Publications by authors named "Ajay Duseja"

217 Publications

Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF.

J Clin Transl Hepatol 2021 Apr 18;9(2):210-219. Epub 2021 Feb 18.

Departments of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background And Aims: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.

Methods: We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy.

Results: Episodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (=0.032), TEG-Clot kinetics (K) time (=0.042), Son-activated clotting time (=0.038) and negatively with clot rate (=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (=0.035) and 20.8% (=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively.

Conclusions: Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding.

Trial Registration: NCT04332484.
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http://dx.doi.org/10.14218/JCTH.2020.00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111111PMC
April 2021

Chronic Hepatitis E With Genotype 1-Masquerading as Allograft Rejection After LiverTransplantation.

J Clin Exp Hepatol 2021 May-Jun;11(3):400-403. Epub 2020 Jul 18.

Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.
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http://dx.doi.org/10.1016/j.jceh.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103309PMC
July 2020

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

J Clin Exp Hepatol 2021 May-Jun;11(3):354-386. Epub 2020 Oct 9.

Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, 110060, Delhi, India.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.
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http://dx.doi.org/10.1016/j.jceh.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103529PMC
October 2020

Percutaneous Cryoablation of Liver Tumors: Initial Experience from a Tertiary Care Center in India.

J Clin Exp Hepatol 2021 May-Jun;11(3):305-311. Epub 2020 Oct 19.

Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Percutaneous ablation is an important part of management strategy for liver tumors. While radiofrequency ablation and microwave ablation are the most widely used ablative techniques, cryoablation (CA) has several technical advantages but has been underused till recently. In this study, we report the initial experience with percutaneous CA of liver tumors.

Methods: This was a retrospective evaluation of consecutive patients with liver tumors who underwent percutaneous CA between October 2018 and August 2019. The ablation procedures were performed under combined ultrasound and computed tomography guidance using argon-helium-based CA systems. The baseline tumor characteristics (including size and location), Barcelona Clinic Liver Cancer stage, and Child-Pugh score were recorded. Each patient underwent a follow-up after 1 month and at 3 months subsequently. Technical success, complete response, local tumor progression, and overall survival were evaluated.

Results: Nine patients (mean age, 62.4 years, median age, 66 years, five men and four women) with 10 liver tumors (mean size, 2.22 cm) underwent CA. Seven (77.8%) patients had hepatocellular carcinoma (HCC), and 2 patients had solitary liver metastasis. One patient with HCC had two lesions, while the rest had only one lesion. Of the two metastatic lesions, one was from carcinoma of the cervix and the other was from jejunal neuroendocrine tumor. Five tumors were located adjacent to the gallbladder, two lesions were adjacent to the right portal vein, two lesions were subcapsular, and one lesion was adjacent to the stomach. Technical success was achieved in all the patients. Complete response was achieved in 7 (77.8%) patients. The median follow-up period was 7 months (range, 3-12 months). There was no local tumor progression and no death during the follow-up period. No procedure-related complication was seen.

Conclusion: Percutaneous CA of hepatic tumors is technically feasible and is a safe and effective ablative technique.
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http://dx.doi.org/10.1016/j.jceh.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103339PMC
October 2020

The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

J Clin Exp Hepatol 2021 May-Jun;11(3):288-298. Epub 2020 Nov 17.

Department of Gastroenterology, BLK Super Speciality Hospital, New Delhi, India.

Background: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality.

Methods: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival.

Results: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics.

Conclusion: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.
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http://dx.doi.org/10.1016/j.jceh.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103312PMC
November 2020

Letter to the Editor: Is BRTO Superior to Endoscopic Cyanoacrylate in Gastric Varices?

Hepatology 2021 Apr 8. Epub 2021 Apr 8.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

We read with interest the study by Luo et al. comparing cyanoacrylate (CA) injection with balloon-occluded retrograde transvenous obliteration (BRTO) for the prevention of rebleed from gastric varices (GVs). However, several issues need to be addressed. Although GV size has consistently been shown to be a significant risk factor for bleeding, the authors have not described the size and morphology of the GVs. Patients in the BRTO arm only underwent preprocedural contrast-enhanced computed tomography (CECT) to delineate the shunt and variceal anatomy (Supplementary Fig. a).
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http://dx.doi.org/10.1002/hep.31853DOI Listing
April 2021

Changing Nomenclature from Nonalcoholic Fatty Liver Disease to Metabolic Dysfunction-Associated Fatty Liver Disease - Not Only Premature But Also Confusing.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):278-279. Epub 2020 Aug 9.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1016/j.jceh.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953006PMC
August 2020

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):270-272. Epub 2020 May 11.

Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.
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http://dx.doi.org/10.1016/j.jceh.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953001PMC
May 2020

Nonalcoholic Fatty Liver Disease: Lessons Learnt in the Last Five Years.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):159-162. Epub 2020 Jul 24.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1016/j.jceh.2020.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953007PMC
July 2020

Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

J Clin Exp Hepatol 2021 Jan-Feb;11(1):97-143. Epub 2020 Oct 1.

Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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http://dx.doi.org/10.1016/j.jceh.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897902PMC
October 2020

Comparison of Elastography Point Quantification with Transient Elastography in Patients with Chronic Viral Hepatitis and Nonalcoholic Fatty Liver Disease: A Pilot Study.

J Clin Exp Hepatol 2021 Jan-Feb;11(1):21-29. Epub 2020 Jul 2.

Departments of Radiodiagnosis and Imaging, Chandigarh, 160012, India.

Aims: The objective of this study was to compare diagnostic accuracy of elastography point quantification (ElastPQ) with transient elastography (TE) and liver histology for measuring liver stiffness in patients with chronic viral hepatitis (CVH) and nonalcoholic fatty liver disease (NAFLD).

Methods: Thirty-two patients with chronic liver disease (CVH and NAFLD) were evaluated by ElastPQ and TE within 7 days of liver biopsy. Within the CVH group, subgroup analysis was carried out in patients with end-stage renal disease (ESRD) and without ESRD. Area under the receiver operating characteristic (AUROC) curves were calculated for ElastPQ and TE.

Results: There were 15 patients with CVH and 17 patients with NAFLD. In the CVH group, there were 8 patients with ESRD and 7 patients without ESRD. Taking liver histopathology as the gold standard, liver stiffness measurement by ElastPQ (ρ = 0.826; < 0.0001) and TE (ρ = 0.649;  < 0.0001) correlated significantly with the stage of fibrosis. AUROCs of ElastPQ and TE for the diagnosis of any fibrosis (F ≥ 1), significant fibrosis (F ≥ 2), and advanced fibrosis (F ≥ 3) were 0.907, 0.959, 0.926 and 0.870, 0.770, 0.881, respectively, in both CVH and NAFLD groups. However, the accuracy of both these techniques was poor in patients with CVH and ESRD (AUROCs for ElastPQ and TE of 0.667 and 0.167 for the diagnosis of significant fibrosis, respectively, and 0.429 and 0.143 for the diagnosis of advanced fibrosis, respectively). The diagnostic accuracy of both ElastPQ and TE for detecting significant fibrosis was excellent in patients with NAFLD (AUROC of 1.000 and 0.936, respectively). ElastPQ was superior to TE in the diagnosis of significant fibrosis in the combined analysis ( = 0.0149) and in the CVH group ( = 0.0391), while both modalities were comparable in patients of the NAFLD group ( = 0.2539).

Conclusion: ElastPQ may be equally accurate as Fibroscan, and large prospective studies are required to validate the same.
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http://dx.doi.org/10.1016/j.jceh.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897856PMC
July 2020

Association between nonalcoholic fatty liver disease and inflammatory periodontal disease: A case‑control study.

J Indian Soc Periodontol 2021 Jan-Feb;25(1):47-54. Epub 2020 Sep 21.

Department of Periodontology, Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India.

Background: Recent evidence suggests an interconnection between chronic periodontal disease and systemic diseases.

Aim: The aim of this study is to evaluate the possible association between nonalcoholic fatty liver disease (NAFLD) and inflammatory periodontal disease among north Indian population.

Settings And Design: Tertiary health care center, cross-sectional case-control observational study.

Materials And Methods: A total of 40 cases, i.e., patients with NAFLD and 40 healthy volunteers were included over a period of 8 months and their periodontal status was compared. The status of their hepatic health was ascertained by anthropometric, imaging, and biochemical evaluation including ultrasound examination of abdomen and transient elastography.

