Background Osteoporosis and obesity are prevalent health conditions that share overlapping risk factors and physiological consequences. After menopause, hormonal changes impact both bone strength and fat distribution. Although fat mass (FM) and lean mass (LM) are important components of body composition, their separate effects on bone mineral density (BMD) are not well understood, especially among Indians. Objective The main objective of this study is to assess how body adiposity, such as FM and LM, is related to BMD in postmenopausal Indian women. Methods A total of 36 postmenopausal women participated in a cross-sectional study at a tertiary care hospital. Participants underwent dual-energy X-ray absorptiometry (DEXA) scans (Hologic Inc., Marlborough, MA, USA) to measure BMD at the spine, hip, wrist, and whole body, along with body composition assessments. Women with secondary causes of osteoporosis, or those on medications affecting bone metabolism, were excluded. Correlations between FM, LM, and BMD were assessed using statistical analysis. Results Among the participants (n = 36), 17 (47.2%) had osteopenia, nine (25.0%) had osteoporosis, and 10 (27.8%) had normal BMD. FM showed significant positive correlations with hip BMD (r = 0.457, p = 0.005), lumbar spine BMD (r = 0.373, p = 0.025), total body BMD (r = 0.349, p = 0.037), and whole-body bone mineral content (WB-BMC) (r = 0.498, p = 0.002). After statistical adjustment, LM correlations were weaker and not statistically significant. Conclusion In Indian postmenopausal women, FM is a stronger predictor of BMD than LM. These findings underscore the importance of considering body fat when assessing and managing osteoporosis risk in this population.

Summary Background In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. Aims We aimed to compare efficacy of 1‐day versus 3‐day terlipressin therapy in cirrhosis patients with AVB post‐endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. Methods In this open‐label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1‐day or 3‐day terlipressin therapy. Results A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day ( n = 75) or 3 days ( n = 75) of terlipressin therapy. One patient from 1‐day arm was excluded. Modified intention‐to‐treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4–9.0) versus 4 (5.3%; 95% CI: 2.0–10.0), risk difference (RD) p = 0.726 and 5‐day mortality rates: 1 (1.4%; 95% CI: 0–7.3) versus 1 (1.3%; 95% CI: 0.2–7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0–20.0) versus 10 (13.3%; 95% CI: 7.0–20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0–10.0) versus 4 (5.3%; 95% CI: 2.0–10.0), RD p = 0.704 were also similar. Patients in the 1‐day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. Conclusions Our results suggest that 1 day of terlipressin therapy is associated with similar 5‐day and 42‐day rebleeding rates, 42‐day mortality and an overall superior safety profile compared with 3‐day of terlipressin therapy. These findings require to be validated in double‐blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).

Abstract Background: The persistence of the COVID-19 pandemic besides its current resurgence and continuously increasing fatalities indicates a vital need for severity assessment at its early stages. Recent studies have already ascribed mortality to chronic inflammation. But the part of trace elements, especially zinc and copper that have been known to possess antiviral roles for a long time is least studied in COVID-19. Methods: The study comprised 122 COVID-19-positive participants admitted to the tertiary care hospital. Among them, eighty-one (~66%) were admitted to ICU under high severity. Levels of Zn and Cu along with CRP were analyzed and compared among ICU and non-ICU admitted patients. Using ROC analysis, the potential and precise levels for defining severity were determined. Results: We found a significant reduction in Zn levels (p=0.001) in ICU-admitted patients compared to the non-ICU group which was more pronounced in females and patients aged above 50 years. Reduction in the levels of Zn is accompanied by elevated CRP levels (p<0.001) in ICU patients with no effect on Cu levels. Upon ROC analysis, Zn and CRP were found to have significant AUC (p<0.0001). Further, CRP to Zn ratio displayed improved AUC with 90% sensitivity indicating their applicability to predict ICU requirements. Conclusions: The present study was primarily aimed to predict the status of zinc and copper in COVID-19 patients and their utility as a prognostic tool for deciding the severity. Our findings indicate that CRP to Zn ratio might feasibly be used to predict the progression of COVID-19 toward severity. Keywords: COVID-19, Severity, Zinc, Copper, CRP

