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1.
Hepatic glycogen storage diseases are associated to microbial dysbiosis.
Colonetti, K, Bento Dos Santos, B, Nalin, T, Moura de Souza, CF, Triplett, EW, Dobbler, PT, Schwartz, IVD, Roesch, LFW
PloS one. 2019;(4):e0214582
Abstract
INTRODUCTION The gut microbiome has been related to several features present in Glycogen Storage Diseases (GSD) patients including obesity, inflammatory bowel disease (IBD) and liver disease. OBJECTIVES The primary objective of this study was to investigate associations between GSD and the gut microbiota. METHODS Twenty-four GSD patients on treatment with uncooked cornstarch (UCCS), and 16 healthy controls had their faecal microbiota evaluated through 16S rRNA gene sequencing. Patients and controls were ≥3 years of age and not on antibiotics. Faecal pH, calprotectin, mean daily nutrient intake and current medications were recorded and correlated with gut microbiome. RESULTS Patients' group presented higher intake of UCCS, higher prevalence of IBD (n = 04/24) and obesity/overweight (n = 18/24) compared to controls (n = 0 and 06/16, respectively). Both groups differed regarding diet (in patients, the calories' source was mainly the UCSS, and the intake of fat, calcium, sodium, and vitamins was lower than in controls), use of angiotensin-converting enzyme inhibitors (patients = 11, controls = 0; p-value = 0.001) multivitamins (patients = 22, controls = 01; p-value = 0.001), and mean faecal pH (patients = 6.23; controls = 7.41; p = 0.001). The GSD microbiome was characterized by low diversity and distinct microbial structure. The operational taxonomic unit (OTU) abundance was significantly influenced by faecal pH (r = 0.77; p = 6.8e-09), total carbohydrate (r = -0.6; p = 4.8e-05) and sugar (r = 0.057; p = 0.00013) intakes. CONCLUSIONS GSD patients presented intestinal dysbiosis, showing low faecal microbial diversity in comparison with healthy controls. Those findings might be due to the disease per se, and/or to the different diets, use of UCSS and of medicines, and obesity rate found in patients. Although the main driver of these differences is unknown, this study might help to understand how the nutritional management affects GSD patients.
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The Range and Reproducibility of the Liver Frailty Index.
Wang, CW, Lebsack, A, Chau, S, Lai, JC
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2019;(6):841-847
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Abstract
The Liver Frailty Index (LFI), composed of 3 performance-based tests (grip strength, chair stands, and balance), is a tool specifically developed in patients with cirrhosis to objectively measure physical function, a critical determinant of health outcomes. We aimed to (1) determine the range of LFI scores in adults with chronic liver disease but without cirrhosis, (2) determine the range of LFI scores in adults without known liver disease, and (3) evaluate reproducibility of the LFI in adults with cirrhosis listed for liver transplantation. Intraclass correlation coefficient (ICC) assessed interrater reliability of the LFI. Included were 91 adults with chronic liver disease, 109 adults without known liver disease, and 166 adults with cirrhosis with median Model for End-Stage Liver Disease-sodium of 16. Median (interquartile range) LFI was 3.6 (3.1-4.1) in adults with cirrhosis, 3.1 (2.5-3.7) in adults with chronic liver disease but not cirrhosis, and 2.7 (2.2-3.2) in adults without liver disease (P < 0.001). Using established LFI cutoffs for robust, prefrail, and frail categories, adults with cirrhosis or chronic liver disease were less likely to be robust (29% versus 53% versus 77%) and more likely to be prefrail (57% versus 42% versus 22%) or frail (14% versus 5% versus 1%) when compared with adults without liver disease (P < 0.001). The LFI had excellent reliability with ICC of 0.93 (95% confidence interval, 0.91-0.95). In conclusion, the LFI has external validity in noncirrhotic populations and is highly reproducible among different raters. This objective assessment tool can be implemented in outpatient clinical practice or research to operationalize the concept of physical frailty.
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The Liver and Celiac Disease.
Rubio-Tapia, A, Murray, JA
Clinics in liver disease. 2019;(2):167-176
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Abstract
Celiac disease is a multisystem disorder. Celiac hepatitis characterized by gluten-responsive mild elevation of transaminases is the more common liver manifestation of celiac disease. Celiac disease may also be associated or coexist with other chronic liver disorders. Shared genetic risk and increased intestinal permeability have been suggested to be the most relevant events in the pathogenesis of liver injury in celiac disease. The aim of this article is to review the full spectrum of liver disorders in patients with celiac disease.
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Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial.
