Frailty has emerged as a powerful predictor of outcomes in patients with cirrhosis and has inevitably made its way into decision making within liver transplantation. In an effort to harmonize ...integration of the concept of frailty among transplant centers, the AST and ASTS supported the efforts of our working group to develop this statement from experts in the field. Frailty is a multidimensional construct that represents the end‐manifestation of derangements of multiple physiologic systems leading to decreased physiologic reserve and increased vulnerability to health stressors. In hepatology/liver transplantation, investigation of frailty has largely focused on physical frailty, which subsumes the concepts of functional performance, functional capacity, and disability. There was consensus that every liver transplant candidate should be assessed at baseline and longitudinally using a standardized frailty tool, which should guide the intensity and type of nutritional and physical therapy in individual liver transplant candidates. The working group agreed that frailty should not be used as the sole criterion for delisting a patient for liver transplantation, but rather should be considered one of many criteria when evaluating transplant candidacy and suitability. A road map to advance frailty in the clinical and research settings of liver transplantation is presented here.
This summary statement about frailty in liver transplantation addresses how to define and measure frailty, and how to incorporate frailty into the care of patients with end‐stage liver disease, including those awaiting liver transplantation.
Background & Aims Sarcopenia, defined as a low level of muscle mass, occurs in patients with cirrhosis. We assessed its incidence among cirrhotic patients undergoing evaluation for liver ...transplantation to investigate associations between sarcopenia and mortality and prognosis. Methods We studied 112 patients with cirrhosis (78 men; mean age, 54 ± 1 years) who were consecutively evaluated for liver transplantation and had a computed tomography scan at the level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle index; sarcopenia was defined by using previously published, sex-specific cutoffs. Results Of the patients studied, 45 (40%) had sarcopenia. Univariate Cox analysis associated mortality with ascites (hazard ratio HR, 2.12; P = .04), encephalopathy (HR, 1.99; P = .04), level of bilirubin (HR, 1.007; P < .01), international normalized ratio (HR, 7.69; P < .001), level of creatinine (HR, 1.01; P = .005), level of albumin (HR, 94; P = .008), serum level of sodium (HR, 89; P < .001), Model for End-Stage Liver Disease (MELD) score (HR, 1.14; P < .01), Child–Pugh score (HR, 2.84; P < .001), and sarcopenia (HR, 2.18; P = .006). By multivariate Cox analysis, only Child–Pugh (HR, 1.85; P = .04) and MELD scores (HR, 1.08; P = .001) and sarcopenia (HR, 2.21; P = .008) were independently associated with mortality. The median survival time for patients with sarcopenia was 19 ± 6 months, compared with 34 ± 11 months among nonsarcopenia patients ( P = .005). There was a low level of correlation between L3 skeletal muscle index and MELD ( r = −0.07; P = .5) and Child–Pugh scores ( r = −0.14; P = .1). Conclusions Sarcopenia is associated with mortality in patients with cirrhosis. It does not correlate with the degree of liver dysfunction evaluated by using conventional scoring systems. Scoring systems should include evaluation of sarcopenia to better assess mortality among patients with cirrhosis.
Background and aims
Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition ...of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.
Methods
We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender‐and body mass index‐specific cutoffs.
Results
Patients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non‐alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P < 0.001), sarcopenic obesity (22 ± 3 vs. 95 ± 22 months, P < 0.001), and myosteatosis (28 ± 5 vs. 95 ± 22 months, P < 0.001) had worse median survival than patients without muscular abnormalities. By multivariate Cox regression analysis, both sarcopenia hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.44–2.77, P < 0.001, and myosteatosis (HR 1.42, 95% CI 1.02–1.07, P = 0.04) were associated with mortality.
Conclusions
Sarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long‐term mortality in cirrhosis.
A review on the dietary flavonoid kaempferol Calderón-Montaño, J M; Burgos-Morón, E; Pérez-Guerrero, C ...
Mini reviews in medicinal chemistry,
04/2011, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific ...investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
Background and Aims
A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. We evaluated ...clinical features, treatment response and outcomes of liver injury following SARS‐CoV‐2 vaccination in a large case series.
Approach and Results
We collected data from cases in 18 countries. The type of liver injury was assessed with the R‐value. The study population was categorized according to features of immune‐mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty‐one cases (59%) were attributed to the Pfizer‐BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford‐AstraZeneca (ChAdOX1 nCoV‐19) vaccine and 16 (18%) cases to the Moderna (mRNA‐1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune‐mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune‐mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow‐up.
Conclusions
SARS‐CoV‐2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune‐mediated features or severe hepatitis. Outcome was generally favorable, but vaccine‐associated liver injury led to fulminant liver failure in one patient.
SARS‐COV‐2 vaccination and liver injury.
Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical ...practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment.
A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis.
The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘<50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’.
These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints.
Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting.
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•Consensus among experts on response criteria in autoimmune hepatitis is lacking.•A consensus on endpoints is required to set a standard for reporting study results.•Herein, the IAIHG presents a statement on 5 agreed response criteria and endpoints.
Performance artist Linda Montano, curious about the influence childhood experience has on adult work, invited other performance artists to consider how early events associated with sex, food, ...money/fame, or death/ritual resurfaced in their later work. The result is an original and compelling talking performance that documents the production of art in an important and often misunderstood community.
Among the more than 100 artists Montano interviewed from 1979 to 1989 were John Cage, Suzanne Lacy, Faith Ringgold, Dick Higgins, Annie Sprinkle, Allan Kaprow, Meredith Monk, Eric Bogosian, Adrian Piper, Karen Finley, and Kim Jones. Her discussions with them focused on the relationship between art and life, history and memory, the individual and society, and the potential for individual and social change. The interviews highlight complex issues in performance art, including the role of identity in performer-audience relationships and art as an exploration of everyday conventions rather than a demonstration of virtuosity.
We report on the role of hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) as an inhibitor of metastasis. HEXIM1 expression is decreased in human metastatic breast cancers when compared with ...matched primary breast tumors. Similarly we observed decreased expression of HEXIM1 in lung metastasis when compared with primary mammary tumors in a mouse model of metastatic breast cancer, the polyoma middle T antigen (PyMT) transgenic mouse. Re-expression of HEXIM1 (through transgene expression or localized delivery of a small molecule inducer of HEXIM1 expression, hexamethylene-bis-acetamide) in PyMT mice resulted in inhibition of metastasis to the lung. Our present studies indicate that HEXIM1 downregulation of HIF(-)1α protein allows not only for inhibition of vascular endothelial growth factor-regulated angiogenesis, but also for inhibition of compensatory pro-angiogenic pathways and recruitment of bone marrow-derived cells (BMDCs). Another novel finding is that HEXIM1 inhibits cell migration and invasion that can be partly attributed to decreased membrane localization of the 67 kDa laminin receptor, 67LR, and inhibition of the functional interaction of 67LR with laminin. Thus, HEXIM1 re-expression in breast cancer has therapeutic advantages by simultaneously targeting more than one pathway involved in angiogenesis and metastasis. Our results also support the potential for HEXIM1 to indirectly act on multiple cell types to suppress metastatic cancer.
Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control ...disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.
We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC.
There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal.
Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
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