Publications by authors named "Deepak Gunjan"

70 Publications

A rare case of complicated pancreatitis due to leptospirosis.

Indian J Med Microbiol 2022 Aug 1. Epub 2022 Aug 1.

Department of Microbiology, AIIMS, New Delhi, India. Electronic address:

The COVID-19 pandemic and the actions taken to combat it have greatly impacted the health infrastructure of all nations. Here we present a rare case of leptospirosis with severe acute pancreatitis, bilateral peripheral gangrene, disseminated intravascular coagulopathy and multiorgan failure. This is a rare presentation of leptospirosis wherein the patient had no history suggestive of acquisition of leptospires. The patient was started on doxycycline but still could not be saved due to the multisystem involvement.
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http://dx.doi.org/10.1016/j.ijmmb.2022.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340559PMC
August 2022

Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study.

J Clin Exp Hepatol 2022 Jul-Aug;12(4):1102-1113. Epub 2022 Jan 24.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 , India.

Background/aims: Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD.

Methods: Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n = 34) with no cirrhosis, ALD (n = 28) and were compared with disease free controls (n = 20).

Results: Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1 kPa [5.9-8.9] vs. ALD:14.3 kPa [9.6-24], < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037-0.17] vs. controls 0.027 [0.021-0.045] ( = 0.001)) and ALD 0.043 [0.03-0.068] vs. controls 0.027 [0.021-0.045] ( = 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2-1089.5] compared to ALD 120.6 [20.1-728]) ( = 0.042) and controls 155.3 [23.8-442.9]) ( = 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5-115]) compared to controls (16.1 [10.8-33.3]) ( < 0.001) and ALD (12.3 [10.1-42.7]) ( < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, < 0.001).

Conclusion: While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.
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http://dx.doi.org/10.1016/j.jceh.2022.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257921PMC
January 2022

Anesthesia for Per-oral endoscopic myotomy (POEM) - not so poetic!

J Anaesthesiol Clin Pharmacol 2022 Jan-Mar;38(1):28-34. Epub 2021 Dec 3.

Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India.

Peroral endoscopic myotomy (POEM) is a promising natural orifice transluminal endoscopic procedure for the treatment of esophageal motility disorders, with similar effectiveness as of Heller myotomy. It is performed under general anesthesia in endoscopy suite. Creation of submucosal tunnel in the esophageal wall is a key component. The continuous insufflation of CO inadvertently tracks into surrounding tissues and leads to capno mediastinum, capno thorax, capno peritoneum, and subcutaneous emphysema. Thus, the challenges, for an anesthesiologist are not only providing remote location anesthesia, increased risk of aspiration during induction, but also early detection of these complications and specific emergency management. Though a therapeutic innovation, POEM remains an interdisciplinary challenge with no specific anesthesia care algorithms and evidence-based recommendations. The purpose of this review is to outline the anesthesia and periprocedural practices based on existing evidence.
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http://dx.doi.org/10.4103/joacp.JOACP_179_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9191809PMC
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

Alterations in Autophagy and Mammalian Target of Rapamycin (mTOR) Pathways Mediate Sarcopenia in Patients with Cirrhosis.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):510-518. Epub 2021 May 21.

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

Background And Aims: The pathophysiology of sarcopenia in cirrhosis is poorly understood. We aimed to evaluate the histological alterations in the muscle tissue of patients with cirrhosis and sarcopenia, and identify the regulators of muscle homeostasis.

Methods: Computed tomography images at third lumbar vertebral level were used to assess skeletal muscle index (SMI) in 180 patients. Sarcopenia was diagnosed based on the SMI cut-offs from a population of similar ethnicity. Muscle biopsy was obtained from the vastus lateralis in 10 sarcopenic patients with cirrhosis, and the external oblique in five controls (voluntary kidney donors during nephrectomy). Histological changes were assessed by hematoxylin and eosin staining and immunohistochemistry for phospho-FOXO3, phospho-AKT, phospho-mTOR, and apoptosis markers (annexin V and caspase 3). The messenger ribonucleic acid (mRNA) expressions for MSTN, FoxO3, markers of ubiquitin-proteasome pathway (FBXO32, TRIM63), and markers of autophagy (Beclin-1 and LC3) were also quantified.

Results: The prevalence of sarcopenia was 14.4%. Muscle histology in sarcopenics showed atrophic angulated fibers ( = 0.002) compared to controls. Immunohistochemistry showed a significant loss of expression of phospho-mTOR ( = 0.026) and an unaltered phospho-AKT ( = 0.089) in sarcopenic patients. There were no differences in the immunostaining for annexin-V, caspase-3, and phospho-FoxO3 between the two groups. The mRNA expressions of MSTN and Beclin-1 were higher in sarcopenics ( = 0.04 and  = 0.04, respectively). The two groups did not differ in the mRNA levels for TRIM63, FBXO32, and LC3.

