Displaying publications 61 - 80 of 97 in total

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  1. Effects of various nonopioid receptor antagonists on the antinociceptive activity of Muntingia calabura extracts in mice
    Zakaria ZA, Hassan MH, Nurul Aqmar MN, Abd Ghani M, Mohd Zaid SN, Sulaiman MR, et al.
    Methods Find Exp Clin Pharmacol, 2007 Oct;29(8):515-20.
    PMID: 18040526
    This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.
  2. Evaluation of live renal donors with three-dimensional contrast-enhanced magnetic resonance angiography in comparison to catheter angiography
    Tan SP, Bux SI, Kumar G, Razack AH, Chua CB, Lee SH, et al.
    Transplant Proc, 2004 Sep;36(7):1914-6.
    PMID: 15518697
    Catheter angiography is traditionally used to determine renal arterial anatomy in live renal donors. Three-dimensional (3D) contrast-enhanced magnetic resonance imaging (MRA) has been suggested as a noninvasive replacement. We assessed the possibility of using MRA in live renal donors in Malaysia.
  3. Fulltext Liver cirrhosis and splenomegaly associated with Schistosoma mansoni in a Sudanese woman in Malaysia: A case report
    Rajoo Y, Mahmud R, Xiang NR, Omar SF, Kumar G, Lim YA, et al.
    Asian Pac J Trop Med, 2015 Apr;8(4):334-6.
    PMID: 25975509 DOI: 10.1016/S1995-7645(14)60341-2
    We report a case of a patient with Schistosoma mansoni infection who presented with liver cirrhosis and splenomegaly. She was diagnosed by a serological test and Kato-Katz thick smear stool examination. The patient was a 52-year-old woman from Sudan who came to Malaysia for a week to visit her sons. The patient lives in the middle of Rabak region, Sudan, a highly endemic area for schistosomiasis where her daily routine includes rearing of cows and farming. The site of toilet and sources of drinking water are canals and wells; both infested with snails. Patient had a long history of exposure and coming into contact with water from these canals and wells.
  4. Biogas production from beverage factory wastewater in a mobile bioenergy station
    Lin CY, Lay CH, Chew KW, Nomanbhay S, Gu RL, Chang SH, et al.
    Chemosphere, 2021 Feb;264(Pt 2):128564.
    PMID: 33065325 DOI: 10.1016/j.chemosphere.2020.128564
    Recently, the production of renewable biogas such as biohydrogen and biomethane from wastewaters through anaerobic fermentation has gained worldwide attention. In the present study, a mobile bioenergy generation station had been constructed based on a high-efficiency hydrogenesis & methanogenesis technology (HyMeTek) developed by Feng Chia University, Taiwan. The substrate was a beverage wastewater having chemical oxygen demand (COD) concentration of 1200 mg/L. This bioenergy station had a feedstock tank (3.8 m3), a nutrient tank (0.8 m3), an acidogenesis tank (AT, 2 m3), two methanogenesis tanks (MT, 4 m3 for each), a membrane bioreactor and a control room. Biogas production rate, methane concentration, COD removal efficiencies, energy efficiency and economical interest of the plant were assessed. The peak total methane production rates for AT (at hydraulic retention time, HRT, 4 h) and MT (at HRT 8 h) were 430 and 7 mL/L·d, respectively. A strategy of shortening HRT was a promising method to enhance biogas quality and energy efficiency. This mobile bioenergy system has commercial potential because it could bring good economic benefit of initial rate of return (58.84%) and payback time (2.68 y).
  5. 3D Flower-Like FeWO4/CeO2 Hierarchical Architectures on rGO for Durable and High-Performance Microalgae Biophotovoltaic Fuel Cells
    Karthikeyan C, Jenita Rani G, Ng FL, Periasamy V, Pappathi M, Jothi Rajan M, et al.
    Appl Biochem Biotechnol, 2020 Nov;192(3):751-769.
    PMID: 32557232 DOI: 10.1007/s12010-020-03352-4
    A facile chemical reduction approach is adopted for the synthesis of iron tungstate (FeWO4)/ceria (CeO2)-decorated reduced graphene oxide (rGO) nanocomposite. Surface morphological studies of rGO/FeWO4/CeO2 composite reveal the formation of hierarchical FeWO4 flower-like microstructures on rGO sheets, in which the CeO2 nanoparticles are decorated over the FeWO4 microstructures. The distinct anodic peaks observed for the cyclic voltammograms of studied electrodes under light/dark regimes validate the electroactive proteins present in the microalgae. With the cumulative endeavors of three-dimensional FeWO4 microstructures, phase effect between rGO sheet and FeWO4/CeO2, highly exposed surface area, and light harvesting property of CeO2 nanoparticles, the relevant rGO/FeWO4/CeO2 nanocomposite demonstrates high power and stable biophotovoltaic energy generation compared with those of previous reports. Thus, these findings construct a distinct horizon to tailor a ternary nanocomposite with high electrochemical activity for the construction of cost-efficient and environmentally benign fuel cells.
  6. Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release
