Publications by authors named "Shiv K Sarin"

210 Publications

APASL-ACLF Research Consortium-Artificial Intelligence (AARC-AI) Model Precisely Predicts Outcomes in Acute-on-Chronic Liver Failure Patients.

Liver Int 2022 Jul 7. Epub 2022 Jul 7.

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

Background And Aims: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF).

Methods: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations, and organ involvement were serially noted for 90-days and utilized for AI modeling. Data were split randomly into train and validation-sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train-set. Outcome prediction abilities were evaluated on validation-sets through area-under-the-curve (AUC), accuracy, sensitivity, specificity, and class-precision.

Results: Among 2481 ACLF patients, 1501 in train and 980 in validation-set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907), and overall-set (0.976) for predicting 30-day outcomes. The AUC and accuracy of XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7-AARC-model(p<0.001) and 12.8% and 10.6% higher than day-7-MELD for 30-day predictions in validation-set(p<0.001). The XGB-model had the highest AUC for 7 and 90-day predictions as well(p<0.001). Day-7 creatinine, international-normalized-ratio (INR), circulatory failure, leucocyte count, and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR, and circulatory failure was able to classify patients in high(~90%), intermediate(~60%), and low risk(~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions.

Conclusions: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.
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http://dx.doi.org/10.1111/liv.15361DOI Listing
July 2022

Intragastric Balloon in Obese Compensated Nonalcoholic Steatohepatitis Cirrhosis Patients Is Safe and Achieves Significant Weight Reduction at 6-Months.

Dig Dis Sci 2022 Jun 28. Epub 2022 Jun 28.

Department of Gastroenterology, Artemis Hospitals, Gurugram, Haryana, India.

Background And Study Aims: Weight reduction is the mainstay treatment for Nonalcoholic steatohepatitis (NASH). intragastric balloon (IGB) placement has proven benefit in terms of weight reduction. The aim of the present study is to assess the safety and efficacy of IGB placement in compensated NASH cirrhosis.

Patients And Methods: Nonalcoholic steatohepatitis cirrhosis patients with CTP ≤ 7, BMI of > 30, and who were unable to achieve weight reduction with lifestyle modification in past 3 months were prospectively enrolled. Spatz3™ adjustable gastric balloon was placed endoscopically. Primary objective was to determine efficacy in weight loss at 6 months, with secondary objectives of reduction in hepatic venous pressure gradient (HVPG), liver fat (controlled attenuation parameter, CAP), liver stiffness measurement (LSM) and clinical events as well as the tolerability and adverse events due to IGB placement.

Results: Altogether 56 cirrhosis patients, with a baseline BMI of 35.24 ± 3.92 and a CTP score of 6.27 ± 1.28 underwent IGB placement. The absolute weight reduction achieved was 15.88 kg (- 16.46%) and reduction in BMI was - 10.1% at 6 months. The percentage total body weight loss of ≥ 10% was achieved in 31 (55.35%) patients. The reduction in HVPG at 6-months was 11.12% (n = 16, 14.18 ± 2.12 to 12.60 ± 1.67 mmHg). The mean reduction in LSM was 28.6% and in CAP was 10.09%. Three (5.36%) patients required removal of IGB before 6-months due to persisting vomiting. No patient developed new-onset decompensation or any serious adverse event.

Conclusion: IGB placement is a safe, well tolerated and effective option for reduction in weight and portal pressure in compensated obese cirrhosis patients.

Trial Registry: Clinicaltrails.gov identifier no: NCT03753438.
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http://dx.doi.org/10.1007/s10620-022-07596-4DOI Listing
June 2022

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis.

Front Immunol 2022 3;13:828949. Epub 2022 Jun 3.

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

Background: Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood.

Methods: A total of 164 decompensated cirrhotic-62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF-and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR.

Results: Frequencies of MDSCs and Tregs were significantly increased ( = 0.011 and = 0.02) with decreased CD4 T cells ( = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) ( = 0.000, = 0.07, and = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels ( = 0.016, = 0.043, and = 0.045). co-cultured MDSCs with T cells drove T-cell apoptosis ( = 0.03, = 0.03) with decreased T-cell proliferation and enhanced FOXP3 expression ( = 0.044 and = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3 Tregs but increased CD4 T-cell functionality and improved survival.

