The Outcome in Cirrhosis after Hospital Discharge is Not Worsened with COVID-19 Infection: A Propensity Score-matched Analysis.

Background: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on the outcome of cirrhosis patients in the posthospitalization period is limited. Aims: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results: Cirrhosis patients with (n = 92) or without (n = 92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P = 0.520), over a similar duration of follow-up [186 (86-271) vs. 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed rehospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs. 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs. 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P = 0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Neutrophil Lymphocyte Ratio can Preempt Development of Sepsis After Adult Living Donor Liver Transplantation.

Background: Development of sepsis is a major contributor to poor outcomes after liver transplant. The neutrophil-lymphocyte ratio (NLR) is an easily calculable inflammatory biomarker. We aim to utilize NLR to diagnose and predict the onset of sepsis in patients undergoing living donor liver transplants (LDLT). Materials and methods: Analysis of the perioperative course of 314 consecutive adult patients who underwent elective ABO compatible LDLT was done. Patients were divided into two cohorts; those who developed sepsis and a control group. Sepsis was defined by the combination of SIRS and clinical/radiological suspicion of infection. NLR was calculated by dividing the percentage of neutrophils by the percentage of lymphocytes in peripheral blood. Results: ostoperatively, 127 out of 314 patients (40.5%) having at least one episode of sepsis were included in the septic cohort and were compared to the 187 (59.5%) patients in the control group. Demographic and baseline characteristics, including NLR (13.74 ± 0.99 vs. 12.65 ± 0.57, P = 0.294) were comparable preoperatively. The NLR of the septic cohort was significantly higher than the control cohort (15.01 ± 1.67 vs. 9.98 ± 0.63, P = 0.001) 3 days prior to sepsis and remained significantly higher till the day of sepsis. The area under the cover was maximum for NLR 1 day prior to the development of sepsis (r = 0.707) with a sensitivity, specificity, positive predictive value, and negative predictive value of 62.4%, 62.2%, 51.4%, and 72.0%, respectively, at a cutoff of 8.5. Conclusion: NLR is a useful tool in diagnosing and pre-empting development of sepsis in LDLT.

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

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%, P < 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.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Does Raised Transaminases Predict Severity and Mortality in Patients with COVID 19?

Background: The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and the effects on morbidity and mortality. Aim: The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary center in northern India. Methods: This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr to Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis. Results: A total of 708 patients with COVID-19 fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR = 25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients, respectively. Serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were elevated in 6.92%, 69.91%, and 80.22% of patients, respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate to severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1 IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1 g/dL increase].Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1 g/dL increase] showed significant association with mortality. Conclusion: Liver function abnormalities are common in patients with COVID-19. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19.

Preliminary clinical assessment and non- toxicity evaluation of an ayurvedic formulation BGR-34 in NIDDM.

In view of the overall health impact of NIDDM, inventers understand the necessity of improving glycemic control in adults with type 2 diabetes. BGR-34 provides an effective treatment option for adults with type 2 diabetes who have been inadequately controlled on lifestyle with or without other oral hypoglycemic agents (OHGAs) such as metformin, sulfonylurea, or a glitazones. BGR-34 is an appropriate option to consider for addition to a managed care drug formulary. Treatment with BGR-34 produced clinically relevant and statistically significant reductions in all three key measures of glucose control studied -FPG, PPBG and HbA1c- when compared with placebo. BGR-34, showed the promising result with respect to glycemic parameters in NIDDM patient with a significant reduction in fasting blood sugar by 34.3%, postprandial blood sugar 35.5% & glycosylated haemoglobin by 20.31% as compared to placebo group showing a reduction by 13.2%, 10.9% & 10.87% respectively. The trial has also been registered to CTRI, India. This study has been registered in the clinical trial registry-India.

Haematological evaluation of sodium fluoride toxicity in oryctolagus cunniculus.

Blood is promptly affected by environmental pollutants and toxicants that can cause many metabolic disorders. The high level of fluoride acts as a potential pollutant, insecticide and rodenticide with very high toxicity, associated with the hematological damage. This study aimed to determine the toxicity of Sodium Fluoride on hematological parameters in Oryctolagus cunniculus. Twenty rabbits were acclimatized and divided in to control group and three experimental groups.Experimental group-I, II and III were treated with 10, 30 and 50 mg/kg body weight doses of Sodium Fluoride orally. Various blood parameters such as TEC, Hb, HCT, MCV, MCH, MCHC, TLC and PLT count were investigated. Result findings showed that values of blood indices in experimental groups were significantly lower than the control group. Oneway ANOVA was applied for statistical analysis. The outcomes of the current studies indicated the reduction in RBC counts (anemia), leukocyte count (leukocytopenia), monocytosis, eosinopenia, neutrophilia and thrombocytosis on fluoride intoxication. Hematological disruptions like microcytic hypochromic anemia and decreased leukocyte count may be linked to the inflammatory effects of Sodium Fluoride on lymphatic organs.

