Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma(HCC),but in non-alcoholic fatty liver disease(NAFLD),up to 50%of patients with HCC had no clinical or histological evidence of cirrhosis.It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis,and each patient should be evaluated on a caseby-case basis based on the profile of specific risk factors identified.For HCC screening in NAFLD,a valid precision-based screening is needed.Currently,when evaluating this population of patients,the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program.Hence,the objective of the present study is to review the epidemiology,the pathophysiology,the histopathological aspects,the current recommendations,and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.

The versatility of mesenchymal stem cells:From regenerative medicine to COVID,what is next?

Mesenchymal stem cells(MSCs)play key roles in regenerative medicine by promoting tissue healing.MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages.Due to their antiinflammatory,angiogenic and immune-modulatory properties,MSCs are suitable for tissue engineering applications and,when associated with biomaterials,their benefits can be improved.Moreover,recently,MSCs have been studied for new clinical applications,such as in the treatment of patients with COVID-19.MSCs regenerative potential has been attributed to their secretome,which comprises extracellular matrix,soluble proteins and several elements,including the release of extracellular vesicles.Even though,in order to explore all their therapeutic potential,it is still necessary to advance in the investigation of their basic cell biology characteristics.

Bioelectrical impedance vector analysis evaluates cellularity and hydration in cirrhotic patients

BACKGROUND Malnutrition in cirrhotic patients is correlated with mortality and a better response to liver transplantation.However,recovery of the nutritional status in these patients is a challenge due to the difficulty in establishing a reliable nutritional diagnosis.The bioelectrical impedance vector analysis(BIVA)method appears as a feasible tool in clinical practice to define the physiological state of cirrhotic patients by assessing hydration and body cellularity.AIM To evaluate body composition in cirrhotic patients using BIVA.METHODS This retrospective cross-sectional study was carried out by following cirrhotic outpatients at a hospital in Porto Alegre,Brazil.A tetrapolar bioelectrical impedance analysis device was used to evaluate cellularity and hydration and to perform the BIVA.The BIVA graphic was elaborated by software and for statistical analysis a significance level of 5%(P≤0.05)was considered.RESULTS One hundred and ninety patients,61.1%males,with a mean age of 56.6±11.0 years,were evaluated.Of these,56.3%had Child-Turcotte-Pugh(CTP)A score,and the prevalent etiology was hepatitis C virus(47.4%).The patients were classified according to cellularity and hydration by the quadrants and ellipses of the BIVA method,quadrant 1(47.9%);quadrant 2(18.9%);quadrant 3(14.2%);and quadrant 4(18.9%).Those classified in quadrant 1 and 2 had a higher phase angle compared to those in quadrants 3 and 4(P<0.001).Quadrant 2 patients had a lower average age than the other groups.The association with CTP score showed that patients in quadrant 2 had a higher proportion of CTP A,and those in quadrant 4 had a higher proportion of CTP C(P<0.052).CONCLUSION The BIVA method allows identification of the cellularity and hydration status of cirrhotic patients,and its association with clinical factors determines the disease severity,age and prognostic index.

Correction:Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellularcholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

Rereading the article“Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant”(DOI:10.5306/wjco.v13.i8.688),published on August 24,we observe,with concern,that figures 3 and 4 are wrong.The authors have attached the correct figures for correction.

Role of the phase angle in the prognosis of the cirrhotic patient:15 years of follow-up