Conclusions: Significant muscle atrophy, increase in autophagy, MSTN gene expression, and an impaired mTOR signaling were seen in patients with sarcopenia and cirrhosis.
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http://dx.doi.org/10.1016/j.jceh.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077178PMC
May 2021

Spectrum of Neuroimaging Abnormalities in Brain in Patients of Acute-on-Chronic Liver Failure.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):343-352. Epub 2021 Aug 21.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background And Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. There is a paucity of data about the spectrum of neuroimaging abnormalities in the brain in ACLF patients. The present study was aimed to study the prevalence of cerebral edema and other parenchymal changes in MR imaging of the brain in patients with ACLF.

Methods: In this prospective observational study, MR imaging was done in patients with ACLF (n = 41), and findings were compared with age and sex-matched patients with acute decompensation (AD) (n = 13) and those with cirrhosis but without any decompensation at recruitment (n = 21).

Results: Forty-one patients with ACLF (24.4% Grade 1 and Grade 2, 51.2% Grade 3) with 14 (34.1%) having cerebral failure were included in the study. T2-weighted (T2W) diffuse white matter hyperintensities (WMHs) and focal WMHs were seen in 17 (41.4%) and 7 (17%) patients, respectively. T1W basal ganglia hyperintensities in 20 (48.7%), cerebral microbleeds (CMBs) in 6 (14.6%), and 2 (4.8%) patients had cerebral edema. In patients with AD, T2W diffuse WMHs were seen in 3 (23%), T2W focal WMHs in 3 (23%) patients. None of the patients with AD had cerebral edema or CMBs. In compensated cirrhosis patients, T2W diffuse WMHs were present in 7 (33.3%), T2W focal WMHs in 5 (23.8%), while 3 (14.2%) patients had CMBs. T1 weighted hyperintensities in basal ganglia were more common in AD [9 (69.2%)] and compensated cirrhosis [15 (71.4%)] as compared to ACLF patients [20 (48.7%)],  = 0.174. The survival time of 30 and 90 days for patients with diffuse T2W WMHs was significantly lesser than patients without T2W WMHs ( = 0.007).

Conclusion: Cerebral edema is uncommon in ACLF patients, and T2-weighted diffuse white matter hyperintensities may be associated with worse outcomes. However, due to the limited scope of the present study, the same needs to be explored further in larger cohorts.
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http://dx.doi.org/10.1016/j.jceh.2021.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077188PMC
August 2021

Comparison of Anthropometry, Bioelectrical Impedance, and Dual-energy X-ray Absorptiometry for Body Composition in Cirrhosis.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):467-474. Epub 2021 Jun 9.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, N. Delhi, India.

Background & Aims: This study was planned to evaluate triceps skinfold thickness (TSFT), mid-arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) for assessing body composition using dual-energy X-ray absorptiometry (DEXA) (reference) and to predict fat mass (FM) and fat-free mass (FFM) in patients with cirrhosis.

Methods: FM and FFM were assessed by using DEXA and BIA. Skin-fold calliper was used for measuring TSFT, and MAMC was calculated. Bland-Altman plot was used to determine agreement and linear regression analysis for obtaining equations to predict FM and FFM.

Results: Patients with cirrhosis (n = 302, 241 male, age 43.7 ± 12.0 years) were included. Bland-Altman plot showed very good agreement between BIA and DEXA for the estimation of FM and FFM. Majority of patients were within the limit of agreement: FM (98%) and FFM (96.4%). BIA shows a positive correlation with DEXA:FM (r = 0.73,  ≤ 0.001) and FFM (r = 0.86,  ≤ 0.001). DEXA (FM and FFM) shows a positive correlation with TSFT (r = 0.69,  ≤ 0.01) and MAMC (r = 0.61,  ≤ 0.01). The mean difference between the observed and predicted value of FM and FFM by BIA in the developmental set was 0.01 and 0.05, respectively; whereas in the validation set, it was -0.13 and 0.86, respectively. The mean difference between the observed and predicted value of TSFT and MAMC in the developmental set was 0.43 and 0.07; whereas, in the validation set, it was 0.16 and 0.48, respectively.

Conclusion: Anthropometry (TSFT and MAMC) and BIA are simple and easy to use and can be a substitute of DEXA for FM and FFM assessment in routine clinical settings in patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jceh.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077186PMC
June 2021

Prevalence and Predictors of Nonalcoholic Fatty Liver Disease in Family Members of Patients With Nonalcoholic Fatty Liver Disease.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):362-371. Epub 2021 Jul 31.

