Immunomodulatory Effect of Phytoactive Compounds on Human Health: A Narrative Review Integrated with Bioinformatics Approach.

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: The objective of this study is to understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259, indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Liver Disease and Cell Therapy: Advances Made and Remaining Challenges.

The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review, we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardized protocols for MSC manufacture and administration. In addition, the emerging role of MSC-derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.

TGFß1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy.

The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGß1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFß1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.

Two Zn(II)/Cd(II) Coordination Polymers as Recyclable Heterogeneous Catalysts for an Efficient Room-Temperature Synthesis of α-Aminonitriles via the Solvent-Free Strecker Reaction.

The α-aminonitriles are versatile building blocks in the synthesis of natural or artificial amino acids as well as important intermediates in organic synthesis. For their synthesis, the three-component Strecker reaction involving an aldehyde or a ketone together with amines and trimethylsilyl cyanide is used. In the literature, hydrothermally produced metal-based heterogeneous Lewis acid catalysts have been utilized in various solvents. In this work, we aimed at a greener approach toward such catalysis by (a) making two precatalysts with d10 metal centers, {[Zn(hipamifba)(H2O)]·2H2O}n (1) and {[Cd(hipamifba)(H2O)2]·2H2O}n (2) (where H2hipamifba = 4-(((4-((carboxymethyl) carbamoyl)phenyl)amino)methyl)benzoic acid), via an easy and scalable room-temperature method, and (b) showcasing the use of these coordination polymers (CPs) as very efficient, recyclable, and heterogeneous catalysts for the Strecker reaction to form α-aminonitriles in high yields under solvent-free reaction at ambient conditions. This has also allowed us to demonstrate the importance of open metal sites in such catalysis through an efficiency comparison between activated 1 and 2. In addition, activated 2 exhibited a wide substrate scope including a natural product Girgensohnine, providing an example of a natural product synthesis by a CP catalyst via an organic transformation such as the Strecker reaction.

Luminescent 2D Pillared-Bilayer Metal-Organic Coordination Networks for Selective Sensing of ReO4- in Water.

For the preference in nuclear energy, one of the high-level liquid waste materials in the form of pertechnetate anion (TcO4-) has become an environmental hazard due to its mobility into groundwater and soil. For its sequestration, numerous efforts have been reported in recent years. However, its selective sensing, even using its nonradioactive surrogate oxidizing perrhenate ion (ReO4-), in aqueous media is very limited. To develop novel materials for such a purpose, we have designed an amino acid-functionalized bent dicarboxylic acid, 4-(((4-((carboxymethyl)carbamoyl)phenyl)amino)methyl)benzoic acid (H2hipamifba), for the strategic room-temperature synthesis of two isostructural and highly luminescent two-dimensional (2D) metal-organic coordination networks (MOCNs), {[Cu(hipamifba)(4,4'-azbpy)]·2CH3OH·2H2O}n (1) and {[Zn(hipamifba)(4,4'-azbpy)]·2CH3OH·2H2O}n (2), where 4,4'-azobipyridine (4,4'-azbpy) as a pillar linker imparts luminescent properties in the architectures. The single-crystal X-ray structural analysis demonstrates that 1 and 2 have pillared-bilayer 2D networks with the sq1/Shubnikov tetragonal plane net topology. These multiresponsive luminescent materials were gainfully employed for the selective sensing of ReO4- in water with a detection limit of 3.4 and 5.4 ppm for 1 and 2, respectively. It is noteworthy to point out that these are the first neutral sensors for such study as the only other two sensors reported in the literature are cationic in nature. Their suitability (selectivity, stability, and recyclability) as excellent water-stable sensors was established through the competitive analyte test and a comparison of pristine and spent samples by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Further, the mechanism of selective detection is explained by the time-resolved studies and density functional theory (DFT) calculations.

Cellular therapies for the treatment of immune-mediated GI and liver disease.

