Publications by authors named "S K Sarin"

835 Publications

Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis.

Virchows Arch 2021 Apr 2. Epub 2021 Apr 2.

Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.

Alcoholic hepatitis (AH) lacks specific histological staging. A novel fibrosis staging that encompasses perisinusoidal fibrosis and cirrhosis sub-stages, substantiated by Hepatic venous pressure gradient (HVPG) and automated fibrosis quantification, is imperative. To correlate novel histological staging system of AH with second-harmonic generation microscopy (SHG)-based q-fibrosis, HVPG, and activated hepatic stellate cells (HSCs). Liver biopsies of AH (n = 175) were staged semi-quantitatively as F0, F1, F2, F3A and F3B and Laennec substages of cirrhosis 4A, 4B and 4C. Stages were correlated with SHG q-fibrosis parameters, HVPG and HSCs. Mean age 41.2 ± 9.4 years, 96.6% males, bilirubin 20.58 ± 8.0 mg/dl and Maddrey's discriminant function 78.9 ± 36.7 displayed advanced fibrosis in 98.6%. With increasing histological stages, an increase in q-fibrosis indices and mean HVPG (p < 0.0001) were recorded; stage 4C showed the most significant difference from other stages (p < 0.000). Stages 3A and 3B were comparable with the stages 4A and 4B, respectively, for q-fibrosis (p = 1) and HVPG (p = 1). HSCs (> 30%) were significantly higher in stage 3 (75%) compared with 4 (49%) and 2 (59%), p = 0.018. Overall agreement for histological staging was excellent for all stages (0.82). SHG quantified fibrosis and HVPG corroborates the novel histological staging of AH. Expansive PCF matches with collagen content and clinical severity to early sub-stages of cirrhosis. This highlights the need for an accurate quantification and inclusion of PCF as a separate stage. SHG-based quantification can be a useful adjunct to histological fibrosis staging systems.
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http://dx.doi.org/10.1007/s00428-021-03089-3DOI Listing
April 2021

Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!

Hepatology 2021 Mar 27. Epub 2021 Mar 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Human serum albumin (HSA) is the most abundant plasma protein and it regulates diverse body functions. In advanced and decompensated cirrhosis patients, serum albumin levels are low due to reduction in hepatocyte mass and loss due to disease per se and multiple therapeutic interventions. Due to its oncotic and non-oncotic properties, administration of human albumin solutions (HAS) has been found to be beneficial in patients undergoing large volume paracentesis, hepatorenal syndrome and spontaneous bacterial peritonitis. Albumin also improves functionality of the immune cells and mitigates the severity and risks of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving quality of life with probable survival benefits. There is however, a need to rationalize the dose, duration, frequency of albumin therapy in different liver diseases and stages of cirrhosis. In acute-on chronic liver failure patients, potentially toxic oxidized isoforms of albumin increase substantially, specially human nonmercaptalbumin1 (HNA1) or 2(HNA2) and nitroso-albumin. The role of HAS administration in such patients is unclear. Whether removal of the pathological and dysfunctional albumin forms in these patients by 'albumin dialysis' is helpful, requires additional studies. Use of albumin is not without adverse events. These include allergic and transfusion reactions, volume overload, antibody formation, coagulation derangements, etc. Considering its cost, limited availability, need of health care setting for its administration, and potential adverse effects; judicious use of HAS in liver diseases is advocated. There is a need of new albumin molecules and economic alternatives in hepatology practice.
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http://dx.doi.org/10.1002/hep.31836DOI Listing
March 2021

Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study.

Indian J Gastroenterol 2021 Mar 27. Epub 2021 Mar 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110 070, India.

Background And Aim: Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), an anti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients.

Methods: In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400 mg thrice daily and VE 400 IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12 months. Primary end-point was change in alanine aminotransferase (ALT)  levels.   RESULTS: Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was a similar reduction in ALT levels in the two groups. Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6 months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003).

Conclusions: These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status.

Trial Registration: Clinical Trials Registry no. NCT01384578.
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http://dx.doi.org/10.1007/s12664-020-01131-xDOI Listing
March 2021

Insights into the Role of Granulocyte Colony-Stimulating Factor in Severe Alcoholic Hepatitis.

