Metabolic dysfunction-associated steatotic liver disease related cirrhosis and incidence of portal vein thrombosis.

BACKGROUND: There is heterogeneous data on whether metabolic-associated steatohepatitis is an independent risk factor for portal vein thrombosis (PVT). We aim to compare the incidence of PVT in patients with cirrhosis with and without metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a single-center retrospective study of patients with cirrhosis seen between 1 January 2016 and 31 January 2021. Patients with a history of hepatocellular cancer, liver transplant, Budd-Chiari syndrome, and intra-abdominal malignancies were excluded. Patients with cirrhosis were followed from their first hepatology visit for 180 days to determine the incidence of PVT. Cox proportional hazard regression was used to determine the relationship between MASLD with PVT. RESULTS: We analyzed data from 2785 patients with cirrhosis who met inclusion and exclusion criteria [mean age: 61.0 ±â€…12.3 years, 44.3% female, 63.8% Whites and mean model for end-stage liver disease-sodium (MELD-Na) score: 11.7 ±â€…6.1]. MASLD was present in 21.7% of patients. A total of 89 patients developed PVT during the follow-up, which was fewer in patients with MASLD [2.0% vs. 3.5%, P = 0.04, unadjusted heart rate (HR): 0.60, 95% confidence interval (CI): 0.27-0.96, P = 0.04]. After adjusting for the demographics, MASLD-related comorbid conditions and MELD-Na score, MASLD was associated with a lower incidence of PVT as compared to non-MASLD cirrhosis (HR: 0.44, 95% CI: 0.21-0.92, P = 0.03). After adjusting for the indicators of Child-Pugh Turcotte score, the risk of PVT in patients with MASLD compared to non-MASLD was not statistically significant (HR: 0.50, 95% CI: 0.22-1.13, P = 0.096). CONCLUSION: PVT incidence was lower in patients with MASLD cirrhosis as compared to non-MASLD cirrhosis. However, the difference was not significantly different after adjusting for liver decompensation.

MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up.

BACKGROUND AND AIMS: A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. APPROACH AND RESULTS: A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). CONCLUSIONS: In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

Cross-domain information fusion for enhanced cell population delineation in single-cell spatial-omics data.

Cell population delineation and identification is an essential step in single-cell and spatial-omics studies. Spatial-omics technologies can simultaneously measure information from three complementary domains related to this task: expression levels of a panel of molecular biomarkers at single-cell resolution, relative positions of cells, and images of tissue sections, but existing computational methods for performing this task on single-cell spatial-omics datasets often relinquish information from one or more domains. The additional reliance on the availability of "atlas" training or reference datasets limits cell type discovery to well-defined but limited cell population labels, thus posing major challenges for using these methods in practice. Successful integration of all three domains presents an opportunity for uncovering cell populations that are functionally stratified by their spatial contexts at cellular and tissue levels: the key motivation for employing spatial-omics technologies in the first place. In this work, we introduce Cell Spatio- and Neighborhood-informed Annotation and Patterning (CellSNAP), a self-supervised computational method that learns a representation vector for each cell in tissue samples measured by spatial-omics technologies at the single-cell or finer resolution. The learned representation vector fuses information about the corresponding cell across all three aforementioned domains. By applying CellSNAP to datasets spanning both spatial proteomic and spatial transcriptomic modalities, and across different tissue types and disease settings, we show that CellSNAP markedly enhances de novo discovery of biologically relevant cell populations at fine granularity, beyond current approaches, by fully integrating cells' molecular profiles with cellular neighborhood and tissue image information.

Statin use in cirrhosis and its association with incidence of portal vein thrombosis.