Conclusion: MDSCs have an immunosuppressive function by expanding FOXP3 Tregs and inhibiting CD4 T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.
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http://dx.doi.org/10.3389/fimmu.2022.828949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205181PMC
June 2022

Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight.

Nat Rev Gastroenterol Hepatol 2022 Jun 16. Epub 2022 Jun 16.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a third of the global population; its burden has grown in parallel with rising rates of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage liver disease, hepatocellular carcinoma, death and liver transplantation and has extrahepatic consequences, including cardiometabolic disease and cancers. Although typically associated with obesity, there is accumulating evidence that not all people with overweight or obesity develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are of normal weight, indicating the importance of metabolic health in the pathogenesis of the disease regardless of body mass index. The clinical profile, natural history and pathophysiology of patients with so-called lean MAFLD are not well characterized. In this Review, we provide epidemiological data on this group of patients and consider overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in those who are above normal weight. This framework provides a conceptual schema for interrogating the MAFLD phenotype in individuals of normal weight that can translate to novel approaches for diagnosis and patient care.
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http://dx.doi.org/10.1038/s41575-022-00635-5DOI Listing
June 2022

Transarterial Chemoembolization (TACE) Combined With Sorafenib versus TACE in Patients With BCLC Stage C Hepatocellular Carcinoma - A Retrospective Study.

J Clin Exp Hepatol 2022 May-Jun;12(3):745-754. Epub 2021 Dec 21.

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

Objective: Advanced-stage hepatocellular carcinoma is a heterogeneous group with limited treatment options. TACE has been advocated recently by various study groups. The purpose of this study was to evaluate if TACE in combination with sorafenib, as well as TACE alone, was safe and efficacious in treating BCLC stage C HCC.

Methods: A retrospective evaluation of the clinical data of 78 patients with BCLC stage C HCC who received either TACE-sorafenib (TS) combination therapy or TACE monotherapy as their first treatment was done. The two groups were compared in terms of radiological tumor response 1 month after the intervention. The two groups were also compared in terms of time to progression (TTP), overall survival (OS), and adverse events.

Results: The disease control rate (44.9% and 25.8%, respectively,  = 0.09) was higher in the TS combination group than in the TACE monotherapy group after 1 month of treatment. The TS combination group had significantly superior TTP and OS than the TACE group (TTP was 4.6 and 3.1 months, respectively,  = 0.001), and OS was 10.1 and 7.8 months, respectively, < 0.001). The TACE-S group had a greater cumulative survival time at 6 months, 9 months, and 1 year than the TACE group (97.9%, 51.1%, 25.7% vs. 90.4%, 51.6%, and 0%, respectively).

Conclusion: TS combination therapy in advanced-stage (BCLC-C) HCC significantly improved disease control rate, TTP, and OS compared with TACE alone, without any significant increase in adverse reactions.
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http://dx.doi.org/10.1016/j.jceh.2021.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168730PMC
December 2021

Application of Noninvasive Tools to Decide the Need for Beta-Blockers for Variceal Bleeding Prophylaxis in Compensated Advanced Liver Disease: A Decision Curve Analysis.

J Clin Exp Hepatol 2022 May-Jun;12(3):917-926. Epub 2021 Sep 25.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India.

Background And Aims: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up.

Methods: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy.

Results: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9-35) months. The 1-year and 3-year rate of VB with all NITs was 5.7-7.4% and 13.2-16.4% among high-risk and 0-2.3% and 0-5% among low-risk subgroups, respectively ( < 0.001) in both viral and nonviral aetiologies. Among patients classified as low risk on Baveno-VI criteria, none developed VB on follow-up. At thresholds of <3% event rate of VB, Baveno-VI (NNT-176), platelet-albumin (NNT-576) and anticipate platelet (NNT-233) criteria were superior, whereas endoscopic stratification was superior above this event rate on DCA.

Conclusions: The use of both elastography and blood-based NITs at baseline can accurately identify the need for NSBB for VB prophylaxis in patients of cACLD on follow-up.
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http://dx.doi.org/10.1016/j.jceh.2021.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168689PMC
September 2021

Epidemiology of liver failure in Asia-Pacific region.