Semin Liver Dis 2021 Jan 9;41(1):67-78. Epub 2021 Feb 9.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Alcohol use disorder is the predominant cause of chronic liver disease globally. The standard of care for the treatment of alcoholic hepatitis, corticosteroids, has been shown to provide a therapeutic response in ∼60% of carefully selected patients with a short-term survival benefit. The patients who do not respond to steroids, or are ineligible due to infections or very severe disease, have little options other than liver transplantation. There is, thus, a large unmet need for new therapeutic strategies for this large and sick group of patients. Granulocyte colony stimulating factor (G-CSF) has been shown to favorably modulate the intrahepatic immune milieu and stimulate the regenerative potential of the liver. Initial studies have shown encouraging results with G-CSF in patients with severe alcoholic hepatitis. It has also been found to help steroid nonresponsive patients. There is, however, a need for careful selection of patients, regular dose monitoring and close observation for adverse events of G-CSF. In this review, we analyze the basis of the potential benefits, clinical studies, cautions and challenges in the use of G-CSF in alcoholic hepatitis.
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http://dx.doi.org/10.1055/s-0040-1719177DOI Listing
January 2021

MAFLD considerations as a part of the global hepatitis C elimination effort: an international perspective.

Aliment Pharmacol Ther 2021 Mar 22. Epub 2021 Mar 22.

Geneva, Switzerland.

Background: The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD).

Aims: To review the potential interaction of HCV and MAFLD.

Methods: We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD.

Results: In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV.

Conclusions: This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.
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http://dx.doi.org/10.1111/apt.16346DOI Listing
March 2021

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.

Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, 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

Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines.

Hepatol Int 2021 Feb 27. Epub 2021 Feb 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.
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http://dx.doi.org/10.1007/s12072-021-10144-3DOI Listing
February 2021

Chronic hepatitis B: the demise of the 'inactive carrier' phase.

Hepatol Int 2021 Feb 27. Epub 2021 Feb 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Chronic hepatitis B (CHB) remains a global healthcare burden. Although the recent developments in the field have led to a reduction in incidence, the morbidity and mortality including liver cirrhosis and hepatocellular carcinoma (HCC) remain a formidable challenge. Advances in understanding the immunopathogenesis of CHB have led to a recent change in clinical categorization. EASL introduced the term hepatitis B 'e' antigen (HBeAg)-negative chronic infection, to replace the historical term 'inactive carrier' disease phase, the commonest CHB phase. Although this disease phase is associated with a favorable prognosis, it is not a truly 'inactive' disease phase with no ostensible liver disease, as inferred by the previous anachronistic terminology, and the risk of spontaneous reactivation and the potential risk of disease progression and HCC development are not negligible. Likewise, the APASL also uses the term "Incidentally Detected Asymptomatic Hepatitis B surface antigen (HBsAg)-positive Subject (IDAHS)", comprising all HBsAg-positive subjects who are incidentally detected during routine tests, without any previous or present symptoms of liver disease. This entity includes HBV infection with varied stages of liver disease. Antiviral treatment is generally reserved for patients with active inflammation and/or at risk of disease progression and HCC development. HBsAg loss is considered an optimal treatment endpoint, and may also be achievable in HBeAg-negative chronic infection and IDAHS. In light of this, and the emerging novel HBV therapies, lowering the treatment threshold and a 'Treat All' approach should now be considered. In this review, we summarize the literature and guidance on HBeAg-negative chronic infection, and we make a concerted effort to present the reasons why the one-dimensional term 'inactive carrier' should be abandoned.
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http://dx.doi.org/10.1007/s12072-021-10137-2DOI Listing
February 2021

Retrospective comparative study of efficacy, safety and outcome of percutaneous intervention for Budd-Chiari syndrome patients with bilirubin less than 3 and 3-6 mg/dl.

Br J Radiol 2021 Apr 17;94(1120):20201157. Epub 2021 Feb 17.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Objective: Comparing the efficacy, safety and outcome of percutaneous intrervention for Budd-Chiari Syndrome (BCS) patients with bilirubin less than 3 and 3-6 mg dl.

Methods And Materials: 188 BCS patients having serum bilirubin ≤6 mg dl and underwent percutaneous interventions were divided into two groups based on bilirubin level: 151 patients having bilirubin <3 mg dl were included in Group 1; and 37 patients having bilirubin 3-6 mg dl were included in Group 2. Both group were compare for technical success (successful recanalization of hepatic venous stenosis or creation of portocaval shunt with post-procedure gradient ≤5 mm of Hg), Safety (procedure-related mortality/morbidity or patient required transplantation) and outcome (resolution of clinical symptoms and survival).