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

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it.

Methodology: The prevalence of NAFLD in patients' family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC).

Results: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800-0.876, < 0.001]. Age ≥30 years and BMI ≥25 kg/m had an odds ratio of 33.5 (95% CI 17.0-66.0, < 0.001) for prediction of NAFLD, in comparison to BMI <25 kg/m and age <30 years.

Conclusion: Family members of patients with NAFLD are at increased risk of NAFLD. Screening strategies using BMI and age ensure early identification and could be beneficial in clinical practice.
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http://dx.doi.org/10.1016/j.jceh.2021.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077183PMC
July 2021

Chronic Pancreatitis in Females is Not Associated With Adverse Pregnancy Outcomes: A Retrospective Analysis.

J Clin Gastroenterol 2022 Apr 25. Epub 2022 Apr 25.

Departments ofGastroenterology and Human Nutrition Unit.

Background: The effects of chronic pancreatitis (CP) on pregnancy and vice versa have not been studied well. We aimed to study the impact of CP on pregnancy-related outcomes and the effect of pregnancy on clinical profile of CP.

Study And Goals: We did a retrospective analysis of all female patients of CP of child-bearing age (above 18 y). The pregnancy-related outcomes of patients with CP were compared with the age-matched 115 controls from the low-risk pregnancy group identified using a simplified antepartum high-risk pregnancy scoring form. The clinical course of CP during pregnancy was compared with the pre-pregnancy course.

Results: Among the 338 eligible patients, 46 patients were included after exclusions. All these 46 patients had at least 1 conception and 41 had at least 1 completed pregnancy with a total of 117 conceptions and 96 completed pregnancies. The pregnancy-related outcomes in patients with CP like abortions (21.7% vs. 11.3%;P=0.087), preterm deliveries (14.6% vs. 10.4%;P=0.47), antepartum course (82.7% vs. 82.6%;P=0.58), stillbirths (4.9% vs. 4.3%;P=0.88), cesarean section (36.6% vs. 34%;P=0.849) were comparable with controls. There was overall improvement in the severity and frequency of pain during pregnancy as compared with the pre-pregnancy symptoms (P=0.001).

Conclusion: CP is not associated with adverse pregnancy outcomes. Also, there is trend toward improvement in the clinical symptoms because of CP during the pregnancy.
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http://dx.doi.org/10.1097/MCG.0000000000001711DOI Listing
April 2022

Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia.

Hepatol Int 2022 Jun 25;16(3):680-690. Epub 2022 Apr 25.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

Background: The role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable.

Aims: To evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia.

Methods: Consecutive patients with cirrhosis with Child-Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation.

Results: Sixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI - 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength (p = 0.65), 6-m gait speed (p = 0.20), 6-min walk distance (p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm.

Conclusion: Addition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269).

Trial Registration Number: CTRI/2019/05/019269 (Clinical Trials Registry of India).
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http://dx.doi.org/10.1007/s12072-022-10334-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037580PMC
June 2022

Response to Medda et al.

Am J Gastroenterol 2022 May 21;117(5):814. Epub 2022 Mar 21.

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

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http://dx.doi.org/10.14309/ajg.0000000000001715DOI Listing
May 2022

Malnutrition by GLIM criteria in chronic pancreatitis: Prevalence, predictors, and its impact on quality of life.

Pancreatology 2022 Apr 16;22(3):367-373. Epub 2022 Feb 16.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India. Electronic address:

Introduction: Malnutrition in chronic pancreatitis (CP) has prognostic value and there is limited data on the prevalence, predictors of malnutrition in CP and its effect on Quality of life (QoL).

Methods: A retrospective study was conducted in patients with CP to assess the prevalence of malnutrition as per the Global Leadership Initiative on Malnutrition (GLIM) criteria. Multivariable-adjusted regression was used to identify independent predictors of both malnutrition and global QoL.

Results: A total of 297 patients were included and the most common etiology of CP was idiopathic (75%) and alcohol (25%). The prevalence of malnutrition was 46.4% as per GLIM criteria. On univariate analysis, the risk of malnutrition was significantly higher in alcoholic etiology (p = 0.001), current alcohol consumption (p = 0.001), smokers (p < 0.001), those having higher cumulative days of pain in last 6 months (p < 0.001) and lower daily calorie intake (p = 0.019). On multivariate analysis, malnutrition was independently associated with current alcohol consumption (Odds ratio: 3.22, p = 0.017), current smokers (OR: 2.23, p = 0.042) and those having higher cumulative days of abdominal pain (OR: 1.01, p < 0.001), while higher daily calorie intake (per 100 kcal) (OR:0.94, p = 0.023) has reduced risk of malnutrition. Malnutrition (p = 0.015) and higher cumulative days of abdominal pain (p < 0.001) were independently associated with lower global QoL in patients with CP.

