Background: Three-dimensional (3D) MR elastography (MRE) derives viscoelastic parameters that may reflect inflammation, but their frequency dependence and the influence of steatosis on inflammation grading and fibrosis staging remain unclear.

Purpose: To investigate 3D multifrequency MRE for assessing hepatic inflammation, fibrosis stage across frequencies, and the influence of steatosis.

Study Type: Prospective.

Population: Sixty-four (40 men, median age: 58 years) participants with chronic liver disease (CLD); 21 (8 men, median age:28 years) healthy volunteers.

Field Strength/Sequence: 3-T; gradient-echo sequence with mechanical vibrations at low (16.7 and 18 Hz), medium (33.4 and 36 Hz), and high (50.1 and 54 Hz) frequencies.

Assessment: In CLD participants, MRE-derived viscoelastic parameters, shear stiffness, storage modulus, loss modulus, and damping ratio were compared with histologically assessed fibrosis, inflammation, and steatosis. MRE test–retest repeatability over 10 min was evaluated in healthy volunteers.

Statistical Tests: Wilcoxon rank sum test, Spearman's correlation, multivariable regression analysis, and area under the receiver operating curve (AUROC). A p value of < 0.05 was considered statistically significant.

Results: Inflammation was significantly independently associated with damping ratio at medium frequency, which showed moderate performance for grading inflammation (AUROC = 0.76–0.83, sensitivity = 0.83–0.84, specificity = 0.70–0.79). Fibrosis staging using shear stiffness and moduli showed high diagnostic performance (AUROC = 0.82–0.95), with comparable accuracy between medium and high frequencies (p = 0.327–0.896). Steatosis was not significantly correlated with MRE overall (p = 0.212–0.459), but was significantly associated with 19% higher stiffness and 20% higher loss modulus at medium frequency in CLD participants without fibrosis or inflammation.

Data Conclusion: Medium frequency 3D MRE demonstrated an independent association with inflammation while preserving accurate fibrosis assessment. Steatosis seemed not to confound MRE-based evaluation.

Level of Evidence: 1.

Technical Efficacy: Stage 2.

Plain Language Summary: Chronic liver disease can cause both inflammation and scarring (fibrosis). Accurate assessment usually requires a biopsy, which is invasive. This study evaluated a noninvasive imaging method called three-dimensional magnetic resonance elastography (3D MRE) in patients who underwent same-day liver biopsy. The researchers tested whether different vibration frequencies could detect inflammation and fibrosis. They found that medium frequency measurements were associated with liver inflammation while still accurately identifying fibrosis. Fat accumulation in the liver did not significantly affect the results. These findings suggest that 3D MRE may help medical doctors assess liver inflammation and fibrosis noninvasively in a single examination.

Eosinophilic Esophagitis is a widely-recognized immune-mediated esophagus disease with distinct clinical and histopathological features, exhibiting an increased global incidence. Therapeutic options encompass either dietary measures or pharmacological approaches, including proton pump inhibitors and topical corticosteroids. The use of monoclonal antibodies is currently under comprehensive evaluation, with a plethora of ongoing clinical trials designed to determine their clinical efficacy. The present case report demonstrates an exceptional case of refractory Eosinophilic Esophagitis, unresponsive to conventional treatment, achieving both clinical and histopathological remission subsequent to initiation of benralizumab treatment. Concurrently, our case underscores the necessity for continued research in the field of monoclonal antibodies for their use as a future treatment approach against Eosinophilic Esophagitis.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of non-Hodgkin lymphoma with characteristic histopathological features and can occur in various extranodal sites, including the gastrointestinal tract. While gastric MALT lymphoma has been extensively researched, primary lymphoma presentation in the colorectal mucosa is rare and lacks any association with Helicobacter pylori infection. Furthermore, there are currently no standardized treatment guidelines for this condition. This report presents a rare case of primary MALT lymphoma that manifested as a broad-based polyp. The diagnosis was confirmed through histopathological and immunohistochemical examination, and the polyp was resected endoscopically with the endoscopic submucosal dissection technique.

CASE PRESENTATION: A 26-year-old man presented with a 2-week history of productive cough and a 1-year history of effort-related dyspnea. His medical history was significant for hay fever and exertion-triggered asthma. He was not taking medicines regularly but was using inhaled salbutamol as needed. He was an ex-smoker, with a previous history of 2-pack years.

BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.

METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).

RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.

CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The complete natural history of NAFLD is unknown because few high-quality follow-up studies have been conducted. Our aim was to find variables predicting disease severity through an extended follow-up with serial biopsies. In a prospective cohort study, 129 patients who enrolled between 1988 and 1993 were asked to participate in a follow-up study on two occasions; biochemical, clinical, and histologic data were documented. The mean time between biopsies was 13.7 (±1.7) and 9.3 (±1.0) years, respectively. At the end of the study period, 12 patients (9.3%) had developed end-stage liver disease and 34% had advanced fibrosis. Out of the 113 patients with baseline low fibrosis (<3), 16% developed advanced fibrosis. Fibrosis progression did not differ among the different stages of baseline fibrosis (P = 0.374). Fifty-six patients (43%) had isolated steatosis, of whom 9% developed advanced fibrosis (3 patients with biopsy-proven fibrosis stage F3-F4 and 2 patients with end-stage liver disease). Fibrosis stage, ballooning, and diabetes were more common in patients who developed end-stage liver disease; however, there were no baseline clinical, histologic, or biochemical variables that predicted clinical significant disease progression. Conclusion: NAFLD is a highly heterogeneous disease, and it is surprisingly hard to predict fibrosis progression. Given enough time, NAFLD seems to have a more dismal prognosis then previously reported, with 16% of patients with fibrosis stage <3 developing advanced fibrosis and 9.3% showing signs of end-stage liver disease. (Hepatology Communications 2018;2:199-210).

It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1 beta, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-gamma, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.