Statistical Data Analysis: Paired -test, multivariate logistic regression analysis using IBM SPSS STATISTICS (version 22.0, Armonk, NY: IBM Corp).

Results: The study revealed that only 11.9% and 20% of participants had periodontitis, in healthy controls and hepatic disease patients, respectively. A statistically significant difference was observed in clinical parameters of periodontal status, except for malocclusion. Comparative analysis of tumor necrosis factor-α (TNF-α), interleukin-6, C-reactive protein, and cytokeratin-18 revealed differences in mean scores, though statistically nonsignificant. Only aspartate transaminase, number of missing teeth, and bleeding on probing (BOP) were observed with higher odds ratios for hepatic disease patients. Spearman correlation analysis revealed significant positive correlations between TNF-α and BOP, for cases.

Conclusion: Patients with hepatic disease showed a higher prevalence of periodontal disease, worse oral hygiene and periodontal health status compared to healthy individuals.
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http://dx.doi.org/10.4103/jisp.jisp_45_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904021PMC
September 2020

Dietary modulations of folic acid affect the development of diethylnitrosamine induced hepatocellular carcinoma in a rat model.

J Mol Histol 2021 Apr 13;52(2):335-350. Epub 2021 Jan 13.

Dept. of Biochemistry, PGIMER, Chandigarh, 160012, India.

The present study evaluated the role of dietary folate modulations in the development of hepatocellular carcinoma (HCC) in a rat model. Male Wistar rats were given diethylnitrosamine (DEN) carcinogen for a period of 18 weeks in addition to different folate modulations. Biochemical parameters were assayed and liver tissues were examined using various histopathological stains viz. Hematoxylin and eosin (H&E), Masson's trichrome, Immunohistochemistry (IHC) staining for arginase-1 and α-smooth muscle actin (SMA). Serum folate and hepatic folate stores were decreased and increased in folate deficiency (FD) and folate oversupplemented (FO) group respectively. Analysis of serum liver function tests revealed deranged liver functioning in all the groups. H&E staining of rat liver demonstrated vague nodularity from 2nd to 8th week, fibrosis from 10th to 15th week, cirrhosis and HCC from 16th to 18th week. Combining the observations of H&E with IHC for arginase-1, 14 (50%), 11 (39.3%) and 17 (58.6%) rats showed HCC positivity in FN (folate normal), FD and FO diets respectively. IHC for α-SMA depicted increased staining with progression of the disease from fibrosis to cirrhosis in all the dietary groups. Collectively, findings of all the histopathological stains, revealed increase in the number of cirrhotic cases and decrease in the number of HCC cases in FD group, indicating delayed progression of HCC with FD. Moreover, FO led to more number of HCC and reduction in the number of cirrhotic cases, signifying early progression of HCC.
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http://dx.doi.org/10.1007/s10735-020-09955-9DOI Listing
April 2021

Genetic and epigenetic disease modifiers: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD).

Transl Gastroenterol Hepatol 2021 5;6. Epub 2021 Jan 5.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Inter-individual and inter-ethnic differences and difference in the severity and progression of liver disease among patients with non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) suggests the involvement of genetic and epigenetic factors in their pathogenesis. This article reviews the genetic and epigenetic modifiers in patients with NAFLD and ALD. Evidence regarding the genetic and epigenetic disease modifiers of NAFLD and ALD was reviewed by searching the available literature. Both genome wide association studies (GWAS) and candidate gene studies pertaining to the pathogenesis in both diseases were included. Clinical implications of the available information are also discussed. Several studies have shown association of both NAFLD and ALD with I148M variant. In addition to the higher prevalence of hepatic steatosis, the I148M PNPLA3 variant is also associated with severity of liver disease and risk of hepatocellular carcinoma (HCC). is the other genetic variant shown to be significantly associated with hepatic steatosis and cirrhosis in patients with NAFLD and ALD. The Membrane bound O-acyltransferase domain-containing 7 () genetic variant is also associated with both NAFLD and ALD. In addition to these mutations, several variants related to the genes involved in glucose metabolism, insulin resistance, lipid metabolism, oxidative stress, inflammatory pathways, fibrosis have also been shown to be the disease modifiers in patients with NAFLD and ALD. Epigenetics involving several micro RNAs and DNA methylation could also modify the disease course in NAFLD and ALD. In conclusion the available literature suggests that genetics and epigenetics are involved in the pathogenesis of NAFLD and ALD which may affect the disease prevalence, severity and response to treatment in these patients.
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http://dx.doi.org/10.21037/tgh.2019.09.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724177PMC
January 2021

Combined PEG3350 Plus Lactulose Results in Early Resolution of Hepatic Encephalopathy and Improved 28-Day Survival in Acute-on-Chronic Liver Failure.