BACKGROUND In 2019,cirrhosis accounted for 2.4%of global deaths.The projection for 2030 is an increase in this index.In recent years,hospitalization costs have escalated by 36%for compensated cirrhosis and 24%for decompensated cirrhosis.Therefore,it is necessary to identify a tool capable of predicting the mortality of these patients according to their clinical condition and consequently extending their survival time.Different studies have shown that the phase angle(PA)can be a feasible method in clinical practice,with the potential to guide assertive patient management in the therapeutic of chronic liver disease.AIM To evaluate the prognostic role of PA in cirrhotic patients over a 15-year followup period.METHODS Retrospective cohort study with 129 cirrhotic patients of both sexes over 18 years old.Diagnosis of cirrhosis by liver biopsy.The first year of data collection was 2007,and data regarding outcomes was collected in 2023.Data were gathered from medical records,such as esophageal varices(EV),EV bleeding,ascites,spontaneous bacterial peritonitis(SBP),encephalopathy,laboratory findings and PA.The cut-off value for the PA was 5.4°,a value described in 2012 by Fernandes et al for 129 patients evaluated in this study and the cut-off points for the Brazilian population presented in percentiles(P),as described by Mattiello et al.The mortality was assessed using the PA percentile through Kaplan-Meier curves and multivariate binary logistic regression models.RESULTS Patients were divided into two groups according to the PA 5.4th(PA>5.4°,n=40;PA≤5.4°,n=89)PA percentile(<P50,n=56;≥P50 n=73).The percentile classification was more accurate in identifying long-term deaths than the 5.4ºPA.Patients with<P50 had a higher number of relevant complications such as ascites,SBP,liver encephalopathy and HCC.PA is strongly correlated with serum albumin(P<0.001),International Normalized Ratio(P=0.01),total bilirubin(P=0.02)and direct bilirubin(P=0.003).PA is correlated with survival time(P<0.001)and length of stay(P=0.02).Logistic regression analysis shows that an increase of 1°in PA enlarges the cirrhotic patient's chance of survival by 17.7%.CONCLUSION PA is a good predictor of morbidity and mortality for cirrhotic patients.The PA by percentile showed greater sensitivity in predicting mortality compared to the cut-off point of 5.4º.

Sarcopenia and non-alcoholic fatty liver disease:Is there a relationship?A systematic review

AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort studies including adult patients(over 18 years) with sarcopenia were selected.The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients.In the screening process,44 fulltext articles were included in the review and 41 studies were excluded.RESULTS Three cross-sectional studies were included.The authors attempted to perform a systematic review,but due to the differences between the studies,a qualitative synthesis was provided.The diagnosis of NAFLD was made by non-invasive methods(image methods or any surrogate markers) in all three evaluated studies.All the studies suggested that there was an independent association between sarcopenia and NAFLD.CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus:a retrospective cohort study

AIM To assess the incidence of hepatocellular carcinoma(HCC) in chronic liver disease due to hepatitis B virus(HBV) or hepatitis C virus(HCV) coinfected with human immunodeficiency virus(HIV).METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.RESULTS Of 804 patients were included(399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger(36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected(P < 0.001). HCC was diagnosed in 36 patients(10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years(95%CI: 0.12-0.46 vs 0.47-1.05)(long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

Noninvasive imaging assessment of non-alcoholic fatty liver disease:focus on liver scintigraphy

Noninvasive diagnoses of nonalcoholic fatty-liver disease(NAFLD) involve the use of serologic markers and imaging methods, such as conventional ultrasonography(US),computed tomography, and magnetic resonance imaging. Although these methods are reliable for the noninvasive detection of moderate to severe fatty changes in the liver, they are not reliable for detecting nonalcoholic steatohepatitis(NASH) and fibrosis. New imaging technologies, such as US-based transient elastography, acoustic radiation force impulse and magnetic resonancebased elastography, can reportedly be used to determine the severity of liver fibrosis associated with NASH. In this context, the field of nuclear medicine through liver scintigraphy has recently been proposed, and is being explored for use in the diagnosis of NASH. More importantly, nuclear medicine may contribute to the distinction between simple steatosis and NASH. For example, the enhanced release of cytokines and the decrease in the phagocytic activity of Kupffer cells play important roles in the pathogenesis of NASH. Removal of technetium-99 m colloid from circulation by Kupffer cell phagocytosis therefore provides a valuable imaging technique. Thus, nuclear medicine is poised to provide useful tools for the evaluation of patients with NAFLD. However, the evidence is still scarce, and more studies with larger samples are needed to identify their role before they are used in clinical practice.

Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: A 10-year retrospective cohort study

AIM To determine the incidence of hepatocellular carcinoma(HCC) and the impact of HCC surveillance on early diagnosis and survival of cirrhotic outpatients. METHODS In this retrospective cohort study, cirrhotic outpatients undergoing HCC surveillance between March 2005 and March 2014 were analyzed. Exclusion criteria were HIV coinfection; previous organ transplantation; diagnosis of HCC at first consultation; missing data in the medical chart; and less than 1 year of follow-up. Surveillance was carried out every six months using ultrasound and serum alpha-fetoprotein determination. Ten-year cumulative incidence and survival were estimated through Kaplan-Meier analysis. RESULTS Four hundred and fifty-three patients were enrolled, of which 57.6% were male. Mean age was 55 years. Hepatitis C virus and heavy use of alcohol were the main etiologic agents of cirrhosis. HCC was diagnosed in 75 patients(16.6%), with an estimated cumulative incidence of 2.6% in the 1st year, 15.4% in the 5th year, and 28.8% in the 10 th year. Median survival was estimated at 17.6 mo in HCC patients compared to 234 mo in non-HCC patients(P < 0.001). Early-stage HCC was more often detected in patients who underwent surveillance every 6 mo or less(P = 0.05). However, survival was not different between patients with early stage vs non-early stage tumors [HR = 0.54(0.15-1.89), P = 0.33].CONCLUSION HCC is a frequent complication in patients with cirrhosis and adherence to surveillance programs favors early diagnosis.

