Cross-sectional examination of ultra-processed food consumption and adverse mental health symptoms.

OBJECTIVE: To explore whether individuals who consume higher amounts of ultra-processed food (UPF) have more adverse mental health symptoms. DESIGN: Using a cross-sectional design, we measured the consumption of UPF as a percentage of total energy intake in kilo-calories using the NOVA food classification system. We explored whether individuals who consume higher amounts of UPF were more likely to report mild depression, more mentally unhealthy days and more anxious days per month using multivariable analyses adjusting for potential confounding variables. SETTING: Representative sample from the United States National Health and Nutrition Examination Survey between 2007 and 2012. PARTICIPANTS: 10 359 adults aged 18+ without a history of cocaine, methamphetamine or heroin use. RESULTS: After adjusting for covariates, individuals with the highest level of UPF consumption were significantly more likely to report at least mild depression (OR: 1·81; 95 % CI1·09, 3·02), more mentally unhealthy (risk ratio (RR): 1·22; 95 % CI 1·18, 1·25) and more anxious days per month (RR: 1·19; 95 % CI 1·16, 1·23). They were also significantly less likely to report zero mentally unhealthy (OR: 0·60; 95 % CI 0·41, 0·88) or anxious days (OR: 0·65; 95 % CI 0·47, 0·90). CONCLUSIONS: Individuals reporting higher intakes of UPF were significantly more likely to report mild depression, more mentally unhealthy and more anxious days and less likely to report zero mentally unhealthy or anxious days. These data add important information to a growing body of evidence concerning the potential adverse effects of UPF consumption on mental health.

Cardiovascular Risk Factors in Young Adolescents: Results from the National Health and Nutrition Examination Survey 1988-2016.

OBJECTIVES: Lifestyle behaviors relevant to cardiovascular health are learned during childhood and continued into adulthood. Children and adolescents who participate in unhealthy behaviors have a higher lifetime risk of cardiovascular disease in adulthood. Public health institutions publish behavior and clinical recommendations designed for adolescents to reduce their lifetime cardiovascular risk. We assessed the prevalence and trends of cardiovascular-relevant behaviors and clinical tests among early adolescents using a nationally representative database. METHODS: In 2020, we compared the prevalence of cardiovascular risk factors among 1408 adolescents surveyed from 1988 to 1994 with that of 1812 adolescents surveyed from 2011 to 2016 by obtaining and comparing measures on physical activity, diet, body mass index, smoking status, cholesterol levels, hemoglobin A1c, sodium intake, and blood pressure. RESULTS: The prevalence of adherence to the current recommendations regarding physical activity, diet, and body weight declined over time. Conversely, the prevalence of adhering to recommendations to avoid smoking increased. Clinical indicators, including blood pressure control and normal measures of hemoglobin A1c and total serum cholesterol, showed mixed results, with more individuals showing signs of hyperglycemia, fewer showing signs of hypercholesterolemia, and the percentage of individuals with abnormal blood pressure remaining the same. The use of cardiometabolic medications also increased during the study period. Finally, the number of adolescents with all seven cardiovascular protective factors declined significantly during the study period, from 27.6% to 9.6%. CONCLUSIONS: Modern American teenagers aged 12 to 16 years have more cardiovascular risk factors relating mostly to diet, exercise, and obesity than those of a prior generation; however, smoking rates have also declined precipitously.

Prevalence of HCV Infection in Adults with Congenital Heart Disease and Treatment with Direct Antiviral Agents.

OBJECTIVES: Hepatitis C virus (HCV) infection affects >3% of the US population, which over time can lead to cirrhosis and hepatocellular carcinoma. The lack of a reliable screening method for HCV before 1992 resulted in a higher prevalence of the virus in adults with congenital heart disease who underwent corrective surgery that required blood transfusions. Direct-acting antiviral agents such as sofosbuvir/ledipasvir have significantly increased the efficacy of HCV therapy, although use of these medications in adults with congenital heart disease has not been described. METHODS: Ours was a retrospective study of 188 adults with congenital heart conditions who had cardiac surgery before 1992. These patients were screened for HCV using HCV antibody followed by HCV RNA if the screening test was positive. RESULTS: Of the 188 adults, 116 (43% male patients, 24-70 years) were screened for the HCV antibody, demonstrating that 104 individuals were negative and 12 subjects were positive for the virus. Subsequently, further testing for the presence of HCV demonstrated 11 of 12 were infected, with an overall prevalence of 9.5%. Five individuals chose to be treated with sofosbuvir/ledipasvir and 5 of 5 have successfully cleared the virus and are considered cured. CONCLUSIONS: Adults with congenital heart disease who underwent cardiac surgery before 1992 warrant being screened for HCV, and, if testing positive, may be considered for therapy using direct-acting antiviral agents with close monitoring for cardiac complications.