Liver Int 2022 08 10;42(9):2093-2109. Epub 2022 Jun 10.

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

The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.
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http://dx.doi.org/10.1111/liv.15328DOI Listing
August 2022

Clinical Outcomes of Transcatheter Arterial Embolization Using N-butyl-2-cyanoacrylate (NBCA) in Cirrhotic Patients.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):353-361. Epub 2021 Aug 26.

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India.

Purpose: To evaluate the clinical outcomes of transcatheter arterial embolization (TAE) with n-butyl-2-cyanoacrylate (NBCA) for treatment of bleeding in cirrhotic patients.

Materials And Methods: A total of 35 cirrhotic patients (26 men, 9 women; mean age, 48.4 ± 11.1) who underwent TAE with NBCA for bleeding from January 2011 to December 2020 were retrospectively analysed. Only cirrhotic patients with active arterial bleeding confirmed on computed tomography (CT) were included. Fifteen patients were hemodynamically unstable before embolization procedure, and coagulopathy was observed in 32 patients. The mean MELD score and Child Pugh score were 24 ± 9.9 and 9.9 ± 2.2, respectively. The mean haemoglobin level and mean number of RBC units transfused before embolization were 7.4 ± 1.4 g/dL and 10.2 ± 4, respectively. The technical, clinical success rate and 30-day mortality rate were evaluated.

Results: Technical success and clinical success rates were achieved in 100% and 82.8% of patients, respectively. Overall 30-day mortality rate was 48%. No major complications related to the embolization procedure was seen. Only the greater number of RBC units transfused before the embolization procedure (OR = 1.81, 95% CI = 1.17-2.80,  = 0.007) was significantly associated with clinical failure. Greater number of RBC units transfused (OR = 1.53, 95% CI: 1.00-2.34,  = 0.004) and higher Child Pugh score (OR 2.44, 95% CI 1.26-4.71,  = 0.008) were significantly associated with higher 30-day mortality rate.

Conclusion: Transcatheter arterial embolization using NBCA can be used as the effective treatment option for bleeding in cirrhotic patients which has a high technical and clinical success despite the grave prognosis associated with cirrhosis.
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http://dx.doi.org/10.1016/j.jceh.2021.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077175PMC
August 2021

Soluble factors and suppressive monocytes can predict early development of sepsis in acute-on-chronic liver failure.

Hepatol Commun 2022 Aug 2;6(8):2105-2120. Epub 2022 May 2.

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

Patients with acute-on-chronic liver failure (ACLF) have a high probability of developing systemic inflammation and sepsis due to immune dysregulation. Fifty-nine patients with ACLF (12 without and 19 with systemic inflammation, and 28 with sepsis) were serially monitored for clinical and immunological changes at baseline, 6 hours, 24 hours, day 3, and day 7 following hospitalization. Ten healthy controls were also included. At all time points, soluble plasma factors and monocyte functions were studied. Patients with ACLF and systemic inflammation showed higher interleukin (IL)-6, vascular endothelial growth factor-a, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β than patients with no systemic inflammation. Patients with ACLF with sepsis had raised (p < 0.001) levels of IL-1Ra, IL-18, and triggering receptor expressed on myeloid cells 1 (TREM1) compared to patients with ACLF-systemic inflammation. Five of the 19 (26.3%) patients with systemic inflammation developed sepsis within 48-72 hours with a rapid rise in plasma levels of IL-1Ra (1203-35,000 pg/ml), IL-18 (48-114 pg/ml), and TREM1 (1273-4865 pg/ml). Monocytes of patients with ACLF with systemic inflammation and sepsis showed reduced human leukocyte antigen-DR but increased programmed death ligand 1 (PD-L1) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) (p < 0.04) expression with increased ETosis by monocytes at baseline and until day 7. Conclusion: High and rising levels of plasma IL-1Ra, IL-18, TREM1 soluble factors, and increased suppressive monocytes (PDL1 , TIM3 ) at baseline can stratify patients with ACLF at high risk of developing sepsis within 48-72 hours of hospitalization.
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http://dx.doi.org/10.1002/hep4.1949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315131PMC
August 2022

Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy.

Hepatol Int 2022 Apr 3;16(2):211-253. Epub 2022 Feb 3.