BACKGROUND AND AIM: Statin use has shown a reduction in hepatic decompensation and portal hypertension. Its association with portal vein thrombosis (PVT) incidence is unknown. We aim to compare the incidence of PVT in patients with and without statin use. METHODS: We excluded patients with a history of hepatocellular cancer, liver transplants, Budd-Chiari syndrome, and intra-abdominal malignancies. Patients with cirrhosis were followed from their first hepatologist clinical encounter (January 1, 2016, to January 31, 2021) for 180 days to determine PVT incidence. We tested the association of statin use with PVT using 1:1 propensity score (PS) matching and Cox proportional hazard regression. RESULTS: We analyzed 2785 patients with cirrhosis (mean age:61.0 ± 12.3 years, 44.3% female, 63.8% White, mean MELD-Na score:11.7 ± 6.1, and statin use:23.1%). A total of 89 patients developed PVT during the follow-up, which was lower in patients with statin use as compared to no statin use (1.3% vs 3.8%, P = 0.001, unadjusted HR:0.28, 95% CI: 0.13-0.62, P = 0.001). After matching for demographics, comorbidities, and hepatic decompensation events, patients with statin use had a lower risk of developing PVT in 180-day follow-up as compared to those without statin use (HR:0.24, 95% CI: 0.10-0.55, P = 0.001). Subgroup analysis showed that statin use was associated with lower PVT incidence in non-NASH (HR: 0.20, 95% CI: 0.07-0.54, P = 0.002) and decompensated cirrhosis (HR: 0.12, 95% CI:0.03-0.53, P = 0.005) than no statin use. CONCLUSION: PVT incidence was lower in decompensated cirrhosis patients with statin use than in those with no statin use. However, this finding needs to be further tested in randomized control trials.

Chicoric acid inserted in protein Z cavity exhibits higher stability and better wound healing effect under oxidative stress.

Oxidative stress is one of the limiting factors that inhibit wound healing. Phytochemicals especially chicoric acid have the potential to act as an antioxidant and scavenge reactive oxygen species, thereby promoting wound healing. However, most of the phytochemicals were easy to be degraded during storage or using due to the oxidative status in wound site. Herein, we introduce a high stable protein Z that can encapsulate chicoric acid during foaming. TEM results showed that the size of protein Z-chicoric acid is in the range of nanoscale (named PZ-CA nanocomposite), and protein Z encapsulation can significantly improve the stability of chicoric acid under oxidative stress. Moreover, PZ-CA nanocomposite exhibited favorable antioxidant properties, biocompatibility, and the ability to promote cell migration in vitro. The role of PZ-CA nanocomposite in skin regeneration was explored by a mice model. Results in vivo suggest that the PZ-CA nanocomposite promotes wound healing with a faster rate as compared with a commercial spray solution, mostly through attenuating the oxidative stress, promoting cell proliferation and collagen deposition. This work not only provides a delivery vector for bioactive molecules, but also develops a kind of nanocomposite with the property of promoting wound healing.

GlycA: Evaluation of a New Biomarker of Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate-severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP. METHODS: We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera® Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 µmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity. RESULTS: Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m2; p < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 µmol/L, p < 0.001) and at discharge (655 vs. 376 µmol/L, p < 0.001). GlycA levels were significantly higher in patients with moderate-severe AP than in those with mild AP at discharge (533 vs. 757 µmol/L, p = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 µmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07-32.2; p = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48-42.0; p = 0.025) than controls. CONCLUSION: Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.

Elevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.

Background Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; P=0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; P=0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; P=0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.

Inhibition of Iron Release from Donkey Spleen Ferritin through Malt-Derived Protein Z-Ferulic Acid Interactions.