INTRODUCTION: Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact. DATA SOURCES: A literature review was carried out using Pubmed. Keywords used for search were 'ATMP', 'immune mediated', 'autoimmune liver disease' and 'immune mediated gastrointestinal conditions', 'cell therapy', 'MSC', 'HSCT', 'Regulatory T cells', 'GVHD', 'Coeliac disease' 'IBD', 'PSC', 'AIH', 'PBC'. No new data were generated or analysed in support of this review. AREAS OF AGREEMENT: There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to 'reset' the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications. AREAS OF CONTROVERSY: There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data. GROWING POINTS: MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies. AREAS TIMELY FOR DEVELOPING RESEARCH: Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further.

Design and Construction of a Luminescent and Highly Stable 3D Metal-Organic Framework with a [Zn4(µ3-OH)2]6+ Core.

A highly stable and luminescent 3D metal-organic framework (MOF), {[Zn4(µ3-OH)2(BTC)2(BBI4PY)2]·10H2O}n (Zn-MOF), with a rare [Zn4(µ3-OH)2]6+ core has been synthesized using a new rigid and functionalized pillar linker, 2,6-bis(pyridin-4-yl)-1,7-dihydrobenzo[1,2-d:4,5-d']diimidazole (BBI4PY) in combination with Zn(OAc)2·2H2O and 1,3,5-benzenetricarboxylic acid (H3BTC) under solvothermal conditions. Unlike other MOFs with the [Zn4(µ3-OH)2]6+ core, Zn-MOF was synthesized without using an external base, as the intrinsic basicity of BBI4PY served the purpose. Furthermore, it retains crystallinity and phase purity up to 350 °C on the basis of TGA and in situ variable temperature PXRD, correlating with its solid-state structure. Using the dehydrated Zn-MOF, water sorption studies show uptake of 220 cm3 g-1 (corresponds to 10 water molecules). A large hysteresis in desorption isotherm signifies strong interactions between adsorbed water and Lewis basic sites present in the framework. The reversible nature of water sorption was further manifested by TGA and PXRD studies. As an example of its application, the highly fluorescent and electron-rich nature of Zn-MOF has been utilized for the selective sensing of Fe3+ and 2,4,6-trinitrophenol (TNP) in water with detection limits of 3.7 and 1.8 ppm, respectively. The mechanistic details for the turn-off quenching have been elucidated with the help of Stern-Volmer plots, spectral overlap, lifetime studies, and density functional theory calculations. This mechanistic evidence reveals that a combination of strong hydrogen bonding with resonance energy transfer and photoinduced electron transfer (PET) processes is synchronously responsible for the quenching of the fluorescence intensity of Zn-MOF.

Cell Therapy for Liver Disease: From Promise to Reality.

Over the last decade, there has been a considerable progress in the development of cell therapy products for the treatment of liver diseases. The quest to generate well-defined homogenous cell populations with defined mechanism(s) of action has enabled the progression from use of autologous bone marrow stem cells comprising of heterogeneous cell populations to allogeneic cell types such as monocyte-derived macrophages, regulatory T cells, mesenchymal stromal cells, macrophages, etc. There is growing evidence regarding the multiple molecular mechanisms pivotal to various therapeutic effects and hence, careful selection of cell therapy product for the desired putative effects is crucial. In this review, we have presented an overview of the cell therapies that have been developed thus far, with preclinical and clinical evidence for their use in liver disease. Limitations associated with these therapies have also been discussed. Despite the advances made, there remain multiple challenges to overcome before cell therapies can be considered as viable treatment options, and these include larger scale clinical trials, scalable production of cells according to good manufacturing practice standards, pathways for delivery of cell therapy within hospital environments, and costs associated with the production.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Comparative effect of indomethacin (IndoM) on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in the kidney, small intestine and liver of rats.