Department of Laboratory Medicine, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.
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http://dx.doi.org/10.1007/s12072-021-10285-5DOI Listing
April 2022

Clinical Outcomes in Patients with Advanced Chronic Liver Disease and Hepatic Venous Pressure Gradient ≤ 10 mm Hg.

Dig Dis Sci 2022 Feb 3. Epub 2022 Feb 3.

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

Background And Aims: Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg predicts clinical decompensation (CD) in cirrhosis. A proportion of cirrhosis patients have HVPG 6-10 mmHg. Their natural history is largely unknown.

Design: Consecutive patients with advanced chronic liver disease (aCLD) [histological cirrhosis(n = 196) or liver stiffness measurement (LSM) > 15 kPa(n = 65)] and HVPG 6-10 mmHg were included. Primary objective was to study their natural course and patterns of CD. We also analyzed the predictors of CD at presentation and on follow-up and response to carvedilol.

Results: Of 261 patients with HVPG 6-10 mmHg, 129(49.4%) had CD at first presentation; 78(29.9%) had single and 51(19.5%) had ≥ 2 CD. The most common CDs were ascites(n = 77) and jaundice(n = 65). A baseline HVPG ≥ 8 mmHg was independently associated with greater risk of CD [HR:1.7; p-0.002, AUROC:0.85(95%CI-0.81-0.91)]. New CD developed in 14.4% patients with compensated aCLD (median duration-23.1 months). Despite comparable baseline HVPG, patients developing new CD had higher HVPG on follow-up(15.3 ± 3.7 vs. 8 ± 2.1 mmHg; p < 0.001). Baseline LSM > 26.6 kPa, portosystemic shunt and serum albumin independently predicted new CD. Overall HVPG response to carvedilol(n = 60) was 23.3%, independent of baseline CD and HVPG. Five-year mortality was higher with ≥ 2 CD compared to single or no CD (23.5, 10 and 3%, respectively; p < 0.001).

Conclusion: Nearly one-half of aCLD patients with HVPG 6-10 mmHg had CD, justifying the need to redefine CSPH. Interventions to reduce portal pressure in patients with HVPG ≥ 8 mmHg might improve long-term outcomes.
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http://dx.doi.org/10.1007/s10620-021-07334-2DOI Listing
February 2022

Early Allograft Dysfunction After Live Donor Liver Transplantation: It's Time to Redefine?

J Clin Exp Hepatol 2022 Jan-Feb;12(1):101-109. Epub 2021 Mar 30.

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

Background: An ideal definition of early allograft dysfunction (EAD) after live donor liver transplantation (LDLT) remains elusive. The aim of the present study was to compare the diagnostic accuracies of existing EAD definitions, identify the predictors of early graft loss due to EAD, and formulate a new definition, estimating EAD-related mortality in LDLT recipients.

Methods: Consecutive adult patients undergoing elective LDLT were analyzed. Patients with technical (vascular, biliary) complications and biopsy-proven rejections were excluded.

Results: There were 19 deaths due to EAD of a total of 304 patients. On applying the existing definitions of EAD, we revealed their limitations of being either too broad with low specificity or too restrictive with low sensitivity in patients with LDLT. A new definition of EAD-LDLT (total bilirubin >10 mg/dL, international normalized ratio [INR] > 1.6 and serum urea >100 mg/dL, for five consecutive days after day 7) was derived after doing a multivariate analysis. In receiver operator characteristics analysis, an AUC for EAD-LDLT was 0.86. The calibration and internal cross-validation of the new model confirmed its predictability.

Conclusion: The new model of EAD-LDLT, based on total bilirubin >10 mg/dL, INR >1.6 and serum urea >100 mg/dL, for five consecutive days after day 7, has a better predictive value for mortality due to EAD in LDLT recipients.
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http://dx.doi.org/10.1016/j.jceh.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766541PMC
March 2021

Survival and Outcome in Patients Receiving Drug-Eluting Beads Transarterial Chemoembolization for Large Hepatocellular Carcinoma (>5 cm).

J Clin Exp Hepatol 2021 Nov-Dec;11(6):674-681. Epub 2021 Feb 15.

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India.