Clinical Profile and Response to Treatment with Pegylated Interferon α 2b and Ribavirin in Chronic Hepatitis C-A Reappraisal from a Tertiary Care Center in Northern India.

AIM: To assess the clinical profile of 80 chronic hepatitis C patients in a tertiary health care center in Northern India and also to study the efficacy and tolerability of pegylated interferon (Peg-IFN) α 2b and ribavirin therapy in a cohort of chronic hepatitis C patients. METHODS: Thirty subjects with chronic hepatitis C (CH-C) with genotypes 2 and 3 received Peg-IFN α 2b 1.5 µg/kg subcutaneously weekly plus daily ribavirin 800 mg for 24 weeks .Subjects with genotype 1 infection received therapy for 48 weeks with ribavirin 1000 mg/day and Peg-IFN α 2b dose remained the same. The primary end point was the sustained viral response (SVR). Drug dosage was modified or temporarily discontinued if anemia or bone marrow suppression developed. RESULTS: The clinical profile of chronic hepatitis C infected patients showed decompensated cirrhosis in the more elderly patients. Genotype 3 was the commonest genotype and was seen in 21 (70%) patients. The mean baseline HCV RNA was high. SVR was achieved less commonly with genotype 1 than with genotype 2/3. Patients who became negative for HCV RNA at 4-weeks (rapid virological response or RVR) and 12 weeks (early virological response or EVR) of treatment showed significantly higher sustained virological response (SVR) rates. Similarly, patients who showed normalization of ALT level at 4-weeks and 12-weeks of treatment showed significant high rate of SVR. Overall treatment was well tolerated. CONCLUSION: In our region, CHC subjects have high viral load and genotype 3 being the most common. Treatment with Peg-IFN α 2b and ribavirin is effective and well tolerated. Genotype 1 was more resistant to the treatment. Patients who achieved RVR and EVR are more likely to achieve SVR. Although the numbers of patients in this study was small, considering the paucity of data of treatment from India, the data is relevant.

Sustained virological response rates to antiviral therapy in genotype 1 and 3 chronic hepatitis C patients: a study from north India.

BACKGROUND: In India, both genotype 3 and 1 are predominant genotypes in patients with chronic hepatitis C (CHC). However, there is scanty data on sustained viral response (SVR) rate with conventionally recommended dual therapy with PEG-IFN and ribavirin. METHODS: In this retrospective study, consecutive patients of CHC of genotypes 1 and 3, attending the single unit of Gastroenterology of our hospital, who received PEG-IFN and ribavirin therapy, were included. Patients who had co-infection with HIV or HBV were excluded. RESULTS: A total of 114 patients were included in the study median age 44 (15-72) years, 79% males. Most common presentation was with chronic hepatitis, while 10 (9%) patients had compensated cirrhosis. Nine (8%) patients had associated diabetes, 16 (14%) patients gave history of significant alcohol abuse. The median baseline HCV RNA level was 3.0 × 10(5) (1.7 × 10(3)-1.8 × 10(7)) IU/mL. The most common genotype was 3 (75%) followed by genotype 1 (25%). 70% patients received PegIFN-α2a (median dose 180 MIU/wk) and 30% patients received PegIFN-α2b (median dose 80 MIU/wk). The median ribavirin dose was 800 (range 800-1200) mg. SVR in genotype 1 was 64% (18/28) while SVR in genotype 3 was 73% (63/86). The factors predicting SVR on univariate analysis were a lower baseline HCV RNA level (less than 3.0 × 10(5)), higher hemoglobin level > 11.8 g/dl, and achievement of rapid virological response (RVR), early virological response (EVR) and end of treatment response (ETR). In multivariate analysis the only baseline factor found independently correlating with SVR was low HCV RNA level (<3.0 × 10(5) IU/mL) (P = 0.003). CONCLUSION: In north India, HCV genotype 3 has a SVR rate of 73%, which is comparable to genotype 1 with SVR rate of 64% when treated with PEG-IFN and ribavirin therapy. A baseline HCV RNA level lower than 3.0 × 10(5) best predicts SVR in addition to achievement of RVR, EVR or ETR.