Indomethacin (IndoM) has prominent anti-inflammatory and analgesic-antipyretic properties. However, high incidence and severity of side-effects on the structure and functions of the kidney, liver and intestine limits its clinical use. The present study tested the hypothesis that IndoM causes multi-organ toxicity by inducing oxidative stress that alters the structure of various cellular membranes, metabolism and hence functions. The effect of IndoM was determined on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in the rat kideny, liver and intestine to understand the mechanism of IndoM induced toxicity. Adult male Wister rats were given IndoM (20 mg/kg) intra-peritoneally in sodium bicarbonate twice a day for 3 d. The body weights of the rats were recorded before and after experimental procedure. IndoM administration significantly increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but inorganic phosphate indicating IndoM induced renal, hepatic and intestinal toxicity. Activity of lactate dehydrogenase along with glucose-6- and fructose-1, 6-bis phosphatase, glucose-6-phosphate dehydrogenase and NADP-malic enzyme increased but malate dehydrogenase decreased in all tissues. Lipid peroxidation (LPO) significantly increased whereas the antioxidant enzymes decreased in all rat tissues studied. The results indicate that IndoM administration caused severe damage to kidney, liver and intestine by icreasing LPO, suppressing antioxidant enzymes and inhibiting oxidative metablolism. The energy dependence was shifted to anaerobic glycolysis due to mitochondrial damage supported by increased gluconeogenesis to provide more glucose to meet energy requirements.

Provider reported barriers and solutions to improve testing among tuberculosis patients 'eligible for drug susceptibility test': A qualitative study from programmatic setting in India.

BACKGROUND: In a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014-15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)-meaning TB patients who were eligible for DST, were not being tested. OBJECTIVES: In this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST. METHODS: This was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed. RESULTS: The key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register. CONCLUSION: Lack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients.

Retrospective Study of Root Canal Configurations of Mandibular Third Molars Using CBCT- Part-II.

INTRODUCTION: Abnormal root canal morphologies of third molars can be diagnostically and technically challenging during root canal treatment. AIM: The aim of this retrospective study was to investigate the root and canal morphology of mandibular third molars in Central India population by using Cone Beam Computed Tomography (CBCT) analysis. MATERIALS AND METHODS: CBCT images of 171 mandibular third molars were observed and data regarding number of roots, number of canals, Vertucci's classification in each root, prevalence of C shaped canal, gender and topographical relation of morphology in mandibular third molar was statistically evaluated. RESULTS: Majority of mandibular third molars had two roots (84.2%) and three canals (64.3%). Most mesial root had Vertucci Type II (55.6%) and Vertucci Type IV (22.2%), distal root had Type I canals (87.5%). Over all prevalence of C shaped canals in mandibular third molars was 9.4%. CONCLUSION: There was a high prevalence of two rooted mandibular third molars with three canals.

High pre-diagnosis attrition among patients with presumptive MDR-TB: an operational research from Bhopal district, India.

BACKGROUND: Pre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014). METHODS: Study was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme). RESULTS: Of 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST. CONCLUSION: High pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required.

Understanding the sensory irregularities of esophageal disease.

Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future.

Evaluation of Fracture Resistance of Endodontically Treated Teeth Filled with Gutta-Percha and Resilon Obturating Material: An In Vitro Study.

BACKGROUND: As per many studies endodontically treated teeth are widely considered to be more susceptible to fracture than vital teeth. Obturation strains and post placement have been a major cause of vertical root fracture. Present study was conducted to compare in vitro fracture resistance after filling with either Gutta-percha or Resilon by lateral condensation techniques in root canals. This study evaluated a new thermoplastic synthetic polymer based on polyester, which contains bioactive and radiopaque filler, Resilon performs every way as Gutta-percha except that it allows the bonding agent to attach to the resin core and the dentin wall thus forming a monoblock. MATERIALS AND METHODS: In the present study 90 freshly extracted single-rooted human mandibular premolar teeth endodontically treated, were cut at the cemento-enamel junction, and were randomly divided into three groups of 30 each as teeth of Group A (Control) received no obturation, Group B teeth were obturated using Gutta-percha/AH26, and Group C teeth were obturated using Resilon/Epiphany obturating kit. Each specimen were mounted in acrylic in a polyvinyl ring and then tested for fracture resistance with the help of an universal testing machine. A compressive force was applied until the root is fractured. The data were subjected to analysis of variance for comparing mean difference of fracture resistance among three groups. Multiple comparisons among these groups were carried out by non-parametric Kruskal-Wallis analysis. A p value of <0.0001 was considered a statistically significant difference. RESULTS: The results obtain after analysis showed no significant differences in the fracture resistance between the two tested groups of endodontic sealers. CONCLUSION: Within the limitation of the present in-vitro study, Resilon/Epiphany sealer performs better than Gutta-percha/AH 26 sealer with lateral condensation technique.

