Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1 -q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Effectiveness and safety of darvadstrocel in patients with complex perianal fistulizing Crohn's disease: a systematic review.

Background: Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management. Method: A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel. Results: In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks. Conclusions: Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.

Ergophysiological evaluation of heart failure patients with reduced ejection fraction undergoing exercise-based cardiac rehabilitation: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to explore in heart failure (HF) patients with reduced ejection fraction (EF) undergoing exercise-based cardiac rehabilitation the following: 1) the comparison of temporal changes between peak oxygen uptake (VO2peak) and first ventilatory threshold (VO2VT1), 2) the association of VO2peak and VO2VT1 changes with physiological factors, and 3) the differential effects of continuous aerobic exercise (CAE) and interval training (IT) on VO2peak and VO2VT1. METHODS: A systematic literature search was conducted in PubMed, CENTRAL, and Scopus. Inclusion criteria were 1) original research articles using exercise-based cardiac rehabilitation, 2) stable HF patients with reduced EF, 3) available values of VO2peak and VO2VT1 (in mL/kg/min) both at baseline and after exercise training with comparison between these time points. RESULTS: Among the 30 eligible trials, 24 used CAE, 5 IT, and one CAE and IT. Multivariable meta-regression with duration of exercise training and percentage of males as independent variables and the change in VO2peak as a dependent variable showed that the change in VO2peak was negatively associated with duration of exercise training (coefficient=-0.061, p=0.027), implying the possible existence of a waning effect of exercise training on VO2peak in the long term. Multivariable meta-regression demonstrated that both age (coefficient=-0.140, p<0.001) and EF (coefficient=-0.149, p<0.001) could predict the change in VO2VT1, whereas only age (coefficient=-0.095, p=0.022), but not EF (coefficient = 0.082, p = 0.100), could predict the change in VO2peak. The posttraining peak respiratory exchange ratio, as an index of maximum effort during exercise testing, correlated positively with the change in VO2peak (coefficient=-0.021, p=0.044). The exercise-induced changes of VO2peak (p = 0.438) and VO2VT1 (p = 0.474) did not differ between CAE and IT groups. CONCLUSIONS: Improvement of endurance capacity during cardiac rehabilitation may be detected more accurately with the assessment of VO2VT1 rather than VO2peak.

SURGICAL INTERVENTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY BOWEL DISEASE AND PERIANAL DISEASE.

OBJECTIVE: Aim: The aim of the study was to investigate the incidence of IBD in gastrointestinal surgery patients and record the disease's characteristics and treatment. PATIENTS AND METHODS: Materials and Methods: A search was carried out in the archives of the gastroenterology clinics of the University General Hospital of Ioannina and the General Hospital of Ioannina "G. Hatzikosta" in Greece. All cases of operated patients from 1980 to 2018 were examined. The duration of the study was 4 months. Data were analyzed with the SPSS program, v.28. RESULTS: Results: The total sample consisted of 1464 patients (n=1464). Most of them (915-62.5%) came from the University General Hospital of Ioannina, while the rest (549-37.5%) came from the GHI hospital "G. Hatzikosta". The mean age of the patients was 47 years (M=47.26, SD=17.34, Min=<1 month, Max=95 years). From the total sample, 58 patients (4%) suffered from IBD; most were men (42-72.41%). Their mean age was approximately 50 years (M=49.63, SD=16.48, Min=25 years, Max=77 years, range=52 years) and most belonged to the age groups of 31-40 years (11 patients- 19.6%) and 21-30 years and 61-70 years (10 patients-17.9%). The perianal disease was present in 43.1% (25 patients). The most frequent type of operation was fistula resection, ligation, curettage-biopsy (24.1%) and opening-drainage (22.4%-13 patients) and the most frequent type of anesthesia was general anesthesia (93.1%-54 patients). CONCLUSION: Conclusions: This long-term study of the patients' data followed up over time showed that the possibility of surgery in patients with IBD is mitigated through systematic monitoring and multifaceted therapeutic treatment.The perianal disease which appeared more often in men shows that it can be diagnosed early and at an early stage and with the new minimally invasive techniques the patient with IBD can be treated with a better quality of life.

The current role of Tofacitinib in acute severe ulcerative colitis in adult patients: A systematic review.

BACKGROUND: Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, is gaining ground as an effective alternative treatment option for the management of acute severe ulcerative colitis, which may prevent emergency colectomy. METHODS: A systematic literature search of PubMed and Embase was undertaken for studies of adult patients with ASUC treated with tofacitinib. RESULTS: In total, two observational studies, seven case series and five case reports incorporating 134 patients who received tofacitinib in ASUC were identified with a follow-up period ranging from 30 days to 14 months. Overall, the pooled colectomy rate was 23.9% (95% CI 16.6-31.2). The pooled 90-day and 6-month colectomy free rate were 79.9% (95% CI 73.1-86.7) and 71.6% (95% CI 64-79.2) respectively. The most frequent adverse event was C. Difficile infection. CONCLUSIONS: Tofacitinib appears to be a promising option for the treatment of ASUC. Randomized clinical trials are required to further access the efficacy, safety and optimal dose of tofacitinib in cases of ASUC.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Prolonged QT Interval in Athletes: Distinguishing between Pathology and Physiology.

