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1.
Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues.
Montagnese, S, Bajaj, JS
Drugs. 2019;(Suppl 1):11-16
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Abstract
Hepatic encephalopathy (HE) has a major impact on health-related quality of life (HRQOL) in patients, which has clinical and psychosocial consequences. HRQOL in cirrhosis has been measured by generic and liver-specific instruments, with most studies indicating a negative impact of HE. HRQOL abnormalities span daily functioning, sleep-wake cycle changes, and the ability to work. Of these, sleep-wake cycle changes have a major effect on HRQOL, which remains challenging to treat. The personal effect of HRQOL is modulated by the presence of HE, the etiology of cirrhosis, and cognitive reserve. Patients with higher cognitive reserve are able to tolerate HE and its impact on HRQOL better than those with a poor cognitive reserve. The impact of HRQOL impairment is felt by patients (higher mortality and poor daily functioning), as well as by caregivers and families. Caregivers of patients with HE bear a major financial and psychological burden, which may affect their personal health and longevity.
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Soluble α-Klotho in Liver Cirrhosis and Alcoholism.
Martín-González, C, González-Reimers, E, Quintero-Platt, G, Martínez-Riera, A, Santolaria-Fernández, F
Alcohol and alcoholism (Oxford, Oxfordshire). 2019;(3):204-208
Abstract
AIMS AND BACKGROUND Alpha Klotho is a transmembrane protein that serves as co-receptor for FGF23. Ectodomain of membrane bound α Klotho may be shed by membrane bound proteases (activated, among other factors, by tumor necrosis factor (TNF)-α) generating the soluble form of the protein (sKl) that functions as a hormone by itself. It modulates calcium influx into cells, blunts IGF-1/Insulin signaling, promotes synthesis of antioxidants, generally slows down tumor progression, delays cell senescence, is neuroprotective and promotes oligodendrocyte maturation and myelin synthesis, and muscle rejuvenation. It may be involved in inflammation and exerts antifibrogenic effects. Some of these pathways may become altered in alcoholism or liver cirrhosis, but data are scattered and scarce and an update is required. METHOD Literature survey. RESULTS AND CONCLUSIONS Alcohol consumption in non-alcoholics is inversely related to sKl, but alcoholic cirrhotics showed higher-than-normal sKl values in association with liver function derangement. In hepatoma cells, the intensity of Klotho staining was related to faster tumor progression and a shortened life span. Among severe alcoholic cirrhotics sKl is directly related to serum TNF-α levels, and, inversely, to brain atrophy. Given the antioxidant, anti-inflammatory, and antifibrogenic effects of Klotho, perhaps the increase in cirrhosis (and in other inflammatory conditions, such as sepsis or cancer) reflects an attempt to regulate increased inflammation, but clinical and experimental research is urgently needed in this field.
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Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis.
Khomich, O, Ivanov, AV, Bartosch, B
Cells. 2019;(1)
Abstract
Liver fibrosis is a regenerative process that occurs after injury. It is characterized by the deposition of connective tissue by specialized fibroblasts and concomitant proliferative responses. Chronic damage that stimulates fibrogenic processes in the long-term may result in the deposition of excess matrix tissue and impairment of liver functions. End-stage fibrosis is referred to as cirrhosis and predisposes strongly to the loss of liver functions (decompensation) and hepatocellular carcinoma. Liver fibrosis is a pathology common to a number of different chronic liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease, and viral hepatitis. The predominant cell type responsible for fibrogenesis is hepatic stellate cells (HSCs). In response to inflammatory stimuli or hepatocyte death, HSCs undergo trans-differentiation to myofibroblast-like cells. Recent evidence shows that metabolic alterations in HSCs are important for the trans-differentiation process and thus offer new possibilities for therapeutic interventions. The aim of this review is to summarize current knowledge of the metabolic changes that occur during HSC activation with a particular focus on the retinol and lipid metabolism, the central carbon metabolism, and associated redox or stress-related signaling pathways.
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Exercise prescription in patients with cirrhosis: Recommendations for clinical practice.
Macías-Rodríguez, RU, Ruiz-Margáin, A, Román-Calleja, BM, Moreno-Tavarez, E, Weber-Sangri, L, González-Arellano, MF, Fernández-Del-Rivero, G, Ramírez-Soto, K
Revista de gastroenterologia de Mexico (English). 2019;(3):326-343
Abstract
Exercise in cirrhosis of the liver is an emerging topic in hepatology. Despite the known benefits of exercise in the general population, there are currently few studies addressing that issue in relation to cirrhosis and more evidence is still needed. Even though some studies have reported an acute, exercise-induced increase in the hepatic venous pressure gradient (HVPG), the opposite (a decrease in the HVPG) has been shown by recent data after an exercise program carried out for>14 weeks. In addition to that benefit, improvement has been described in the metabolic profile, quality of life, muscle mass, cardiopulmonary function, and nutritional status. Together, those features make exercise in cirrhosis a very attractive intervention. However, certain aspects must be taken into account before prescribing exercise in that population and they include cardiovascular risk, musculoskeletal disorders, and complications related to cirrhosis. After considering those factors, an individually tailored exercise program should be developed for each patient, according to the points stated above and the desired goal. Information about exercise-limiting factors, type of exercise prescribed, monitoring methods, and concomitant nutritional therapy is provided in the present review.
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Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis.
Bajaj, JS, Fagan, A, Gavis, EA, Kassam, Z, Sikaroodi, M, Gillevet, PM
Gastroenterology. 2019;(6):1921-1923.e3
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Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study.