Background: The role of hepatic venous pressure gradient (HVPG) in predicting further decompensation in cirrhosis patients with acute variceal bleeding (AVB) is not known. We aimed to evaluate the role of HVPG in predicting further decompensation in cirrhosis patients with AVB Methods: In this prospective study, 145 patients with cirrhosis with esophageal or gastric AVB were included. HVPG was measured on the day of the AVB. Decompensating events occurring after 42-days of AVB were considered further decompensation. Results: The median age of the study cohort was 44 years; 88.3% males. The predominant etiology of cirrhosis was alcohol (46.2%). Overall, 40 (27.6%) patients developed further decompensation during median follow-up of 296 days following AVB. Gastro intestinal bleeding n = 27 (18.6%) and new-onset/worsening ascites n = 20 (13.8%) were the most common decompensating events. According to the multivariate model, HVPG was an independent predictor of any further decompensation in esophageal AVB patients but not in gastric variceal bleeding patients. HVPG cut-off of ≥16 mmHg predicted further decompensation in the esophageal AVB. However, HVPG was not an independent predictor of mortality. Conclusion: HVPG measured during an episode of acute variceal hemorrhage from esophageal varices predicts further decompensating events in cirrhosis patients.

Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. Biopsy-proven 641 NAFLD patients (55.2

Background and Aim: In patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic band ligation is unclear. Expert guidelines recommend vasoconstrictor therapy for 1-day to 5-days. We aimed to compare the efficacy of 1-day terlipressin therapy vs 3-days of terlipressin in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare the rebleeding rates at 5-days between the two groups. The secondary objectives were to compare rebleeding and mortality at 6 weeks and the HVPG response rate.

BACKGROUND:The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI.METHODS:Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group.RESULTS:Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related).CONCLUSIONS:Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.KEY MESSAGES:

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hy-pertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness mea-surement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes. ( J CLIN EXP HEPATOL 2023;13:37-47)

Background Acute kidney injury (AKI) considerably increases the risk of short-term mortality in acute-on-chronic liver failure (ACLF) but predicting AKI is not possible with existing tools. Our study aimed at de novo discovery of AKI biomarkers in ACLF. Methods This observational study had two phases- (A) Discovery phase in which quantitative proteomics was carried-out with day-of-admission plasma from ACLF patients who initially had no-AKI but either progressed to AKI (n=10) or did not (n=9) within 7 days of admission and, (B) Validation phase in which selected biomarkers from the discovery phase were validated by ELISA in a larger set of ACLF plasma samples (n=93) followed by sub-group analyses. Results Plasma proteomics revealed 56 differentially expressed proteins in ACLF patients who progressed to AKI vs those who did not. The metallothionein protein-family was upregulated in patients who progressed to AKI and was validated by ELISA as significantly elevated in both- (i) ACLF-AKI vs no-AKI (p-value ≤ 0.0001) and (ii) progression to AKI vs no-progression to AKI (p-value ≤ 0.001). AUROC for AKI vs no-AKI was 0.786 (p-value ≤0.001) and for progression to AKI vs no-progression to AKI was 0.7888 (p-value ≤0.001). Kaplan-Meier analysis revealed that ACLF patients with plasma MT concentration >5.83 ng/mL had a high probability of developing AKI by day 7 (p-value ≤0.0001). High expression of metallothionein genes was found in post-mortem liver biopsies of ACLF patients. Conclusion Day-of-admission measurements of plasma metallothionein can act as predictive biomarkers of AKI in ACLF.

Background and Aim: Body mass index (BMI) is associated with the risk of developing non alcoholic fatty liver disease (NAFLD). The exact relationship between BMI and outcomes in patients with NAFLD is not well defined. We aimed to assess the clinical presentations, outcomes, development of liver-related events (LRE) and non-LREs in patients with NAFLD based on BMI. Methods: Records of patients attending the Liver Clinic at our institute from 2000-2021 were reviewed. Baseline demographics, comorbidities, biochemical and elastographic measurements were assessed and the development of any LRE- hepatocellular carcinoma, variceal bleeding, hepatic encephalopathy were analyzed. Non liver related events- new onset hypertension, diabetes mellitus or extrahepatic malignancies were also reviewed. Histologic findings in patients who had undergone liver biopsy were correlated with BMI. Results: 957 patients with follow up >1 year were included for analysis of whom 287 had available liver biopsies (30%). Patients were categorized based on BMI (Asia-Pacific guidelines for Asians) as normal (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2) and obese (>25 kg/m2) with the absolute numbers in each group being 116 (12.2%), 164 (17.1%) and 677 (70.7%), respectively with a male predominance (67.8%). Prevalence of diabetes mellitus, hypertension, metabolic syndrome and dyslipidemia were significantly higher at baseline in the obese with no significant differences in liver related parameters. Obese patients had significantly higher median liver stiffness values 6.8 (4.9-9.0) kPa and CAP score 321 (290-348) dB/m as compared to overweight and normal BMI subjects. There were no differences in fibrosis stage and grade of hepatic steatosis between the 3 groups. On follow up there were no significant differences in cause of mortality, progression of liver disease, new LRE and development of new onset diabetes and hypertension across the BMI groups. Conclusion: Patients with obesity may have greater metabolic derangements as compared to normal or overweight individuals but this does not translate to more severe liver disease or adverse outcomes in these patients. Although intuitive, the dose response relationship between BMI and severity of NAFLD is not linear.