Results: Technical success was 94.7% in Group 1-89.1% in Group 2 with overall success rate was 93.6%. No significant differences observed between the two groups in regards to procedure related complication. Overall transplant-free survival at 1 and 5 years after intervention in both groups was 96.3 and 91.2% respectively. 1-year and 5-year survivals in Group 1 was 96.7%, and 93.1%, whereas Group 2 was 94.6 and 90.1% with no statically significantly difference between the two groups ( = 0.59). Percutaneous intervention results are good in patients having bilirubin up to 6 mg dl, . mild to moderate liver dysfunctions.

Conclusion: Technical success, survival and outcome of percutaneous intervention in BCS patients having serum bilirubin 3-6 mg dl was comparable to patients having bilirubin level <3 mg dl.

Advances In Knowledge: Percutaneous intervention treatment is suitable for treatment for symptomatic BCS patients having bilirubin up to 6 mg  dl.
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http://dx.doi.org/10.1259/bjr.20201157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010545PMC
April 2021

Degree of Portal and Systemic Hemodynamic Alterations Predict Recurrent AKI and Chronic Kidney Disease in Patients With Cirrhosis.

Hepatol Commun 2021 Feb 6;5(2):293-308. Epub 2020 Nov 6.

Department of Hepatology Institute of Liver and Biliary sciences New Delhi India.

The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child-Turcotte-Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta-blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow-up of 379 (interquartile range: 68-869) days, AKI developed at a rate of 0.37 episodes per person-year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868;  < 0.001), CKD (subdistribution hazard ratio 0.74 [0.54-1.02]), and mortality (hazard ratio 0.21 [0.06-0.73]) were observed in beta-blocker responders. Albuminuria was an independent risk factor for recurrent AKI, CKD, and mortality ( < 0.05). Lower systemic vascular resistance index predicted hemodynamic response (odds ratio 2.04 [1.29-3.22]), cumulative AKI episodes (ratio of means 0.10 [0.08-0.14]), and development of CKD (subdistribution hazard ratio 0.70 [0.58-0.83]). Higher hepatic venous pressure gradient (≥17 mm Hg) predicted AKI episodes (ratio of means 1.76 [1.32-2.35]) but not CKD. High portal pressure and severe vasodilatation predispose patients with cirrhosis to repeated AKI episodes and development of CKD. Response to beta-blockers and therapies targeting the vasodilatory state could prevent frequent AKI and the risk of CKD development. Albuminuria could serve as an early marker of renal dysfunction in patients with cirrhosis.
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http://dx.doi.org/10.1002/hep4.1607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850308PMC
February 2021

Co-orchestration of acute kidney injury and non-kidney organ failures in critically ill patients with cirrhosis.

Liver Int 2021 Feb 3. Epub 2021 Feb 3.

Department of Hepatology, Institute of Liver and Biliary Science, New Delhi, India.

Background & Aims: Little is known on the course of acute kidney injury (AKI) and its relation to non-kidney organ failures and mortality in critically ill patients with cirrhosis (CICs).

Methods: We conducted a large prospective, single-centre, observational study in which CICs were followed up daily, during the first 7 days of intensive care, collecting prespecified criteria for AKI, extrarenal extrahepatic organ failures (ERH-OFs) and systemic inflammatory response syndrome (SIRS).

Results: A total of 291 patients admitted to ICU were enrolled; 231 (79.4%) had at least one ERH-OFs, 168 (58%) had AKI at presentation, and 145 (49.8%) died by 28 days. At day seven relative to baseline, 151 (51.8%) patients had progressive or persistent AKI, while the rest remained free of AKI or had AKI improvement. The 28-day mortality rate was higher among patients with progressive/persistent AKI (74.2% vs 23.5%; P < .001) or maximum stage 3 of AKI in the first week. Two-level mixed logistic regression modelling identified independent baseline risk factors for progressive/persistent AKI, including 3 to 4 SIRS criteria, infections due to multidrug-resistant bacteria (MDR), elevated serum bilirubin, and number of ERH-OFs. Follow-up risk factors included increases in bilirubin and chloride levels, and new development of 2 or 3 ERH-OFs.

Conclusions: Our results show that among CICs admitted to the ICU, the stage and course of AKI in the first week determines outcomes. Strategies combating MDR infections, multiorgan failure, liver failure and intense systemic inflammation could prevent AKI progression or persistence in CICs.
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http://dx.doi.org/10.1111/liv.14809DOI Listing
February 2021

Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: A propensity-score matched study from AARC.

