226 males, 222 females). Total without NAFLD: 475 (198 males, 234 females). Note: DM was in exclusion criteria	Cross-sectional study	ROME III	Ultrasound; Chinese Society of Hepatology, Chinese Medical Association diagnosis criteria for NAFLD	IBS incidence: 104 (23.2%) of NAFLD patients vs 54 (12.5%) of patients without NAFLD. NAFLD incidence in patients with IBS symptoms: 65.8% of patients with IBS-like symptoms had NAFLD. Higher detection rate of IBS-like symptoms with more severe NAFLD (P < 0.05). Mild NAFLD (Group A): 24 out of 212 (11.3%). Moderate NAFLD (Group B): 52 out of 188 (27.7%). Severe NAFLD (Group C): 28 out of 48 (58.3%)	Risk factors for IBS-like symptoms: BMI (P = 0.049). Triglycerides (P = 0.034). Fatty liver (P = 0.047). Ethnicity-Han, Uygur (P = 0.008)
Hasanian et al[21], 2018	Egypt	100 consecutive patients diagnosed with IBS (49 males, 51 females): 45% IBS-C 23% IBS-D 32% IBS-M. Further divided into: Mild IBS (n = 42); Moderate IBS (n = 43); Severe IBS (n = 15)	Cross-sectional study	ROME III	Ultrasound	74% of IBS patients had NAFLD. Moderate/severe NAFLD significantly associated with moderate/severe IBS. 22.4% moderate/severe IBS patients (95%CI: 15.8%-31.5%) vs 4.8% mild IBS patients: (95%CI: 2.7%-7.9%) (P = 0.001)	Predictors of moderate/severe IBS: NAFLD (P = 0.026); Metabolic Syndrome (P = 0.011)
Zheng et al[22], 2011	China	No. of patients: 200 (89 males, 111 females) (1) Both NAFLD and IBS: 25; (2) Either NAFLD or IBS: 36; and (3) Neither IBS nor NAFLD: 139	Cross-sectional study	ROME III	Ultrasound; NAFLD diagnosis based on Chinese Society of Hepatology, Chinese Medical Association	25 subjects (12.5%) had both NAFLD and IBS	NAFLD and IBS overlap group compared to group without NAFLD and IBS Overlap had higher: BMI (P = 0.045); TG (P = 0.035); TC (P = 0.038); HDL-C (P = 0.045); LDL-C (P = 0.031); FBG (P = 0.023). NAFLD and IBS overlap group compared to the either NAFLD or IBS group had higher: Hypertension (P = 0.041); Obesity (P = 0.034); Dyslipidemia (P = 0.020); Diabetes (P = 0.037); Digestive system diseases (P = 0.037). GIT sensory threshold: NAFLD and IBS overlap group had lower threshold of the following compared to either NAFLD or IBS group: FSV (P = 0.034); DSV (P = 0.032); MTV (P = 0.035); PSV (P = 0.027)
Franco et al[23], 2022	United States	No. of patients: 130 patients with NAFLD (49 males, 81 females)	Cross-sectional study	ROME IV	ICD-10 Code	38 (29.2%) patients with NAFLD fulfilled Rome IV IBS criteria	Increased prevalence of depression (18.4% vs 5.4%, P = 0.01) and anxiety (31.6% vs 9.8%, P = 0.002) in NAFLD patients with IBS compared to those without IBS. Independent predictors of IBS in NAFLD: Female gender (OR: 5.69, P = 0.001); Depression (OR: 1.23, P < 0.001); BMI (OR: 0.90, P = 0.02)
Wu et al[24], 2022	United Kingdom	No. of patients: 396838 (189759 males, 207079 females). NAFLD population: 153203	Prospective cohort study; United Kingdom Biobank	ICD-10 Code	Fatty Liver Index	7129 cases of incident IBS in NAFLD patients (cumulative incidence rate of 1.49 (95%CI: 1.46–1.53) per 1000 person-years). NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 1.05-1.17). Increased risk of IBS in higher FLI quartile	Subgroup analysis showed increased IBS risk for: Age (P < 0.003); Gender (Female) (P < 0.001)
Singh et al[25], 2013	India	No. of patients: 632 patients with incidentally detected NAFLD (484 males, 148 females)	Retrospective analysis	Not documented	Ultrasound diagnosis and grading of liver steatosis by two radiologists in a blinded study	186 (29.4%) out of 632 NAFLD patients had IBS	-

IBS: Irritable bowel syndrome; NAFLD: Non-alcoholic fatty liver disease; BMI: Body mass index; TG: Triglyceride; TC: Total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; FBG: Fasting blood glucose; FSV: First sensation volume; DSV: Defaecating sensation volume; MTV: Maximum tolerable volume; PSV: Painful sensation volume; ICD-10: International classification of diseases-10.