Conclusion: Malnutrition is frequent in patients with CP; and current alcohol consumption, smoking and higher cumulative days of abdominal pain independently predicts risk of developing malnutrition. Patients with malnutrition and higher cumulative days of pain has poorer quality of life.
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http://dx.doi.org/10.1016/j.pan.2022.02.004DOI Listing
April 2022

Acute Variceal Bleed in Cirrhosis is Associated With Reversible Changes in Tight Junction Protein Expression in the Intestine: A Proof-of-Concept Study.

J Clin Exp Hepatol 2022 Jan-Feb;12(1):89-100. Epub 2021 Apr 3.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

Background: Tight junction proteins (TJPs) play an important role in gut-barrier dysfunction in cirrhosis and its complications such as acute variceal bleed (AVB). However, the dynamics of TJPs expression after AVB, its relation to bacterial translocation, and impact on clinical outcome is largely unknown.

Aims: The aim of this study was to study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. In addition, the relation of TJP expression to endotoxemia and clinical outcomes was assessed.

Methods: In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB (non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with a 6-month survival.

Results: Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi ( < 0.001 and 0.013) and crypts ( < 0.001 and 0.012), respectively, compared with the controls. Claudin-4 expression was similar in villi ( = 0.079), but lower in crypts ( = 0.007) in patients with cirrhosis. Claudin-2 expression was upregulated on serial biopsies in both villi and crypts ( = 0.003 and 0.001, respectively) in AVB-cirrhosis with postbleed expression comparable with those with non-AVB cirrhosis. IgG anti-endotoxin antibody levels were elevated in cirrhosis with no correlation with claudin-2/4 expression. Claudin-2 expression independently predicted survival at 6 months.

Conclusion: Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.
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http://dx.doi.org/10.1016/j.jceh.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766542PMC
April 2021

European Working Group on Sarcopenia in Older People (EWGSOP2) Criteria With Population-Based Skeletal Muscle Index Best Predicts Mortality in Asians With Cirrhosis.

J Clin Exp Hepatol 2022 Jan-Feb;12(1):52-60. Epub 2021 Apr 8.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, India.

Background/aims: Multiple definitions of sarcopenia exist and the acceptable criterion that best predicts outcome is lacking. We estimated the prevalence of sarcopenia based on four criteria and assessed their utility in predicting mortality in cirrhotics.

Methods: In a prospective observational study, consecutive Asian patients with cirrhosis underwent testing for handgrip strength (HGS) and estimation of skeletal muscle index (SMI) using computed tomography at the third lumbar vertebra. Sarcopenia was defined based on the Western cut-off (WC; SMI < 50 cm/m for men and <39 cm/m for women), Asian cut-off (AC; SMI < 36.5 cm/m for men and 30.2 cm/m for women), European Working Group on Sarcopenia in Older People-2nd meeting (EWGSOP2) definition incorporating low HGS (<27 kg for men and <16 kg for women) with low SMI (defined by the WC), and EWGSOP2 definition with low HGS and low SMI (defined by AC). Risk factors for mortality were assessed using multivariate Cox-proportional hazards.

Results: We included 219 patients with cirrhosis (168 men; mean age 42.6 years) with 50.2% patients having decompensation. Alcohol was the commonest aetiology (33.3%). The prevalence of sarcopenia was highest with the WC (men: 82.1%; women: 62.7%). There was a weak concordance among all criteria (Fleiss' kappa 0.23, 95% confidence interval [CI] 0.10-0.37). Overall, 12-month survival was 86.1% (81.1-91.3%) over a median (interquartile range) follow-up of 12 (6-15) months. Ascites (hazards ratio [HR] 6.27 [95% CI 1.6-24.1]; 0.007) and SMI (HR 0.92 [0.85-0.98];  = 0.021) were independent predictors of mortality. The 12-month mortality rate was higher in patients with sarcopenia, irrespective of criteria (log rank  < 0.05). Low HGS and low SMI (defined by AC) was the best for predicting mortality (HR 3.04 [1.43-6.43];  = 0.004).

Conclusion: A weak concordance exists amongst various diagnostic definitions of sarcopenia. Sarcopenia diagnosed by a combination of low HGS and population-specific SMI cut-off (AC) best predicts mortality.
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http://dx.doi.org/10.1016/j.jceh.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766536PMC
April 2021

Duration of Fasting During Acute Variceal Bleeding in Chronic Liver Disease: Perceptions and Practices of Gastroenterologists.