detection results were true septa.587 nodules were annotated from 25 H&E images by the pathologist.525 nodules were detected from the SHG/TPEF images using qNodules.Comparing the qNodules results and true nodules, 82% of the true nodules were detected by the algorithm and 95% of the algorithm detection results were true nodules.The repeatability of qSepta and qNodules were 95% and 99% respectively.Figure: Examples of septa and nodules detection.Conclusion: qSepta and qNodules algorithms can accurately detect septa and nodules in NASH cirrhotic patients.This can be used to develop more sophisticated algorithms to correlate with HVPG and study the natural history of NASH cirrhosis and treatment response.

Introduction: Data are limited on antibody response to the ChAdOx1 nCoV-19 vaccine (AZD1222; Covishield®) in cirrhosis. We studied the antibody response following two doses of the ChAdOx1 vaccine, given 4–12 weeks apart, in cirrhosis. Methods: Prospectively enrolled, 131 participants (71% males; age 50 (43–58); alcohol-related etiology 14, hepatitis B 33, hepatitis C 46, cryptogenic 21, autoimmune 9, others 8; Child–Turcott–Pugh class A/B/C 52/63/16). According to dose intervals, the participants were grouped as ≤6 weeks (group I), 7–12 weeks (group II), and 13–36 weeks (group III). Blood specimens collected at ≥4 weeks after the second dose were tested for anti-spike antibody titre (ASAb; positive ≥ 0.80 U/mL) and neutralizing antibody (NAb; positive ≥20% neutralization) using Elecsys Anti-SARS-CoV-2 S (Roche) and SARS-CoV-2 NAb ELISA Kit (Invitrogen), respectively. Data are expressed as number (proportion) and median (interquartile range) and compared using non-parametric tests. Results: Overall, 99.2% and 84% patients developed ASAb (titre 5440 (1719–9980 U/mL)) and NAb (92 (49.1–97.6%)), respectively. When comparing between the study groups, the ASAb titres were significantly higher in group II than in group I (2613 (310–7518) versus 6365 (2968–9463), p = 0.027) but were comparable between group II and III (6365 (2968–9463) versus 5267 (1739–11,653), p = 0.999). Similarly, NAb was higher in group II than in group I (95.5 (57.6–98.0) versus 45.9 (15.4–92.0); p < 0.001), but not between the groups II and III (95.5 (57.6–98.0) versus 92.4 (73.8–97.5); p = 0.386). Conclusion: Covishield® induces high titres of ASAb and NAb in cirrhosis. A higher titre is achieved if two doses are given at an interval of more than six weeks.

BackgroundAcute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. MethodsACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90days. Survival analysis was performed using Kaplan Meier survival curves. ResultsA total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. ConclusionTPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.