Protein-small molecule interactions naturally occur in foodstuffs, which could improve the properties of protein and small molecules. Meanwhile, they might affect the bioavailability and nutritional value of proteins. Ferritin, as an iron-storage protein, has been a focus of research. However, the complexity of foodstuffs enables the interaction between ferritin and food components, especially polyphenols, which can induce iron release from ferritin. Thus, the application of ferritin in food is limited. Inspired by the natural-occurring, strong protein-polyphenol interactions in beer, to inhibit the iron release of ferritin, the malt-derived protein Z (PZ) was chosen to interact with ferulic acid (FA), an abundant reductant in malt, beer, and other foodstuffs. The analysis of the interaction between PZ and FA was carried out using fluorescence spectroscopy, the results of which suggest that one PZ molecule can bind with 22.11 ± 2.13 of FA, and the binding constant is (4.99 ± 2.13) × 105 M-1. In a molecular dynamics (MD) simulation, FA was found to be embedded in the internal hydrophobic pocket of PZ, where it formed hydrogen bonds with Val-389 and Tyr-234. As expected, compared to iron release induced by FA, the iron release from donkey spleen ferritin (DSF) induced by FA decreased by 86.20% in the presence of PZ. Meanwhile, based on the PZ-FA interaction, adding PZ in beer reduced iron release from DSF by 40.5% when DSF:PZ was 1:40 (molar ratio). This work will provide a novel method of inhibiting iron release from ferritin.

Potential enzymes involved in beer monoterpenoids transformation: structures, functions and challenges.

Monoterpenes are important flavor and fragrance compounds in food. In beer, the monoterpenes mainly come from hops added during boiling process. Biotransformations of monoterpene which occurred during fermentation conferred beer with various kinds of aroma profiles, which can be mainly attributed to the contribution of enzymes in yeast. However, there are few reports on the identification and characterization of these enzymes in yeast. Illustrating the structure and functions of key enzymes related to transformations will broaden their potential applications in beer or other foodstuffs. Monoterpenoids including terpene hydrocarbons (limonene, myrcene, and pinene) and terpene alcohol (linalool, geraniol, nerol, and citronellol) gave the beer flower-like or fruit-like aroma. The biotransformation of monoterpenes and monoterpene alcohols in bacteria and yeast, and potential enzymes related to the transformation of them are reviewed here. Enzymes primarily are dehydrogenases including linalool dehydrogenase/isomerase, geraniol/geranial dehydrogenase, nerol dehydrogenase and citronellol dehydrogenase. Most of them are substrate-specific or substrate-specific after modifications by biotechnology methods, and part of them have been expressed in E. coli, while the purification and catalytic rate is very low. Efforts should be made to acquire abundant enzymes, and to fabricate enzyme-expressing yeast, which can be further applied in beer fermentation system.highlightsMonoterpenoids contributed to the flavor of food, especially beer.Transformation of monoterpenoids occurred during fermentation.Various kinds of enzymes are involved in the transformation of monoterpenoids in bacteria, yeast, etc.Crystal structures of these enzymes have been partially resolved.Few enzymes are further applied in food system to obtain abundant flavor.

Binding of curcumin to barley protein Z improves its solubility, stability and bioavailability.

Although excessive pharmaceutical activities of curcumin have been reported, the poor solubility, low stability and low bioavailability greatly limited its application. In this study, the interaction between protein Z (PZ) and curcumin, and the effects of PZ on the stability and bioavailability of curcumin were investigated. Fluorescence quenching results indicated that curcumin molecule binds PZ with a stoichiometry of 4:1, and the binding affinity is stronger than other reported protein carriers. Molecular dynamics simulation results suggested that curcumin binds in the hydrophobic region of PZ, and the interaction was maintained mainly by hydrogen-bond (Pro-287, Asn-340 and Tyr-234). PZ-curcumin complex possessed better encapsulation efficiency (64.10 %) and loading capacity (5.49 µg/mg) for curcumin. In addition, binding with PZ not only improved the thermal, light and digestive stability of curcumin significantly, but lowered its toxic effect on Caco-2 cells and improved relative bioavailability (305 %) compared with that of curcumin only.

Roles of Proteins/Enzymes from Animal Sources in Food Quality and Function.