J Clin Exp Hepatol 2021 Nov-Dec;11(6):753-755. Epub 2021 Jun 9.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1016/j.jceh.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617526PMC
June 2021

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.

J Clin Exp Hepatol 2022 May-Jun;12(3):876-886. Epub 2021 Oct 29.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported.

Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave.

Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes.

Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves.

Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.
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http://dx.doi.org/10.1016/j.jceh.2021.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553413PMC
October 2021

Immediate and Long-Term Outcomes of Percutaneous Radiological Interventions for Hemorrhagic Complications in Acute and Chronic Pancreatitis.

J Vasc Interv Radiol 2021 11 17;32(11):1591-1600.e1. Epub 2021 Aug 17.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Purpose: To evaluate and compare the immediate and long-term outcomes of radiological interventions for hemorrhagic complications in patients with acute and chronic pancreatitis.

Materials And Methods: This retrospective study, conducted between January 2014 and June 2020, included all patients with acute and chronic pancreatitis presenting with hemorrhagic complications who underwent angiography and/or embolization. Their clinical, angiographic, and embolization details were evaluated and correlated with procedure success, complications, recurrence, and mortality. The patients were subgrouped into groups A (acute pancreatitis) and C (chronic pancreatitis), and comparisons were made.

Results: The study included 141 patients (mean age, 36.3 ± 11.2 years; 124 men), of whom 106 patients had abnormal angiography findings and underwent embolization. Of them, group A had 50 patients (56 lesions) and group C had 56 patients (61 lesions). All the patients in group A had severe acute pancreatitis, with a mean computed tomography severity index of 7.6. The technical and clinical success rates of embolization, complications, recurrence, and long-term outcomes were not significantly different between the groups. Group A had significantly higher mortality due to sepsis and organ failure. Embolic agents did not have any significant association with complications, recurrence, and mortality. After a mean follow-up of 2 years, 72.5% of the patients were asymptomatic, and none had symptoms attributable to embolization.

Conclusions: Success, complications, and recurrence after embolization for hemorrhagic complications were comparable between acute and chronic pancreatitis. Acute pancreatitis was associated with significantly higher mortality. Embolic agents did not significantly influence the outcomes. None had long-term adverse effects attributable to embolization.
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http://dx.doi.org/10.1016/j.jvir.2021.08.004DOI Listing
November 2021

Response to Zhai and Tang.

Am J Gastroenterol 2021 10;116(10):2144

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

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http://dx.doi.org/10.14309/ajg.0000000000001415DOI Listing
October 2021

Outcomes of Portal Pressure-Guided Therapy in Decompensated Cirrhosis With Index Variceal Bleed in Asian Cohort.

J Clin Exp Hepatol 2021 Jul-Aug;11(4):443-452. Epub 2020 Nov 13.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

Background And Aims: Hemodynamic response to pharmacotherapy improves survival in patients with cirrhosis post variceal bleeding, but long-term outcomes remain unexplored especially in this part of the world. We aimed to study the long-term impact of portal pressure reduction on liver-related outcomes after index variceal bleed.

Methods: Patients with hepatic venous pressure gradient (HVPG) more than 12 mm Hg after index variceal bleed were given non-selective beta-blockers in combination with variceal band ligation. HVPG response was assessed after 4 weeks. Patients were followed up for rebleed events, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis.

Results: Forty-eight patients (29 responders and 19 non-responders) were followed up for a median duration of 45 (24-56) months. Rebleeding rates at 1, 3 and 5 years were 10.3%, 20.7% and 20.7% in responders and 15.8%, 44.7% and 51.1% in non-responders, respectively (Gray's test,  = 0.044). Survival rates at 1, 3 and 5 years were 89.7%, 72.1% and 51.9% in responders and 89.5%, 44% and 37.7% in non-responders, respectively (log-rank test,  = 0.1). Both severity of liver disease (MELD score, multivariate sub-distributional hazards ratio: 1.166 [1.014-1.341],  = 0.030) and HVPG non-response (multivariate sub-distributional hazards ratio: 2.476 [1.87-7.030],  = 0.045) predicted rebleeding risk while survival was dependent only on severity of liver disease (MELD > 12, multivariate hazards ratio: 2.36 [1.04-5.38],  = 0.041).

Conclusion: Baseline severity of liver disease predicted survival and rebleed in these patients. Hemodynamic response, although associated with lower rebleeding rate, had limited impact on survival.
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http://dx.doi.org/10.1016/j.jceh.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267357PMC
November 2020

Endoscopic transmural drainage tailored to quantity of necrotic debris versus laparoscopic transmural internal drainage for walled-off necrosis in acute pancreatitis: A randomized controlled trial.