Telgenkamp, I, Kusters, YHAM, Schalkwijk, CG, Houben, AJHM, Kooi, ME, Lindeboom, L, Bons, JAP, Schaper, NC, Joris, PJ, Plat, J, et al
The Journal of clinical endocrinology and metabolism. 2019;(7):2719-2727
Abstract
CONTEXT Hepatokines have emerged as potential mediators of obesity-associated comorbidities, such as type 2 diabetes, cardiovascular disease, fractures, and central hypogonadism. OBJECTIVE To assess whether weight loss-induced changes in hepatokines are mediated by intrahepatic triglyceride (IHTG) content. DESIGN Cross-sectional study and randomized controlled trial. SETTING General community. PARTICIPANTS Metabolically healthy, lean men (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52). INTERVENTION Men with abdominal obesity were randomized to 8-week dietary weight loss or no weight loss. MAIN OUTCOME MEASURES IHTG and serum hepatokines, that is, serum IGF1, IGF binding protein 1 (IGFBP1), SHBG, fibroblast growth factor 21 (FGF21), fetuin A, and plasma fetuin B. RESULTS All hepatokines, except for fetuin B, were significantly different between lean men and men with obesity. After the weight-loss intervention (-10.3 kg; 95% CI, -11.4 to-9.2), serum IGF1, IGFBP1, SHBG, and fetuin A approached the values observed in lean men. Cross-sectional associations were observed between IHTG and IGF1 (β = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (β = 2.1; 95% CI, 1.3 to 2.9) in lean men and men with abdominal obesity combined. Weight loss resulted in a reduction of IHTG (treatment effect, -2.2%; 95% CI, -3.4% to -1.2%) that was associated with a change in IGF1 (β = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (β = -0.18; 95% CI, -0.29 to -0.07). Mediation analyses showed that only the weight loss-induced change in serum IGF1 was mediated by IHTG (mediated effect, 32.7%; 95% CI, 4.6% to 79.2%). CONCLUSIONS Dietary weight loss has differential effects on hepatokines. This study shows that the change in serum IGF1 levels after dietary weight loss is mediated by the change in IHTG content.
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The Relevance of Toxic AGEs (TAGE) Cytotoxicity to NASH Pathogenesis: A Mini-Review.
Sakasai-Sakai, A, Takata, T, Takino, JI, Takeuchi, M
Nutrients. 2019;(2)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins. Glyceraldehyde (GA) is a metabolic intermediate of sugars, and GA-derived AGEs (known as toxic AGEs (TAGE)) have been implicated in the development of NASH. TAGE accumulates more in serum or liver tissue in NASH patients than in healthy controls or patients with simple steatosis. Furthermore, the TAGE precursor, GA, causes cell damage through protein dysfunctions by TAGE modifications and induces necrotic-type hepatocyte death. Intracellular TAGE may leak outside of necrotic-type cells. Extracellular TAGE then induce inflammatory or fibrotic responses related to the pathology of NASH in surrounding cells, including hepatocytes and hepatic stellate cells. This review focuses on the contribution of TAGE to the pathology of NASH, particularly hepatic cell death related to NASH.
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Effect of Soy Milk on Metabolic Status of Patients with Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial.
Eslami, O, Shidfar, F, Maleki, Z, Jazayeri, S, Hosseini, AF, Agah, S, Ardiyani, F
Journal of the American College of Nutrition. 2019;(1):51-58
Abstract
OBJECTIVE Studies in experimental models of nonalcoholic fatty liver disease (NAFLD) have reported positive effects of soy components in improving metabolic parameters. Whether such effects could be achieved through consumption of whole soy foods in patients with NAFLD is still unclear. Therefore, this trial was conducted to assess the effects of soy milk on metabolic parameters of patients with NAFLD. METHODS This parallel randomized clinical trial was conducted on 70 patients with NAFLD. Patients in the soy milk group consumed 240 ml of soy milk daily as a part of low-calorie diet (i.e., 500-deficit calorie diet) for 8 weeks. Patients in the control group just followed the low-calorie diet. Grade of fatty liver, liver enzymes, lipid profile, serum high-sensitivity C-reactive protein (hs-CRP), and anthropometric indices were measured at baseline and the end of the trial. RESULTS At the end of the trial, the soy milk group had significantly higher reduction in serum alanine aminotransferase (ALT) (-12.06 ± 17.61 IU/L in the soy milk group versus -5 ± 8.58 IU/L in the control group, p = 0.04) and hs-CRP (-1.32 ± 1.60 mg/L in the soy milk group versus -0.36 ± 1.54 mg/L in the control group, p = 0.01) compared to the control group. However, changes in fatty liver grade and other liver enzymes, including aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase, as well as lipid profile and anthropometric indices were not significantly different between the treatment groups. CONCLUSION Consumption of soy milk in the context of a restricted-calorie diet for 8 weeks had favorable effects on serum ALT and hs-CRP in patients with NAFLD.
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Literature review of liver injury induced by Tinospora crispa associated with two cases of acute fulminant hepatitis.