Animal proteins are good sources of protein for human, due to the composition of necessary amino acids. The quality of food depends significantly on the properties of protein inside, especially the gelation, transportation, and antimicrobial properties. Interestingly, various kinds of molecules co-exist with proteins in foodstuff, and the interactions between these can significantly affect the food quality. In food processing, these interactions have been used to improve the texture, color, taste, and shelf-life of animal food by affecting the gelation, antioxidation, and antimicrobial properties of proteins. Meanwhile, the binding properties of proteins contributed to the nutritional properties of food. In this review, proteins in meat, milk, eggs, and fishery products have been summarized, and polysaccharides, polyphenols, and other functional molecules have been applied during food processing to improve the nutritional and sensory quality of food. Specific interactions between functional molecules and proteins based on the crystal structures will be highlighted with an aim to improve the food quality in the future.

Associations between alcohol consumption and hepatic steatosis in the USA.

Despite being widely recognized as a common cause of fatty liver, the exact impact of alcohol consumption on hepatic steatosis in the general population is elusive. The recent National Health and Nutrition Examination Survey (NHANES) allowed us to examine this relationship among US adults. Herein, we extracted data on detailed alcohol consumption and controlled attenuation parameter (CAP) by FibroScan from 4509 participants in NHANES 2017-2018. Compared to metabolic risk factors such as diabetes and obesity, the association between alcohol consumption and CAP was less significant. In multivariable analysis, only those drinking 5-7 times per week showed significant increases in CAP scores. Although both frequency and quantity of drinking were positively associated with CAP score, only frequency remained significant after adjustment for quantity and binge drinking. These epidemiological observations suggested that the impact of alcohol on hepatic steatosis was much smaller than metabolic factors and dependent upon the frequency of drinking.

Functional reciprocity of proteins involved in mitosis and endocytosis.

Mitosis and endocytosis are two fundamental cellular processes essential for maintaining a eukaryotic life. Mitosis partitions duplicated chromatin enveloped in the nuclear membrane into two new cells, whereas endocytosis takes in extracellular substances through membrane invagination. These two processes are spatiotemporally separated and seemingly unrelated. However, recent studies have uncovered that endocytic proteins have moonlighting functions in mitosis, and mitotic complexes manifest additional roles in endocytosis. In this review, we summarize important proteins or protein complexes that participate in both processes, compare their mechanism of action, and discuss the rationale behind this multifunctionality. We also speculate on the possible origin of the functional reciprocity from an evolutionary perspective.

The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance.

As a core component of the mitotic checkpoint complex, BubR1 has a modular organization of molecular functions, with KEN box and other motifs at the N terminus inhibiting the anaphase-promoting complex/cyclosome, and a kinase domain at the C terminus, whose function remains unsettled, especially at organismal levels. We generate knock-in BubR1 mutations in the Drosophila genome to separately disrupt the KEN box and the kinase domain. All of the mutants are homozygously viable and fertile and show no defects in mitotic progression. The mutants without kinase activity have an increased lifespan and phenotypic changes associated with attenuated insulin signaling, including reduced InR on the cell membrane, weakened PI3K and AKT activity, and elevated expression of dFoxO targets. The BubR1 kinase-dead mutants have a reduced cap cell number in female germaria, which can be rescued by expressing a constitutively active InR. We conclude that one major physiological role of BubR1 kinase in Drosophila is to modulate insulin signaling.

Selective deletion of ENTPD1/CD39 in macrophages exacerbates biliary fibrosis in a mouse model of sclerosing cholangitis.