Pancreatology 2021 Oct 21;21(7):1291-1298. Epub 2021 Jun 21.

Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background And Aims: Both endoscopic and laparoscopic transmural internal drainage are practiced for drainage of walled-off necrosis (WON) following acute pancreatitis (AP) but the superiority of either is not established. Our aim was to compare transperitoneal laparoscopic drainage with endoscopic drainage using either lumen apposing metal stents (LAMS) or plastic stents tailored to the amount of necrotic debris in WON.

Methods: In a randomized controlled trial, adequately powered to exclude the null hypothesis, patients with symptomatic WON were randomized to either endoscopic or laparoscopic drainage. In the endoscopy group, two plastic stents were placed if the WON contained <1/3rd necrotic debris and a LAMS was placed if it was >1/3rd. Primary outcome was resolution of WON within 4 weeks without re-intervention for secondary infection. Secondary outcome was overall success (resolution of WON at 6 months) and adverse events.

Results: Forty patients were randomized: 20 to each group. Baseline characteristics were comparable between the groups. Primary outcome was similar between the groups [16 (80%) in laparoscopy and 15 (75%) in endoscopy group; p = 0.89]. The overall success was similar [18 (90%) in laparoscopy vs. 17 (85%) in endoscopy; p = 0.9]. Median duration of hospital stay was shorter in endoscopy group [4 (4-8) vs. 6 days (5-9); p = 0.03]. Adverse events were comparable between the groups.

Conclusion: Laparoscopic drainage was not superior to endoscopic transmural drainage with placement of multiple plastic stent or LAMS depending on the amount of necrotic debris for symptomatic WON in AP. The hospital stay was shorter with the endoscopic approach.
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http://dx.doi.org/10.1016/j.pan.2021.06.006DOI Listing
October 2021

Development of a machine learning model to predict bleed in esophageal varices in compensated advanced chronic liver disease: A proof of concept.

J Gastroenterol Hepatol 2021 Oct 13;36(10):2935-2942. Epub 2021 Jun 13.

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

Background And Aim: Risk stratification beyond the endoscopic classification of esophageal varices (EVs) to predict first episode of variceal bleeding (VB) is currently limited in patients with compensated advanced chronic liver disease (cACLD). We aimed to assess if machine learning (ML) could be used for predicting future VB more accurately.

Methods: In this retrospective analysis, data from patients of cACLD with EVs, laboratory parameters and liver stiffness measurement (LSM) were used to generate an extreme-gradient boosting (XGBoost) algorithm to predict the risk of VB. The performance characteristics of ML and endoscopic classification were compared in internal and external validation cohorts. Bleeding rates were estimated in subgroups identified upon risk stratification with combination of model and endoscopic classification.

Results: Eight hundred twenty-eight patients of cACLD with EVs, predominantly related to non-alcoholic fatty liver disease (28.6%), alcohol (23.7%) and hepatitis B (23.1%) were included, with 455 (55%) having the high-risk varices. Over a median follow-up of 24 (12-43) months, 163 patients developed VB. The accuracy of machine learning (ML) based model to predict future VB was 98.7 (97.4-99.5)%, 93.7 (88.8-97.2)%, and 85.7 (82.1-90.5)% in derivation (n = 497), internal validation (n = 149), and external validation (n = 182) cohorts, respectively, which was better than endoscopic classification [58.9 (55.5-62.3)%] alone. Patients stratified high risk on both endoscopy and model had 1-year and 3-year bleeding rates of 31-43% and 64-85%, respectively, whereas those stratified as low risk on both had 1-year and 3-year bleeding rates of 0-1.6% and 0-3.4%, respectively. Endoscopic classification and LSM were the major determinants of model's performance.

Conclusion: Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs.
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http://dx.doi.org/10.1111/jgh.15560DOI Listing
October 2021

Long-term Outcomes with Carvedilol versus Propranolol in Patients with Index Variceal Bleed: 6-year Follow-up Study.

J Clin Exp Hepatol 2021 May-Jun;11(3):343-353. Epub 2020 Aug 25.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

Aims And Background: There is limited information on comparison of clinical outcomes with carvedilol for secondary prophylaxis following acute variceal bleed (AVB) when compared with propranolol. We report long-term clinical and safety outcomes of a randomised controlled trial comparing carvedilol with propranolol with respect to reduction in hepatic venous pressure gradient (HVPG) in patients after AVB.

Methods: We conducted a post-hoc analysis of patients recruited in an open-label randomized controlled trial comparing carvedilol and propranolol following AVB, and estimated long-term rates of rebleed, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis.