Nutritional evaluation in cirrhosis: Emphasis on the phase angle

Protein-calorie malnutrition(PCM) is a common condition in cirrhotic patients, leading to a worse prognosis, complications, poor quality of life and lower survival rates. Among ways of assessing nutritional status, there are anthropometric methods such as the evaluation of the triceps skinfold, the arm circumference, the arm muscle circumference and the body mass index, and nonanthropometric methods such as the subjective global assessment, the handgrip strength of non-dominant hand, and the bioelectrical impedance analysis(BIA). PCM is frequently under-diagnosed in clinical settings in patients with cirrhosis due to the limitations of nutritional evaluation methods in this population. BIA is a useful method, but cannot be indicated in patients with abnormal body composition. In these situations, the phase angle(PA) has been used, and can become an important tool in assessing nutritional status in any situation. The PA is superior to anthropometric methods and might be considered as a nutritional indicator in cirrhosis. The early characterization of the nutritional status in patients with cirrhosis means an early nutritional intervention, with a positive impact on patients' overall prognosis. Among the usually accepted methods for nutritional diagnosis, the PA provides information in a quick and objective manner.

Cardiac stress testing and coronary artery disease in liver transplantation candidates： Meta-analysis

AIM To evaluate the diagnostic value of dobutamine stress echocardiography(DSE) and myocardial perfusion scintigraphy(MPS) in predicting coronary artery disease(CAD) in cirrhotic patients listed for liver transplantation(LT), using invasive coronary angiography(ICA) as gold-standard.METHODS Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, EMBASE, MEDLINE(PubMed), BIREME(Biblioteca Regional de Medicina), LILACS(Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually.RESULTS The search strategy retrieved 322 references for DSE and 90 for MPS. In the final analysis, 10 references for DSE and 10 for MPS were included. Pooled sensitivity was 28% and 61% for DSE and MPS and specificity was 82% and 74%, for diagnosis of CAD using ICA as gold-standard, respectively.CONCLUSION DSE and MPS do not have adequate sensitivity for determination of whether CAD is present, despite having significant specificity.

Metabolic Syndrome and DNA Damage: The Interplay of Environmental and Lifestyle Factors in the Development of Metabolic Dysfunction

The Metabolic Syndrome (MetS) is a complex condition which is characterized by increased risk factor for cardiovascular diseases, such as dyslipidemia, hypertension and central obesity, in addition to increased risk for type 2 diabetes mellitus (T2DM). All of these factors alone have a notable relationship with DNA damage. However, when the risks are combined, the extent for major outcomes being related to DNA damage (cancer), the consequence can be accelerated by the metabolic dysfunction. This article will illustrate the scientific evidence of the role of DNA damage in MetS, as well as discuss the interplay of major risks factors (air pollution, physical inactivity and dietary interventions) in genomic stability.

Anti-Inflammatory Effects of Physical Exercise on Obesity

Obesity is a disease of epidemic proportions, associated with chronic inflammation in response to increased secretion of inflammatory cytokines originating in adipose tissue. Exercise has been shown to be effective in combating these changes. The aim of this study was to review the anti-inflammatory effect of physical exercise in the pathogenesis of obesity. We conducted a search of the terms “exercise”, “obesity” and “inflammation” on Medline and PubMed databases, restricting results to clinical trials published since 2011. The retrieved studies showed that physical exercise could, via different pathways, reduce levels of CRP, IL-6 and TNF-α, as well as other proinflammatory markers. Additionally, exercise was able to increase expression of genes related to the production of nitric oxide, positively modulating endothelial function and chronic inflammation in obese patients, with or without caloric restriction. In conclusion, aerobic exercise of moderate intensity is an effective intervention strategy for chronic inflammation associated with obesity.