    Kumar GP, Phani AR, Prasad RG, Sanganal JS, Manali N, Gupta R, et al.
    Int J Pharm, 2014 Aug 25;471(1-2):146-52.
    PMID: 24858388 DOI: 10.1016/j.ijpharm.2014.05.033
    Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract, respiratory and skin infections in animals. However, low solubility and low bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is an inert, non toxic polymer with excellent hydrophilic properties, besides it can enhance bioavailability by forming drug polymer conjugates. With the aim of increasing solubility and bioavailability, enrofloxacin thin films were prepared using PVP as a polymer matrix. The obtained oral thin films exhibited excellent uniformity and mechanical properties. Swelling properties of the oral thin films revealed that the water uptake was enhanced by 21%. The surface pH has been found to be 6.8±0.1 indicating that these films will not cause any irritation to oral mucosa. FTIR data of the oral thin films indicated physical interaction between drug and polymer. SEM analysis revealed uniform distribution of drug in polymer matrix. In vitro drug release profiles showed enhanced release profiles (which are also pH dependant) for thin films compared to pure drug. Antibacterial activity was found to be dose dependent and maximum susceptibility was found on Klebsiella pneumonia making this preparation more suitable for respiratory infections.
  7. Fulltext A Novel Rank Aggregation-Based Hybrid Multifilter Wrapper Feature Selection Method in Software Defect Prediction
    Balogun AO, Basri S, Mahamad S, Capretz LF, Imam AA, Almomani MA, et al.
    Comput Intell Neurosci, 2021;2021:5069016.
    PMID: 34868291 DOI: 10.1155/2021/5069016
    The high dimensionality of software metric features has long been noted as a data quality problem that affects the performance of software defect prediction (SDP) models. This drawback makes it necessary to apply feature selection (FS) algorithm(s) in SDP processes. FS approaches can be categorized into three types, namely, filter FS (FFS), wrapper FS (WFS), and hybrid FS (HFS). HFS has been established as superior because it combines the strength of both FFS and WFS methods. However, selecting the most appropriate FFS (filter rank selection problem) for HFS is a challenge because the performance of FFS methods depends on the choice of datasets and classifiers. In addition, the local optima stagnation and high computational costs of WFS due to large search spaces are inherited by the HFS method. Therefore, as a solution, this study proposes a novel rank aggregation-based hybrid multifilter wrapper feature selection (RAHMFWFS) method for the selection of relevant and irredundant features from software defect datasets. The proposed RAHMFWFS is divided into two stepwise stages. The first stage involves a rank aggregation-based multifilter feature selection (RMFFS) method that addresses the filter rank selection problem by aggregating individual rank lists from multiple filter methods, using a novel rank aggregation method to generate a single, robust, and non-disjoint rank list. In the second stage, the aggregated ranked features are further preprocessed by an enhanced wrapper feature selection (EWFS) method based on a dynamic reranking strategy that is used to guide the feature subset selection process of the HFS method. This, in turn, reduces the number of evaluation cycles while amplifying or maintaining its prediction performance. The feasibility of the proposed RAHMFWFS was demonstrated on benchmarked software defect datasets with Naïve Bayes and Decision Tree classifiers, based on accuracy, the area under the curve (AUC), and F-measure values. The experimental results showed the effectiveness of RAHMFWFS in addressing filter rank selection and local optima stagnation problems in HFS, as well as the ability to select optimal features from SDP datasets while maintaining or enhancing the performance of SDP models. To conclude, the proposed RAHMFWFS achieved good performance by improving the prediction performances of SDP models across the selected datasets, compared to existing state-of-the-arts HFS methods.
  8. Surpassing the current limitations of high purity H2 production in microbial electrolysis cell (MECs): Strategies for inhibiting growth of methanogens
    Kadier A, Kalil MS, Chandrasekhar K, Mohanakrishna G, Saratale GD, Saratale RG, et al.
    Bioelectrochemistry, 2018 Feb;119:211-219.
    PMID: 29073521 DOI: 10.1016/j.bioelechem.2017.09.014