Background/aims: This study aimed to study the outcome and survival of patients with large hepatocellular carcinoma (HCC) receiving drug-eluting beads (DEBs) transarterial chemoembolization (TACE). In addition, tumor morphologies were correlated with the response and survival to analyze the association of morphology with the outcome.

Methods: Patients with large HCC (>5 cm) who underwent DEB-TACE for palliation were analyzed retrospectively. Patients were assessed for objective response (OR) and overall survival (OS), which was calculated from the first session of DEB-TACE to the last follow-up/death. OR and OS were calculated for the entire study group and were compared among the subgroups consisting of solitary versus multifocal HCC, unilobar versus bilobar disease, well-defined versus ill-defined HCC, and HCC with homogeneous enhancement versus HCC with heterogeneous enhancement.

Results: Sixty-seven DEB-TACE procedures were performed in 25 patients (average: 2.7 ± 1.4 sessions per patient). The mean lesion size was 9.9 ± 4.5 cm. Of 25 patients, 13 (52%) had multifocal HCC. Unilobar disease was seen in 15 patients (60%). The mean duration of follow-up was 24.4 months. OR at 6 and 12 months were 56% and 48%, respectively, with well-defined lesions showing better OR. The median OS was 28 months (95% confidence interval, 12.3-43.6). OS rate at 12 and 24 months was 92% and 57%, respectively. OS was seen to be superior in well-defined HCC and unilobar disease.

Conclusion: In this study, DEB-TACE has shown to have a good response in patients having large/multifocal HCC with preserved liver functions. Well-defined HCC and unilobar disease have a better response and survival.
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http://dx.doi.org/10.1016/j.jceh.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617544PMC
February 2021

Feasibility, effectiveness and cost of a decentralized HCV care model among the general population in Delhi, India.

Liver Int 2022 03 29;42(3):532-540. Epub 2021 Nov 29.

FIND, Geneva, Switzerland.

Background And Aims: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population.

Methods: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured.

Results: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action.

Conclusions: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.
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http://dx.doi.org/10.1111/liv.15112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299915PMC
March 2022

Tadalafil improves erectile dysfunction and quality of life in men with cirrhosis: a randomized double blind placebo controlled trial.

Hepatol Int 2021 Nov 14. Epub 2021 Nov 14.

Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.

Background And Aims: Patients with cirrhosis have high prevalence of erectile dysfunction (ED). The aim of this study was to study the efficacy and safety of tadalafil for ED in patients with cirrhosis.

Methods: 140 cirrhotic males with ED were randomized into tadalafil 10 mg daily (n = 70) or placebo (n = 70) for 12 weeks. ED was diagnosed if erectile function (EF) domain score was < 25 in International Index of Erectile Function (IIEF) questionnaire. The erectile function domain consists of six questions concerning erection frequency, erection firmness, frequency of partner penetration, frequency of maintaining erection after penetration, ability to maintain erection to completion of intercourse and confidence in achieving and maintaining erection. Primary outcome was proportion of patients having an increase in > 5 points in EF domain of the IIEF. Generalized Anxiety Disorder 7 (GAD-7) questionnaire was used for screening and severity measuring of GAD. The presence of depression was screened using the Patient Health Questionnaire (PHQ-9) and the assessment of health related quality of life was done using the Short Form (36) Health Survey.

Results: At the end of 12 weeks, more patients in tadalafil group achieved > 5 points increase in the EF domain of the IIEF when compared with the placebo group [44(62.9%) vs. 21(30%), p < 0.001]. At the end of 12 weeks, patients receiving tadalafil had significantly more change in scores on the erectile function domain, orgasmic function domain, intercourse satisfaction domain, overall satisfaction domain, erection vaginal penetration rates and successful intercourse; significantly more decline in the GAD-7 and PHQ-9 scores; significantly more improvement in scores of five of the eight domains of SF-36 (general health perception, vitality score, social functioning, role emotional and mental health) and the mental component summary rates when compared with placebo. The development of side effects and the changes in HVPG were not significantly different between the two groups.

Conclusions: Tadalafil therapy may enhance erectile function, improve anxiety, depression and quality of life; and is well tolerated by men with cirrhosis (CTP score < 10) and ED. However, further larger and long-term studies are needed to confirm these results and look for rarer side effects of using tadalafil in patients with cirrhosis.