LOGIQ E9 Shear Wave Elastrography for Detection of Liver Fibrosis in Patients with Chronic Hepatitis C Virus.

OBJECTIVES: Shear wave elastography (SWE) is an emerging technology that assesses hepatic fibrosis. The aim of our study was to determine the diagnostic accuracy of General Electric (GE) Healthcare's LOGIQ E9 SWE in patients with chronic hepatitis C virus using liver biopsy as the reference standard. METHODS: The liver stiffness of 43 subjects with hepatitis C virus was assessed using LOGIQ E9 SWE immediately before they underwent liver biopsy. The Fibrosis-4 Index (FIB-4) and Aspartate Aminotransferase-to-Platelet Index (APRI) were calculated, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: Mild hepatic fibrosis (F0-F2) was noted in 30 of the 43 (69.7%) patients and advanced disease (F3-F4) was seen in 13 of the 43 (30.3%) individuals. Using the GE LOGIQ E9 SWE proposed cutoff value of ≥9.4 kPa for advanced fibrosis, the sensitivity, specificity, PPV, and NPV were only 69.2%, 73.3%, 52.9%, and 84.6%, respectively. The post hoc analysis identified best cutoff values of <9.4 and ≥12 kPa, thereby classifying 76% of patients with an NPV of 84.6% and a PPV of 85.7%. The Aminotransferase-to-Platelet Index results were as follows: 83.3%, sensitivity, 95.2% specificity, 83.3% PPV, and 95.2% NPV in 27 of the individuals (37% remained unclassifiable). The FIB-4 Index demonstrated 100% sensitivity, 76.9% specificity, 66.6% PPV, and 100% NPV; however, 24 (56%) of the patients were classified within the indeterminate range. CONCLUSIONS: In our cohort, the proposed GE LOGIQ value of ≥9.4 kPa did not adequately discriminate subjects with advanced fibrosis. Further prospective evaluation of our post hoc analyses is warranted to identify the ideal cutoff values for the LOGIQ E9 system.

Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Fibroblast growth factor 21 (FGF21) regulates metabolism and protects cells against stress. Efruxifermin is a bivalent Fc-FGF21 analogue that replicates FGF21 agonism of fibroblast growth factor receptor 1c, 2c, or 3c. The aim of this phase 2b study was to assess its efficacy and safety in patients with non-alcoholic steatohepatitis (NASH) and moderate (F2) or severe (F3) fibrosis. METHODS: HARMONY is a multicentre, randomised, double-blind, placebo-controlled, 96-week, phase 2b trial that was initiated at 41 clinics in the USA. Adults with biopsy-confirmed NASH, defined by a non-alcoholic fatty liver disease activity score (NAS) of 4 or higher and scores of 1 or higher in each of steatosis, ballooning, and lobular inflammation, with histological stage F2 or F3 fibrosis, were randomly assigned (1:1:1), via an interactive response system, to receive placebo or efruxifermin (28 mg or 50 mg), subcutaneously once weekly. Patients, investigators, pathologists, site staff, and the sponsor were masked to group assignments during the study. The primary endpoint was the proportion of patients with improvement in fibrosis of at least 1 stage and no worsening of NASH, based on analyses of baseline and week 24 biopsies (liver biopsy analysis set [LBAS]). A sensitivity analysis evaluated the endpoint in the full analysis set (FAS), for which patients with missing biopsies were considered non-responders. This trial is registered with ClinicalTrials.gov, NCT04767529, and is ongoing. FINDINGS: Between March 22, 2021, and Feb 7, 2022, 747 patients were assessed for eligibility and 128 patients (mean age 54·7 years [SD 10·4]; 79 [62%] female and 49 male [38%]; 118 [92%] white; and 56 [41%] Hispanic or Latino) were enrolled and randomly assigned to receive placebo (n=43), efruxifermin 28 mg (n=42; two randomised patients were not dosed because of an administrative error), or efruxifermin 50 mg (n=43). In the LBAS (n=113), eight (20%) of 41 patients in the placebo group had an improvement in fibrosis of at least 1 stage and no worsening of NASH by week 24 versus 15 (39%) of 38 patients in the efruxifermin 28 mg group (risk ratio [RR] 2·3 [95% CI 1·1-4·8]; p=0·025) and 14 (41%) of 34 patients in the efruxifermin 50 mg group (2·2 [1·0-5·0]; p=0·036). Based on the FAS (n=128), eight (19%) of 43 patients in the placebo group met this endpoint versus 15 (36%) of 42 in the efruxifermin 28 mg group (RR 2·2 [95% CI 1·0-4·8]; p=0·033) and 14 (33%) of 43 in the efruxifermin 50 mg group (1·9 [0·8-4·3]; p=0·123). The most frequent efruxifermin-related adverse events were diarrhoea (16 [40%] of 40 patients in the efruxifermin 28 mg group and 17 [40%] of 43 patients in efruxifermin 50 mg group vs eight [19%] of 43 patients in the placebo group; all events except one were grade 1-2) and nausea (11 [28%] patients in the efruxifermin 28 mg group and 18 [42%] patients in the efruxifermin 50 mg group vs ten [23%] patients in the placebo group; all grade 1-2). Five patients (two in the 28 mg group and three in the 50 mg group) discontinued due to adverse events. Serious adverse events occurred in four patients in the 50 mg group; one was defined as drug related (ulcerative esophagitis in a participant with a history of gastro-oesophageal reflux disease). No deaths occurred. INTERPRETATION: Efruxifermin improved liver fibrosis and resolved NASH over 24 weeks in patients with F2 or F3 fibrosis, with acceptable tolerability, supporting further assessment in phase 3 trials. FUNDING: Akero Therapeutics.

Patient and endoscopic characteristics and clinical outcomes in subjects with non-variceal GI bleeding referred for transarterial embolization: a single-center experience.

PURPOSE: Management of massive non-variceal upper gastrointestinal bleeding (NV-UGIB) can be challenging. Transarterial Embolization (TAE) is often the first therapeutic approach when endoscopic therapy fails before surgery. The purpose of this study is to analyze the technical success, and outcome for our patients with an NV-UGIB referred for TAE. METHOD: This retrospective analysis included 74 consecutive patients with an NV-UGIB in whom TAE was performed after endoscopic treatment between February 2016 to May 2019 at Prisma Health-Upstate Greenville Memorial Hospital. RESULTS: TAE was 98.7% technically successful, with a failure due to severe celiac stenosis, and 85.1% clinically successful. Most TAEs were performed empirically due to lack of extravasation yet were clinically as effective as targeted TAE. We noted a 30-day rebleeding rate and mortality rate of 14.8% and 13.5%, respectively. No complications were reported during the angiographic procedure. Subjects with coagulopathy had more rebleeding (45.5% vs. 17.5%, p = 0.040), and mortality (30% vs 7.4%, p = 0.012). Mortality was also associated with the number of transfused packed blood cells (13.6 ± 8.4 vs. 6.1 ± 5.4, p = 0.020) units and hypotension on admission (27.8% vs. 8.9%, p = 0.043). Interestingly, subjects that underwent left gastric artery (LGA) compared to non-LGA embolization had a higher rebleeding rate of (37.5% vs. 8.6%, p = 0.004) and a greater mortality rate of (37.5% vs. 6.9%, p = 0.002). CONCLUSION: TAE is clinically effective in the presence or absence of contrast extravasation to treat uncontrolled or high-risk NV-UGIB. Less effective clinical outcomes regarding TAE targeting the LGA warrant further investigation.