Purinergic signaling is important in the activation and differentiation of macrophages, which play divergent roles in the pathophysiology of liver fibrosis. The ectonucleotidase CD39 is known to modulate the immunoregulatory phenotype of macrophages, but whether this specifically impacts cholestatic liver injury is unknown. Here, we investigated the role of macrophage-expressed CD39 on the development of biliary injury and fibrosis in a mouse model of sclerosing cholangitis. Myeloid-specific CD39-deficient mice (LysMCreCd39fl/fl) were generated. Global CD39 null (Cd39-/-), wild-type (WT), LysMCreCd39fl/fl, and Cd39fl/fl control mice were exposed to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to induce biliary fibrosis. Hepatic hydroxyproline levels, liver histology, immunohistochemistry, mRNA expression levels, and serum biochemistry were then assessed. Following 3 weeks of DDC-feeding, Cd39-/- mice exhibited more severe fibrosis, when compared to WT mice as reflected by morphology and increased liver collagen content. Myeloid-specific CD39 deletion in LysMCreCd39fl/fl mice recapitulated the phenotype of global Cd39-/-, after exposure to DDC, and resulted in similar worsening of liver fibrosis when compared to Cd39fl/fl control animals. Further, DDC-treated LysMCreCd39fl/fl mice exhibited elevated serum levels of transaminases and total bilirubin, as well as increased hepatic expression of the profibrogenic genes Tgf-ß1, Tnf-α, and α-Sma. However, no clear differences were observed in the expression of macrophage-elaborated specific cytokines between LysMCreCd39fl/fl and Cd39fl/fl animals subjected to biliary injury. Our results in the DDC-induced biliary type liver fibrosis model suggest that loss of CD39 expression on myeloid cells largely accounts for the exacerbated sclerosing cholangitis in global CD39 knockouts. These findings indicate that macrophage expressed CD39 protects from biliary liver injury and fibrosis and support a potential therapeutic target for human hepatobiliary diseases.

Further Defining the 2012 Multi-Society Task Force Guidelines for Surveillance of High-risk Adenomas: Is a 3-Year Interval Needed for All Patients?

GOALS: We set out to determine whether variation from this 3-year follow-up interval was associated with the finding of subsequent high-risk adenoma (HRA). BACKGROUND: HRAs include the following: (1) an adenoma measuring ≥10 mm, (2) ≥3 adenomas found during a single procedure, and (3) an adenoma with high-grade dysplasia or villous architecture. The current Multi-Society Task Force guideline for timing of surveillance colonoscopy after removal of a HRA is 3 years. STUDY: In 2016, we analyzed 495 patients who had a HRA removed during a 2008 colonoscopy. We compared the frequency of finding another HRA at follow-up intervals. We used the current guidelines as our referent group and performed logistical regression to identify whether any patient characteristics, procedural factors, or type of HRA predicted the development of HRAs on follow-up colonoscopy. RESULTS: Individuals who followed-up at a median of 4.5 years did not have more HRA on follow-up compared with those who followed-up at 3 years (25.2% vs. 21.0%, P=0.062). These groups had similar baseline characteristics. Older individuals, male gender, having a history of polyps, and piecemeal resection of an HRA predicted future HRAs. The removal of ≥3 adenomas in 2008 as well as a combination of multiple, large, and advanced polyps showed a higher risk of future HRAs. CONCLUSIONS: The 2012 Multi-Society Task Force recommendation of 3-year follow-up after removal of HRAs may not apply to all patients. We showed that a combination of patient demographics, procedural factors, and pathology best determines the surveillance colonoscopy interval.

Lipoprotein metabolism in liver diseases.

PURPOSE OF REVIEW: The liver is the central hub of lipoprotein metabolism. A complex relationship exists between dyslipidemia and chronic liver diseases (CLDs). Recent advances in the genetics of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) exemplify the pivotal role of lipoprotein metabolism in the pathogenesis of CLD. We review these relationships in four quintessential forms of CLD: NAFLD, ALD, cholestatic liver disease and cirrhosis, with a focus on recent discoveries. RECENT FINDINGS: An I148 M variant in patatin-like phospholipase domain-containing protein 3 (PNPLA3) and an E167K variant in transmembrane 6 superfamily 2 (TM6SF2) are major genetic risk factors for the development and progression of NAFLD. These genetic variants also increase the risk of ALD. Both PNPLA3 and TM6SF2 are involved in the hepatic assembly of very low-density lipoprotein. The discovery of these two genetic variants highlights the risk of CLD when environmental factors are combined with functional modifications in the lipoprotein metabolism pathway. SUMMARY: The relationship between CLD and lipoprotein metabolism is reciprocal. On the one hand, the progression of CLD impairs lipoprotein metabolism; on the other hand, modifications in lipoprotein metabolism can substantially increase the risk of CLD. These relationships are at play among the most common forms of CLD affecting a significant proportion of the population.