Trial Registration: ClinicalTrials.gov identifier number NCT03566914; first posted date: June 25, 2018.
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http://dx.doi.org/10.1007/s12072-021-10264-wDOI Listing
November 2021

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

Hepatol Int 2021 Dec 4;15(6):1376-1388. Epub 2021 Oct 4.

Department of Hepatology, Cardinal Santos Medical Centre, Manila, Philippines.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

Methods: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

Results: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01).

Conclusions: ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.
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http://dx.doi.org/10.1007/s12072-021-10206-6DOI Listing
December 2021

Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Tertiary Care Center Experience.

Indian J Radiol Imaging 2021 Apr 4;31(2):270-276. Epub 2021 Aug 4.

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

Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) occurring in 30 to 40% of cases. The presence of PVTT in HCC is regarded as an advanced disease that confers poor prognosis and survival. Transarterial chemoembolization (TACE) has traditionally been considered to be contraindicated in cases of PVTT, due to the risk of hepatic infarction, and further deteriorate liver function. We evaluated safety, technical efficacy, and outcomes of TACE in HCC with PVTT. From search results of the hospital database, out of 652 patients who underwent TACE for HCC, 73 patients of HCC with PVTT were retrospectively evaluated. Post-TACE tumor response by computed tomography (CT)/magnetic resonance imaging (MRI) imaging as per modified response evaluation criteria in solid tumors (mRECIST) criteria, if any occurrence of acute hepatic failure was assessed. Prognostic factors influencing survival were also determined. In our study population, the mean age of the patients was 58 years. The 12- and 24-month survival rates were 59 and 14%, respectively, with an overall median survival of 12.3 months. A total of 58.9% patients had branch portal vein tumor thrombus and 41.1% had tumor thrombus in the main portal vein. We did not encounter any mortality or acute liver failure following TACE in a 30-day period. Both univariate and multivariate analysis revealed Child-Pugh score ( = 0.01) and the extent of tumoral thrombus ( 0.004) as a significant prognostic factor. Patients with branch PVTT, no ascites, and Child-Pugh A had better survival than those having main portal vein tumor thrombus, ascites, and Child-Pugh B. Our study concluded that TACE can achieve good disease control and improved survival in HCC with portal vein invasion despite being considered as a relative contraindication. Technical expertise, selection of patients, such as superselective catheterization and preserved liver function, are the key factors for a safe therapeutic procedure. Child-Pugh score and extent of portal vein invasion were the significant prognostic factors determining survival.
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http://dx.doi.org/10.1055/s-0041-1734367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448240PMC
April 2021

G-CSF in acute-on-chronic liver failure - Art of 'patient selection' is paramount!

J Hepatol 2022 02 1;76(2):472-473. Epub 2021 Sep 1.

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

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http://dx.doi.org/10.1016/j.jhep.2021.08.022DOI Listing
February 2022

Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH.

Int J Mol Sci 2021 Aug 6;22(16). Epub 2021 Aug 6.

Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.

Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH).

Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls.

Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle.

Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
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http://dx.doi.org/10.3390/ijms22168489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395158PMC
August 2021

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

Dig Dis Sci 2022 Aug 14;67(8):4223-4233. Epub 2021 Aug 14.

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070, India.

Background And Aims: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes.

Methods: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days.

Results: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality.

Conclusions: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.
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http://dx.doi.org/10.1007/s10620-021-07185-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364303PMC
August 2022

Sustained expression of inflammatory monocytes and activated T cells in COVID-19 patients and recovered convalescent plasma donors.

Immun Inflamm Dis 2021 12 6;9(4):1279-1290. Epub 2021 Aug 6.

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

Introduction: Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID-19) patients and recovered patients.

Methods: Moderate COVID-19 patients (n = 34) at Lok Nayak Hospital, New Delhi, and COVID-19 recovered patients (n = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals (n = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry.

Results: A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1-α, monocyte chemotactic protein-1, macrophage migration inhibitory factor, vascular endothelial growth factor-A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)-6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon-γ response, and increased level of acute-phase protein SAA1 in the serum of COVID-19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL-18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8 T cells, A proliferation-inducing ligand, and B-cell activating factor receptor B cells compared with healthy subjects.