    Microbial electrolysis cells (MECs) are perceived as a potential and promising innovative biotechnological tool that can convert carbon-rich waste biomass or wastewater into hydrogen (H2) or other value-added chemicals. Undesired methane (CH4) producing H2 sinks, including methanogens, is a serious challenge faced by MECs to achieve high-rate H2 production. Methanogens can consume H2 to produce CH4 in MECs, which has led to a drop of H2 production efficiency, H2 production rate (HPR) and also a low percentage of H2 in the produced biogas. Organized inference related to the interactions of microbes and potential processes has assisted in understanding approaches and concepts for inhibiting the growth of methanogens and profitable scale up design. Thus, here in we review the current developments and also the improvements constituted for the reduction of microbial H2 losses to methanogens. Firstly, the greatest challenge in achieving practical applications of MECs; undesirable microorganisms (methanogens) growth and various studied techniques for eliminating and reducing methanogens activities in MECs were discussed. Additionally, this extensive review also considers prospects for stimulating future research that could help to achieve more information and would provide the focus and path towards MECs as well as their possibilities for simultaneously generating H2 and waste remediation.
  9. Fulltext Green synthesis of reduced graphene oxide by using tropical microalgae and its application in biophotovoltaic devices
    Tee JY, Ng FL, Keng FS, Lee CW, Zhang B, Lin S, et al.
    iScience, 2024 Apr 19;27(4):109564.
    PMID: 38617563 DOI: 10.1016/j.isci.2024.109564
    The successful commercialization of algal biophotovoltaics (BPV) technology hinges upon a multifaceted approach, encompassing factors such as the development of a cost-efficient and highly conductive anode material. To address this issue, we developed an environmentally benign method of producing reduced graphene oxide (rGO), using concentrated Chlorella sp. UMACC 313 suspensions as the reducing agent. The produced rGO was subsequently coated on the carbon paper (rGO-CP) and used as the BPV device's anode. As a result, maximum power density was increased by 950% for Chlorella sp. UMACC 258 (0.210 mW m-2) and 781% for Synechococcus sp. UMACC 371 (0.555 mW m-2) compared to bare CP. The improved microalgae adhesion to the anode and improved electrical conductivity of rGO brought on by the effective removal of oxygen functional groups may be the causes of this. This study has demonstrated how microalgal-reduced GO may improve the efficiency of algal BPV for producing bioelectricity.
  10. Fulltext Evaluation of selected tropical marine microalgal cultures for use in biophotovoltaic platforms
    Tay ZH, Ng FL, Thong CH, Lee CW, Gnana Kumar G, Al-Sehemi AG, et al.
    Appl Microbiol Biotechnol, 2024 Dec;108(1):1-14.
    PMID: 38194143 DOI: 10.1007/s00253-023-12951-0
    In this study, the bioelectrical power generation potential of four tropical marine microalgal strains native to Malaysia was investigated using BPV platforms. Chlorella UMACC 258 produced the highest power density (0.108 mW m-2), followed by Halamphora subtropica UMACC 370 (0.090 mW m-2), Synechococcus UMACC 371 (0.065 mW m-2) and Parachlorella UMACC 245 (0.017 mW m-2). The chlorophyll-a (chl-a) content was examined to have a linear positive relationship with the power density (p 
  11. Anti-cancerous efficacy and pharmacokinetics of 6-mercaptopurine loaded chitosan nanoparticles
    Kumar GP, Sanganal JS, Phani AR, Manohara C, Tripathi SM, Raghavendra HL, et al.
    Pharmacol Res, 2015 Oct;100:47-57.
    PMID: 26232590 DOI: 10.1016/j.phrs.2015.07.025
    6-Mercaptopurine is a cytotoxic and immunosuppressant drug. The use of this drug is limited due to its poor bioavailability and short plasma half-life. In order to nullify these drawbacks, 6-mercaptopurine-chitosan nanoparticles (6-MP-CNPs) were prepared and evaluated to study the influence of preparation conditions on the physicochemical properties by using DLS, SEM, XRD and FTIR. The in vitro drug release profile at pH 4.8 and 7.4 revealed sustained release patterns for a period of 2 days. The nanoformulations showed enhanced in vitro anti-cancer activities (MTT assay, apoptosis assay, cell cycle arrest and ROS indices) on HT-1080 and MCF-7 cells. In vivo pharmacokinetics profiles of 6-MP-CNPs showed improved bioavailability. Thus, the results of the present study revealed that, the prepared 6-MP-CNPs have a significant role in increasing anti-cancer efficacy, bioavailability and in vivo pharmacokinetics profiles.
  12. Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals
    Zakaria ZA, Raden Mohd Nor RN, Hanan Kumar G, Abdul Ghani ZD, Sulaiman MR, Rathna Devi G, et al.
    Can J Physiol Pharmacol, 2006 Dec;84(12):1291-9.
    PMID: 17487238