Huang, WT, Tu, CY, Wang, FY, Huang, ST
Complementary therapies in medicine. 2019;:286-291
Abstract
INTRODUCTION Species of Tinospora are used as herbal remedies for the treatment of various diseases with very few toxic effects having been reported. Tinospora cordifolia (TCF) has been reported to effectively prevent hepatotoxicity. However, there are an increasing number of cases revealing that Tinospora crispa (TCP) might have the negative effect of inducing hepatotoxicity. Because of the similar leaves, people may mistake TCP for TCF, and consume it with the purpose of protecting liver function. OBJECTIVE Find out the misusing level of TCP and TCF and which chemical compound in TCP might induce hepatotoxicity. METHODS We report two cases of acute fulminant hepatitis associated with chronic use of TCP. Given that the two herbs were misidentified in these two reports, we investigated the frequency of erroneous identification by using three keywords ("Guduchi", "Tinospora cordifolia", "Tinospora crispa") to search images from the Google Images database. To further clarify the influence of liver function between TCP and TCF, we searched PubMed (up to 29 July 2018) for relevant publications on clinical trials or case reports. RESULTS Based on web review, over 35 percent of websites failed to accurately identify these two herbs. The different effects on liver function between TCP and TCF were compared through literature review. It indicated that TCF exerted liver protection, TCP had a contrary effect, suggesting its cis-Clerodane-type furano-diterpenoids might be an important factor of inducing hepatotoxicity. CONCLUSIONS We concluded that people might cause hepatic injury or even death without correctly identifying these two Tinospora species.
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Research digest: SGLT2 inhibition in kidney and liver disease.
Preiss, D, Sattar, N
The lancet. Diabetes & endocrinology. 2019;(6):427
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Autoimmune Hepatitis A Case Report and Literature Review.
Hong, AS, Desta, M, Hong, JM, Ohning, GV, Pillinger, MH, Saxena, A, Modjinou, DV
Bulletin of the Hospital for Joint Disease (2013). 2019;(2):146-152
Abstract
INTRODUCTION Autoimmune hepatitis (AIH) is a cause of chronic liver disease. It is usually suspected based on clinical presentation and laboratory findings, but the diagnosis relies on the presence of specific autoantibodies and characteristic histology. Other unexplained findings should always prompt investigation for coexisting syndromes. CASE PRESENTATION The patient is a 60-year-old Hispanic female with a history of mild asthma presented with exertional and pleuritic chest pain with weight loss, arthralgia, subjective fever, and night sweats for the last 3 months. Given the nonspecific nature of the presentation, further workup was pursued. Laboratory results indicated pancytopenia, elevated INR, and positive autoimmune panel including ANA, anti-chromatin, anti-histone, and rheumatoid factor as well as abnormal C3 and C4. Subsequent liver biopsy with interface hepatitis lead to a diagnosis of AIH with concurrent systemic lupus erythematosus suspected. CONCLUSION The diagnostic work up for AIH is multimodal and aims to differentiate other etiologies such as congestive hepatopathy, iron overload, viral hepatitis, and other autoimmune liver diseases. In this particular case, unusual clinical and laboratory findings led to diagnosis of the overlap syndrome. Treatment for both was necessary to prevent further progression of disease.
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Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease.
Ryu, H, Park, HC, Kim, H, Heo, J, Kang, E, Hwang, YH, Cho, JY, Lee, KB, Oh, YK, Oh, KH, et al
PloS one. 2019;(4):e0214912
Abstract
OBJECTIVE Autosomal dominant polycystic kidney disease (ADPKD) patients with massive organomegaly suffer from pressure-related complications including malnutrition. In this study, we analyzed the efficacy of segmental bioelectrical impedance analysis (BIA) for objective and quantitative nutritional assessment in ADPKD patients. DESIGN AND METHODS We conducted a cross-sectional study, to evaluate the clinical utility of segmental BIA for assessing the nutritional status of ADPKD patients. BIA measurements was assessed according to modified subjective global assessment (SGA) scores and were compared with data from a healthy population. The association between BIA measurements and the height adjusted kidney and liver volumes (htTKLV), were analyzed. SUBJECTS A total of 288 ADPKD patients, aged ≥ 18 years old, were analyzed. MAIN OUTCOME MEASURES Nutritional status was evaluated with SGA and segmental BIA. The htTKLV were measured in each patients using computed tomonography images. RESULTS Higher ratios of extracellular water to total body water (ECW/TBW) in the whole-body (ECW/TBWWB), trunk (ECW/TBWTR), and lower extremities (ECW/TBWLE) and lower phase angle of lower extremities (PhALE) correlated with lower SGA scores in the ADPKD population and in both gender. The four parameters, ECW/TBWWB, ECW/TBWTR, and ECW/TBWLE of >0.38 and PhALE of <5.8 θ were associated with malnutrition in ADPKD patients. These correlations were preserved in the subgroup analysis for chronic kidney disease stages 1-3A. Compared to healthy populations' data, body fluid parameters and segmental ECW/TBW values, except for the upper extremities (ECW/TBWUE), were greater in ADPKD patients. Increased htTKLV was an independent risk factor for malnutrition in ADPKD. The highest correlation with htTKLV was observed for the ECW/TBWTR (r = 0.466), followed by ECW/TBWWB (r = 0.407), ECW/TBWLE (r = 0.385), PhALE (r = -0.279), and PhATR (r = 0.215). CONCLUSIONS These results demonstrated that segmental BIA parameters of ECW/TBWWB, ECW/TBWTR, ECW/TBWLE and PhALE provide useful information on nutritional status including the impact of organomegaly in ADPKD.