J Clin Gastroenterol 2020 Oct 13. Epub 2020 Oct 13.

Hepatology.

Background And Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality in those with hepatic encephalopathy (HE). Polyethylene glycol (PEG) 3350 electrolyte solution can ensure rapid gut catharsis, which may resolve HE more effectively than lactulose. In this open-label-randomized trial, we compared PEG+lactulose versus lactulose alone in ACLF with HE grade ≥2 for efficacy and outcome.

Patients And Methods: Patients were randomized to receive PEG (2 L q12 h) followed by lactulose (30 mL q8 h) or standard medical treatment [SMT, lactulose (titrated 30 mL q8 h)]. Endpoints were HE grade improvement at 24 hours, 48 hours, and 7 days using hepatic encephalopathy scoring algorithm (HESA), ammonia reduction, HE resolution, and survival benefit.

Results: Of 60 patients, 29 were randomized to PEG+lactulose arm and 31 to SMT. In the PEG arm, early reduction in HESA score was noted in more persons [18 (62.1%) vs. 10 (32.2%); P=0.021] with a shorter median time to HE resolution [4.5 (3 to 9) d vs. 9 (8 to 11) d; P=0.023]. On multivariate analysis, age [hazard ratio (HR),1.06 (1.00 to 1.13); P=0.03], HESA score [HR, 6.01 (1.27 to 28.5); P=0.024], and model for end-stage liver disease [HR, 1.26 (1.01 to 1.53); P=0.022] were predictors of mortality at 28 days. Ammonia level or reduction did not correlate with HE grades. Adverse events included excessive diarrhea (20.6% vs. 9.6%) in the PEG and SMT arms, albeit without dyselectrolytemia or worsened renal function. In the PEG versus SMT arm, survival at 28 days were 93.1% versus 67.7% (P=0.010) and at 90 days was 68.9% versus 48.3% (P=0.940), respectively, with fewer persons relapsing with HE in the PEG arm.

Conclusions: PEG resulted in early and sustained HE resolution with improved short-term survival making, it a suitable and safe drug in patients with acute HE in ACLF.
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http://dx.doi.org/10.1097/MCG.0000000000001450DOI Listing
October 2020

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

J Clin Exp Hepatol 2020 Sep-Oct;10(5):477-517. Epub 2020 Apr 22.

Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.
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http://dx.doi.org/10.1016/j.jceh.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527855PMC
April 2020

Sofosbuvir and Velpatasvir combination is safe and effective in treating chronic hepatitis C in end-stage renal disease on maintenance haemodialysis.

Liver Int 2021 04;41(4):705-709

Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background & Aims: There is emerging data on the use of Sofosbuvir-based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) on maintenance haemodialysis (MHD). We evaluated the safety and efficacy of Sofosbuvir plus Velpatasvir fixed-dose combination in CHC patients with ESRD on MHD.

Methods: Fifty-one CHC patients with ESRD on MHD were included in a real-life prospective study. All patients irrespective of genotype; presence of cirrhosis; treatment naive or experienced status were treated with full-dose Sofosbuvir (400 mg) plus Velpatasvir (100 mg) fixed-dosed combination given daily for 12 weeks. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR). Side effects if any were recorded in all patients.

Results: The median HCV RNA level in 51 CHC patients [Males 41 (80.4%), mean age 42.8 ± 14.6 years] was 2.0 × 10 IU/mL. HCV genotype was available in 19 patients with predominant genotype 1 in 15 (79%) patients. Ten (19.6%) patients had evidence of cirrhosis (defined as LSM ≥ 12.5 kPa on Transient Elastography), and 8 (15.6%) patients were treatment experienced. Testing for ETR was done in 36 patients and all 36 (100%) patients achieved ETR, and 49 patients (96%) achieved SVR 12. All 51 patients tolerated the Sofosbuvir + Velpatasvir combination, with none of the patients reporting any serious adverse event.