    The present study was carried out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of the aqueous extract of Melastoma malabathricum leaves in experimental animals. The antinociceptive activity was measured using abdominal constriction, hot-plate, and formalin tests, whereas the anti-inflammatory and antipyretic activities were measured using carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, which was obtained after soaking the air-dried leaves in distilled water for 72 h and then preparing in concentrations of 10%, 50%, and 100% (v/v), was administered subcutaneously 30 min prior to subjection to the above mentioned assays. At all concentrations tested, the extract was found to exhibit significant (P < 0.05) antinociceptive, anti-inflammatory, and antipyretic activities in a concentration-independent manner. Our findings that the aqueous extract of M. malabathricum possesses antinociceptive, anti-inflammatory, and antipyretic activities supports previous claims on its traditional uses to treat various ailments.
  13. Fulltext Optimised spectral effects of programmable LED arrays (PLA)s on bioelectricity generation from algal-biophotovoltaic devices
    Ng FL, Phang SM, Lan BL, Kalavally V, Thong CH, Chong KT, et al.
    Sci Rep, 2020 09 30;10(1):16105.
    PMID: 32999346 DOI: 10.1038/s41598-020-72823-9
    The biophotovoltaic cell (BPV) is deemed to be a potent green energy device as it demonstrates the generation of renewable energy from microalgae; however, inadequate electron generation from microalgae is a significant impediment for functional employment of these cells. The photosynthetic process is not only affected by the temperature, CO2 concentration and light intensity but also the spectrum of light. Thus, a detailed understanding of the influences of light spectrum is essential. Accordingly, we developed spectrally optimized light using programmable LED arrays (PLA)s to study the effect on algae growth and bioelectricity generation. Chlorella is a green microalga and contains chlorophyll-a (chl-a), which is the major light harvesting pigment that absorbs light in the blue and red spectrum. In this study, Chlorella is grown under a PLA which can optimally simulate the absorption spectrum of the pigments in Chlorella. This experiment investigated the growth, photosynthetic performance and bioelectricity generation of Chlorella when exposed to an optimally-tuned light spectrum. The algal BPV performed better under PLA with a peak power output of 0.581 mW m-2 for immobilized BPV device on day 8, which is an increase of 188% compared to operation under a conventional white LED light source. The photosynthetic performance, as measured using pulse amplitude modulation (PAM) fluorometry, showed that the optimized spectrum from the PLA gave an increase of 72% in the rETRmax value (190.5 μmol electrons m-2 s-1), compared with the conventional white light source. Highest algal biomass (1100 mg L-1) was achieved in the immobilized system on day eight, which translates to a carbon fixation of 550 mg carbon L-1. When artificial light is used for the BPV system, it should be optimized with the light spectrum and intensity best suited to the absorption capability of the pigments in the cells. Optimum artificial light source with algal BPV device can be integrated into a power management system for low power application (eg. environment sensor for indoor agriculture system).
  14. Anaerobic membrane bioreactors for biohydrogen production: Recent developments, challenges and perspectives
    Aslam M, Ahmad R, Yasin M, Khan AL, Shahid MK, Hossain S, et al.
    Bioresour Technol, 2018 Dec;269:452-464.
    PMID: 30145004 DOI: 10.1016/j.biortech.2018.08.050
    Biohydrogen as one of the most appealing energy vector for the future represents attractive avenue in alternative energy research. Recently, variety of biohydrogen production pathways has been suggested to improve the key features of the process. Nevertheless, researches are still needed to overcome remaining barriers to practical applications such as low yields and production rates. Considering practicality aspects, this review emphasized on anaerobic membrane bioreactors (AnMBRs) for biological hydrogen production. Recent advances and emerging issues associated with biohydrogen generation in AnMBR technology are critically discussed. Several techniques are highlighted that are aimed at overcoming these barriers. Moreover, environmental and economical potentials along with future research perspectives are addressed to drive biohydrogen technology towards practicality and economical-feasibility.
  15. Valorization of nano-based lignocellulosic derivatives to procure commercially significant value-added products for biomedical applications
    As V, Kumar G, Dey N, Karunakaran R, K A, Patel AK, et al.
    Environ Res, 2023 Jan 01;216(Pt 2):114400.
    PMID: 36265604 DOI: 10.1016/j.envres.2022.114400
