Assessment of the Performance of Non-invasive Criteria for the Evaluation of Clinically Significant Portal Hypertension in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Assessment of clinically significant portal hypertension (CSPH) non-invasively using a combination of liver stiffness measurement (LSM) and platelet counts is proposed as an alternative to hepatic venous pressure gradient (HVPG) estimation. Utility of these criteria in compensated advanced chronic liver disease (cACLD) patients of different etiologies including nonalcoholic steatohepatitis (NASH) with BMI  >  30 kg/m2 was studied in a large cohort. METHODS: Consecutive patients of cACLD with available anthropometric and laboratory details, LSM, and HVPG were included in a retrospective analysis. A LSM of ≥ 25 kPa alone and LSM ≤ 15 kPa plus platelets ≥ 150 × 109/L were evaluated as non-invasive rule-in and rule-out criteria for CSPH, respectively. The NASH-ANTICPATE model (composite of BMI, platelets, and LSM) was evaluated in patients with obese NASH. RESULTS: Patients with cACLD (n = 626) (mean age: 50.8 ± 12.4 years, 74.2% males) with alcohol (ALD, 30.3%), NASH (26.4%), hepatitis C (HCV, 16.6%), hepatitis B (HBV,10.2%) etiology were included. The prevalence of CSPH was  >  80% across all etiologies except in HBV (62.5%) and in obese non-NASH (71-72%). The rule-in criteria had a PPV  >  90% for all etiologies except in HBV (80.8%). The rule-out criteria had a negative predictive value (NPV) of 65%, 53%, and 40% in ALD, HCV, and NASH, respectively. The NASH-ANTCIPATE model had specificity of 100% and NPV of 33% to detect CSPH in obese NASH (n = 62). CONCLUSIONS: LSM ≥ 25 kPa predicted CSPH in most etiologies except HBV. A significant proportion of patients have CSPH despite satisfying the rule-out criteria. The NASH-ANTICIPATE model is specific but fails to exclude CSPH in nearly two-third patients with obesity and NASH. There is a need for precise disease-specific non-invasive models for detecting CSPH.

Ethosomes-based gel formulation of karanjin for treatment of acne vulgaris: in vitro investigations and preclinical assessment.

The aim of the present study was to develop and characterize karanjin-loaded ethosomes-based gel formulation for enhanced topical delivery and effective therapy of skin acne. Karanjin-loaded ethosomes (K-ETH) presented a nanometric size of 140.87 ± 2.35 nm, entrapment of 71.41 ± 2.74% and enhanced permeation with 1.9 times increase in the flux and 2.4 times higher skin deposition compared to the hydro-ethanolic solution of karanjin. The DSC analysis confirmed successful entrapment of the karanjin within the ethosomes. The developed ethosomes were incorporated in the carbopol gel for adequate application on the skin surface. The ethosomal gel (K-EGF) also exhibited greater penetration in the rat skin as revealed by CLSM. The optimized K-EGF formulation was non-irritant to the skin as evident by Draize score test and histopathological examination. The highest zone of inhibition, 30.0 ± 1.52 mm and 36.22 ± 0.57 mm was produced by the K-EGF against Propionibacterium acnes and Staphylococcus epidermidis, respectively, indicating substantial antibacterial properties of the K-EGF. DPPH assay indicated its potent antioxidant effects. Substantial anti-inflammatory effects in the carrageenan-induced edema in the rat paw were evident with inhibition of rat paw edema by 66.66% and 70.37% upon application of K-EGF and standard anti-inflammatory agent, respectively. Anti-acne effects were also evident with K-EGF treatment with significant decrease in number and size of sebaceous gland units in dermis. Overall, the above findings vouch for a therapeutic opportunity to improve topical delivery of karanjin in acne treatment employing ethosomal gels as the promising carrier system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02978-3.

Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study.

BACKGROUND AND AIM: Hepatic venous pressure gradient (HVPG), although an important determinant in predicting rebleeding after an episode of acute variceal bleed (AVB), is seldom utilized in clinical practice. We aimed to study the role of liver stiffness measurement (LSM) after variceal bleeding as a potential noninvasive predictor of rebleed. METHODS: This was a post hoc analysis of clinical trial of patients undergoing HVPG (postbleed HVPG) and LSM (postbleed LSM) assessment within 3-5 days of index AVB. HVPG response was assessed after 4 weeks of pharmacotherapy. Comparative assessment of long-term rebleeding rates stratified using postbleed LSM, postbleed HVPG, and HVPG response was performed. Decision curve analysis (DCA) was conducted to identify the most appropriate tool for routine use. RESULTS: Long-term clinical and HVPG response data were available for 48 patients post-AVB, of whom 45 patients had valid postbleed LSM. Rebleeding occurred in 13 (28%) patients over a median follow-up of 4 years with no early rebleeds. Postbleed LSM >30 kPa and baseline HVPG >15 mm Hg were optimal cutoffs for identifying patients at high risk of rebleeding. Time-dependent receiver operating characteristic curves and competing risk analysis accounting for death showed similar discriminative values for all three stratification tools. At usual risk thresholds, HVPG response had maximum benefit on DCA followed by postbleed LSM. On DCA, 50-60 additional HVPGs were required to detect one additional patient at high risk of rebleed. CONCLUSION: Liver stiffness measurement during AVB can potentially be used as an alternative to portal pressure indices in decompensated cirrhosis to identify those at high risk of late-onset rebleed.