22 March 2019: Original Paper
Etiology of Liver Disease and Cardiovascular Abnormalities in Patients on a Liver Transplantation Waiting List
Michalina Galas ABCDEF 1, Renata Glówczyńska ABDEF 1*, Zbigniew Lewandowski C 2, Andrzej Cacko CD 3, Joanna Raszeja-Wyszomirska BD 4, Piotr Milkiewicz BD 4, Marek Krawczyk DE 5, Krzysztof Zieniewicz DE 5, Grzegorz Opolski ADE 1
DOI: 10.12659/AOT.913061
Ann Transplant 2019; 24:162-167
Abstract
BACKGROUND: The classical cardiovascular risk factors and changes in the circulatory system secondary to end-stage liver disease (ESLD) are associated with an increased risk of cardiac abnormalities (CAs) in patients waiting for liver transplantation (LTx). The aim of this study was to assess the relationship between the etiology of liver disease and the presence of CAs in patients qualified for LTx.
MATERIAL AND METHODS: The study enrolled patients qualified to LTx due to ESLD at the Clinical Hospital of the Medical University of Warsaw between 2013 and 2016. Out of 396 patients: 65, 157, 117, and 57 had ESLD due to the alcoholic liver disease (ALD), viral infections (VIR), autoimmune disorders (AUTO), and different etiologies (OTHER), respectively.
RESULTS: An increased frequency of hypertension and diabetes mellitus were observed in ALD and VIR groups, while for hyperlipidemia, the highest rates were observed in ALD and AUTO groups. Significant differences in CAs rates were observed for resting tachycardia, prolonged QT interval, bradycardia, and left ventricular diastolic dysfunction. After adjustment for age, MELD, and Child-Pugh scores, hyperlipidemia (26% vs. 7–15%, p<0.048) was most frequently observed in the AUTO group, while poor aerobic capacity (49% vs. 21–34%, p<0.009) dominated in the OTHER group.
CONCLUSIONS: The frequency of hyperlipidemia, and poor aerobic capacity were directly related to the etiology of liver disease, while the remaining associations resulted from effects of age, MELD, and Child-Pugh score.
Keywords: Cardiomyopathies, Cardiovascular Abnormalities, Liver Cirrhosis, Liver Transplantation, Autoimmune Diseases, Cardiovascular Diseases, End stage liver disease, Hepatitis, Viral, Human, Hyperlipidemias, Liver Diseases, Alcoholic, Organ Dysfunction Scores, perioperative period, Risk Factors, Waiting Lists
Background
Many liver diseases lead to progressive and irreversible damage, and the only definitive method of treatment is liver transplantation. The multiple etiologies of liver diseases and their different courses affect the heterogeneity in the group of candidates for liver transplantation in terms of age and the occurrence of extrahepatic symptoms and accompanying diseases, among which cardiovascular diseases predominate. An additional clinical burden on these patients is the presence of circulatory irregularities typical of liver failure and portal hypertension. The occurrence of myocardial systolic and/or diastolic dysfunction and electrophysiological abnormalities in the course of cirrhotic cardiomyopathy (cirrhotic cardiomyopathy, CCM) pose a threat of serious complications in situations of high hemodynamic burden, which is a major surgery, such as LTx [1,2]. To safely perform the LTx procedure and improve their distant prognosis, it is necessary to know the risk profile of potential liver recipients. Therefore, the aim of this study was to examine whether the occurrence of cardiovascular abnormalities, as a potential source of complications in the perioperative period, are dependent on the etiology of the liver diseases among patients listed for liver transplantations.
Material and Methods
STATISTICAL METHODS:
Statistical analysis consisted of examining the association between the etiology of liver disease and the incidence of CV risk factors and cardiovascular abnormalities (CA). The crude rates of these events were calculated in each group of interest and compared using Fisher’s exact test. The adjusted-for-age, MELD, and Child-Pugh score rates were estimated by logistic regression analysis. The analysis was performed using the SAS System 9.4 [4] and supported by the method of van Belle et al. [5]. The p value less than 0.05 was considered statistically significant, while p values lower than 0.10 were regarded as on the verge of significance.
Results
Among patients qualified for LTx (Table 1), the most numerous group was patients with viral etiology (39%), followed by autoimmune etiology (30%), and alcohol (16%) and other etiology (14%). In terms of disease severity, patients with ALD had the highest MELD score, while the lowest MELD scores were found in patients with viral and other etiologies (Table 2).
We found some association of etiology with the presence of CV risk factors in routine cardiac work-up in the pretransplant qualification procedure. When compared to AUTO and OTHER groups, the ALD and VIR groups had significantly higher frequencies of hypertension (38% and 45% in ALD and VIR, respectively
We noticed some differences in rates of CAs on additional exams in these 4 etiological groups. QTc prolongation (44% and 37% in ALD and VIR, respectively
Due to the heterogeneity of etiological groups in terms of MELD, Child-Pugh score, and age, multiple logistic regression analysis was performed to estimate adjusted age, MELD, and Child-Pugh points rates of CAs (Table 3). We found that regardless of age, MELD and Child-Pugh scores, only hyperlipidemia among AUTO patients, and poor aerobic capacity among OTHER patients were significantly higher compared to the remaining ones (p<.048, p<.009, Table 4). Higher rates of resting tachycardia in OTHER (13%) and bradycardia in AUTO (31%) where observed to be on the verge of significance.
Discussion
LIMITATIONS OF THE STUDY:
The MELD and Child-Pugh scores, which are intended to be used as indicators of liver failure severity, do not take into account all the features of liver damage. This study used the classic MELD score values. It is possible that the currently used modified MELD indicators would be better for use in this work (e.g., MELD-Na or HCC-MELD) [23]. The number of patients with heart failure and history of ventricular arrhythmias was too small (especially among ALD patients) to be included in statistical analysis. CPET trials were not performed in 15% of patients; however, the percentage of disqualified patients in the individual groups did not differ significantly. Although the OTHER group consisted of patients with common features (ascites, emaciation), it was as a whole a heterogeneous set of patients.
Conclusions
The increased frequency of hyperlipidemia in the autoimmune group and increased rates of poor aerobic capacity in a group of OTHER etiologies were directly related to the etiology of liver disease, as these relationships were obtained after adjustment for age and liver dysfunction.
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