Mirjana Index

[Joslyn Moreci]

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Background: Lung function testing in small children is cumbersome. However, reduced variability of tidal breathing recorded using impedance pneumography (IP) during sleep was recently found to be a potential objective marker of wheeze in children aged 1-5 years. We aimed to investigate how an acute bronchial obstruction (BO) and its severity, and recovery thereof reflect in expiratory variability index (EVI).

Methods: EVI was measured using a wearable IP system (Ventica) during sleep in 40 healthy controls (aged 1.5-5.9 years) and 30 patients hospitalized due to acute BO (aged 1.3-5.3 years). In healthy controls, EVI was measured for 1-3 nights at their homes. Patients were measured for several nights during hospitalization, as practically feasible, and at home 2 and 4 weeks post-discharge.

Prognosis in alcoholic liver cirrhosis is better than in cirrhosis due to other etiologies, but much depends on the patient's ability to abstain from alcohol consumption, socioeconomic factors, and the availability of family support [1]. Prognosis is also reported to be worse in women [2]. The 5-year survival is about 60% in patients who abstain versus 40% in those who continue to consume alcohol [3]. In the later stages of disease, when signs of decompensation such as persistent ascites and jaundice are dominant features, abstinence has less influence on prognosis [4]. At that stage, both in alcoholic cirrhosis and in alcoholic hepatitis, mortality is the highest within the 1-year follow-up, while with active alcoholic patients it can be measured in weeks [5]. The best indicators of prognosis are the histological findings on liver biopsy; poor prognostic features include zone 3 fibrosis, perivenular fibrosis, and alcoholic hepatitis [6].

In clinical practice, a number of scoring systems are also used to estimate prognosis. The most important prognostic scores are the Child-Turcotte-Pugh (CTP) score, developed in 1973 by Pugh's modification of the Child-Turcotte score [7], and the Model for End-Stage Liver Disease (MELD) score, which was originally developed to predict 3-month survival in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt [8]. In 2003, the CTP score was remodeled by the inclusion of the serum creatinine level in the formula [9], which has improved its predictive accuracy and justified the wider use of the CTP score in day-to-day clinical practice [10,11].

In February 2002, the organ allocation system for liver transplantation in the USA started to base its prioritization technique on the MELD score [12]. The MELD score has been shown to be a valid, independent predictor of short-term as well as the long-term survival of patients with end-stage liver disease [13]. Recently, the MELD score was remodeled by the inclusion of the serum sodium in the calculation of the numerical value.

There is much diversity among patients with alcoholic liver disease and it is therefore advantageous to include a large number of potential indicators in the scoring system used to determine prognosis. According to Kamath et al. [13], among the various prognostic scores used to assess mortality in alcoholic cirrhosis, the CTP score is a very reliable indicator.

Alcoholic cirrhosis is essentially a disease of addiction which, in many cases, is very difficult to control and treat, hence the importance of monitoring and evaluating the patient. Patients need to abstain from alcohol for at least 6 months, and only then can they be presented to the surgical team for the transplant preparation. There is much controversy regarding the length of the abstinence period and the optimal time for transplantation. Surgeons are also confronted by ethical issues; for example, should transplantation be offered to the severely ill alcoholic patient in the terminal stage who has not adhered to recommendations regarding abstinence, and whose only hope of cure is a liver transplant [14].

Organ and tissue transplantation is successful only if everyone involved in the process, including physicians and medical institutions, respect and consider the best interests of the patients. It is also very important to honor the ethical, moral, and religious values of society [15]. In terms of the optimal timing for liver transplantation in patients with alcoholic cirrhosis, Veldt et al. [16] emphasized the importance of achieving abstinence from alcohol. Abstinence can significantly change the prognosis in the patient; it leads to stabilization of the patient's condition and results in lowering the CTP score to A, which is not an indication for liver transplantation. This shows preserved functional reserve of the liver, and these patients have significantly longer survival. Veldt et al. [16 ]found that patients who continued to drink alcohol after hospital treatment for advanced liver cirrhosis died within 6-10 months. The authors concluded that those patients who do not improve their condition despite abstinence are the ones for whom transplantation is indicated.