Risk stratification of adolescents for the screening of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver conditions in adolescence are associated with premature mortality in adulthood. Effective screening could impact the population burden of this disease. OBJECTIVES: We sought to determine which adolescents should be screened for non-alcoholic fatty liver using vibration-controlled transient elastography. METHODS: We simulated a non-alcoholic fatty liver screening program of 938 adolescents from the National Health and Nutritional Examination Survey of 2017/2018. We stratified subjects by body mass index and metabolic parameters and analyzed our data using standard diagnostic statistical measures. RESULTS: The weighted prevalence of non-alcoholic fatty liver and non-alcoholic fatty liver disease was 24.4%, and 3.8%, respectively. For all subjects with obesity (21.8% of the population), screening identified 61.8% of the non-alcoholic fatty liver cases. In a category of all subjects with obesity and overweight subjects with metabolic abnormalities (26.7% of the population), screening identified 71.2% of non-alcoholic fatty liver cases. CONCLUSIONS: The two groups most likely to benefit by transient elastography screening are adolescents with obesity and overweight adolescents with one metabolic abnormality. These criteria reduce the number of individuals to be tested by approximately 80% (from an approximate 32 million adolescents to 6-7.5 million adolescents), while retaining a diagnostic accuracy of 84%-85%.

Serum Alanine Transaminase Is an Inadequate Nonalcoholic Fatty Liver Screening Test in Adolescents: Results From the National Health and Nutrition Examination Survey 2017-2018.

Nonalcoholic fatty liver disease (NAFLD) is common in overweight adolescents, and screening with serum alanine transaminase (ALT) levels is recommended by the American Academy of Pediatrics. We sought to determine if ALT is an accurate adolescent screening measure for NAFLD in a nationally representative sample of overweight adolescents. Diagnosis of NAFLD was determined using vibration-controlled transient elastography. Analyses were performed to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index at various serum ALT cutoff levels. Receiver operating curves were generated in order to determine ALT's discrimination capability. Males and females were analyzed separately. While average measures (mean and median) of ALT were higher in subjects with NAFLD, ALT provided only minimal discrimination with AUROC (area under the receiver operating characteristic) values of .66 in males and .67 in females. In a nationally representative sample of overweight and obese adolescents, serum ALT level functioned inadequately as a screening test to detect NAFLD.

High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo.

NAFLD (non-alcoholic fatty liver disease), associated with obesity and the cardiometabolic syndrome, is an important medical problem affecting up to 20% of western populations. Evidence indicates that mitochondrial dysfunction plays a critical role in NAFLD initiation and progression to the more serious condition of NASH (non-alcoholic steatohepatitis). Herein we hypothesize that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species). To test this concept, C57BL/6 mice were pair-fed a control diet and HFD containing 35% and 71% total calories (1 cal approximately 4.184 J) from fat respectively, for 8 or 16 weeks and liver hypoxia, mitochondrial bioenergetics, NO (nitric oxide)-dependent control of respiration, and 3-NT (3-nitrotyrosine), a marker of protein modification by RNS, were examined. Feeding a HFD for 16 weeks induced NASH-like pathology accompanied by elevated triacylglycerols, increased CYP2E1 (cytochrome P450 2E1) and iNOS (inducible nitric oxide synthase) protein, and significantly enhanced hypoxia in the pericentral region of the liver. Mitochondria from the HFD group showed increased sensitivity to NO-dependent inhibition of respiration compared with controls. In addition, accumulation of 3-NT paralleled the hypoxia gradient in vivo and 3-NT levels were increased in mitochondrial proteins. Liver mitochondria from mice fed the HFD for 16 weeks exhibited depressed state 3 respiration, uncoupled respiration, cytochrome c oxidase activity, and mitochondrial membrane potential. These findings indicate that chronic exposure to a HFD negatively affects the bioenergetics of liver mitochondria and this probably contributes to hypoxic stress and deleterious NO-dependent modification of mitochondrial proteins.

Healthy Behavior Adherence: The National Health and Nutrition Examination Survey, 2005-2016.