Conclusions: Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells.
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http://dx.doi.org/10.1002/iid3.476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427128PMC
December 2021

Letter to the Editor: Salvage TIPS for Refractory Variceal Bleed-More Questions Than Answers!

Hepatology 2021 12 16;74(6):3557-3558. Epub 2021 Sep 16.

Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32092DOI Listing
December 2021

Upgrading Hepatic Differentiation and Functions on 3D Printed Silk-Decellularized Liver Hybrid Scaffolds.

ACS Biomater Sci Eng 2021 08 28;7(8):3861-3873. Epub 2021 Jul 28.

Regenerative Engineering Laboratory, Department of Textile and Fiber Technology, Indian Institute of Technology-Delhi, New Delhi 110016, India.

We developed hybrid liver-specific three-dimensional (3D) printed scaffolds using a solubilized native decellularized liver (DCL) matrix and silk fibroin (SF) and investigated their ability to support functional cultures of hepatic cells. Rat livers were decellularized by perfusing detergents via the portal vein, solubilized using pepsin to form DCL, and characterized. SF blended with gelatin (8% w/v) was optimized with varying percentages of DCL to obtain silk gelatin-DCL bioink (SG-DCL). Different compositions of SG-DCL were studied by rheology for optimum versatility and print fidelity. 3D printed six-layered scaffolds were fabricated using a sophisticated direct-write 3D bioprinter. Huh7 cells were cultured on the 3D printed scaffolds for 3 weeks. 3D printed SG scaffolds without DCL along with 2D films (SG and SG-DCL) and 2D culture on tissue culture Petri dish control were used for comparative studies. The DCL matrix showed the absence of cells in histology and SEM. The combined SG-DCL ink at all of the studied DCL percentages (1-10%) revealed shear-thinning behavior in the printable range. The storage modulus value for the SG-DCL ink at all DCL percentages was higher than the loss modulus. In comparison to 2D controls, hepatic cells cultured on 3D SG-DCL revealed increased proliferation until 2 weeks and an upregulated expression of hepatocyte markers, including asialoglycoprotein receptor 1 (). The Wnt pathway gene β was upregulated by more than 4-fold in 3D SG-DCL on day 3, while it showed a decline on day 7 as compared to 3D SG and also 2D controls. The expression of the epithelial cell adhesion molecule () was however lower in both 2D SG-DCL (2-fold) and 3D SG-DCL (2.5-fold) as compared to that in 2D controls. Immunofluorescence studies validated the protein expression of in 3D SG-DCL. Albumin (ALB) was not identified on SG scaffolds but prominently expressed in 3D SG-DCL constructs. In comparison to 2D SG, both ALB (1.8-fold) and urea (5-fold) were enhanced in cells cultured on 3D SG-DCL on day 7 of culture. Hence, the SG-DCL 3D printed scaffolds provide a conducive microenvironment for elevating differentiation and functions of hepatic cells possibly through an involvement of the Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00671DOI Listing
August 2021

Multi-omics analysis of respiratory specimen characterizes baseline molecular determinants associated with SARS-CoV-2 outcome.

iScience 2021 Aug 9;24(8):102823. Epub 2021 Jul 9.

Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.

Rapid diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection still remains a major challenge. A multi-omic approach was adopted to analyze the respiratory specimens of 20 SARS-CoV-2-positive, 20 negative and 15 H1N1 pdm 2009 positive cases. Increased basal level of MX1 (MX dynamin-like GTPase 1) and WARS (tryptophan-tRNA ligase) correlated with SARS-CoV-2 infection and its outcome. These markers were further validated in 200 suspects. MX1>30pg/ml and WARS>25ng/ml segregated virus positives [AUC = 94% CI: (0.91-0.97)] and severe patients [AUC>0.85%]. Our results documented significant increase in immune activation; metabolic reprograming and decrease in oxygen transport, wound healing and others linked proteins and metabolites in patients with coronavirus disease 2019 (COVID-19). Multi-omics profiling correlated with viremia and segregated asymptomatic patients with COVID-19. Additionally, we identified increased respiratory pathogens (Burkholderiales, Klebsiella pneumonia) and decreased lactobacillus salivarius (FDR<0.05) in COVID-19 specimens. In conclusion, increased basal MX1 and WARS levels correlates with SARS-CoV-2 infection and could aid in the identification of patient's predisposed to higher severity.
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http://dx.doi.org/10.1016/j.isci.2021.102823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268673PMC
August 2021

Erratum to "Combined Balloon-, Plug- and Coil-assisted Retrograde Transvenous Obliteration of Multiple Portosystemic Shunts to Treat Recurrent Hepatic Encephalopathy: A Case Report" [J Clin Exp Hepatol 10 (2020) 402-406].