Neurological and behavioral manifestations of cerebral malaria:An update

Neglected tropical diseases are a group of tropical diseases endemic in poor countries even though medical treatment and cures are available. They are considered a global health problem due to the severity of the physiological changes they induce in their hosts. Malaria is a disease caused by Plasmodium sp. that in its cerebral form may lead to acute or long-term neurological deficits, even with effective antimalarial therapy, causing vascular obstruction, reduced cerebral blood flow and many other changes. However, Plasmodium falciparum infection can also develop into a cerebral malaria(CM) disease that can produce neurological damage. This review will discuss the mechanisms involved in the neuropathology caused by CM, focusing on alterations in cognitive, behavior and neurological functions in human and experimental models.

Melatonin restores zinc levels,activates the Keap1/Nrf2 pathway,and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity

BACKGROUND Melatonin(MLT)is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations,due to its action against free radicals.AIM To evaluate the effect of MLT on carbon tetrachloride(CCl_(4))induced liver injury in rats in terms of oxidative stress,reticular stress,and cell damage.METHODS Twenty male Wistar rats(230-250 g)were divided into four groups:Control rats,rats treated with MLT alone,rats treated with CCl_(4)alone,and rats treated with CCl_(4)plus MLT.CCl_(4)was administered as follows:Ten doses every 5 d,ten every 4 d,and seven every 3 d.MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment(16th wk).RESULTS MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl_(4)treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity,with a lower reduction in serum zinc levels,guaranteeing a reduction in liver damage;additionally,it increased the expression of nuclear factor(erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1.MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress,i.e.,glucose-regulated protein 78 and activating transcription factor 6,as well as of heat shock factor 1 and heat shock protein 70.CONCLUSION MLT has a hepatoprotective effect in an experimental model of CCl_(4)-induced liver injury,since it reduces oxidative stress,restores zinc levels,and modulates endoplasmic reticulum stress.

Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

BACKGROUND Cholangiocarcinoma(CC)is a rare tumor that arises from the epithelium of the bile ducts.It is classified according to anatomic location as intrahepatic,perihilar,and distal.Intrahepatic CC(ICC)is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis.Mixed hepatocellular carcinoma-CC(HCC-CC)is a rare neoplasm that shows histologic findings of both HCC and ICC within the same tumor mass.Due to the difficulties in arriving at the correct diagnosis,patients eventually undergo liver transplantation(LT)with a presumptive diagnosis of HCC on imaging when,in fact,they have ICC or HCC-CC.AIM To evaluate the outcomes of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma on pathological examination after liver transplant.METHODS Propensity score matching was used to analyze tumor recurrence(TR),overall mortality(OM),and recurrence-free survival(RFS)in LT recipients with pathologically confirmed ICC or HCC-CC matched 1:8 to those with HCC.Progression-free survival and overall mortality rates were computed with the Kaplan-Meier method using Cox regression for comparison.RESULTS Of 475 HCC LT recipients,1.7%had the diagnosis of ICC and 1.5%of HCC-CC on pathological examination of the explant.LT recipients with ICC had higher TR(46%vs 11%;P=0.006),higher OM(63%vs 23%;P=0.002),and lower RFS(38%vs 89%;P=0.002)than those with HCC when matched for pretransplant tumor characteristics,as well as higher TR(46%vs 23%;P=0.083),higher OM(63%vs 35%;P=0.026),and lower RFS(38%vs 59%;P=0.037)when matched for posttransplant tumor characteristics.Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC.There was no significant difference between the outcomes in either pairing.CONCLUSION Patients with ICC had worse outcomes than patients undergoing LT for HCC.The outcomes of patients with HCC-CC did not differ significantly from those of patients with HCC.

Relationship between phase angle,steatosis,and liver fibrosis in patients coinfected with human immunodeficiency virus/hepatitis C virus