BACKGROUND: The physiological QT prolongation in athletes is expected to widen the gray zone between physiology and pathology of QT, increasing the diagnostic challenges encountered in athletes with QT prolongation. SUMMARY: According to international recommendations for electrocardiogram in athletes, further evaluation for long QT syndrome (LQTS) is indicated in male athletes with corrected QT (QTc) ≥470 ms and in female athletes with QTc ≥480 ms. Apart from QTc ≥500 ms, diagnostic challenges arise in borderline cases of QTc prolongation, where further clinical investigations are needed to be performed to clarify whether LQTS exists. Clinical diagnostic investigations, including exercise testing, are more readily available, convenient, and easily interpretable, as well as less costly than genetic testing for LQTS. The main findings on exercise testing that are suggestive of LQTS can be the paradoxical prolongation of QTc during exercise and QTc ≥480 ms at fourth min of recovery. KEY MESSAGES: Exercise testing appears to have an important role in the diagnostic evaluation of athletes with prolonged QT interval, when genetic testing is not available.

Medical, Endoscopic and Surgical Management of Stricturing Crohn's Disease: Current Clinical Practice.

The development of fibrostenotic intestinal disease occurs in approximately one-third of patients with Crohn's disease and is associated with increased morbidity. Despite introducing new biologic agents, stricturing Crohn's disease remains a significant clinical challenge. Medical treatment is considered the first-line treatment for inflammatory strictures, and anti-TNF agents appear to provide the most considerable benefit among the available medical treatments. However, medical therapy is ineffective on strictures with a mainly fibrotic component, and a high proportion of patients under anti-TNF will require surgery. In fibrotic strictures or cases refractory to medical treatment, an endoscopic or surgical approach should be considered depending on the location, length, and severity of the stricture. Both endoscopic balloon dilatation and endoscopic stricturoplasty are minimally invasive and safe, associated with a small risk of complications. On the other hand, the surgical approach is indicated in patients not suitable for endoscopic therapy. This review aimed to present and analyze the currently available medical, endoscopic, and surgical management of stricturing Crohn's disease.

Gastric metastasis from breast cancer presenting as dysphagia.

Gastric metastasis from breast cancer occurs infrequently and causes non-specific symptoms, usually attributed to the underlying disease. Furthermore, endoscopic findings are almost identical to primary gastric cancer, making the immunohistochemical examination of biopsies necessary for diagnosis. We present the case of a 64-year-old woman who was diagnosed with lobular breast cancer 3 years ago and received chemotherapy with evidence of remission. The patient presented with dyspepsia and progressive dysphagia for the last 6 months, not responsive to PPI treatment. Upper endoscopy revealed partial occlusion of the cardio-esophageal junction and thickened gastric folds resembling linitis plastica. However, immunohistochemical analysis of endoscopic biopsies showed infiltration of gastric mucosa by lobular breast cancer cells, making the diagnosis of gastric metastasis. Therefore, clinicians' awareness of possible gastric metastasis is warranted in patients with a history of advanced breast cancer and severe gastric symptoms.

A Four-Probiotics Regimen Combined with A Standard Helicobacter pylori-Eradication Treatment Reduces Side Effects and Increases Eradication Rates.

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.

The efficacy of immunomodulators in the prevention and suppression of anti-drug antibodies to anti-tumor necrosis factor therapy in inflammatory bowel disease.

The development of biological agents against tumor necrosis factor (TNF) has revolutionized the management of inflammatory bowel disease (IBD), frequently achieving induction and maintenance of remission in both ulcerative colitis and Crohn's disease. However, a loss of response due to the development of anti-drug antibodies (ADA) is seen annually in approximately 20% of IBD patients receiving anti-TNF therapy. Current evidence suggests that the use of immunomodulators (IMM), such as thiopurines (azathioprine and 6-mercaptopurine) or methotrexate, may prevent or suppress ADA formation. In this article, we present a comprehensive review of the available literature regarding the efficacy of IMM in the prevention and suppression of ADA development to anti-TNF therapy in patients with IBD.

Current noninvasive modalities in Crohn's disease monitoring.