Conclusion: Sofosbuvir plus Velpatasvir fixed-dose combination is safe and effective in treating CHC in patients with ESRD on MHD.
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http://dx.doi.org/10.1111/liv.14685DOI Listing
April 2021

Letter: long-term abdominal drains in refractory ascites-evolving concept of palliative care in decompensated cirrhosis.

Aliment Pharmacol Ther 2020 10;52(7):1266-1267

Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.1111/apt.15944DOI Listing
October 2020

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

Liver Int 2021 01;41(1):150-157

Dayanand Medical College and Hospital, Ludhiana, India.

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 < .001), independent of age, CTP, MELD and AARC scores.

Conclusion: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.
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http://dx.doi.org/10.1111/liv.14671DOI Listing
January 2021

Neutrophil dysfunction predicts 90-day survival in patients with acute on chronic liver failure: A longitudinal case-control study.

JGH Open 2020 Aug 5;4(4):595-602. Epub 2020 May 5.

Department of Hepatology Post Graduate Institute of Medical Education and Research Chandigarh India.

Background And Aim: Innate immune disarray is a key component in the development and progression of acute on chronic liver failure (ACLF) and predisposition to infections. We evaluated the neutrophil dysfunction and its impact on outcomes in patients with ACLF.

Methods: Forty patients with acute decompensation of cirrhosis (10 each of grades 0, 1, 2, and 3 ACLF) and 10 healthy controls were prospectively evaluated for neutrophil immunophenotype (NP), neutrophil phagocytic capacity (NPC), and oxidative burst (OB) in both resting and stimulated conditions. The patients were followed up for 90 days or until death or transplant, whichever was earlier.

Results: NP was normal (in %) and NPC (in mean fluorescence intensity [MFI]) was better in controls compared to patients with ACLF (83.74 ± 12.38 63.84 ± 22.98; = 0.007 and 98.33 ± 130.60 18.73 ± 17.88, = 0.001, respectively). Resting OB was higher in patients with ACLF compared to controls (97 ± 4.9% 91 ± 9%; = 0.034), but it failed to increase further after stimulation, suggesting an immune exhaustion. NP was normal (in %) and NPC (in MFI) was better in 90-day survivors compared to nonsurvivors (78 ± 11.9 62.2 ± 24.11, = 0.02 and 33.3 ± 22.7 16.36 ± 13.3; = 0.004, respectively). Phenotypically normal neutrophils >71.7% had 78.6% sensitivity and 65.4% specificity with an area under receiver operating curve (AUROC) of 0.70 (95% confidence interval [CI]: 0.55-0.90); = 0.017, and NPC >17.32. MFI had 71.4% sensitivity and 69.6% specificity with an AUROC of 0.73 (95% CI: 0.54-0.86), = 0.035, in predicting 90-day survival.

Conclusion: Neutrophils have impaired bactericidal function in patients with ACLF compared to healthy adults. Neutrophil phenotype and phagocytic capacity may be used to predict 90-day survival in patients with ACLF.
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http://dx.doi.org/10.1002/jgh3.12344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411642PMC
August 2020

Intrahepatic Arterioportal Fistula: A Rare Cause of Portal Hypertension After Deceased Donor Liver Transplant.

Exp Clin Transplant 2020 10 7;18(5):645-648. Epub 2020 Aug 7.

From the Division of General Surgery and Liver Transplantation, Hospital Oswaldo Cruz, Pernambuco University, Recife, Pernambuco, Brazil.

