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1.
Assessment of Malnutrition, Sarcopenia and Frailty in Patients with Cirrhosis: Which Tools Should We Use in Clinical Practice?
Buchard, B, Boirie, Y, Cassagnes, L, Lamblin, G, Coilly, A, Abergel, A
Nutrients. 2020;(1)
Abstract
Malnutrition is a common comorbidity in patients with cirrhosis. Its prognostic value is indisputable as it greatly affects the evolution of liver diseases. It has a major impact on both morbi-mortality before and after liver transplantation. Being now integrated in the definition of malnutrition and recognized as a new entity in the international classification of diseases, physicians have taken great interest in sarcopenia. Its negative consequences on the fate of patients with cirrhosis are well-demonstrated. The concept of frailty has recently been enlarged to chronic liver diseases as symptoms of impaired global physical functioning. In this article, we will discuss the definitions of malnutrition and emphasize its links with sarcopenia and frailty. We will show the relevance of frailty and sarcopenia in the course of liver diseases. The emerging role of muscle depletion on the cardiorespiratory system will also be highlighted. The importance of body composition will be demonstrated and the main tools reviewed. Finally, we adapted the definition of malnutrition to patients with cirrhosis based on the assessment of sarcopenia together with reduced food intakes.
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2.
Natural History of Nonalcoholic Fatty Liver Disease: Implications for Clinical Practice and an Individualized Approach.
Grgurevic, I, Podrug, K, Mikolasevic, I, Kukla, M, Madir, A, Tsochatzis, EA
Canadian journal of gastroenterology & hepatology. 2020;:9181368
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide, associated with epidemics of overweight and resulting metabolic syndrome (MetS). Around 20-30% of patients with NAFLD develop progressive liver fibrosis, which is the most important predictor of liver-related and overall morbidity and mortality. In contrast to classical understanding, no significant association has been demonstrated between the inflammatory component of NAFLD, i.e., nonalcoholic steatohepatitis (NASH), and the adverse clinical outcomes. Older age (>50 years) and presence of type 2 diabetes mellitus, in addition to some genetic variants, are most consistently reported indicators of increased risk of having liver fibrosis. However, critical driving force for the progression of fibrosis and risk factors for this have still not been fully elucidated. Apart from the genetic profile, gut dysbiosis, weight gain, worsening of insulin resistance, and worsening of liver steatosis represent candidate factors associated with unfavourable development of liver disease. Cardiovascular events, extrahepatic malignancies, and liver-related deaths are the leading causes of mortality in NAFLD. As patients with advanced fibrosis are under highest risk of adverse clinical outcomes, efforts should be made to recognize individuals under risk and rule out the presence of this stage of fibrosis, preferably by using simple noninvasive tools. This process should start at the primary care level by using validated biochemical tests, followed by direct serum tests for fibrosis or elastography in the remaining patients. Patients with advanced fibrosis should be referred to hepatologists for aggressive lifestyle modification and correction of the components of MetS, and cirrhotic patients should be screened for hepatocellular carcinoma and oesophageal varices.
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3.
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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4.
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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5.
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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6.
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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7.
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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8.
To salt or not to salt?-That is the question in cirrhosis.
Haberl, J, Zollner, G, Fickert, P, Stadlbauer, V
Liver international : official journal of the International Association for the Study of the Liver. 2018;(7):1148-1159
Abstract
Ascites is the most common complication of patients with cirrhosis, resulting from portal hypertension and vasodilatation. It is associated with an increased risk for the development of hyponatraemia and renal failure and has a high mortality rate of 20% per year. The development of ascites represents a baleful sign in the course of disease in cirrhosis. To prevent complications of cirrhosis and improve quality of life, an effective management of ascites is pivotal. Combined salt restriction and diuretic therapy is recommended as first-line therapy in numerous clinical practice guidelines. In contrast, there has been a debate on whether a strict salt-restricted diet for cirrhosis patients should be used at all since salt restriction may increase the risk for malnutrition which in turn may negatively impact on quality of life and survival. This review aims to summarize the current pros and cons regarding salt restriction in patients with cirrhosis and proposes the importance of achieving a sodium balance throughout different stages of cirrhosis.
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9.
Non-Alcoholic Fatty Liver Disease in Patients with HIV Infection.
Papagianni, M, Tziomalos, K
AIDS reviews. 2018;(3):171-173
Abstract
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with HIV infection and appears to be more severe than in HIV-uninfected patients. Both metabolic (e.g., obesity and insulin resistance) and HIV-related factors (e.g., antiretroviral treatment and inflammation) play a role in the pathogenesis of NAFLD in this population. Accordingly, all patients with HIV infection should be evaluated for the presence of NAFLD. Ultrasound is the first-line diagnostic procedure, but non-alcoholic steatohepatitis has to be diagnosed with liver biopsy. However, non-invasive methods, including serological markers and transient elastography, might also be useful in this population. Lifestyle changes represent the cornerstone of treatment. Bariatric surgery, pioglitazone, and vitamin E can be considered in patients with significant fibrosis or at high risk for progression of NAFLD, including those with type 2 diabetes mellitus, metabolic syndrome, elevated transaminases, or pronounced necroinflammation. However, there are no studies that evaluated the safety of efficacy of diet, exercise, or pharmacotherapy in this population. Therefore, research is needed to identify safe and effective pharmacological treatments for NAFLD in patients with HIV infection.
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10.
Management of ascites and hepatorenal syndrome.
Piano, S, Tonon, M, Angeli, P
Hepatology international. 2018;(Suppl 1):122-134
Abstract
Ascites represents the most common decompensating event in patients with liver cirrhosis. The appearance of ascites is strongly related to portal hypertension, which leads to splanchnic arterial vasodilation, reduction of the effective circulating volume, activation of endogenous vasoconstrictor systems, and avid sodium and water retention in the kidneys. Bacterial translocation further worsens hemodynamic alterations of patients with cirrhosis and ascites. The first-line treatment of uncomplicated ascites is a moderate sodium-restricted diet combined with diuretic treatment. In patients who develop refractory ascites, paracentesis plus albumin represents the most feasible option. Transjugular intrahepatic portosystemic shunt placement is a good alternative for selected patients. Other treatments such as vasoconstrictors and automated low-flow pumps are two potential options still under investigations. Ascites is associated with a high risk of developing further complications of cirrhosis such as dilutional hyponatremia, spontaneous bacterial peritonitis and/or other bacterial infections and acute kidney injury (AKI). Hepatorenal syndrome (HRS) is the most life-threatening type of AKI in patients with cirrhosis. The most appropriate medical treatment in patients with AKI-HRS is the administration of vasoconstrictors plus albumin. Finally, ascites impairs both the quality of life and survival in patients with cirrhosis. Thus, all patients with ascites should be evaluated for the eligibility for liver transplantation. The aim of this article is to review the management of patients with cirrhosis, ascites and HRS.