Carrat, F, Fontaine, H, Dorival, C, Simony, M, Diallo, A, Hezode, C, De Ledinghen, V, Larrey, D, Haour, G, Bronowicki, JP, et al
Lancet (London, England). 2019;(10179):1453-1464
Abstract
BACKGROUND Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort. METHODS We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458. FINDINGS Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27). INTERPRETATION Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection. FUNDING INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
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Outcomes of Bariatric Surgery in Patients with Cirrhosis.
Miñambres, I, Rubio, MA, de Hollanda, A, Breton, I, Vilarrasa, N, Pellitero, S, Bueno, M, Lecube, A, Marcuello, C, Goday, A, et al
Obesity surgery. 2019;(2):585-592
Abstract
CONTEXT Information concerning the risk-benefit profile of bariatric surgery in subjects with liver cirrhosis is scarce. Our aim was to describe the long-term outcomes of bariatric surgery in a cohort of patients with liver cirrhosis submitted to bariatric surgery. METHODS This was a multicenter, retrospective observational study performed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), with a review of patients with cirrhosis who had undergone bariatric surgery during the period from April 2004 to March 2017 in ten public reference hospitals in Spain. RESULTS Data on 41 patients with cirrhosis submitted to obesity surgery were collected (mean age 53.8 ± 7.9 years, 46.3% women, presurgical BMI 45 ± 8.3 kg/m2). All but one patient belonged to Child-Pugh class A, and sleeve gastrectomy was conducted in 68.3% of cases. Percentage of total weight loss (%TWL) was 26.33 ± 8.3% and 21.16 ± 15.32% at 1 and 5 years after surgery, respectively. This was accompanied by a significant reduction of type 2 diabetes, high blood pressure, and dyslipidemia and by an improvement of liver enzymes over time. Model for End-Stage Liver Disease (MELD) index increased from 7.2 ± 1.9 to 9.8 ± 4.6 after 5 years. Seven patients (17%) developed early postsurgical complications. No postsurgical mortality was observed. During follow-up, only five patients developed liver decompensation. CONCLUSIONS Bariatric surgery in selected patients with liver cirrhosis has metabolic benefits that could have a positive impact on liver prognosis. TRIAL REGISTRATION Controlledtrials.com Identifier: 10.1186/ISRCTN15009106.
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Refractory Ascites in Liver Cirrhosis.
Adebayo, D, Neong, SF, Wong, F
The American journal of gastroenterology. 2019;(1):40-47
Abstract
Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
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Controversies in Diagnosing Sarcopenia in Cirrhosis-Moving from Research to Clinical Practice.
Sinclair, M
Nutrients. 2019;(10)
Abstract
Sarcopenia, defined as loss of muscle mass and function, is increasingly recognized as a common consequence of advanced cirrhosis that is associated with adverse clinical outcomes. Despite the recent proliferation in publications pertaining to sarcopenia in end-stage liver disease, there remains no single 'best method' for its diagnosis. The inability to identify a gold standard is common to other specialties, including geriatrics from which many diagnostic tools are derived. Controversies in diagnosis have implications for the accuracy and reproducibility of cohort studies in the field, largely prohibit the introduction of sarcopenia measurement into routine patient care and impede the development of clinical trials to identify appropriate therapies. Difficulties in diagnosis are partly driven by our ongoing limited understanding of the pathophysiology of sarcopenia in cirrhosis, the mechanisms by which it impacts on patient outcomes, the heterogeneity of patient populations, and the accuracy, availability and cost of assessments of muscle mass and function. This review discusses the currently studied diagnostic methods for sarcopenia in cirrhosis, and outlines why reaching a consensus on sarcopenia diagnosis is important and suggests potential ways to improve diagnostic criteria to allow us to translate sarcopenia research into improvements in clinical care.
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10.
Reduced Serum Sphingolipids Constitute a Molecular Signature of Malnutrition in Hospitalized Patients With Decompensated Cirrhosis.
Rachakonda, V, Argemi, J, Borhani, AA, Bataller, R, Tevar, A, Behari, J
Clinical and translational gastroenterology. 2019;(3):e00013
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Abstract
INTRODUCTION Malnutrition is a leading cause of morbidity and mortality in cirrhosis. Although multiple noninvasive measures of nutritional status have been studied, no consensus exists for early identification of malnutrition in cirrhosis. Serum metabolomics offers a novel approach for identifying biomarkers in multiple disease states. To characterize alterations in metabolic pathways associated with malnutrition in hospitalized cirrhotic patients and to identify biomarkers for disease prognosis. METHODS In this cross-sectional, observational cohort study, 51 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on low mid-arm muscle circumference and dominant handgrip strength. Anthropometric measurements and computed tomography body composition analysis were performed. Serum was collected after overnight fasting for unbiased metabolomics analysis. RESULTS Malnourished cirrhotic patients exhibited mild reductions in skeletal muscle index, with more marked reductions in visceral fat index. Seventy-one biochemicals were significantly altered in malnourished subjects. The serum metabolite profile was significantly different between nourished and malnourished cirrhotic patients. Pathway analysis demonstrated that only sphingolipid metabolic pathways were significantly enriched in altered metabolites. Hierarchical clustering revealed that sphingolipid metabolites clustered into nourished and malnourished cohorts. Spearman analysis demonstrated multiple statistically significant correlations between sphingolipid species and Model for End-Stage Liver Disease-Sodium. Using logistic regression, we identified 8 sphingolipids that were significantly associated with malnutrition after controlling for Model for End-Stage Liver Disease-Sodium, age, and gender. CONCLUSIONS Malnutrition in hospitalized cirrhotic patients is characterized by reductions in multiple sphingolipid species. Dysregulated sphingolipid metabolism may be involved in the pathophysiology of malnutrition in cirrhosis and potentially serve as a biomarker of nutritional status in this population.