Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic ...viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.
Acute kidney injury (AKI) is one of the most common and morbid complications of decompensated cirrhosis. Management of AKI is dictated by cause: prerenal AKI is treated with volume resuscitation; ...hepatorenal syndrome (HRS), with intravenous albumin and vasoconstrictors; and acute tubular necrosis, with supportive care. However, differentiating between causes is difficult using creatinine-based definitions of AKI alone. The use of novel kidney biomarkers in AKI and cirrhosis provides an opportunity to improve both the diagnosis and prognosis of this vulnerable population. This review examines the challenges of AKI in cirrhosis and the research experience around novel kidney biomarkers in cirrhosis. Specific focus is paid to the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL), which has been the most studied in liver disease and has demonstrated the strongest performance in differentiating the cause of AKI (acute tubular necrosis vs functional injury such as prerenal AKI or HRS), as well as improving the prognostic performance of mortality prediction models such as the model for end stage liver disease (MELD) score. We advocate for the discussion of incorporating markers such as NGAL in the next iteration of HRS guidelines and identify areas for future research in this clinical condition.
Ascites is the most frequent complication of patients with cirrhosis. Ascites is related to increased renal sodium retention as a result of increased activity of the renin–angiotensin–aldosterone ...system in response to marked vasodilation of the splanchnic circulation. Management of uncomplicated ascites is based on a low‐sodium diet and diuretics. However, approximately 10% of patients develop refractory ascites during follow‐up, which is associated with a poor prognosis. The treatment of choice in patients with refractory ascites is large‐volume paracentesis associated with intravenous albumin. Moreover, patients who develop refractory ascites should be considered as candidates for liver transplantation. Patients with ascites are all at risk of developing spontaneous bacterial peritonitis (SBP). SBP is a common infection in patients with cirrhosis with a risk of mortality of 20%. Empirical antibiotics are the treatment of choice in patients with SBP but differ depending on the acquisition site of infection, because nosocomial infections have a higher risk of being caused by multiresistant bacteria. In addition to antibiotic treatment, all patients with SBP should also receive intravenous albumin. This review summarizes the management of uninfected ascites and SBP in cirrhosis.
Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is ...energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF.
We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy individuals.
Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 comprised a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher the plasma levels of inflammatory markers, tumor necrosis factor α, soluble CD206, and soluble CD163. ACLF was characterized by intense proteolysis and lipolysis; amino acid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid β-oxidation; and extra-mitochondrial amino acid metabolism giving rise to metabotoxins.
In ACLF, intense systemic inflammation is associated with blood metabolite accumulation and profound alterations in major metabolic pathways, in particular inhibition of mitochondrial energy production, which may contribute to the development of organ failures.
Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. We identified a 38-metabolite blood fingerprint specific for ACLF that revealed mitochondrial dysfunction in peripheral organs. This may contribute to organ failures.
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•Metabolomics performed in sera of a large series of patients with acute decompensation (AD) of cirrhosis, with/without ACLF.•Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF relative to those with AD.•38 metabolites comprised a distinctive ACLF fingerprint, whose intensity correlated with systemic inflammation.•The ACLF fingerprint represented increases in glycolysis and related pathways.•Fingerprint indicated reduced mitochondrial ATP-producing fatty acid β-oxidation which may contribute to organ failure(s).
Primary care is the ideal setting for early identification of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a potentially progressive disease that may lead to cirrhosis and liver ...cancer but is frequently underrecognized because subjects at risk are often not evaluated. Controlled attenuation parameter (CAP) is a reliable method for non-invasive quantification of liver fat. It has the advantage of simultaneous measurement of liver stiffness (LS), an estimate of liver fibrosis. There is no information on CAP in subjects with risk factors from primary care.
To investigate the prevalence of hepatic steatosis, as estimated by CAP, in subjects from the community with metabolic risk factors and correlate findings with clinical and biochemical characteristics and LS.
Population-based study of 215 subjects with metabolic risk factors without known liver disease identified randomly from a primary care center. A control group of 80 subjects matched by age and sex without metabolic risk factors was also studied. CAP and LS were assessed using Fibroscan.
Subjects with risk factors had CAP values higher than those of control group (268±64 vs 243±49dB/m,p<0.001). Prevalence of severe steatosis (CAP> 280dB/m) in subjects with risk factors was 43%. In multivariate analysis, fatty liver index (FLI) and HOMA were independent predictive factors of severe steatosis. There was a direct correlation between CAP and FLI values (r = 0.52,p<0.001). Interestingly, prevalence of increased LS was 12.6% in the risk group vs 0% in the control group (p<0.001). Increased LS occurred predominantly in subjects with high CAP values.
A high proportion of subjects with metabolic risk factors seen in primary care have severe steatosis. FLI could be used as a surrogate of CAP. Increased LS was found in a significant proportion of subjects with risk factors but not in control subjects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Liver cirrhosis Ginès, Pere; Krag, Aleksander; Abraldes, Juan G ...
The Lancet (British edition),
10/2021, Letnik:
398, Številka:
10308
Journal Article
Recenzirano
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, ...autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the ...world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.
We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses.
We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates.
The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.
Impairment of kidney function is common in acute‐on‐chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill‐defined. Aims of the current ...study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI‐on‐CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p < 0.001 vs. ACLF). Frequency of CKD alone was low and similar in both groups (4% and 3%, respectively); only a few patients with ACLF (4%) had no kidney dysfunction. AKI in ACLF was associated with poor kidney and patient outcomes compared with no ACLF (AKI resolution: 54% vs. 89%; 3‐month survival: 51% vs. 86%, respectively; p < 0.001 for both). Independent predictive factors of 3‐month survival were Model for End‐Stage Liver Disease–Sodium score, ACLF status, and urine neutrophil gelatinase–associated lipocalin (NGAL). AKI is almost universal in patients with ACLF, sometimes associated with CKD, whereas CKD alone is uncommon. Prognosis of AKI depends on ACLF status. AKI without ACLF has good prognosis. Best predictors of 3‐month survival are MELD‐Na, ACLF status, and urine NGAL.
Impairment of kidney function is common in acute‐on‐chronic liver failure (ACLF) but patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill‐defined. Aims of current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. The results of this study show that AKI (acute kidney injury) is almost universal in patients with ACLF, sometimes associated with CKD, while CKD alone is uncommon and that prognosis of AKI depends on ACLF status.
Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4
T cells in the blood and intestines of patients with celiac disease display a ...surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4
T cells specific for disease-driving antigens in multiple autoimmune conditions.
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