INTRODUCTION: Leading public health institutions recommend participation in several evidence-based behaviors, including exercise, a healthy diet, and maintenance of a normal BMI while simultaneously avoiding cigarette smoking and excessive alcohol consumption. The investigators attempted to evaluate the collective adherence to these recommendations and population trends in these behaviors by evaluating nationally representative surveys over a period of 12 years. METHODS: In 2019, the data from 26,194 National Health and Examination Survey participants who provided answers to survey questions regarding diet, physical activity, and usage of cigarettes and alcohol were analyzed. BMI was obtained from the examination data. Adherence to each behavior and the constellation of all 5 behaviors was assessed and tracked over a 12-year timeframe. RESULTS: The smoking rates (p=0.01) and adherence to a healthy BMI declined over time (p=0.03). The total percentage of subjects who participated in all 5 behaviors ranged from 4.4% to 6.3%, whereas subjects who performed 2 or fewer behaviors ranged from 45.4% to 48.3%. Greater education (p<0.0001), higher SES (p<0.0001), and being a female participant (p<0.0001) predicted higher behavior scores. CONCLUSIONS: Only 1 in 5 Americans engage in 4 or more healthy behaviors, whereas almost half of them participate in fewer than 3 healthy behaviors. Increased participation in numerous healthy behaviors can decrease premature mortality, decrease the burden of chronic diseases, improve life quality, and provide substantial economic benefits. A public health practice of targeting a constellation of behaviors as opposed to individual behaviors is needed.

A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis.

BACKGROUND & AIMS: Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-alpha (TNF-alpha) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-alpha-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis. METHODS: Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score > or = 15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points. RESULTS: There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5-6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3-16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04). CONCLUSIONS: In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.

Human mesenteric adipose tissue plays unique role versus subcutaneous and omental fat in obesity related diabetes.

BACKGROUND/AIMS: Obesity is a common and rapidly growing health problem today. Obesity is characterized by the increase of body fat and an excess of total body fat and, in particular, visceral fat accumulation, is considered to be a risk factor for type 2 diabetes mellitus. To determine whether the malfunction of the mesenteric adipose tissue plays an important role in the diabetic related metabolic syndrome, in this study, lipolysis and gene expression in the subcutaneous, omental and mesenteric adipose tissue of the diabetic subjects were evaluated. METHODS: Lipolysis and real time PCR were utilized to determine adipocyte function. RESULTS: Basal adipose tissue glycerol release is higher in diabetics than that of the non diabetics in all three fat depots. Isoproterenol (ISO) significantly increases glycerol release in subcutaneous, omental and mesenteric adipose tissues of non diabetic subjects but it stimulated glycerol release was significantly impaired in all three fat depots of the diabetic subjects. Gene expression studies indicate that leptin, Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Fatty acid translocase (FAT/CD36) and 11beta-hydroysteroid dehydrogenase (HSD) gene expression were significantly up regulated in the mesenteric adipose tissue of the diabetic patients. CONCLUSION: Human mesenteric adipose tissue in obese diabetic subjects has high basal glycerol release and impaired isoproterenol stimulated glycerol release. The obesity-related gene expressions in the mesenteric adipose tissue are up regulated, suggesting that the alterations of these genes in mesentery adipose depot may play a critical role in insulin resistance of type 2 diabetes and metabolic syndrome.

The utility of the "NAFLD fibrosis score" in morbidly obese subjects with NAFLD.

BACKGROUND: To date, the noninvasive diagnostic tests for hepatic fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) have proven to be suboptimal. We evaluated the validity of a recently proposed "NAFLD fibrosis score" to identify liver fibrosis in morbidly obese individuals with elevated and normal alanine aminotransferase (ALT) levels. METHODS: Medical records of 401 patients that underwent a gastric bypass operation and intraoperative liver biopsy were analyzed. Three hundred thirty one patients with biopsy-proven NAFLD were included in the study (group A). These patients were divided into two ALT groups based on their levels according to the new proposed normal range: group B elevated level (ALT > 19 U/L in females and >30 U/L in males, n = 221) and group C normal ALT (n = 110). Diagnostic accuracy of the system was assessed for the presence/absence of any fibrosis, significant fibrosis (stage 2-4), and advanced fibrosis (stages 3 and 4) in all of the groups. RESULTS: The prevalence of advanced fibrosis in our cohort was about 14%. The low NAFLD fibrosis score demonstrated high accuracy for ruling out advanced fibrosis, with negative predictive value (NPV) of 98 and 99% in groups A and B, respectively. The NPV for significant fibrosis in groups A, B, and C was 87, 88, and 88%, respectively. The respective positive predictive value for the high NAFLD fibrosis score for the presence of any fibrosis was 88, 95, and 77% in groups A, B, and C. CONCLUSIONS: The NAFLD fibrosis score may be a useful noninvasive approach for excluding significant and advanced fibrosis and in morbidly obese patients.