Results: Forty-eight patients (25 taking carvedilol; 23 propranolol) were followed up for 6 years from randomization. More number of patients on carvedilol had HVPG response when compared with those taking propranolol (72%- carvedilol versus 47.8% propranolol, p = 0.047). Comparable 1-year and 3-year rates of rebleed (16.0% and 24.0% for carvedilol versus 8.9% and 36.7% for propranolol; p = 0.457) and survival (94.7% and 89.0% for carvedilol versus 100.0% and 79.8% for propranolol; p = 0.76) were obtained. New/worsening ascites was more common in those receiving propranolol (69.5% vs 40%; p = 0.04). Other clinical decompensations and complications of liver disease occurred at comparable rates between two groups. Drug-related adverse-events were similar in both groups.

Conclusion: Despite higher degree of HVPG response, long-term clinical, survival and safety outcomes in carvedilol are similar to those of propranolol in patients with decompensated cirrhosis after index variceal bleed with the exception of ascites that developed less frequently in patients with carvedilol.
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http://dx.doi.org/10.1016/j.jceh.2020.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103346PMC
August 2020

Effect of Vitamin D Supplementation on Vitamin D Level and Bone Mineral Density in Patients With Cirrhosis: A Randomized Clinical Trial.

Am J Gastroenterol 2021 10;116(10):2098-2104

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

Introduction: In patients with cirrhosis, highly prevalent vitamin D deficiency and low bone mineral density (BMD) increase the burden of disease, and role of vitamin D supplementation is not clear. So, our aim was to determine the effect of vitamin D supplementation on vitamin D level and BMD in patients with cirrhosis.

Methods: Patients with cirrhosis (18-60 years) of any etiology were enrolled. We measured serum 25(OH)D, parathyroid hormone, thyroid-stimulating hormone, free T4, bone-specific alkaline phosphatase, insulin-like growth factor (IGF)-1, and health-related quality of life at entry and at 1 year; however, serum calcium was measured at 3-month interval. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine and left hip neck at entry and after 1 year. Statistical analysis was performed according to intention-to-treat analysis.

Results: Of 390 screened patients with cirrhosis, 164 participants (82 in each group) were randomized. There was significant increase in 25(OH)D levels in intervention group after 1 year (33.7 [24.3-45.7] ng/mL vs 23.1 [17-28.2] ng/mL; P < 0.001) when compared with placebo. The mean difference in BMD at lumbar spine and left hip neck was not significantly changed after 1 year of intervention with vitamin D between both groups. There was no significant change in both the groups in levels of calcium, thyroid-stimulating hormone, parathyroid hormone, free T4, IGF-1, and bone-specific alkaline phosphatase and quality of life.

Discussion: Supplementation with vitamin D for 1 year improves vitamin D levels but did not result in improvement in BMD at lumbar spine and left hip neck in patients with cirrhosis.
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http://dx.doi.org/10.14309/ajg.0000000000001272DOI Listing
October 2021

Determinants of Outcomes in Autoimmune Hepatitis Presenting as Acute on Chronic Liver Failure Without Extrahepatic Organ Dysfunction upon Treatment With Steroids.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):171-180. Epub 2020 Aug 22.

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

Background And Aims: Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids.

Methods: In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified.

Results: Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-day transplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%).

Conclusion: Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.
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http://dx.doi.org/10.1016/j.jceh.2020.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953011PMC
August 2020

Letter to the Editor: Balloon-Occluded Retrograde Transvenous Obliteration for Prevention of Gastric Variceal Rebleeding: A Paradigm Shift?

Hepatology 2021 09;74(3):1721-1722

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

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http://dx.doi.org/10.1002/hep.31821DOI Listing
September 2021

Systematic review and meta-analysis: Is there any role for antioxidant therapy for pain in chronic pancreatitis.

JGH Open 2021 Mar 24;5(3):329-336. Epub 2020 Oct 24.

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

Chronic pancreatitis (CP) is an irreversible disease with increased oxidative stress. The therapeutic role of antioxidants for pain reduction in CP is debatable. A systematic review of articles in PubMed and Embase until February 2020 was performed. Only randomized controlled trials conducted on humans to evaluate the therapeutic effects of antioxidants for pain in CP were included. Studies of other design, nonhuman studies, and those that did not objectively assess pain were excluded. Twelve articles and four articles were eligible for qualitative and quantitative analysis, respectively. The four included studies had a total of 352 participants. Pain reduction as measured by a visual analog scale was not significantly different in the antioxidant group compared to placebo (standardized mean difference = -0.14 [95% confidence interval [CI] = -0.44 to 0.17]; = 0.38). Number of pain-free participants was also similar (odds ratio [OR] = 1.59 [0.97-2.59]; = 0.06). There was no difference in outcome when comparing different etiologies of CP or age group. The reduction in the number of analgesics used did not differ between both groups. Antioxidants were not associated with increased adverse events (OR = 2.59 [CI = 0.77-8.69]; = 0.12). A qualitative analysis on the effect on quality of life did not suggest any significant improvement with antioxidants. There was no significant pain reduction or change in quality of life in CP patients with use of antioxidants. This makes their routine use in the management of CP questionable. However, further studies may identify a subgroup where they are more useful.
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http://dx.doi.org/10.1002/jgh3.12433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936613PMC
March 2021

