The Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Comparison with current models and CLIF-SOFA score

Prognosis for patients with cirrhosis admitted to intensive care unit (ICU) is poor. ICU prognostic models are more accurate than liver-specific models. We identified predictors of mortality, developed a novel prognostic score (Royal Free Hospital (RFH) score), and tested it against established prognostic models and the yet unvalidated Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) model

Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The rfh cirrhosis Gfr

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis leading to significant differences between "true" and calculated glomerular filtration rate (GFR). We compared the performance of MDRD-4, MDRD-6 and CKD-EPI with "true" GFR and the impact of this difference on MELD calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulas. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. "True" GFR (mGFR) was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the MDRD formula. Subsequently, a corrected MELD was calculated and was compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the measured GFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis respectively. A difference>20 ml/min/1.73m(2) between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation derived (R(2) =74·6%) was: GFR=45·9x(creatinine(-0) ·(836) )x(urea(-0) ·(229) )x(INR(-0) ·(113) )x(age(0) ·(129) )x(sodium(0) ·(972) )x1·236(if male)x0·92(if moderate/severe ascites). The model was a good fit and showed the greatest accuracy compared to that of existing formulae. CONCLUSION: We developed and validated a new accurate model for GFR assessment in cirrhosis, the RFH cirrhosis GFR, using readily available variables. This remains to be tested and incorporated in prognostic scores in patients with cirrhosis

Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis

BACKGROUND: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.METHODS: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).RESULTS: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p &lt; 0.001) and higher in patients with SOFA &gt; 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p &lt; 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p &lt; 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p &lt; 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p &lt; 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p &lt; 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p &lt; 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p &lt; 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p &lt; 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p &lt; 0.001; PPV = 0.57), baseline MELD &gt; 26 (OR 3.97; 95% CI 1.92-8.22; p &lt; 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88).CONCLUSIONS: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.</p

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Sex‐Based Disparities in Liver Transplant Rates in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87057/1/j.1600-6143.2011.03498.x.pd

Evolving role of semaglutide in NAFLD: in combination, weekly and oral administration

Non alcoholic fatty disease (NAFLD) is the most common chronic liver disease that is managed in the liver departments. It seems that the prevalence of the disease is rising worldwide and as it has the same pathogenetic pathways with metabolic syndrome, treatments that target components of the metabolic syndrome seem promising for the therapy of NAFLD as well. In this review we discuss the evolving role of semaglutide, which is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that has been already approved for the treatment of type II diabetes mellitus (T2DM) and obesity

Sarcopenia As a Predictor of Survival and Complications of Patients With Cirrhosis After Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review/meta-analysis evaluated the impact of sarcopenia in patients with cirrhosis before liver transplantation (LT) on outcomes after LT. METHODS: A systematic search was conducted in six medical databases until February 2022. The primary outcome was overall mortality after LT, while several secondary outcomes including liver graft survival and rejection, the need for transfusions, the length of the intensive care unit (ICU) and hospital stay, and surgical complications were evaluated. Sub-group analyses and meta-regression analyses were also performed. RESULTS: Fifty-three studies were evaluated in the systematic review, of which 30, including 5875 patients, were included in the meta-analysis. All studies included were cohort studies of good/high quality on the Newcastle-Ottawa scale (NOS), while in our analysis no publication bias was found, although there was substantial heterogeneity between the studies. Muscle mass was assessed using skeletal muscle index (SMI) in 14 studies, psoas muscle area (PMA) in seven studies, and psoas muscle index (PMI) in four studies. The prevalence of pre-LT sarcopenia ranged from 14.7% to 88.3%. Pre-LT sarcopenia was significantly associated with post-LT mortality (Relative Risk [RR] = 1.84, 95% CI:1.41,2.39), as well as with a high risk of infections post-LT, surgical complications, fresh frozen plasma (FFP) transfusions, and ICU length of stay (LOS). CONCLUSIONS: Pre-LT sarcopenia in patients with cirrhosis is a strong risk factor for clinically meaningful adverse outcomes after LT. Assessment may help identify patients at the highest risk for poor outcomes who may benefit from targeted interventions