Liver Int 2021 Feb 2. Epub 2021 Feb 2.

Départment of Hepatology Institute of Liver and Biliary Science, New Delhi, India.

Background And Aim: Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients.

Methods: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE.

Results: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA.

Conclusions: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.
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http://dx.doi.org/10.1111/liv.14806DOI Listing
February 2021

Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.

Clin Gastroenterol Hepatol 2021 Jan 29. Epub 2021 Jan 29.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. Electronic address:

Background: High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain.

Methods: In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5.

Results: ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE.

Conclusion: In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079).
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http://dx.doi.org/10.1016/j.cgh.2021.01.036DOI Listing
January 2021

Pooled nasopharyngeal swab collection in a single vial for the diagnosis of SARS CoV-2 infection: An effective cost saving method.

Indian J Med Microbiol 2021 Jan 27. Epub 2021 Jan 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background: Pool testing is one of the strategy to expedite testing capacities while simultaneously conserving various diagnostic kits, reagents and consumables and time. In the present study, we investigated potential role of combined specimen collection technique for the diagnosis of SARS-CoV-2 virus infection where five nasopharyngeal swabs were collected from different individuals and pooled together in a single viral transport medium (VTM).

Material And Methods: This pilot study was conducted on different cohorts of Delhi state. Two nasopharyngeal swabs were collected from each enrolled individual. One swab was put into VTM vial to be further used for individual swab testing (ID). The other swab was put into a fresh VTM for pool swab collection. Each pool comprised five swabs collected from five different patients in one VTM vial. Both IDs and pools were tested in parallel for the detection of SARS-CoV-2 using real time PCR.

Results: A total of 46 pools were collected from 230 enrolled individuals.Among 230 ID tested, 60 were found to be positive for both E and RdRp gene. Among 46 pools, 25 pools included all negatives samples and remaining 21 pools included one or more positives. Comparing ID with pool results, overall concordance was seen in 42 pools (91.3%). Four pools showed false positive results as all included samples on ID testing were found to be negative. Considering ID results as reference, swab pool showed 100% sensitivity, 84% specificity, 84% positive predictive value and 100% negative predictive value.

Conclusion: The pooling of swab strategy could be beneficial only among asymptomatic in low prevalence areas.
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http://dx.doi.org/10.1016/j.ijmmb.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839627PMC
January 2021

Liver Transplantation Reverses Hepatic Myelopathy in 2 Children With Hepatitis A Infection.

Child Neurol Open 2021 Jan-Dec;8:2329048X20983763. Epub 2021 Jan 11.

Pediatric Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.

Objectives: To report 2 children with acute hepatic myelopathy after hepatitis A infection who recovered completely after living donor liver transplantation.

Methods: All the children admitted into liver intensive care unit (LICU) from November 1st 2018 to 31st October 2019, were evaluated for the neurological features. The data was collected from the admission register of the LICU unit in children below 15 years age. Medical records of these children were reviewed and data collected. Established clinical criteria were used to categorize the various grades of hepatic encephalopathy/myelopathy.

Results: 37 children were seen over 1-year period between 6 months to 15 years age. There were 24 male(64.9%) and 13 females. Acute liver failure was seen in 19 (51.3%) and acute on chronic liver failure in 18 (48.7%). There were 10 cases of hepatitis A in acute liver failure group,10 of 19 cases (52.6%), while Wilson's disease and undetermined etiology group formed the chronic group. 2 cases of hepatic myelopathy were seen in acute liver failure following hepatitis A infection. Both these children underwent live liver donor transplantation and recovered completely. Further in hepatitis A group,3 children had spontaneous recovery, 4 died and 1 child was discharged with end of life care. Overall out of all 37 children with liver failure,20 (54%) were discharged, 6 (16.2%) were advised end of life care and 11 (29.8%) died.

Conclusion: Two cases (10.5%) of reversible hepatic myelopathy were seen in acute liver failure group of 19 cases. 18 out of 37 (48.6%) children had residual neurological features at discharge time.
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http://dx.doi.org/10.1177/2329048X20983763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804343PMC
January 2021

Omega-3 fatty acid lipid emulsions are safe and effective in reducing endotoxemia and sepsis in acute-on-chronic liver failure: An open-label randomized controlled trial.

