Longitudinal changes in bone mineral density may be associated with long-term survival in patients with cirrhosis: A proof of concept of study.

INTRODUCTION: The impact of longitudinal changes in different body components measured via body composition analysis (BCA) on liver-related outcomes in patients with cirrhosis is poorly understood. We evaluated the prognostic relevance of longitudinal changes in body composition over one year in patients with cirrhosis. METHODS: This was a follow-up study of a randomized controlled trial evaluating changes in bone density measured via dual energy X-ray absorptiometry (DEXA) upon vitamin D supplementation. Patients with available anthropometric indices, fat mass (FM), fat-free mass (FFM), bone-density at lumbar spine (LD) and left femur-neck (FD) (assessed by T score) at two time points one year apart were assessed for outcomes. The prognostic relevance of change in parameters such as ΔFM, ΔFFM, ΔLD and ΔFD over one year was assessed and compared with baseline model for end-stage liver disease (MELD) score. RESULTS: Patients with cirrhosis (n=112) (mean age 41.8±12 years, 58.5% males) were followed up for median duration of 5.7 years interquartile range [IQR 3.5-5.7], with five-year survival rate of 77%. On serial BCA, ΔLD (p=0.029) and ΔFD (p=0.003) emerged as significant predictors of survival, whereas ΔFM (p=0.479), ΔFFM (p=0.245) and ΔBMI (p=0.949) were not. The area under curve of ΔLD and MELD score for predicting survival was 0.636 (0.5-0.773) and 0.664 (0.555-0.773), respectively. ΔFD<0.1 over one year had sensitivity and specificity of 70.4% and 56.5% to predict poor survival. The combination of ΔFD, MELD and ascites predicted five-year survival with an optimism-corrected c-statistic of 0.785. CONCLUSION: Among body composition parameters, changes in bone mineral density correlate best with survival and have prognostic relevance similar to that of ascites and MELD score.

Antiviral Activity of Svarnvir-IV Tablet Assayed for Activity Against SARS-CoV-2 In Vitro.

The coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, has become a global pandemic in a very short time span. While several vaccines have been developed in the last year, specific treatments for CoV infection are still being explored. Thus, the situation highlights the need to develop safe and efficacious antiviral therapeutics. Ayurvedic Rasayana therapy has been traditionally used in India for its holistic healing systems and proven history of empirical use. There is emerging evidence that Ayurvedic treatment methodologies and herbal medicines may be effective strategies in combating COVID-19. The present study is aimed at evaluating the antiviral and therapeutic activity of an Ayurvedic herbomineral formulation (Svarnvir-IV tablet, 450 mg) against the SARS-CoV-2 virus in vitro. A cell-based assay was conducted to evaluate the cytotoxicity of the Svarnvir-IV tablets (Aimil Pharmaceuticals, Delhi, India) for the determination of virucidal activity assessment (at 2 hours) and therapeutic activity assessment (at 1 hour, 2 hours, and 4 hours). When incubated with SARS-CoV-2 virus at 0.1 multiplicity of infection (MoI) for two hours, Svarnvir-IV tablet exhibited virucidal activity against SARS-CoV-2 with an EC50 value of 0.0058 mg/ml. It also exhibited therapeutic activity when treated with cells infected with the SARS-CoV-2 virus (0.1 MoI) for 1 hour, 2 hours and 4 hours post-infection, with an EC50 value of 0.094 mg/ml, 0.023 mg/ml, and 0.05 mg/ml, respectively. The original supporting data obtained from this study, along with existing Ayurvedic traditional information, has shown encouraging results.

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

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).

Ameliorative effect of a standardized polyherbal combination in methotrexate-induced nephrotoxicity in the rat.

Context: Nephrotoxicity is a renal dysfunction that arises from direct exposure to environmental chemicals or as a side effect of therapeutic drugs. Boerhaavia diffusa Linn. (Nyctaginaceae), Rheum emodi Wall. Ex. Meissn. (Polygonaceae), Nelumbo nucifera Gaertn. (Nelumbonaceae) and Crataeva nurvala Buch-Ham. (Capparidaceae) are well-recognized medicinal plants of Indian traditional system of medicine used for kidney disorders.Objectives: The present investigation was undertaken to develop a chromatographically characterized polyherbal combination and to evaluate its nephroprotective activity.Materials and methods: Roots of B. diffusa and R. emodi, flowers of N. nucifera and stem bark of C. nurvala were extracted by decoction using 70% ethanol. Response surface methodology (RSM) was used for the optimization of extraction parameters. Polyherbal combinations with different doses (150-300 mg/kg) were tested against methotrexate-induced nephrotoxicity in Wistar rats.Results: The optimized extract contained 27% phenols and 15% flavonoids, which showed 75% 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging potential. Based on the retention time of high-performance liquid chromatography (HPLC) analysis, 17 out of 122 constituents were found common in all extracts and combinations. Two combinations showed significantly higher (p ≤ 0.05) DPPH scavenging potential and xanthine oxidase inhibition. The half maximal inhibitory concentration (IC50) of the best combination for DPPH scavenging and xanthine oxidase inhibition were 80 and 74 µg/mL, respectively. Treatment of methotrexate-induced nephrotoxic rats with polyherbal combination significantly (p ≤ 0.05) improved the kidney function markers, oxidative stress markers and histological parameters.Discussion and conclusion: The developed combination was found to be effective in nephrotoxicity; it can be explored further for the management of drug-induced nephrotoxicity and other chronic kidney diseases.