Model for End-Stage Liver Disease score predicts mortality in critically ill cirrhotic patients

Purpose

Cirrhosis is a common condition that complicates the management of patients who require critical care. There is interest in identifying scoring systems that may be used to predict outcome because of the poor odds for recovery despite high-intensity care. We sought to evaluate how Model for End-Stage Liver Disease (MELD), an organ-specific scoring system, compares with other severity of illness scoring systems in predicting short- and long-term mortality for critically ill cirrhotic patients.

Materials and methods

This was a retrospective cohort study involving seven intensive care units (ICUs) in a tertiary care, academic medical center. Adult patients with cirrhosis who were admitted to an ICU between 2001 and 2008 were evaluated. Severity of illness scores (MELD and Sequential Organ Failure Assessment [SOFA]) were calculated on admission and at 24 and 48 hours. The primary end points were 28-day and 1-year all-cause mortality.

Results

Of 19 742 ICU hospitalizations, 848 had cirrhosis. Relevant data were available for 521 patients (73%). Of these cases, 353 patients (69.5%) were admitted to medical ICU (MICU), and the other 155 (30.5%), to surgical unit. Alcohol abuse and hepatitis C were the most common reasons for cirrhosis. Patients who died within 28 days were more likely to receive mechanical ventilation, pressors, and renal replacement therapy. Among 353 medical admissions, both MELD and SOFA were found to be significantly associated with both 28-day and 1-year mortality. Among the 155 surgical admissions, both scores were found to be not significant for 28-day mortality but were significant for 1 year.

Conclusions

Our results demonstrate that the prognostic ability of a variety of scoring systems strongly depends on the patient population. In the MICU population, each model (MELD + SOFA, MELD, and SOFA) demonstrates excellent discrimination for 28-day and 1-year mortality. However, these scoring systems did not predict 28-day mortality in the surgical ICU group but were significant for 1-year mortality. This suggests that patients admitted to a surgical ICU will behave similarly to their MICU cohort if they survive the perioperative period.     

Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria

Liver transplantation (LT) for hepatocellular carcinoma is still a hot topic, and the main factor that is associated with the success of treatment is to determine the patients who will benefit from LT. Milan criteria have been defined 25 years ago and still is being used for patient selection for LT. However, in living donor LT, the Milan criteria is being extended. Current criteria for patient selection do not only consider morphologic characteristics such as tumor size and number of tumor nodules but also biologic markers that show tumor aggressiveness is also being considered. In the present review article, we have summarized all the criteria and scoring systems regarding LT for hepatocellular carcinoma. All criteria have 5-year overall survival rates that were comparable to the Milan Criteria and ranged between 60%-85%. On the other hand, it was seen that the recurrence rates had increased as the Milan criteria were exceeded; the 5-year recurrence rates ranged between 4.9% to 39.9%. Treatment of hepatocellular carcinoma needs a multidisciplinary approach. Ideal selection criteria are yet to be discovered. The same is true for treatment modalities. The goal will be achieved by a harmonic interplay between basic science researchers and clinicians.     

Aetiology of cirrhosis of the liver has an impact on survival predicted by the Model of End-stage Liver Disease score

Background Originally, aetiology of liver disease has been incorporated into the computation of the Model of End‐stage Liver Disease (MELD) score. Clinical observations prompted us to hypothesize that patients with viral and alcoholic cirrhosis may differ in predicted survival rates. Until now, no large representative studies evaluated the impact of aetiology on long‐term survival predicted by the Child–Pugh and MELD scores. Materials and methods Four hundred and ninety‐three patients who underwent transjugular intrahepatic portosystemic shunt implantation in Vienna, Austria, and Palermo, Italy, were included in this retrospective study. The main analyses were a logistic regression model and a Cox proportional hazards regression model calculating the interaction of the aetiology with the scores. Results Both groups had similar survival rates (median 1377 and 1721 days for viral and alcoholic cirrhosis, respectively; P = 0.58), but patients with viral cirrhosis had significantly lower MELD scores (P = 0.002). In the Cox analysis, aetiology had a significant impact on the prediction of overall survival by MELD score. For 3‐month survival, MELD score was adequately predictive for both groups. For 1‐year survival, aetiology had a significant impact on survival, indicating that patients with identical scores but different aetiologies differed in survival rates. When stratifying patients into high‐ and low‐risk patients (MELD < 16 vs. MELD ≥ 16), aetiology of cirrhosis had no impact on the predictive value for low‐risk patients; high‐risk‐patients (MELD ≥ 16) with viral cirrhosis had significantly lower survival rates than patients with alcoholic cirrhosis and identical scores. With regard to Child–Pugh Score, no significant differences between the two patient groups and in the prediction of 3‐month and 1‐year survival could be observed. Conclusions Our study suggests that aetiology of cirrhosis has an impact on 1‐year survival predicted by the MELD score. This becomes more apparent in patients with advanced stage of liver disease (MELD ≥ 16). Since MELD score is used for ranking patients for liver transplantation and waiting times are regularly longer than 3 months, our observations suggest that with increasing time on the waiting list and severity of disease, patients with viral cirrhosis may have a disadvantage in the current allocation policy.     