Refractory Hepatic Hydrothorax: A Rare Complication of Systemic Sclerosis and Presinusoidal Portal Hypertension.

We report on a rare case of refractory hepatic hydrothorax in an individual with Scleroderma/CREST syndrome and noncirrhotic portal hypertension. Portal pressure measurements revealed a normal transjugular hepatic venous portal pressure gradient, mild pulmonary hypertension, and an unremarkable liver biopsy except for mild sinusoidal dilation. Pulmonary hypertension, cardiac diastolic dysfunction, and chronic kidney disease were determined to be the causes of his refractory pleural effusions and ascites. Over the year, he underwent 50 thoracenteses and 20 paracenteses averaging 10-12 liters/week. Repeat pulmonary evaluation determined his pulmonary pressures to be normal and a secondary review of the "unremarkable" liver biopsy noted mild venous outflow obstruction and possibly Nodular Regenerative Hyperplasia (NRH). Repeat portal pressures indirectly and directly confirmed the existence of presinusoidal portal hypertension that has been associated with NRH. A transjugular intrahepatic portal systemic shunt (TIPS) was placed and he has not required thoracentesis or paracentesis over the past 18 months.

FibroSURE and elastography poorly predict the severity of liver fibrosis in Fontan-associated liver disease.

OBJECTIVE: As the population of patients with Fontan circulation surviving into adulthood increases, hepatic cirrhosis has grown to be a significant cause of morbidity and mortality. Early detection of advanced hepatic fibrosis is imperative for proper intervention and consideration for heart or combined heart/liver transplantation. Noninvasive biomarkers and elastography have been evaluated for their diagnostic utility with variable results in the Fontan population. DESIGN: The cohort included 14 patients age 26.4 SD 7.5 who underwent Fontan surgery. All patients were evaluated with FibroSURE, shear wave elastography (SWE), hepatic duplex sonography, and liver biopsy. Liver fibrosis on biopsy was evaluated according to the congestive hepatic fibrosis system. RESULTS: In our cohort, 100% of patients had fibrosis with 36% demonstrating advanced fibrosis. FibroSURE agreed with liver biopsy in only 5 out of 14 cases (36%): underestimating in 7 and overestimating in 2 individuals. SWE agreed with liver biopsy in 0% of cases: overestimating in 10 and underestimating in 4 cases. None of the duplex sonography indices predicted the presence or severity of liver fibrosis. CONCLUSION: This study demonstrates that children who have undergone a Fontan procedure universally develop some hepatic fibrosis and a significant number have advanced fibrosis by adulthood. The FibroSURE blood test, SWE, and hepatic duplex sonography were unable to accurately predict the presence or severity of hepatic fibrosis when compared with liver biopsy. Further studies are needed to investigate novel noninvasive methods and/or biomarkers that can adequately detect advanced hepatic fibrosis before the development of cirrhosis and hepatic decompensation.

Postmenopausal Deep Infiltrating Endometriosis of the Colon: Rare Location and Novel Medical Therapy.

We report an uncommon case of deep infiltrating endometriosis of the colon presenting as iron deficiency anemia nine years after hysterectomy with bilateral salpingo-oophorectomy. The endometrial implant was found at the hepatic flexure, an exceedingly rare location for endometriosis invasion with no cases distinctly reported in the literature. Additionally, the presentation of gastrointestinal endometriosis as iron deficiency anemia is not well documented in the literature. Instead of surgery, we prescribed a novel medical therapeutic approach using conjugated estrogen-bazedoxifene to antagonize the proliferative effects of estrogen on endometrial tissue. After five months of therapy and repeat colonoscopy, no evidence of endometrial tissue remained in the hepatic flexure.