The objectives of this study were: (1) to examine which prognostic markers are good indicators of decompensation of alcoholic liver cirrhosis, (2) to find out which prognostic score is the best predictor of mortality in patients with decompensated alcoholic liver cirrhosis in hospital conditions, (3) to examine which of the remodeled CTP scores and derived MELD scores has the best sensitivity and specificity in the determining a deadly outcome in patients with terminal alcoholic liver cirrhosis, and (4) which of these scores can be actively applied in monitoring alcoholic patients listed for liver transplantation for the purpose of better positioning of the potential recipient and reducing mortality of patients listed for the liver transplantation.

This was a prospective study. Eighty-seven patients with alcoholic liver cirrhosis (males: 79, females: 8) and 39 with nonalcoholic liver cirrhosis (males: 19, females: 20) were followed up during 29-month period. In the nonalcoholic cirrhosis group, those who did not consume alcohol, the causes of terminal liver cirrhosis included hepatitis B infection, hepatitis C infection, cryptogenic cirrhosis, primary biliary cirrhosis, and Wilson disease. The exclusion criteria were malignant disease of the liver or of any other organ, preexisting renal disease, and decompensated heart failure.

For each patient, laboratory biochemical parameters were determined and prognostic scores were calculated during hospitalization. In-hospital mortality was also monitored. Blood was collected for estimation of serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase (GGT), total bilirubin, serum sodium, and international normalized ratio (INR). The demographic, clinical, and biochemical characteristics of the 2 groups of patients are shown in Table 1.

The prognostic scores that were evaluated included the following: CTP score, CTP creatinine-modified I score (CTP crea I score), CTP creatinine-modified II score (CTP crea II score), Model for End-Stage Liver Disease (MELD) score, MELD sodium-modified (MELD Na score), integrated score, updated MELD score, United Kingdom MELD score, and MELD score remodeled by serum sodium index (MESO index).

Statistical analysis was performed using SPSS 16.0 (SPSS Inc., Chicago, IL, USA). For descriptive statistics, the data are presented as the arithmetic mean SD, median and interquartile range, or in the form of absolute or relative numbers. Data were tested for normality using the Kolmogorov-Smirnov test. A t test was used for comparisons of the means of normally distributed data and the Mann-Whitney U test for data that were not normally distributed. The Kaplan-Meier survival analysis in relation to the variables examined was applied. The log-rank test was used to compare average survival in relation to the tested parameters. Cox regression analysis was used to assess the ability of each of the scores for predicting mortality in alcoholic cirrhosis patients. Discriminatory ability was evaluated using receiver operating characteristic (ROC) curve analysis [17].

In this study, patients with alcoholic cirrhosis had significantly higher levels of serum GGT and serum bilirubin than patients with nonalcoholic cirrhosis. Serum sodium levels did not differ significantly between the groups. The INR was higher in alcoholic cirrhosis patients, but the difference was not statistically significant. Xie et al. [18], found that in patients with alcoholic cirrhosis, aspartate aminotransferase and GGT levels were significantly higher than in the control group, and that serum bilirubin, an integral part of the MELD score, was not an independent predictor of mortality [18], which differed from the results of our current study. This difference can be explained by differences in the patient population. In the abovementioned study, the authors analyzed a more heterogeneous group of patients with respect to the decompensation stage of the terminal cirrhosis, while our study focused only on patients with decompensated cirrhosis.

In the present study, in both groups, the most common indication for admission to hospital was ascites with edema. Although the alcoholic cirrhosis group had a large proportion (>50%) of patients with CTP score C, the difference from the nonalcoholic group was not statistically significant, probably because patients in both groups had been admitted with similar indications. Hence, this finding could indicate that the CTP score is useful indicator of decompensation of terminal cirrhosis, regardless of etiology. The remodeled CTP scores - CTP crea I and CTP crea II scores - were also found to be excellent indicators of the decompensation of alcoholic cirrhosis, as they were statistically significantly higher in the group of alcoholic patients in a phase of decompensated disease. This result points out the role of creatinine in qualifying of the disease decompensation by scores that include it in their formula. Among the MELD scores, the basic MELD score and MELD Na score were well correlated with decompensation of alcoholic cirrhosis.

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