Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. METHODS: This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. RESULTS: Of the 161 participants (Crohn's disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91-15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06-10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01). CONCLUSIONS: Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk.

Combined endothelin a blockade and chlorthalidone treatment in a rat model of metabolic syndrome.

Experiments determined whether the combination of endothelin A (ETA) receptor antagonist [ABT-627, atrasentan; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid] and a thiazide diuretic (chlorthalidone) would be more effective at lowering blood pressure and reducing renal injury in a rodent model of metabolic syndrome compared with either treatment alone. Male Dahl salt-sensitive rats were fed a high-fat (36% fat), high-salt (4% NaCl) diet for 4 weeks. Separate groups of rats were then treated with vehicle (control), ABT-627 (ABT; 5 mg/kg per day, in drinking water), chlorthalidone (CLTD; 5 mg/kg per day, in drinking water), or both ABT plus CLTD. Mean arterial pressure (MAP) was recorded continuously by telemetry. After 4 weeks, both ABT and CLTD severely attenuated the development of hypertension, whereas the combination further reduced MAP compared with ABT alone. All treatments prevented proteinuria. CLTD and ABT plus CLTD significantly reduced nephrin (a podocyte injury marker) and kidney injury molecule-1 (a tubulointerstitial injury marker) excretion. ABT, with or without CLTD, significantly reduced plasma 8-oxo-2'-deoxyguanosine, a measure of DNA oxidation, whereas CLTD alone had no effect. All treatments suppressed the number of ED1(+) cells (macrophages) in the kidney. Plasma tumor necrosis factor receptors 1 and 2 were reduced only in the combined ABT and CLTD group. These results suggest that ABT and CLTD have antihypertensive and renal-protective effects in a model of metabolic syndrome that are maximally effective when both drugs are administered together. The findings support the hypothesis that combined ETA antagonist and diuretic treatment may provide therapeutic benefit for individuals with metabolic syndrome consuming a Western diet.

The Impact of NAFLD on Hospitalization Outcomes in Patients With Inflammatory Bowel Diseases: Nationwide Analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with inflammatory bowel diseases (IBD). Yet, the impact of NAFLD on outcomes, along with the contribution of nonmetabolic factors to NAFLD development, is unclear. To investigate these topics, we conducted a nationwide study examining the impact of NAFLD on hospitalization outcomes in IBD patients after adjusting for metabolic factors. METHODS: Patients with IBD-related hospitalizations were identified using the Nationwide Readmissions Database from 2016 to 2018. Inflammatory bowel disease patients with and without NAFLD were matched based on IBD type, age, sex, metabolic syndrome, and diabetes mellitus. Primary outcomes were IBD-related readmission, IBD-related surgery, and death. Secondary outcomes were length of stay (LOS) and cost of care (COC). The primary multivariable model adjusted for obesity, dyslipidemia, Charlson-Deyo comorbidity index, hospital characteristics, payer, patient income, and elective status of admissions. RESULTS: Nonalcoholic fatty liver disease was associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.90; P < .01) and death (adjusted hazard ratio, 2.73; P < .01), 0.71-day longer LOS (P < .01), and $7312 higher COC (P < .01) in those with Crohn's disease. Nonalcoholic fatty liver disease was also associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.65; P < .01), 0.64-day longer LOS (P < .01), and $9392 (P < .01) higher COC, but there was no difference in death in those with UC. No differences in risk of IBD-related surgery were observed. CONCLUSIONS: Nonalcoholic fatty liver disease is associated with worse hospitalization outcomes in IBD patients after adjusting for metabolic factors. These data suggest nonmetabolic factors may be implicated in the pathogenesis of NAFLD in IBD patients and may contribute to worsened clinical outcomes.

A 77-Year-Old Woman With Capillary Hypoxia and Perioral Cyanosis.

CASE PRESENTATION: A 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Spo2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia.