J Gastroenterol Hepatol 2021 Jan 15. Epub 2021 Jan 15.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background And Aim: Sepsis is an important determinant of the outcome of acute-on-chronic liver failure (ACLF) patients. Omega-3 fatty acids (FAs) are known to suppress inflammation, reduce morbidity, and mortality in postoperative and critically ill patients. We aimed to evaluate the effect of intravenous omega-6 and omega-3 FA lipid emulsions in ACLF patients.

Methods: Ninety ACLF patients were randomly allocated to three groups: Gr. A received no lipid emulsions, Gr. B received omega-6 FAs, and Gr. C received omega-3 FAs. The primary and secondary aims were to compare the effects of lipid emulsions on immune modulation, the incidence of bacterial sepsis, and mortality at day 28.

Results: The baseline characteristics of the patients were comparable. Serum endotoxin levels remained suppressed by 22% in Gr. C compared with a 4% and 12% rise in Gr. B and A (P < 0.001). Omega-3 FAs also suppressed C-reactive protein levels and neutrophil-to-lymphocyte ratio in Gr. C. Compared with Gr. A, omega-3 FAs reduced sepsis by 86% (HR, 0.14; 95% CI 0.04-0.43; P < 0.001). Omega-3 FAs significantly increased the expression of TLR2 and TLR4 on both CD14 and CD16 monocytes, and TLR4, on macrophages and neutrophils. There were no serious adverse events, except transient flushing in 20% and 16.6% of patients receiving omega-6 FAs and omega-3 FAs, respectively.

Conclusion: Omega-3 FAs are safe and effective in reducing systemic inflammation, endotoxemia, and sepsis in patients with ACLF. These lipid emulsions could also be considered as effective sources of immunonutrition in such sick patients.
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http://dx.doi.org/10.1111/jgh.15400DOI Listing
January 2021

COVID-19 in Liver Transplant Recipients - A Series with Successful Recovery.

J Clin Transl Hepatol 2020 Dec 10;8(4):467-473. Epub 2020 Oct 10.

Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, India.

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.
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http://dx.doi.org/10.14218/JCTH.2020.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782113PMC
December 2020

Comparison of Smartphone Augmented Reality, Smartglasses Augmented Reality, and 3D CBCT-guided Fluoroscopy Navigation for Percutaneous Needle Insertion: A Phantom Study.

Cardiovasc Intervent Radiol 2021 Jan 6. Epub 2021 Jan 6.

Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.

Purpose: To compare needle placement performance using an augmented reality (AR) navigation platform implemented on smartphone or smartglasses devices to that of CBCT-guided fluoroscopy in a phantom.

Materials And Methods: An AR application was developed to display a planned percutaneous needle trajectory on the smartphone (iPhone7) and smartglasses (HoloLens1) devices in real time. Two AR-guided needle placement systems and CBCT-guided fluoroscopy with navigation software (XperGuide, Philips) were compared using an anthropomorphic phantom (CIRS, Norfolk, VA). Six interventional radiologists each performed 18 independent needle placements using smartphone (n = 6), smartglasses (n = 6), and XperGuide (n = 6) guidance. Placement error was defined as the distance from the needle tip to the target center. Placement time was recorded. For XperGuide, dose-area product (DAP, mGy*cm) and fluoroscopy time (sec) were recorded. Statistical comparisons were made using a two-way repeated measures ANOVA.

Results: The placement error using the smartphone, smartglasses, or XperGuide was similar (3.98 ± 1.68 mm, 5.18 ± 3.84 mm, 4.13 ± 2.38 mm, respectively, p = 0.11). Compared to CBCT-guided fluoroscopy, the smartphone and smartglasses reduced placement time by 38% (p = 0.02) and 55% (p = 0.001), respectively. The DAP for insertion using XperGuide was 3086 ± 2920 mGy*cm, and no intra-procedural radiation was required for augmented reality.

Conclusions: Smartphone- and smartglasses-based augmented reality reduced needle placement time and radiation exposure while maintaining placement accuracy compared to a clinically validated needle navigation platform.
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http://dx.doi.org/10.1007/s00270-020-02760-7DOI Listing
January 2021

Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients.

Clin Mol Hepatol 2021 01 3;27(1):175-185. Epub 2020 Dec 3.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background/aims: Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC.

Methods: Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included.

Results: Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2-10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P<0.001) male (97.7% vs. 67.7%), younger (40-50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC.

Conclusion: One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.
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http://dx.doi.org/10.3350/cmh.2020.0068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820216PMC
January 2021

Early Hepatocellular Carcinoma Treated by Radiofrequency Ablation-Mid- and Long-Term Outcomes.