Management of Class-II Furcation Complicated with Endodontic involvement using Two Different Regenerative Materials.

This paper presents a case series of furcation involved teeth complicated with endodontic involvement which were treated with periodontal, endodontic and restorative procedures using different bone regenerative materials like; (a) Calcium phosphosilicate bone substitute having bioactive glass 69% mixed with glycerin 19% and poly-ethylene 12% dispensed in a putty form; (b) hydroxyapatite 70% and ß-tricalcium phosphate 30% dispensed in granular form. All the cases were randomly selected having Grade II furcation defect with primary or secondary endodontic involvement. All cases were under observation for a period of 9 months. Measurements at 9 months post-surgery demonstrated that dental putty as bone graft substitute which was in combination of bioactive glass mixed with glycerine and polyethylene glycol showed better result as compared granular bone graft which was in combination of hydroxyapatite and ß-tricalcium phosphate.

Effect of saliva contamination on the shear bond strength of a new self-etch adhesive system to dentin.

AIMS AND OBJECTIVES: To evaluate the effect of saliva contamination on the shear bond strength of a new two-step self-etch adhesive (P90 system adhesive) to dentin and to determine the effect of contaminant removing treatments on the recovery of bond strengths. MATERIALS AND METHODS: The buccal surfaces of 40 human premolars were ground to expose dentin. The specimens were randomly divided into four groups. Group 1 is uncontaminated and serves as the control group. Further groups were divided based on the step in the bonding sequence when the contamination had occurred as follows: Group 2 (primer, saliva contamination, rinse and dry), group 3 (after procedure of group 2, reapplication of primer), and group 4 (after procedure like in control group, saliva contamination, rinse and dry). Filtek P90 composite resin cylinders of 3 mm diameter and 3 mm length were fabricated on the surfaces. Shear bond strength testing was done in an Instron Universal Testing Machine and the data were subjected to one-way analysis of variance (ANOVA) and Student's t-test. RESULTS: With P90 system adhesive, group 2 and group 4 showed lower shear bond strength than group 1 (control) and group 3 (P < 0.05). CONCLUSION: Saliva contamination significantly decreased the shear bond strength of the adhesive to dentin.

Severe asymptomatic non-alcoholic fatty liver disease in routine diabetes care; a multi-disciplinary team approach to diagnosis and management.

OBJECTIVES: To prospectively use a non-invasive algorithm to identify asymptomatic, advanced non-alcoholic fatty liver disease (NAFLD) in a secondary care diabetes clinic and to determine the short-term effect of a multi-disciplinary team (MDT) approach in a liver clinic. RESEARCH DESIGN AND METHODS: NAFLD Fibrosis Score (NFS) was calculated in 64 asymptomatic patients with type 2 diabetes. Advanced fibrosis was identified using transient elastography and confirmed with liver biopsy. In a subsequent retrospective study, 95 patients newly referred to the NAFLD MDT clinic were investigated and the impact of the MDT approach assessed. RESULTS: 25/64 (39.0%) of patients with diabetes had a low NFS (<-1.455). 39/64 (61.0%) patients had a high or indeterminate NFS and were referred for review in the NAFLD MDT clinic, of which 23/39 attended for assessment. 19/23 (82.6%) were diagnosed with NAFLD, of which 6/19 (31.6%) patients had a positive transient elastography (≥8 kPa). Liver biopsy confirmed advanced fibrosis in 5/6 cases, with moderate fibrosis in 1 case. In the retrospective study, 65/95 (68.4%) new referrals to the NAFLD MDT clinic had a diagnosis of NAFLD. Over a median 98 days (IQR 70-182) follow-up, there was a significant improvement in weight (-0.8 kg; P = 0.024), total cholesterol (-0.2 mmol/L; P = 0.044), ALT (alanine transmaminase, -12.5 IU/L; P < 0.001) and GGT (gammu-glutamyl transferase, -13.0 IU/L; P < 0.0001). 7/28 (25%) of patients with diabetes achieved >5% weight loss. CONCLUSIONS: A significant proportion of asymptomatic patients attending type 2 diabetes clinics have undiagnosed advanced NAFLD fibrosis. An MDT approach to NAFLD results in short-term improvements in metabolic and liver parameters.