Crohn's disease (CD) is characterized by a remitting and relapsing course. Longstanding active CD may result in accumulating intestinal damage and disease-related complications. In contrast, mucosal healing is associated with significant improvement in the health-related quality of life, longer periods of disease remission and lower risk of disease progression, complications, hospitalizations, intestinal surgeries, as well as a lower risk of developing colorectal cancer. Mucosal healing, the new treatment endpoint in CD, made necessary the development of noninvasive, accurate, objective and reliable tools for the evaluation of CD activity. Ileocolonoscopy with biopsies remains the reference standard method for the evaluation of the colonic and terminal ileal mucosa. However, it is an invasive procedure with a low risk of complications, allowing the investigation of only a small part of the small bowel mucosa without being able to assess transmural inflammation. These disadvantages limit its role in the frequent follow up of CD patients. In this review, we present the currently available biomarkers and imaging modalities for the noninvasive assessment of CD activity.

Inflammatory Bowel Disease and Patients With Mental Disorders: What Do We Know?

Inflammatory bowel disease (IBD) is a multisystemic disease with a wide range of extraintestinal manifestations in both ulcerative colitis and Crohn's disease, while increasing evidence supports the interaction between gut and central nervous system, described as "gut-brain axis". According to epidemiological studies, it seems that patients with IBD present more frequently with impaired mental status compared to the general population, leading to diagnostic and management problems in this group of patients. The association between IBD and mental disorders, such as dementia and autism spectrum disorders, has not been fully clarified; genetic factors and the gut-brain axis seem to be involved. The purpose of this review is to present and analyze the epidemiological data about this issue, describe the possible pathogenetic mechanisms and discuss some considerations about the management of patients with IBD and impaired mental status.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Diagnosis, epidemiology and management of serrated polyposis syndrome: a comprehensive review of the literature.

Serrated polyp associated colorectal cancer (CRC) develops from an alternative mechanism of colorectal carcinogenesis and accounts for 10-15% of all CRC. Serrated polyposis syndrome (SPS) occurs infrequently and is characterized by the occurrence of multiple serrated polyps (hyperplastic polyps, sessile serrated lesions and traditional serrated adenomas) throughout the colon and/or rectum and has been strongly associated with development of CRC. However, SPS is frequently unrecognized, due to application failure of the WHO criteria regarding diagnosis and/or missed serrated polyps during endoscopy. The management of SPS requires surveillance at regular intervals and removal of large serrated polyps. Endoscopic resection suitability and technique depends on lesion size and the endoscopist's experience. In this manuscript, we present an update regarding SPS epidemiology, molecular characteristics, management, surveillance strategies and endoscopic resection techniques.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities.

Vaccines, cytokines, and adoptive cellular therapies (ACT) represent immuno-therapeutic modalities with great development potential, and they are currently approved for the treatment of a limited number of advanced malignancies. The most up-to-date knowledge on the regulation of the anti-cancer immune response has recently led to the development and approval of inhibitors of immune checkpoints, which have produced unprecedented clinical activity in several hard to treat solid malignancies. However, severe adverse events (AEs) represent a limitation to the use of these drugs. Currently approved checkpoint inhibitors block cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand (PD-L1), resulted in increased survival of patients with several solid and hematologic malignancies. The most common treatment AEs associated with these drugs are fatigue, rash, and auto-immune/inflammatory reactions. Many of the immune-related AEs are reversible and the strategies for their management include supportive care either with or without treatment withdrawal; nevertheless, in severe cases, hospitalization and treatment with immune suppressants, and/or immunomodulators may be required. Steroid therapy is a critical component of the treatment algorithm; nevertheless, the associated immunosuppression may compromise the antitumor response. This article provides a comprehensive and narrative review of luminal gastrointestinal and hepatic complications, including recommendations for their investigation and management.

New insights into intestinal failure-associated liver disease in adults: A comprehensive review of the literature.

Intestinal failure-associated liver disease (IFALD) remains one of the most common and serious complications of parenteral nutrition (PN), causing a wide spectrum of hepatic manifestations from steatosis and mild cholestasis to portal hypertension and end-stage liver failure. The prevalence of IFALD depends on the diagnostic criteria and ranges from 4.3% to 65%. Moreover, many factors are shown to contribute to its development, including nutrient deficiencies, toxicity of PN, infections, and alterations of bile acid metabolism and gut microbiota. Prevention and management of IFALD aim at ameliorating or eliminating the risk factors associated with IFALD. The use of PN formulations with a lower ratio omega-6-to-omega-3 polyunsaturated fatty acids, cycle PN, optimization of enteral stimulation and prevention and early treatment of infections constitute the main therapeutic targets. However, failure of improvement and severe IFALD with end-stage liver failure should be considered as the indications of intestinal transplantation. The aim of this review is to provide an update of the epidemiology, pathophysiology, and diagnosis of IFALD in the adult population as well as to present a clinical approach of the therapeutic strategies of IFALD and present novel therapeutic targets.