Resolution of nonalcoholic steatohepatits after gastric bypass surgery.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been increasingly recognized as a common chronic liver condition. Previous studies have been variable regarding the histological outcomes after rapid weight loss. The aim of this study was to characterize the histopathologic changes in NASH following laparoscopic Roux-en-Y Gastric Bypass surgery (LRYGBP). METHODS: We retrospectively analyzed paired needle liver biopsies taken during and following LRYGBP in 39 patients according to the recent NIH-based NAFLD criteria. RESULTS: The cohort included 33 females and 6 males (range 24-57 years). 23 patients (58.9%) had steatohepatitis, 12 with fatty liver (30.7%), and 4 were normal (10.2%). Follow-up needle liver biopsies were performed at a mean interval of 18 months (range 6-41 months). No significant differences in length or number of portal tracts between the paired biopsies were noted. The mean decrease in weight and BMI was 50.2 kg and 18.2 kg/m2, respectively. The initial prevalence of hepatic pathology: steatosis (89.7%), hepatocellular ballooning (58.9%), and centrilobular/perisinusoidal fibrosis (50%) improved significantly after LRYGBP: steatosis (2.9%), ballooning (0%), and centrilobular fibrosis (25%). Mitigation in the lobular inflammation score (2.23+/-0.63 vs 1.95+/-0.56, P=0.01) and stage of fibrosis (1.14+/-1.05 to 0.72+/-0.97, P=0.002) were also noted. However, no improvements were detected in portal tract inflammation and fibrosis. CONCLUSIONS: Over a mean period of 18 months, histological improvements and resolution of NASH occurs after LRYGBP. Long-term studies are warranted to assess for potential changes in the portal regions or relapse of NASH that could result with weight regain or malnutrition.

Influence of liver biopsy heterogeneity and diagnosis of nonalcoholic steatohepatitis in subjects undergoing gastric bypass.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic condition that can progress to cirrhosis and hepatocellular cancer. The most progressive form of NAFLD is nonalcoholic steatohepatitis (NASH). Currently, the only method to diagnose NASH is with a liver biopsy; however. sampling error may limit diagnostic accuracy. We investigated the discordance of paired liver biopsies in individuals undergoing gastric bypass. METHODS: Two liver biopsies, composite size of > or = 25 mm and > or = 8 portal tracts (PTs), were obtained from the left lobe in 31 subjects. Group 1 included specimens at least 15 mm in length with > or = 4 PTs compared to a second biopsy of at least 10 mm and > or = 4 PTs (Group 2). RESULTS: The mean specimen size (number of PTs) for group 1 was 20.4 +/- 4.2 mm (11.7 +/- 5.5 PTs) and group 2 was 16.1 +/- 5.3 mm (8.2 +/- 4.1 PTs). Prevalence of NASH was 26% in Group 1 and 32% in Group 2. Sampling discordance was greatest for portal fibrosis (26%), followed by zone 3 fibrosis (13%) and ballooning degeneration (3%). The negative predictive values from Group 1 liver biopsies for NASH and portal fibrosis were only 83% and 67%, respectively. CONCLUSIONS: The results demonstrate that significant sampling variability exists in class 2 and 3 obese individuals undergoing screening liver biopsies for NAFLD. The degree and histopathological discordance is dependent upon zonal location and types of injury. Nevertheless, a 25-mm biopsy specimen without zone 3 cellular ballooning or fibrosis appears adequate to exclude the diagnosis of NASH.

Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.

The prevalence of nonalcoholic steatohepatitis is greater in morbidly obese men compared to women.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver injury that is common in morbidly obese subjects. It has been shown that gender differences exist in the spectrum of nonalcoholic fatty liver disease (NAFLD). The focus of this study was to further characterize these gender differences based on ATP III criteria used to diagnose the metabolic syndrome (MS). METHODS: We retrospectively assessed NAFLD 58 men and 307 women who underwent gastric bypass, for the presence of NASH, MS, and positive predictors of NASH. RESULTS: There was no statistical difference in age, gender, or the presence of diabetes. The prevalence of NASH in men and women was 60.3% and 30.9%, respectively (P<0.001). Multivariate logistic analysis showed an association of male gender with NASH (2.7; 95% CI, 1.3-5.6, P=0.006) as well as age, AST, and diabetes. MS was diagnosed in 91.4% and 76.2% of men and women (P=0.008), and men tended to have more criteria for MS compared to women. The only positive predictor of MS that was statistically significant between genders was high triglycerides (P=0.003). Controlling for BMI and excess body weight produced similar results. CONCLUSIONS: Gender differences do exist within NAFLD and MS, that may be associated with free fatty acid flow to the liver.