肝癌肝移植术前和术中癌细胞血行转移与肿瘤分化、微血管侵犯相关性研究

目的:探讨检测血播散肝癌细胞内AFP-mRNA评估肝癌肝移植术前和术中微转移与肿瘤分化、微血管侵犯的相关性。方法:采用RT-PCR联合荧光标记探针杂交法定量检测30例血清AFP阳性肝癌肝移植患者术前、术中血播散肝癌细胞内AFP-mRNA,病理分析肿瘤分化程度及微血管侵犯。结果:30例肝癌肝移植术前与术中肺动脉、外周动脉、外周静脉、门静脉血中播散肝癌细胞内AFP-mRNA阳性率以及拷贝数有显著差异(P<0.05);术前、中肿瘤播散组与无肿瘤播散组的微血管侵犯有显著差异(P<0.01);术前肿瘤播散组与术前无肿瘤播散组肿瘤分化无显著差异(P>0.05);术中肿瘤播散组与术中肿瘤无播散组肿瘤分化有显著差异(P<0.01)。结论:RT-PCR联合荧光标记探针杂交法能够检测到肝癌患者血液中播散肿瘤细胞,并且以肺动脉血阳性率最高;肝移植手术过程可以引起肿瘤细胞播散,且与肿瘤分化、微血管侵犯相关。     

Preoperative Controlling Nutritional Status plus Tumor Burden Score for the Assessment of Prognosis after Curative Liver Resection for Hepatocellular Carcinoma

ObjectiveThere are no previous studies analyzing the prognostic predictive value of adding the tumor factor (i.e., Tumor Burden (TB) score) to the Controlling Nutritional Status (CONUT) score for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the value of the CONUT plus TB (CONUT-TB) score as a prognostic predictor in patients with HCC undergoing liver resection.MethodsBetween 2015 and 2018, 96 consecutive patients with HCC underwent liver resection at our institution. Patients undergoing repeated liver resection and combined resection of a metastatic lesion were excluded. Patients were divided into 2 groups according to their CONUT-TB scores according to a cutoff value. Clinicopathologic prognostic factors for survival were analyzed using a database containing the medical records.ResultsThe optimal cutoff value of the CONUT-TB score determined by using a minimum p value approach was 13 points. Among the 81 patients included in the analytic cohort, 71 patients had low (<13) and 10 patients had high (>13) CONUT-TB scores. The overall 3-year survival rate of patients following liver resection for HCC in the high-CONUT-TB group was significantly worse than that of patients in the low-CONUT-TB group (62.5 vs. 89.3%, p = 0.003). Multivariate analysis indicated that a high CONUT-TB score was independently associated with overall survival after liver resection (p = 0.010).ConclusionThe CONUT-TB score is a valuable predictor of survival in patients with HCC after liver resection.     

Model for End-Stage Liver Disease Score Predicts Development of First Episode of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis

ObjectiveTo examine whether baseline model for end-stage liver disease (MELD) score in patients with cirrhosis and ascites predicts the future development of first spontaneous bacterial peritonitis (SBP) episode.MethodsA retrospective case-control study was performed at three academic centers to select patients admitted with first SBP episode (cases) and those with ascites admitted for decompensation without SBP (controls). Medical records from these centers were reviewed between January 1, 2008, and December 31, 2013. Cases and controls were matched (1:2) for age, sex, and race. Conditional logistic recession models were built to determine whether baseline MELD score (within a month before hospitalization) predicts first SBP episode.ResultsOf 697 patients (308, 230, and 159 from centers A, B, and C, respectively), cases and controls were matched in 94%, 89%, and 100% at three respective centers. In the pooled sample, probability of SBP was 11%, 31%, 71%, and 93% at baseline MELD scores less than or equal to 10, from 11 to 20, from 21 to 30, and greater than 30, respectively. Compared with MELD score less than or equal to 10, patients with MELD scores from 11 to 20, 21 to 30, and greater than 30 had six- (3- to 11-), 29- (12- to 69-), and 115- (22- to 598-) folds (95% CI) risk of SBP, respectively. Based on different MELD score cutoff points, MELD score greater than 17 was most accurate in predicting SBP occurrence. Analyzing 315 patients (152 cases) with available data on ascitic fluid protein level controlling for age, sex, and center, MELD score but not ascitic fluid protein associated with first SBP episode with respective odds ratios of 1.20 (1.14 to 1.26) and 0.88 (0.70 to 1.11).ConclusionBaseline MELD score predicts first SBP episode in patients with cirrhosis and ascites.     

