Acute-on-chronic liver failure (ACLF) is a distinct clinical entity and differs from acute liver failure and decompensated cirrhosis in timing, presence of acute precipitant, course of disease and ...potential for unaided recovery. The definition involves outlining the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific timeframe. The pathophysiology of ACLF relates to persistent inflammation, immune dysregulation with initial wide-spread immune activation, a state of systematic inflammatory response syndrome and subsequent sepsis due to immune paresis. The disease severity and outcome can be predicted by both hepatic and extrahepatic organ failure(s). Clinical recovery is expected with the use of nucleoside analogues for hepatitis B, and steroids for severe alcoholic hepatitis and, possibly, severe autoimmune hepatitis. Artificial liver support systems help remove toxins and metabolites and serve as a bridge therapy before liver transplantation. Hepatic regeneration during ongoing liver failure, although challenging, is possible through the use of growth factors. Liver transplantation remains the definitive treatment with a good outcome. Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF.
Background and Aim
Sepsis is an important determinant of the outcome of acute‐on‐chronic liver failure (ACLF) patients. Omega‐3 fatty acids (FAs) are known to suppress inflammation, reduce morbidity, ...and mortality in postoperative and critically ill patients. We aimed to evaluate the effect of intravenous omega‐6 and omega‐3 FA lipid emulsions in ACLF patients.
Methods
Ninety ACLF patients were randomly allocated to three groups: Gr. A received no lipid emulsions, Gr. B received omega‐6 FAs, and Gr. C received omega‐3 FAs. The primary and secondary aims were to compare the effects of lipid emulsions on immune modulation, the incidence of bacterial sepsis, and mortality at day 28.
Results
The baseline characteristics of the patients were comparable. Serum endotoxin levels remained suppressed by 22% in Gr. C compared with a 4% and 12% rise in Gr. B and A (P < 0.001). Omega‐3 FAs also suppressed C‐reactive protein levels and neutrophil‐to‐lymphocyte ratio in Gr. C. Compared with Gr. A, omega‐3 FAs reduced sepsis by 86% (HR, 0.14; 95% CI 0.04–0.43; P < 0.001). Omega‐3 FAs significantly increased the expression of TLR2 and TLR4 on both CD14+ and CD16+ monocytes, and TLR4, on macrophages and neutrophils. There were no serious adverse events, except transient flushing in 20% and 16.6% of patients receiving omega‐6 FAs and omega‐3 FAs, respectively.
Conclusion
Omega‐3 FAs are safe and effective in reducing systemic inflammation, endotoxemia, and sepsis in patients with ACLF. These lipid emulsions could also be considered as effective sources of immunonutrition in such sick patients.
Indigenous folk rice cultivars often possess remarkable but unrevealed potential in terms of nutritional attributes and biotic stress tolerance. The unique cooking qualities and blissful aroma of ...many of these landraces make it an attractive low-cost alternative to high priced Basmati rice. Sub-Himalayan Terai region is bestowed with great agrobiodiversity in traditional heirloom rice cultivars. In the present study, ninety-nine folk rice cultivars from these regions were collected, purified and characterized for morphological and yield traits. Based on traditional importance and presence of aroma, thirty-five genotypes were selected and analyzed for genetic diversity using micro-satellite marker system. The genotypes were found to be genetically distinct and of high nutritive value. The resistant starch content, amylose content, glycemic index and antioxidant potential of these genotypes represented wide variability and 'Kataribhog', 'Sadanunia', 'Chakhao' etc. were identified as promising genotypes in terms of different nutritional attributes. These cultivars were screened further for resistance against blast disease in field trials and cultivars like 'Sadanunia', 'T4M-3-5', 'Chakhao Sampark' were found to be highly resistant to the blast disease whereas 'Kalonunia', 'Gobindabhog', 'Konkanijoha' were found to be highly susceptible. Principal Component analysis divided the genotypes in distinct groups for nutritional potential and blast tolerance. The resistant and susceptible genotypes were screened for the presence of the blast resistant pi genes and association analysis was performed with disease tolerance. Finally, a logistic model based on phenotypic traits for prediction of the blast susceptibility of the genotypes is proposed with more than 80% accuracy.
Indian soils are inherently poor in quality due to the warm climate and erosion. Conversion of land uses like forests to croplands and faulty management practices in croplands further cause soil ...degradation. This study aimed to understand the extent of these impacts in a small representative part of eastern India, covering Himalayan terai and nearing alluvial plains. Soils were collected from (i) forests, (ii) croplands (under agricultural practices for more than 50-60 years) and (iii) converted lands (converted from forests to croplands or tea gardens over the past 15-20 years). Different soil quality indicators were assessed and soil quality index (SQI) was generated to integrate, scale and allot a single value per soil. Results indicated that continuous organic matter deposition and no disturbances consequence the highest presence of soil carbon pools, greater aggregation and maximum microbial dynamics in forest soils whereas high application of straight fertilizers caused the highest available nitrogen and phosphorus in cropland soils. The SQI scorebook indicated the best soil quality under forests (xMACRON 0.532), followed by soils of converted land (xMACRON 0.432) and cropland (xMACRON 0.301). Comparison of the SQI spatial distribution with land use and land cover confirmed the outcome. Possibly practices like excessive tillage, high cropping intensity, no legume in crop rotations, cultivation of heavy feeder crops caused degraded soil quality in croplands. This study presented an example of soil quality degradation in India due to land use change and faulty management practices. Such soil degradation on a larger scale may affect future food security.
Background and Aim
Plasma‐exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional ...Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients.
Methods
Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE.
Results
ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); PE (n = 131), FPSA (n = 31) or were continued on standard medical therapy (SMT) (n = 1704). In the PRS‐matched cohort (n = 208, ALS‐119; PE‐94, FPSA‐25), SMT‐89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42‐24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5‐11.1), and lower liver‐failure‐related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage‐associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti‐inflammatory cytokine interleukin‐1 receptor antagonist (IL‐1RA) compared to non‐responders. PE was associated with lesser adverse effects as compared to FPSA.
Conclusions
PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma‐exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.
The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association ...between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.
The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage ...liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.
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