Background and Aim: Acute kidney injury (AKI) is a central event in acute-on-chronic-liver failure (ACLF) and considerably increases the risk of short-term mortality. However, currently there are no biomarkers to predict AKI in ACLF. Our study aimed at de novo discovery of AKI biomarkers in ACLF. Methods: The study had two phases- (A) discovery phase in which quantitative plasma proteomics was carried out with day-of-admission samples collected from ACLF patients who presented with no-AKI but progressed to AKI (n=10) or did not progress to AKI(n=9) within 10 days of admission and, (B) Validation phase in which selected biomarkers were evaluated by ELISA in a larger cohort of ACLF plasma samples (n=93) followed by sub-group analyses. Results: Quantitative proteomics identified 56 differentially expressed plasma proteins in ACLF patients who progressed to AKI vs those who did not. The metallothionein family of proteins formed a prominent group among the upregulated proteins in ACLF patients who progressed to AKI. ELISA based validation showed significant upregulation of MT in ACLF-AKI vs no-AKI(p-value=0.0001) and in progression to AKI vs no-progression to AKI(p-value<0.001). AUROC for AKI vs no-AKI was 0.786(p-value <0.001) and for progression to AKI vs no-progression to AKI was 0.7888 (p-value=0.001). Kaplan-Meier analysis revealed that ACLF patients with plasma MT concentration >5.83 ng/mL had a high probability of developing AKI by day 7 (p-value=0.0001). PCR analysis showed high expression of metallothionein 1 and 2 genes in post-mortem liver biopsies from ACLF patients. We found that MT/ Albumin ratios were highly elevated in ACLF AKI vs no-AKI and in ACLF progression to AKI vs no-progression to AKI. Conclusions: Overall, our study led to the identification of plasma metallothionein as a potential day-of-admission biomarker for the prediction of AKI in ACLF patients and provided a basis to explore metallothionein in the pathogenesis of AKI in ACLF.

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.

BACKGROUND Platelet transfusion in acute variceal bleeding (AVB) is recommended by few guidelines and is common in routine clinical practice, even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear. AIM To determine how platelet counts, platelets transfusions, and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control, rebleeding, and mortality. METHODS Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB. The outcomes were assessed as the risk of rebleeding at days 5 and 42, and risk of death at day 42, considering the platelet counts and platelet transfusion. Propensity score matching (PSM) was used to compare the outcomes in those who received platelet transfusion. Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Cox-proportional hazard model for rebleeding and for 42-d mortality. RESULTS The study included 913 patients, with 83.5% men, median age 45 years, and Model for End-stage Liver Disease score 14.7. Platelet count < 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L were found in 23 (2.5%), 168 (18.4%), and 722 (79.1%) patients, respectively. Rebleeding rates were similar between the three platelet groups on days 5 and 42 (13%, 6.5%, and 4.7%, respectively, on days 5, P = 0.150; and 21.7%, 17.3%, and 14.4%, respectively, on days 42, P = 0.433). At day 42, the mortality rates for the three platelet groups were also similar (13.0%, 23.2%, and 17.2%, respectively, P = 0.153). On PSM analysis patients receiving platelets transfusions (n = 89) had significantly higher rebleeding rates on day 5 (14.6% vs 4.5%; P = 0.039) and day 42 (32.6% vs 15.7%; P = 0.014), compared to those who didn't. The mortality rates were also higher among patients receiving platelets (25.8% vs 23.6%; P = 0.862), although the difference was not significant. On multivariate analysis, platelet transfusion and not platelet count, was independently associated with 42-d rebleeding. Hepatic encephalopathy was independently associated with 42-d mortality. CONCLUSION Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB; however, platelet transfusion increased rebleeding on days 5 and 42, with a higher but non-significant effect on mortality.

Background: Major depressive disorder (MDD) is one of the most common psychiatric disorders and only less than 50% of MDD patients achieve remission after the first antidepressant trial. Hence, it is important to understand the factors associated with response to various antidepressant medications. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. BDNF and Val66Met polymorphism in the BDNF gene has a role in MDD. This study aimed to determine the association of rs6265 polymorphism and serum BDNF level with response to treatment in MDD patients. Methods: The study included 200 subjects, consisting of 100 MDD patients treated with oral antidepressants and 50 treated with ECT, and 50 healthy controls. Serum BDNF levels were estimated using ELISA and rs6265 polymorphism was genotyped using tetra-primer ARMS PCR. Results: Val66Met polymorphism had an association with MDD, and in MDD patients with Met allele was associated with a better response to antidepressants. Serum BDNF level was significantly higher in MDD patients compared to healthy individuals. In MDD patients, lower serum BDNF level was associated with better ECT outcomes. Conclusions: Val66Met polymorphism in BDNF gene and serum BDNF level has the potential to be used as a biomarker for the prediction of response to oral antidepressants and ECT in MDD patients. The presence of the Met allele might be used to predict the chances of occurrence of MDD in the future. The results of our study might form a basis for the development of personalized treatment for MDD in the future.