Acoustic Radiation Force Impulse Elastography for Chronic Liver Disease: Comparison with Ultrasound-Based Scores of Experienced Radiologists,Child-Pugh Scores and Liver Function Tests

The purpose of our study was to investigate whether acoustic radiation force impulse (ARFI) elastography provides better diagnostic performance for diagnosis of chronic liver disease and correlates better with Child-Pugh scores and liver function tests, compared with an ultrasound (US) scoring system based on visual assessment of conventional B-mode US images by experienced radiologists. Five hundred and twenty-one patients with clinically proven chronic liver disease (n = 293), fatty liver (n = 95) or normal liver (n = 133) were included in this study. B-mode liver US and ARFI elastography were performed in all patients. ARFI elastography was performed at least five times, with each measurement obtained at a different area of the right hepatic lobe; mean shear wave velocity (SWV) was calculated for each patient. The mean SWV was compared with US-based scores from two radiologists (based on liver surface nodularity, parenchyma echotexture and hepatic vein contour), Child-Pugh scores and liver function tests. The mean SWV of the normal liver group was 1.08 m/s ± 0.15; of the fatty liver group, 1.02 m/s ± 0.16; and of the chronic liver disease group, 1.66 m/s ± 0.60 (p < 0.001). The area under the receiver operating characteristics curve of the mean SWV in ARFI elastography was significantly higher than that of the conventional B-mode US-based scores by two radiologists (0.89 vs. 0.74 and 0.77, p < 0.05), with a sensitivity of 75.4% and a specificity of 89.5% at the cut-off value of 1.22 m/s. The sensitivity of the mean SWV was significantly higher than the US-based scores (p < 0.001), although the specificity was not (p > 0.05). The mean SWV was better correlated with Child-Pugh scores and all liver function tests (except total protein) than the US-based scores from two radiologists. In conclusion, ARFI elastography showed better diagnostic performance than visual assessment of experienced radiologists for diagnosis of chronic liver disease, as well as for evaluation of the severity of chronic liver disease. (E-mail: leejy4u@snu.ac.kr)     

Nonalcoholic Fatty Liver Disease: Review of Management for Primary Care Providers

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the United States and worldwide. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is a leading indication for liver transplant. Comorbidities associated with NAFLD development and NASH include type 2 diabetes, obesity, metabolic syndrome, and dyslipidemia. Extrahepatic morbidity and mortality are considerable as NAFLD is associated with an increased risk of cardiovascular disease and chronic kidney disease. Once NAFLD is diagnosed, the presence of liver fibrosis is the central determinant of hepatic prognosis. Severe liver fibrosis requires aggressive clinical management. No pharmacologic agents have regulatory approval in the United States for the treatment of NAFLD or NASH. Management is centered on efforts to reduce underlying obesity (lifestyle, medications, surgical or endoscopic interventions) and metabolic derangements (prediabetes, type 2 diabetes, hypertension, hyperlipidemia, and others). Current pharmacologic therapy for NAFLD is limited mainly to the use of vitamin E and pioglitazone, although other agents are being investigated in clinical trials. Cardiovascular and metabolic risk factors must also be assessed and managed. Here, NAFLD evaluation, diagnosis, and management are considered in the primary care setting and endocrinology clinics.     

Approaches to Gene Therapy of Complex Multigenic Diseases: Cancer as a Model and Implications for Cardiovascular Disease and Diabetes

The general concept of gene therapy is now well established and accepted by the medical, scientific and public policy communities, and is rapidly being implemented in human experimental studies. In addition to the initial models of single gene defects, target diseases have now come to include multigenic and multifactorial diseases such as human cancer, neurodegenerative diseases such as Parkinson's disease and firms of cardiovascular disease. While many conceptual and technical obstacles must still be overcome before therapy for disorders such as coronary artery disease and diabetes mellitus will easily be approached at the genetic level, the early results with several multigenic disease models gives some cause for optimism that gene therapies for even those complicated disorders will eventually become available.     

Controlled Attenuation Parameter (CAP): A Novel VCTE™ Guided Ultrasonic Attenuation Measurement for the Evaluation of Hepatic Steatosis: Preliminary Study and Validation in a Cohort of Patients with Chronic Liver Disease from Various Causes

There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10⁻¹⁶). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis. (E-mail: magali.sasso@echosens.com)