A 43-year-old male patient, who received a deceased donor liver transplant for background ethanol-related decompensated cirrhosis, presented 7 months after transplant with mild abdominal distension and pain. On evaluation, the patient had thrombocytopenia, high serum-ascites albumin gradient ascites, and deranged liver functions. The Doppler study of the splenoportal axis showed hepatofugal flow in the recipient's portal vein, normal hepatic veins, a normal liver, splenomegaly, mild ascites, and multiple periportal collaterals. A transjugular liver biopsy and a hepatic venous pressure gradient measurement were done, which suggested mild portal tract inflammation with portal tract fibrosis with prominent portal venous thickening and normal hepatic venous pressure gradient (4 mm). However, the patient had a progressive increase in ascites and a dramatic increase in serum bilirubin level. A triple-phase computed tomography was done that showed rapid contrast flow in both the portal and hepatic arterial phase, suggesting arterialization of the portal flow with possible suspicion of a communicating arterioportal fistula. The patient underwent digital subtraction angiography, which was followed by an embolization of the arterioportal fistula. After embolization, serum bilirubin gradually decreased and ascites resolved. A repeat Doppler of the portal venous system showed established hepatopetal flow with progressively rising portal flow velocities.
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http://dx.doi.org/10.6002/ect.2020.0119DOI Listing
October 2020

Animal Naming Test - a simple and accurate test for diagnosis of minimal hepatic encephalopathy and prediction of overt hepatic encephalopathy.

Clin Exp Hepatol 2020 Jun 8;6(2):116-124. Epub 2020 May 8.

Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Aim Of The Study: Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encepha-lopathy (HE). We compared the usefulness of the Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) for the diagnosis of MHE and the prediction of the development of overt episodes of HE.

Material And Methods: 103 consecutive patients with liver cirrhosis without overt HE were subjected to PHES and ANT evaluation. The receiver-operating characteristic curve was used to determine the optimum cut-off of the ANT value for the diagnosis of MHE.

Results: Thirty-seven (35.9%) patients had MHE as assessed by altered PHES. ANT (< 14) was positive in 36 (34.95%) patients with MHE with a sensitivity of 89.19% and specificity of 95.7%, positive predictive value (PPV) of 91.67%, negative predictive value (NPV) of 94.03% and diagnostic accuracy of 93.20%. The area under the curve for diagnosis of MHE was 0.978 (95% CI: 0.954-1.0). MHE patients had significantly lower ANT as compared to non-MHE patients and controls (10.81 ±0.324 vs. 15.27 ±0.147 vs. 15.78 ±0.192, respectively, = 0.01). ANT correlated with PHES ( = 0.752, = 0.001) and also with Child-Pugh ( = -0.408, = 0.001) and MELD ( = -0.318, = 0.001) scores. During follow-up, 14 patients in the MHE group and 4 in the non-MHE group developed overt episodes of HE ( = 0.001).

Conclusions: ANT is simple and accurate for the diagnosis of MHE and prediction of overt episodes of HE in patients with cirrhosis and correlates well with the Child-Pugh and MELD scores.
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http://dx.doi.org/10.5114/ceh.2019.95105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380476PMC
June 2020

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

J Clin Exp Hepatol 2020 Jul-Aug;10(4):339-376. Epub 2020 Apr 28.

Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.
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http://dx.doi.org/10.1016/j.jceh.2020.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335721PMC
April 2020

Impact of Preexisting Chronic Liver Disease on the Outcome of Patients With COVID-19 Disease.

Gastroenterology 2021 04 15;160(5):1893-1894. Epub 2020 Jun 15.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1053/j.gastro.2020.05.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837182PMC
April 2021

The autophagy gene ATG16L1 (T300A) variant is associated with the risk and progression of HBV infection.

Infect Genet Evol 2020 10 8;84:104404. Epub 2020 Jun 8.

Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan 1732 34, Himachal Pradesh, India. Electronic address:

Autophagy pathway genes variants that play crucial roles in immune responses are involved in many diseases but their role in viral diseases is ill-defined. ATG16L1 gene plays a crucial role in the autophagy process. In this study, we have investigated the role of ATG16L1 variant T300A in the risk of HBV infection. rs2241880 (T300A) variant in 551 HBV infected patients (at various stages of infection) and 247 healthy controls were genotyped applying PCR-RFLP. Data analysis revealed that mutant allele G contributes to the risk of hepatitis B infection. Mutant alleles were significantly associated the HBV risk in allelic (OR = 1.31; 95%CI = 1.06-1.63, p = .01) and homozygous (OR = 1.87; 95%CI = 1.17-2.99, p = .009) models. On stratifying HBV infected individuals according to the stage of infection, a significant association was observed in asymptomatic (allelic; OR = 1.52; 95%CI = 1.10-2.09, p = .01 and homozygous; OR = 2.30; 95%CI = 1.22-4.36, p = .01) and chronic (allelic; OR = 1.36; 95%CI = 1.07-1.73, p = .01 and homozygous; OR = 2.07; 95%CI = 1.22-3.53, p = .008) stages of infection. High HBV DNA levels were associated with mutant genotype GG in asymptomatic and chronic carriers. Significantly higher ALT levels were observed in the liver cirrhosis patients with mutant genotypes. In conclusion, our data suggest that rs2241880 mutant allele carriers (allelic and homozygous models) were associated with increased risk of hepatitis B virus infection in North Indian population.
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http://dx.doi.org/10.1016/j.meegid.2020.104404DOI Listing
October 2020