Posttransplant Lymphoproliferative Disorder Isolated to the Adrenal Gland in a Liver Transplant Patient.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication that accounts for up to 20% of malignancies after solid organ transplantation. We describe a rare case of isolated PTLD in the adrenal gland occurring 7 months after liver transplant in a patient who developed a primary Epstein-Barr virus infection. He was treated with rituximab and his immunosuppression regimen was minimized. We review the incidence, pathogenesis, presentation, and management of PTLD in the liver-transplant population. Our case highlights the variation in the presentation of PTLD and the importance of a high index of suspicion among the at-risk group.

Genetic Determinants of Circulating Lipoproteins in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Recent genome-wide association studies have identified 2 genetic polymorphisms in association with nonalcoholic fatty liver disease (NAFLD): patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2), both of which appear to influence the production of very low density lipoprotein (VLDL). The impact of these genetic variations on lipoprotein metabolism in the setting of nonalcoholic steatohepatitis and liver fibrosis are not fully characterized. MATERIALS AND METHODS: We measured comprehensive lipoprotein profiles by nuclear magnetic resonance among 170 serially recruited patients in an NAFLD registry, and determined their relationships with PNPLA3 and TM6SF2 genotypes. RESULTS: In this cohort, 72% patients had at least 1 allele of either PNPLA3 I148M or TM6SF2 E167K, and 30% carried 2 alleles. In multivariate models adjusting for histologic features of nonalcoholic steatohepatitis and liver fibrosis, PNPLA3 I148M is associated with a decrease in VLDL particle size. Both PNPLA3 I148M and TM6SF2 E167K genotypes were associated with increases in the size of low density lipoprotein (LDL) and high density lipoprotein particles, phenotypes considered atheroprotective. When adjusted for both genotypes, NAFLD activity score, in particular the degree of hepatic steatosis was strongly associated with increases in the size of VLDL particles, the concentration of LDL, especially small LDL particles, and a decrease in the size of high density lipoprotein particles, all of which are linked with a proatherogenic phenotype. CONCLUSIONS: PNPLA3 and TM6SF2 are common genetic variants among NAFLD patients and impact lipoprotein profiles in slightly different ways. The interactions between genotypes, hepatic steatosis, and lipoprotein metabolism shed lights on the pathophysiology of NAFLD, and provide opportunities for personalized treatment in the era of emerging NAFLD therapeutics.

Characterizing Normal Bowel Frequency and Consistency in a Representative Sample of Adults in the United States (NHANES).

OBJECTIVES: Our current understanding of normal bowel patterns in the United States (US) is limited. Available studies have included individuals with both normal and abnormal bowel patterns, making it difficult to characterize normal bowel patterns in the US. The current study aims to (1) examine frequency and consistency in individuals with self-reported normal bowel habits and (2) determine demographic factors associated with self-reported normalcy. METHODS: This study used data from adult participants who completed bowel health questions as part of the National Health and Nutrition Examination Survey (NHANES) in 2009-2010 and who reported normal bowel patterns (N=4,775). Data regarding self-perceived bowel health; stool frequency; stool consistency (using the Bristol Stool Form Scale (BSFS)); and demographic factors were analyzed. RESULTS: 95.9% of the sample reported between 3 and 21 BMs per week. Among men, 90% reported a BSFS between 3 and 5, while for women it was 2-6. After controlling for age, the following demographic variables were associated with normalcy: male sex, higher education, higher income, <2 daily medications, and high daily fiber intake. Hispanic ethnicity was significantly associated with abnormal self-reported bowel habits. CONCLUSIONS: This is the first study to evaluate normal bowel frequency and consistency in a representative sample of adults in the US. The current findings bolster the common "3 and 3" metric of normal frequency (3 BMs/day to 3 BMs/week) while also suggesting different criteria for normal consistency for men and women. Finally, this study provides novel information about demographic factors associated with normal frequency and consistency.