J Clin Exp Hepatol 2020 Nov-Dec;10(6):563-573. Epub 2020 May 4.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.

Background: Radiofrequency ablation (RFA) is a standard treatment for small inoperable hepatocellular carcinoma (HCC). Studies on mid- and long-term outcome of RFA as first-line therapy for HCC from India are limited.

Methods: We evaluated consecutive HCC patients who underwent RFA as primary treatment modality at our institute between July 2009 and April 2016. The median follow-up period was 26 months, range 1-84 months. We evaluated post-RFA tumor response, disease-free survival (DFS), overall survival (OS), and local tumor progression (LTP). Prognostic factors were also analyzed.

Results: In 147 patients (male:female = 121:26; mean age, 59.2 years), 209 RFA sessions were done for 228 lesions (mean size of 21.5 ± 8.3 mm, range 10-50 mm). Primary success rate was 94.2%. The estimated cumulative proportion survival at 1, 3, and 5 years was 90.2%, 63.8%, and 60.2%, respectively. The cumulative incidence of LTP estimated at 1, 3, and 5 years was 13.1%, 19.7%, and 20.1%, respectively. The mean estimate of LTP-free survival was 53.6 months (95% confidence interval: 0.49-0.58) which is 58.2 months in <3 cm lesions and 20.4 months in >3 cm lesions ( < 0.01). There was no significant difference in LTP rates between lesions in perivascular versus nonperivascular location ( = 0.71) and surface versus parenchymal lesions ( = 0.66). The mean DFS was 30.3 months (95% CI: 25.6-35.0). For OS, age and Child-Turcotte-Pugh class B were significant factors while for LTP, tumor size >3 cm was significant. Higher baseline alpha-fetoprotein level and LTP were poor predictors for DFS. Complication rate per RFA session was 7/209 (3.3%).

Conclusions: RFA is a safe and effective curative modality for first-line treatment of HCC < 3 cm.
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http://dx.doi.org/10.1016/j.jceh.2020.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719976PMC
May 2020

Hepatocellular carcinoma: Clinicopathologic associations amidst marked phenotypic heterogeneity.

Pathol Res Pract 2021 Jan 24;217:153290. Epub 2020 Nov 24.

Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India. Electronic address:

Background: Hepatocellular carcinoma (HCC) is characterized by marked phenotypic and molecular heterogeneity. Clinico-morphologic phenotypes and associations are important surrogate markers of molecular aberrations; therefore have immense relevance for targeted therapy. There is paucity of published literature on critical analysis of HCC heterogeneity and morphological alliance.

Aims: To assess the heterogeneity and dominance of histomorphological features, and to explore clinicopathological associations in HCC.

Methods: Retrospective cross-sectional study of 217 HCC tissue specimens was performed for the assessment of prevalence of major histological patterns, cytological features, and clinicopathological correlation.

Results: Homogeneous architecture with a single dominant histological pattern was a rarity. Single pattern constituting ≥50 % of the tumour was found in less than 1/5th of the cases. Macrotrabecular HCC represented 9.2 % of cases. The simultaneous presence of 2-3 patterns or atypical variants and/ or cytological characteristics was recorded in 25 % and 30 % respectively. Significant clinicopathological associations: Pseudoglandular with microtrabecular pattern-cholestasis, showed better differentiation and early-stage; macrotrabecular pattern frequently occurred with pleomorphic giant cells, higher tumour stage, higher AFP levels; solid pattern often showed clear cells. Noticeable mutual exclusions were MD bodies with microtrabecular and pseudoglandular patterns; Compact pattern with neutrophilic clusters and cholestasis. Larger tumours were significantly more heterogeneous; however, heterogeneity did not correlate with outcome CONCLUSIONS: HCC displays immense heterogeneity with an amalgamation of different histomorphological patterns and features; nevertheless, there are certain reproducible associations and omissions. Tumor biopsies agree fairly well with large specimens. Characterization of phenotypic heterogeneity, dominance, associations, and exclusions in individual patients provides vital information.
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http://dx.doi.org/10.1016/j.prp.2020.153290DOI Listing
January 2021

Letter to the Editor: Relevance of Circulating Extracellular Vesicles Carrying Sphingolipid Cargo in Alcoholic Hepatitis: Need for More Validation!

Hepatology 2021 Jan 8;73(1):471-472. Epub 2020 Dec 8.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.31465DOI Listing
January 2021

Role of EEG in Predicting Outcome of Hepatic Encephalopathy Patients.

