Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors

Rodríguez-Duque, Juan Carlos; Calleja, José Luís; Iruzubieta, Paula; Hernández‐Conde, Marta; Rivas-Rivas, Coral; Vera, María Isabel Paredes; García, Maria José; Pascual, Marta; Castro, Beatriz; García-Blanco, Agustín; García-Nieto, Enrique; Olmo, Soraya Curiel-del; Cagigal, María Luisa; Lopez-Montejo, Lorena; Fernández-Lamas, Tatiana; Rasines, Laura; Fortea, José Ignacio; Vaqué, José P.; Frias, Yza Nubia; Rivero, Montserrat; Arias-Loste, María Teresa; Crespo, Javier

doi:10.1016/j.cgh.2022.01.039

Cited by 35 publications

(74 citation statements)

References 22 publications

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“…Several sensitivity analyses were used to test the robustness of the results. Based on the fully adjusted models, we further: (1) excluded the incident IBD that occurred in the first 2-year period to reduce the potential reverse causality; (2) excluded individuals with baseline colorectal cancer (identified with ICD-10 code C18, C19, and C20 through cancer registry); (3) excluded participants with concomitant liver diseases (identified with ICD-10 code B16-19, E83.0, E83.1, E88.0, I82.0, K70, K73.2, K73.9, K74.3-5, K75.4, K76.5, K83.0 through inpatient data) other than MAFLD to avoid the confounding effect of other liver diseases [34]; (4) adjusted for the use of non-steroidal anti-inflammatory drugs, antibiotics, or proton-pump inhibitors; (5) refilled the missing values using multiple imputation method [35]; (6) Excluding new-onset individuals with MAFLD identified in the repeat assessment of the UK Biobank; (7) investigated the association between the AST to ALT ratio and incident IBD as it is a common indicator for liver function test; (8) investigated associations of liver function makers with IBD in subgroups stratified by the normal range of these markers; and (9) evaluated the association between individuals with MAFLD with different probability of advanced fibrosis and risk of IBD. R 4.1.1 and SAS 9.4 (SAS Institute).…”

Section: Discussionmentioning

confidence: 99%

“…However, current studies on the comorbidity of IBD and MAFLD are limited and with few prospective evidence. Data from a cross-sectional study including 2549 Spanish showed a significantly higher prevalence of MAFLD among individuals with IBD than the general population (42% vs. 32%) [6]. But the direction of the association could not be clarified due to the crosssectional design.…”

Section: Introductionmentioning

confidence: 96%

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Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

Chen

Dan

et al. 2022

Hepatol Int

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Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. Methods A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006–2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. Results With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants’ circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. Conclusions Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

Chen

Dan

et al. 2022

Hepatol Int

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“…A measurement was considered to be valid if ten readings with a mean interquartile range lower than 30% were obtained [ 31 ]. Liver stiffness measurements (LSM) were collected in kilopascals (kPa) using specific cut-off values corresponding to different stages of fibrosis, namely ≥5.6 kPa for mild fibrosis (F1), ≥7.2 kPa for significant fibrosis (F2), ≥9.7 kPa for advanced fibrosis (F3), and 12.5 kPa for liver cirrhosis (F4) [ 24 , 32 , 33 ]. CAP values were expressed in decibels/meter (dB/m), with the following cut-off values: ≥248 dB/m for mild steatosis (S1), ≥268 for moderate steatosis (S2), and ≥280 for severe steatosis (S3) [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Screening for Liver Steatosis and Fibrosis in Patients with Inflammatory Bowel Disease Using Vibration Controlled Transient Elastography with Controlled Attenuation Parameter

Trifan

Stafie

Rotaru

et al. 2022

JCM

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Background and Aims: Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, hepatic injury being of concern in these patients. Current literature reports an increased prevalence of liver steatosis and fibrosis in subjects with IBD and the pathophysiology is yet to be completely understood. The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with IBD, as well as to determine the factors that connect these two disorders. Methods: From September 2021 to June 2022, 82 consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter (CAP) was used to assess the presence of NAFLD, with a cut-off score for CAP of 248 dB/m. Significant liver fibrosis was considered at a cut-off for liver stiffness measurements (LSM) of 7.2 kPa. Results: In total, 82 IBD patients (54.8% men, mean age of 49 ± 13 years) were included, 38 (46.3%) of them being diagnosed with NAFLD, with a mean CAP score of 286 ± 35.4 vs. 203 ± 29.7 in patients with IBD only. Age (β = 0.357, p = 0.021), body mass index (BMI) (β = 0.185, p = 0.048), disease duration (β = 0.297, p = 0.041), C—reactive protein (β = 0.321, p = 0.013), fasting plasma glucose (β = 0.269, p = 0.038), and triglycerides (β = 0.273, p = 0.023) were strongly associated with the presence of liver steatosis. The multivariate analysis showed that older age, BMI, and disease duration were strongly associated with significant liver fibrosis in our group. Conclusions: NAFLD is a multifaced pathology with growing prevalence among IBD patients. Additional studies are needed to completely understand this problem and to create a solid evidence-based framework for more effective preventative and intervention strategies.

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“…Although NAFLD can progress to cirrhosis or liver cancer if it worsens to nonalcoholic steatohepatitis [1,6], it is unclear whether patients with IBD will develop nonalcoholic steatohepatitis over time. However, the most recent relevant study showed progression of metabolic-associated fatty liver disease to liver brosis in patients with IBD [39]. Moreover, progression of NAFLD is an important factor in the development of IFALD, which is a life-threatening complication in patients with long-term malnutrition caused by chronic intestinal failure.…”

Section: Discussionmentioning

confidence: 99%

Worsening nutritional status in non-obese patients with inflammatory bowel disease is reflected by nonalcoholic fatty liver disease: a retrospective study

Nagata

Funakoshi

Morihara

et al. 2023

Preprint

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Aim The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify characteristics of NAFLD in non-obese patients with IBD. Methods Patients with IBD who underwent abdominal computed tomography (CT) examination at our hospital between 2005 and 2020 were retrospectively identified and enrolled in the study. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters. Results Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In non-obese patients (defined as patients with a body mass index < 25 kg/m2), CRP (P < 0.0001) and alanine aminotransferase (P = 0.0183) levels were higher and the albumin level (P = 0.0046) and prognostic nutritional index (PNI; P = 0.0022) values were lower in patients with NAFLD than in those without NAFLD. The PNI value was positively correlated (P = 0.0001) and the CRP level was negatively correlated (P = 0.0008) with the hepatosplenic ratio. However, the PNI (P < 0.05) and CRP level (P < 0.001) improved numerically over time after computed tomography in the group with NAFLD than in the group without NAFLD. Conclusions Worsening nutritional status may be an indicator of NAFLD in patients with IBD. Diagnosis of NAFLD on CT imaging might be useful in patients with IBD not only for early detection of NAFLD but also for assessment of the need for therapeutic intervention for IBD.

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Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors

Cited by 35 publications

References 22 publications

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

Screening for Liver Steatosis and Fibrosis in Patients with Inflammatory Bowel Disease Using Vibration Controlled Transient Elastography with Controlled Attenuation Parameter

Worsening nutritional status in non-obese patients with inflammatory bowel disease is reflected by nonalcoholic fatty liver disease: a retrospective study

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