Case of cholestatic jaundice associated with papillary carcinoma of thyroid: a multidisciplinary challenge.

BMJ Case Rep 2021 Feb 5;14(2). Epub 2021 Feb 5.

Gastroenterology and Human Nutrition Unit, AIIMS, New Delhi, India

The report describes a patient with cholestatic jaundice who had incidentally detected parathyroid hormone-independent hypercalcaemia. The differential diagnosis for this presentation includes systemic granulomatous and infiltrative disorders, drug-induced liver injury and malignancy. As the initial investigations were non-contributory towards the aetiology, she was given steroids and later plasma exchange for symptomatic treatment. The differentials were revised again in view of no clinical and biochemical response. A repeat fine-needle aspiration cytology of the thyroid nodule (seen on positron emission tomography/CT) revealed papillary carcinoma of the thyroid. The patient underwent total thyroidectomy. There was a complete normalisation of liver function tests and serum calcium, and resolution of pruritus 3 months post surgery. She was retrospectively diagnosed as a case of papillary carcinoma of the thyroid with paraneoplastic manifestations-hypercalcaemia and cholestatic jaundice-which got resolved with treatment of the primary tumour.
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http://dx.doi.org/10.1136/bcr-2020-236372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871217PMC
February 2021

Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma.

Sci Rep 2021 02 2;11(1):2824. Epub 2021 Feb 2.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.
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http://dx.doi.org/10.1038/s41598-021-82266-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854650PMC
February 2021

Outcome of Conservative Therapy in Coronavirus disease-2019 Patients Presenting With Gastrointestinal Bleeding.

J Clin Exp Hepatol 2021 May-Jun;11(3):327-333. Epub 2020 Oct 3.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background/objective: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19.

Methods: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included.

Results: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay.

Conclusion: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.
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http://dx.doi.org/10.1016/j.jceh.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833290PMC
October 2020

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

JGH Open 2021 Jan 13;5(1):81-90. Epub 2020 Nov 13.

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

Background And Aims: Decompensated cirrhosis in autoimmune hepatitis has poor prognosis. Besides liver transplant, treatment for this entity is undefined. We explored the outcomes of autoimmune hepatitis (AIH)-related decompensated cirrhosis with active disease on treatment with steroids.

Methods: In this retrospective analysis, clinical data, laboratory parameters, and prognostic scores, such as baseline model for end-stage liver disease (MELD) scores, were compared among patients of AIH with decompensated cirrhosis with mild/no ascites ( = 38), gross ascites ( = 24), and compensated cirrhosis ( = 32) when administered steroids. The primary outcome was transplant-free survival at 12 months. Biochemical remission rates and other adverse events were also assessed and compared between these groups.

Results: Steroids were initiated at lower doses (25 mg/day-mild/no ascites, 20 mg/day-gross ascites) in patients with decompensated cirrhosis and at 40 mg/day in those with compensated cirrhosis. Transplant-free survival was 25.4%, 74.6%, and 96.9% ( = 0.001), and biochemical remission occurred in 5.1%, 49.0%, and 64.1% ( = 0.001) at 12 months in patients with gross ascites, mild/no ascites, and compensated cirrhosis, respectively. Infections were seen more frequently in decompensated cirrhosis, while other adverse events were comparable. Among decompensated cirrhosis, those with mild/no ascites had better prognostic scores, fewer posttreatment infections, and more frequent biochemical remission than those with gross ascites, achieving rates comparable to compensated cirrhosis. On multivariate analysis, the MELD score (subdistributional hazards ratio [sHR]; 95% confidence interval: 1.153 [1.07-1.24]; = 0.001) and ascites (sHR: 2.556 [1.565-5.65]; = 0.020) predicted survival.

Conclusion: Type and severity of decompensation affect outcomes in patients with AIH-related cirrhosis. Those with mild/no ascites have comparable outcomes to those with compensated cirrhosis upon treatment with low-dose steroids.
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http://dx.doi.org/10.1002/jgh3.12451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812520PMC
January 2021
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