Macrotrabecular Hepatocellular Carcinoma: An Aggressive Subtype of Hepatocellular Carcinoma.

The macrotrabecular (MT) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype. We retrospectively reviewed 231 HCC cases. Detailed pathologic evaluation for histologic patterns, including MT-pattern, was performed for each case and recorded as percentage involved at 10% intervals. MT-pattern was defined as having trabeculae >6 cells thick. After excluding all recognized HCC subtypes, remaining cases were deemed conventional HCC (CV-HCC) and served as controls. HCCs with a component of ≥10%, ≥30% and ≥50% MT-pattern were identified in 41 (17.7%), 24 (10.4%) and 4 (1.7%) cases, respectively. The clinicopathologic features of HCCs with 10% to 29% MT-pattern (n=17, 7.4%) were largely similar to CV-HCC. No significant difference was observed between the 30% and 49% (n=20) and ≥50% (n=4) MT groups, hence these were combined for further analysis as MT-HCC. MT-HCCs (≥30% MT-pattern) were larger tumors (5.5 vs. 3.1 cm), were less likely to be associated with cirrhosis (54% vs. 79%), were more likely to have hepatitis B (21% vs. 5%) and less likely hepatitis C infection (33% vs. 58%) compared with CV-HCC. MT-HCC was associated with the presence of anaplastic tumor cells (42% vs. 14%), higher alpha-fetoprotein level, higher AJCC stage, and higher histologic grade. Compared with patients with CV-HCC, patients with MT-HCC had poorer overall survival. Patients with MT-HCC who underwent primary resection or transplantation had a higher recurrence rate and worse recurrence-free survival. Our findings suggest that ≥30% MT-pattern could be used as the more appropriate cut-off for defining MT-HCC, which represents a unique and aggressive HCC histologic subtype.

NSAID associated bilateral renal infarctions: a case report.

Renal infarctions (RIs) are caused by interruptions in the renal arterial blood flow. RIs are generally considered to be rare, however we present the case of a 37 year old woman whose renal infarction was likely due to the vasoconstrictive effects of non-steroidal anti-inflammatory drugs. Although high-dose non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause a decrease in renal perfusion, they have not been accepted as causative agents in renal infarction. Theoretically, patients in prostaglandin dependent states should be more vulnerable to renovascular vasoconstriction and resulting hypoperfusion in the presence of NSAIDs. Given the high prevalence of NSAID use, we suspect that this mechanism of renal injury may be more prevalent than previously thought.

Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions.

BACKGROUND/AIMS: α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. METHODS: Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. RESULTS: One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. CONCLUSIONS: Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed.

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis.

BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. RESULTS: Plasma GPC3 levels in HCC patients were very low (0-3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. CONCLUSION: The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.

Expression profile and prognostic value of glypican-3 in post-operative South Korean hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) patients commonly experience poor overall survival (OS) and disease-free survival (DFS) after curative surgical resection. Glypican-3 (GPC3) has been suggested as a prognostic biomarker for post-operative survival. However, few to none of these studies have included South Korean patients. This study aimed to determine GPC3 expression rate, clinical correlation, and post-operative prognostic value in South Korean HCC patients who underwent curative surgical resection. Surgically resected tissues from 185 HCC patients were collected and assembled into tissue microarrays (TMAs), which were stained for GPC3 by immunohistochemistry. GPC3 expression rates were correlated with clinicopathological information, and survival analyses were performed to assess the prognostic value of GPC3. GPC3 expression was present in 153 patients (82.7%). GPC3-positive patients were younger with higher frequencies of microvascular invasion and higher AFP levels than GPC3-negative patients. There was no significant difference in survival between GPC3-negative and GPC3-positive patients. Based on multivariate analysis, GPC3 expression was not a prognostic marker for post-operative survival. In South Korean HCC patients, GPC3 expression was more frequent in HCCs with aggressive features, but it was not an independent prognostic biomarker.

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

AIM: To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. METHODS: This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS: The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION: The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.