Neurodiagn J 2020 Dec 18;60(4):272-288. Epub 2020 Nov 18.

Department of Hepatology, Institute of Liver and Biliary Sciences , New Delhi, India.

A retrospective analysis of 151 patients with hepatic encephalopathy (HE) who were admitted to the liver intensive care unit (LICU) and liver transplant intensive care unit (TICU) and underwent electroencephalographic (EEG) testing was performed. We describe a method of grading the EEGs of patients with HE and predicting their subsequent outcomes. All liver failure patients with HE who underwent routine EEG testing in the LICU or TICU between October 1, 2018 and March 31, 2019, at the Institute of Liver and Biliary Sciences (ILBS) were enrolled in this analysis. The data was analyzed using Statistical Package for the Social Sciences (SPSS). The patients were divided into four grades of HE based on established EEG criteria (HE-EEG). One hundred fifty-one patients [127 Male (84%), 24 Female (16%)] with HE who underwent EEG testing were enrolled. Ages ranged from 3 to 74 years, with a mean age of 48.34 years and median interquartile range (IQR) of 49 years (38-60 years). Ninety-five patients (62.9%) had grade 1 and 2 hepatic encephalopathy, with a statistically significant, worse outcome seen in grades 3 and 4 HE patients. Seizures were seen in 30 (20.1%) of HE patients. Fifteen of 30 patients with seizures (50%) were in the ethanol and nonalcoholic steatohepatitis (NASH) groups. Forty-four of 59 (74.6%) MRIs and 35 of 60 (58.3%) CTs demonstrated some type of brain abnormality in these patients. Imaging abnormalities and the presence of seizures did not contribute to a statistically worse outcome. EEG has an important role in predicting the outcome and prognosis in HE. Patients with grade 3 or 4 HE-EEG, or with progressive worsening of HE-EEG grading were associated with the highest mortality rates.
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http://dx.doi.org/10.1080/21646821.2020.1824959DOI Listing
December 2020

APASL practical recommendations for the management of hepatocellular carcinoma in the era of COVID-19.

Hepatol Int 2020 Dec 11;14(6):920-929. Epub 2020 Nov 11.

Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-city, Yamanashi, Japan.

Background: COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic.

Aims: We develop these recommendations to preserve adequate clinical practice for the management of HCC.

Methods: Experts of HCC in the Asia-Pacific region exchanged opinions via webinar, and these recommendations were formed.

Results: Close contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it.

Conclusions: These are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.
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http://dx.doi.org/10.1007/s12072-020-10103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655459PMC
December 2020

Current Concepts in Coagulation Profile in Cirrhosis and Acute-on-Chronic Liver Failure.

Clin Liver Dis (Hoboken) 2020 Oct 3;16(4):158-167. Epub 2020 Nov 3.

Department of Hepatology Institute of Liver and Biliary Sciences New Delhi India.

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http://dx.doi.org/10.1002/cld.976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609701PMC
October 2020

Evaluation of genotype MTBDRplus V2 and genotype MTBDRsl V2 for the diagnosis of extrapulmonary tuberculosis in India.

Tuberculosis (Edinb) 2020 12 23;125:102014. Epub 2020 Oct 23.

World Health Organization, New Delhi, India.

Microbiological diagnosis of extra-pulmonary tuberculosis (EPTB) has been one of the most difficult aspects of tuberculosis (TB) management. Availability of better imaging and diagnostic modalities has led to an increase in the number of diagnosed cases. The current upsurge in multidrug-resistant tuberculosis warrants routine testing of EPTB samples for resistance at baseline with shorter turn-around time. A total of 369 EPTB specimens were subjected to Ziehl-Neelsen (ZN) stain, liquid culture (LC) with phenotypic drug susceptibility testing, MTBDRplus V.2 and MTBDRsl V.2. The molecular categorisation of resistant specimens was further reconfirmed with sequencing. The sensitivity and specificity of MTBDRplus V.2 to detect Mycobacterium tuberculosis (MTB) when compared to ZN stain was 97.9% and 89.2%, respectively while it was 73.4% and 83.8%, respectively when compared to LC. Similarly, for MTBDRsl V.2, the sensitivity and specificity for detection of MTB when compared with ZN was 95.6% and 91.9%, respectively and 75% and 89.2%, respectively when compared to LC. In smear-positive specimens, 94% (141/150) and 86% (129/150) valid results were observed in MTBDRplus V.2 and MTBDRsl V.2, respectively. The utilisation of both MTBDRplus V.2 and MTBDRsl V.2 for the diagnosis of smear-positive EPTB specimens would be useful in programmatic management of TB in high-burden settings.
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http://dx.doi.org/10.1016/j.tube.2020.102014DOI Listing
December 2020

Complications and Management of the Thoracic Endovascular Aortic Repair.