    Biowaste, produced from nature, is preferred to be a good source of carbon and ligninolytic machinery for many microorganisms. They are complex biopolymers composed of lignin, cellulose, and hemicellulose traces. This biomass can be depolymerized to its nano-dimensions to gain exceptional properties useful in the field of cosmetics, pharmaceuticals, high-strength materials, etc. Nano-sized biomass derivatives overcome the inherent drawbacks of the parent material and offer promises as a potential material for a wide range of applications with their unique traits such as low-toxicity, biocompatibility, biodegradability and environmentally friendly nature with versatility. This review focuses on the production of value-added products feasible from nanocellulose, nano lignin, and xylan nanoparticles which is quite a novel study of its kind. Dawn of nanotechnology has converted bio waste by-products (hemicellulose and lignin) into useful precursors for many commercial products. Nano-cellulose has been employed in the fields of electronics, cosmetics, drug delivery, scaffolds, fillers, packaging, and engineering structures. Xylan nanoparticles and nano lignin have numerous applications as stabilizers, additives, textiles, adhesives, emulsifiers, and prodrugs for many polyphenols with an encapsulation efficiency of 50%. This study will support the potential development of composites for emerging applications in all aspects of interest and open up novel paths for multifunctional biomaterials in nano-dimensions for cosmetic, drug carrier, and clinical applications.
  16. Fulltext Recent Advancements in Emerging Technologies for Healthcare Management Systems: A Survey
    Junaid SB, Imam AA, Balogun AO, De Silva LC, Surakat YA, Kumar G, et al.
    Healthcare (Basel), 2022 Oct 03;10(10).
    PMID: 36292387 DOI: 10.3390/healthcare10101940
    In recent times, the growth of the Internet of Things (IoT), artificial intelligence (AI), and Blockchain technologies have quickly gained pace as a new study niche in numerous collegiate and industrial sectors, notably in the healthcare sector. Recent advancements in healthcare delivery have given many patients access to advanced personalized healthcare, which has improved their well-being. The subsequent phase in healthcare is to seamlessly consolidate these emerging technologies such as IoT-assisted wearable sensor devices, AI, and Blockchain collectively. Surprisingly, owing to the rapid use of smart wearable sensors, IoT and AI-enabled technology are shifting healthcare from a conventional hub-based system to a more personalized healthcare management system (HMS). However, implementing smart sensors, advanced IoT, AI, and Blockchain technologies synchronously in HMS remains a significant challenge. Prominent and reoccurring issues such as scarcity of cost-effective and accurate smart medical sensors, unstandardized IoT system architectures, heterogeneity of connected wearable devices, the multidimensionality of data generated, and high demand for interoperability are vivid problems affecting the advancement of HMS. Hence, this survey paper presents a detailed evaluation of the application of these emerging technologies (Smart Sensor, IoT, AI, Blockchain) in HMS to better understand the progress thus far. Specifically, current studies and findings on the deployment of these emerging technologies in healthcare are investigated, as well as key enabling factors, noteworthy use cases, and successful deployments. This survey also examined essential issues that are frequently encountered by IoT-assisted wearable sensor systems, AI, and Blockchain, as well as the critical concerns that must be addressed to enhance the application of these emerging technologies in the HMS.
  17. Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy
    Anand L, Choudhury A, Bihari C, Sharma BC, Kumar M, Maiwall R, et al.
    Hepatology, 2019 08;70(2):587-596.
    PMID: 30113706 DOI: 10.1002/hep.30205
    Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.
  18. Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models
    Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.
    Hepatol Int, 2017 Sep;11(5):461-471.
    PMID: 28856540 DOI: 10.1007/s12072-017-9816-z
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

    METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

    RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

    CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

  19. Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study
    Choudhury A, Kumar M, Sharma BC, Maiwall R, Pamecha V, Moreau R, et al.
    J Gastroenterol Hepatol, 2017 Dec;32(12):1989-1997.
    PMID: 28374414 DOI: 10.1111/jgh.13799
    BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis.

    METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.

    RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P 

  20. Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure
    Duseja A, De A, Taneja S, Choudhury AK, Devarbhavi H, Hu J, et al.
    Liver Int, 2021 01;41(1):150-157.
    PMID: 32970356 DOI: 10.1111/liv.14671
    BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF).

    METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively.

    RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P 

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