BACKGROUND Malnutrition,lipodystrophy,and dyslipidemia are prevalent characteristics in patients with human immunodeficiency virus(HIV)infection with or without previous treatment.Such a clinical condition can lead to the hypothesis of the presence of hepatic steatosis with possible progression to fibrosis and the risk of hepatocellular carcinoma.Notably,a low phase angle(PA),evaluated by bioelectrical impedance analysis(BIA),is an independent prognostic marker of clinical progression and survival in HIV-infected patients.AIM To evaluate the relationship between PA and body composition with steatosis and hepatic fibrosis in HIV/hepatitis C virus(HCV)-coinfected patients.METHODS A retrospective observational study by convenience sampling of coinfected HIV/HCV patients,in which all patients underwent transient elastography(Fibroscan)and BIA evaluation.Student’s t test was used for group comparisons,and Spearman’s or Pearson’s correlation test was used when appropriate.The significance level was set at 5%,and analyses were performed using SPSS version 21.0.RESULTS Forty-three patients who received antiretroviral therapy met the inclusion criteria,and 23(53.5%)were under treatment with protease inhibitors(PIs).There was no difference in PA between those who used PIs and those who did not(P=0.635).There was no correlation between fibrosis grade and PA(P=0.355)or lean mass(P=0.378).There was a significant inverse correlation between the controlled attenuation parameter(CAP)and lean mass(P=0.378),positive correlation between PA and lean mass(P=0.378),and negative correlation between PA and fatty mass(P=0.378),although the CAP and PA were not correlated.When evaluated by sex,no significant correlations were found.CONCLUSION PA determines the muscle function of HIV/HCV-coinfected patients,and the CAP values reinforce the association with lean mass,suggesting that patients require early nutritional interventions.

The Impact of the Essential Fatty Acids (EFA) in Human Health

Linoleic (LA) and α-linolenic acids (ALA) are considered essential fatty acids (EFA) because they are not produced by the human body. This way, EFAs sources must come from the diet. The primary dietary source of n-3 fatty acids is ALA, found in seeds and seed oils. Other important sources are fish oils such as tuna, salmon and herring. Currently, numerous studies suggest possible benefits of essential fatty acids in human health, such as in cardiovascular, cognitive and eye health, and also during pregnancy and childhood. This paper also discusses the impact of fatty acids in human metabolism, and the available evidence regarding its risks. It addresses the relevant debate regarding a general ban of trans fatty acids (TFA) from the world food market, because of the cardiovascular risks associated with its consumption.

Resting energy expenditure in cirrhotic patients with and without hepatocellular carcinoma

BACKGROUND The diagnosis of malnutrition in patients with independent hepatocellular carcinoma(HCC)varies from 20%to 50%,is related to important complications and has a direct impact on the prognosis.Determination of the resting energy expenditure(REE)has become an important parameter in this population,as it allows therapeutic adjustments to recover their nutritional status.The REE in cirrhosis,with and without HCC,is not clearly defined,and requires the identification and definition of the best nutritional approach.AIM To evaluate the REE of patients with cirrhosis,with and without HCC.METHODS This is a prospective observational study evaluating the REE of 118 patients,33 with cirrhosis and hepatocellular carcinoma and a control group of 85 patients with cirrhosis without HCC,using indirect calorimetry(IC),bioimpedance,and predictive formulas.RESULTS The REE determined by IC in cirrhotic patients with HCC was 1643±364 and in those without HCC was 1526±277(P=0.064).The REE value as assessed by bioimpedance was 1529±501 for those with HCC and 1660±385 for those without HCC(P=0.136).When comparing the values of REE determined by IC and predictive formulas in cirrhotics with HCC,it was observed that only the formulas of the Food and Agriculture Organization(FAO)/World Health Organization(WHO)(1985)and Cunningham(1980)presented values similar to those determined by IC.When comparing the REE values determined by IC and predictive formulas in cirrhotics without HCC,it was observed that the formulas of Schofield(1985),FAO/WHO(1985),WHO(2000),Institute of Medicine(IOM)(2005)and Katch and McArdie(1996)presented values similar to those determined by IC.CONCLUSION The FAO/WHO formula(1985)could be used for cirrhotic patients with or without HCC;as it is the one with the values closest to those obtained by IC in these cirrhotic patients.

Diet as an epigenetic factor in inflammatory bowel disease

Inflammatory bowel disease(IBD)has as a main characteristic the exacerbation of the immune system against enterocytes,compromising the individual’s intestinal microbiota.This inflammatory cascade causes several nutritional deficiencies,which further compromise immunological functioning and,as a result,worsen the prognosis.This vicious cycle can be interrupted as the patient’s dietary pattern meets their needs according to their clinical condition,acting directly on the inflammatory process of IBD through the interaction of food,intestinal microbiota,and epigenome.Specific nutritional intervention for IBD has a crucial role in preventing and managing disease activity.This review addresses epigenetic modifications through dietary compounds as a mechanism for modulating the intestinal microbiota of patients with IBD.