Aorta (Stamford) 2020 Jun 5;8(3):49-58. Epub 2020 Nov 5.

George Washington University Hospital, Washington, District of Columbia.

Endovascular treatment in thoracic aortic diseases has increased in use exponentially since Dake and colleagues first described the use of a home-made transluminal endovascular graft on 13 patients with descending thoracic aortic aneurysm at Stanford University in the early 1990s. Thoracic endovascular aneurysm repair (TEVAR) was initially developed for therapy in patients deemed unfit for open surgery. Innovations in endograft engineering design and popularization of endovascular techniques have transformed TEVAR to the predominant treatment choice in elective thoracic aortic repair. The number of TEVARs performed in the United States increased by 600% from 1998 to 2007, while the total number of thoracic aortic repairs increased by 60%. As larger multicenter trials and meta-analysis studies in the 2000s demonstrate the significant decrease in perioperative morbidity and mortality of TEVAR over open repair, TEVAR became incorporated into standard guidelines. The 2010 American consensus guidelines recommend TEVAR to be "strongly considered" when feasible for patients with degenerative or traumatic aneurysms of the descending thoracic aorta exceeding 5.5 cm, saccular aneurysms, or postoperative pseudoaneurysms. Nowadays, TEVAR is the predominant treatment for degenerative and traumatic descending thoracic aortic aneurysm repair. Although TEVAR has been shown to have decreased early morbidity and mortality compared with open surgical repair, endovascular manipulation of a diseased aorta with endovascular devices continues to have significant risks. Despite continued advancement in endovascular technique and devices since the first prospective trial examined the complications associated with TEVAR, common complications, two decades later, still include stroke, spinal cord ischemia, device failure, unintentional great vessel coverage, access site complications, and renal injury. In this article, we review common TEVAR complications with some corresponding radiographic imaging and their management.
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http://dx.doi.org/10.1055/s-0040-1714089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644296PMC
June 2020

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.

United European Gastroenterol J 2020 Nov 5:2050640620967898. Epub 2020 Nov 5.

Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.

Background: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.

Objective: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.

Methods: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.

Results: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.

Conclusion: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.
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http://dx.doi.org/10.1177/2050640620967898DOI Listing
November 2020

Identification of miRNAs associated with dendritic cell dysfunction during acute and chronic hepatitis B virus infection.

J Med Virol 2021 Jun 10;93(6):3697-3706. Epub 2020 Nov 10.

Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.

The uptake or expression of hepatitis B virus (HBV) proteins by dendritic cells (DCs) is considered important for disease outcome. Differential expression of microRNA (miRNA) may have a role in viral persistence and hepatocellular injury. The miRNA expression was investigated by microarray in DCs from different stages of HBV infection and liver disease namely, immune active (IA; n = 20); low replicative (LR; n = 20); HBeAg negative (n = 20); acute viral hepatitis (AVH, n = 20) and healthy controls (n = 20). miRNA levels were analyzed by unsupervised hierarchical clustering and principal component analyses and validated by quantitative polymerase Chain Reaction (qPCR). The miRNA-messenger RNA (mRNA)regulatory networks identified 19 miRNAs and 12 target gene interactions in major histocompatibility complex and other immune pathways. miR-2278, miR-615-3p, and miR-3681-3p were downregulated in the IA group compared to healthy control, miR-152-3p and miR-3613-3p in the LR group compared to IA group and miR-152-3p and miR-503-3p in HBe negative compared to LR group. However, miR-7-1-1-3p, miR-192-5p, miR-195-5p, and miR-32-5p in LR, miR-342-3p, and miR-940 in HBe negative, and miR-34a-5p, miR-130b-3p, miR-221-3p, miR-320a, miR-324-5p, and miR-484 in AVH were upregulated. Further, qPCR confirmed changes in miRNA levels and their target genes associated with antigen processing and presentation. Thus, a deregulated network of miRNAs-mRNAs in DCs seems responsible for an impaired immune response during HBV pathogenesis.
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http://dx.doi.org/10.1002/jmv.26629DOI Listing
June 2021