J Clin Exp Hepatol 2021 Jul-Aug;11(4):518. Epub 2020 Dec 23.

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India.

[This corrects the article DOI: 10.1016/j.jceh.2019.12.002.].
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http://dx.doi.org/10.1016/j.jceh.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267354PMC
December 2020

Liver Transplantation Society of India Guidelines for the Management of Acute Liver Injury Secondary to Yellow Phosphorus-Containing Rodenticide Poisoning Using the Modified Delphi Technique of Consensus Development.

J Clin Exp Hepatol 2021 Jul-Aug;11(4):475-483. Epub 2020 Oct 6.

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

Background: Acute liver failure caused by the ingestion of yellow phosphorus-containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice.

Methods: A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed.

Results: The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience.

Conclusion: Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.
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http://dx.doi.org/10.1016/j.jceh.2020.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267358PMC
October 2020

Prevalence of and Factors Associated with Sleep-Wake Abnormalities in Patients with Cirrhosis.

J Clin Exp Hepatol 2021 Jul-Aug;11(4):453-465. Epub 2020 Oct 24.

Department of Hepatology and Liver Transplantation, New Delhi, India.

Background & Aims: Sleep-wake abnormalities [poor nighttime sleep and excessive daytime sleepiness (EDS)] are common in patients with cirrhosis. The aim of this study was to assess the prevalence of sleep-wake abnormalities and clinical factors associated with these abnormalities in a group of patients with cirrhosis.

Methods: 1098 patients with cirrhosis [Child Turcotte Pugh (CTP) class A, 22.2%; CTP class B, 29.2% and CTP class C, 48.6%], with either no ascites or mild ascites controlled on diuretics, and no history of or current overt hepatic encephalopathy were included in the study.

Results: Poor nighttime sleep and EDS were found in 569 (51.8%) and 489 (44.5%) patients respectively. On multivariate analysis, factors associated with poor nighttime sleep were CTP class C (vs. class A), presence of minimal hepatic encephalopathy (MHE), intermediate or evening type of diurnal preference category (vs. morning type), high risk for obstructive sleep apnea (OSA), diuretic use, presence of major depression, and presence of generalized anxiety disorder (GAD). Factors associated with EDS on multivariate analysis were CTP class B and C (vs. class A), intermediate or evening type of diurnal preference category (vs. morning type), high risk for OSA, presence of major depression, and presence of GAD.

Conclusions: Sleep-wake abnormalities are common in patients with cirrhosis. CTP status, diurnal preference chronotype, risk of OSA, major depression and GAD are associated with both poor nighttime sleep and EDS. MHE and diuretic use are associated with poor nighttime sleep, but not with EDS.
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http://dx.doi.org/10.1016/j.jceh.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267360PMC
October 2020

Plasma Exchange in Acute and Acute on Chronic Liver Failure.

Semin Liver Dis 2021 11 14;41(4):476-494. Epub 2021 Jul 14.

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

Liver failure in the context of acute (ALF) and acute on chronic liver failure (ACLF) is associated with high mortality in the absence of a liver transplant. For decades, therapeutic plasma exchange (TPE) is performed for the management of immune-mediated diseases. TPE has emerged as an attractive extracorporeal blood purification technique in patients with ALF and ACLF. The basic premise of using TPE is to remove the toxic substances which would allow recovery of native liver functions by facilitating liver regeneration. In recent years, encouraging data have emerged, suggesting the benefits of TPE in patients with liver failure. TPE has emerged as an attractive liver support device for the failing liver until liver transplantation or clinical recovery. The data in patients with ALF suggest routine use of high-volume TPE, while the data for such a strategy are less robust for patients with ACLF.
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http://dx.doi.org/10.1055/s-0041-1730971DOI Listing
November 2021
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