Freeze-dried microspheres for selective intra-arterial radionuclide therapy: an affordable solution.

Nucl Med Commun 2020 Aug;41(8):817-823

Departments of Nuclear Medicine and PET.

Objective: Selective intra-arterial radionuclide therapy (SIRT) using radiolabelled microspheres is for the delivery of therapeutic radioisotope to liver cancers and thus, sparing healthy liver. Several radiolabelled microspheres are commercially available. The main issue associated with these microspheres is affordability. Re-188 is a generator produced radionuclide, emits high energy therapeutic beta particle and imageable gamma photons for pre- and post-therapy dosimetry.

Methods: Tc-99m/Re-188 labelled microspheres have been developed and quality control tests have been performed for suitable clinical use. The clinical studies with Re-188 microspheres for SIRT have been performed. Post-therapy images were acquired for dosimetry.

Results: The microspheres were found to possess spherical morphology of less than 20 µm size. The quality control revealed the suitability of microspheres for intravenous administration. The preliminary studies in thirty patients demonstrated good retention in tumor and high tumor to normal liver ratio. Re-188 microspheres were well tolerated by patients. Same microspheres labelled with either Tc-99m or Re-188 were used for pretherapy dosimetry and Re-188 labeled microspheres for therapy (SIRT) as a single-day procedure.

Conclusion: The freeze-dried microspheres may emerge as highly cost-effective candidates for both pre-therapy dosimetry and SIRT and may benefit a large population with inoperable liver cancer.
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http://dx.doi.org/10.1097/MNM.0000000000001225DOI Listing
August 2020

Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease: The Gut and Obesity Asia initiative.

World J Gastroenterol 2020 May;26(19):2416-2426

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Background: Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population.

Aim: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).

Methods: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.

Results: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] 49 [41-55] years; < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk ( < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] low risk 66 [38-103], = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).

Conclusion: The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.
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http://dx.doi.org/10.3748/wjg.v26.i19.2416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243652PMC
May 2020

Natural History of Simple Steatosis or Nonalcoholic Fatty Liver.

Authors:
Arka De Ajay Duseja

J Clin Exp Hepatol 2020 May-Jun;10(3):255-262. Epub 2019 Sep 20.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The histological spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. Ballooning degeneration of hepatocytes with or without fibrosis is the key feature that differentiates NASH from NAFL. Liver biopsy is the only reliable method for diagnosing NAFL and differentiating it from NASH. Although the epidemiology of NAFLD is well described, the need for invasive biopsy limits our knowledge of the community prevalence of NAFL. Recent data suggest that the biochemical composition of hepatic steatosis may have a bearing on the disease. Triglycerides, the most commonly accumulated lipid, have a cytoprotective role because of their inert nature. Several paired liver biopsy studies and longitudinal follow-up studies have shown that NAFL is not completely benign as previously envisaged. NAFL can indeed progress to NASH and severe fibrosis, with progression being influenced by presence of baseline or worsening metabolic risk factors. Overall, NAFL carries a low risk of liver-related and overall mortality although the risk of cardiovascular mortality is similar to that of NASH. Current concepts suggest the presence of a dynamic bidirectional cycling between NAFL and NASH with slow progression of fibrosis in majority of the patients. The fact that ultimately it is the onset of progressive fibrosis that dictates clinical outcomes brings into question the relevance of distinguishing NAFL from NASH.
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http://dx.doi.org/10.1016/j.jceh.2019.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212297PMC
September 2019