|Year : 2022 | Volume
| Issue : 4 | Page : 222-228
MELD-Na score, Acute Physiologic and Chronic Health Evaluation II score, and SOFA score and their association with mortality in critically ill COVID-19 patients with liver injury: A retrospective single-center study
Sandra Gomez-Paz1, Eric Lam2, Luis Gonzalez-Mosquera2, Brian Berookhim2, Paul Mustacchia1, Joshua Fogel3, Sofia Rubinstein4
1 Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nassau University Medical Center, New York, USA
2 Department of Internal Medicine, Nassau University Medical Center, New York, USA
3 Department of Business Management, Brooklyn College, New York, USA
4 Department of Internal Medicine, Division of Nephrology and Hypertension, Nassau University Medical Center, New York, USA
|Date of Submission||16-Apr-2022|
|Date of Acceptance||12-Jul-2022|
|Date of Web Publication||26-Dec-2022|
Dr. Sofia Rubinstein
Department of Internal Medicine, Nassau University Medical Center, Division of Nephrology and Hypertension, 2201 Hempstead Turnpike, Box 49, East Meadow, New York 11554
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The Acute Physiologic and Chronic Health Evaluation II (APACHE-II), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease modified for Sodium concentration (MELD-Na) scores are validated to predict disease mortality. We studied the prognostic utility of these scoring systems in critically ill coronavirus disease 2019 (COVID-19) patients with liver injury.
Methods: This was a retrospective study of 291 confirmed COVID-19 and liver injury patients requiring intensive care unit level of care. These patients required supplemental oxygen requirement with fraction of inspired oxygen >55% and/or the use of vasopressor. MELD-Na, SOFA, and APACHE-II scores were adjusted. Outcomes were mortality and length of stay (LOS).
Results: SOFA (odds ratio: 0.78, 95% confidence interval: 0.63–0.98, P < 0.05) was associated with decreased odds for mortality. APACHE-II and MELD-Na were not associated with mortality or LOS.
Conclusions: We suggest that the novel nature of COVID-19 necessitates new scoring systems to predict outcomes in critically ill COVID-19 patients with liver injury.
Keywords: Acute Physiologic and Chronic Health Evaluation II, acute, coronavirus disease 2019, intensive care unit, liver failure, mortality
|How to cite this article:|
Gomez-Paz S, Lam E, Gonzalez-Mosquera L, Berookhim B, Mustacchia P, Fogel J, Rubinstein S. MELD-Na score, Acute Physiologic and Chronic Health Evaluation II score, and SOFA score and their association with mortality in critically ill COVID-19 patients with liver injury: A retrospective single-center study. Int J Crit Illn Inj Sci 2022;12:222-8
|How to cite this URL:|
Gomez-Paz S, Lam E, Gonzalez-Mosquera L, Berookhim B, Mustacchia P, Fogel J, Rubinstein S. MELD-Na score, Acute Physiologic and Chronic Health Evaluation II score, and SOFA score and their association with mortality in critically ill COVID-19 patients with liver injury: A retrospective single-center study. Int J Crit Illn Inj Sci [serial online] 2022 [cited 2023 Feb 9];12:222-8. Available from: https://www.ijciis.org/text.asp?2022/12/4/222/364738
| Introduction|| |
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious viral pathogen with 9%–46% of patients having critical illness requiring intensive care unit level of care (ICU-LC)., ICU-LC for COVID-19 has high mortality rates ranging up to 35%., Reported risk factors associated with critical illness for COVID-19 are older age; male gender; and comorbidities of hypertension, diabetes mellitus, morbid obesity, and chronic lung disease. Some report substance abuse increases the risk for COVID-19 infection. The association of substance abuse, including alcohol abuse, with mortality in critically ill COVID-19 patients with liver injury has not been studied.
In critically ill COVID-19 patients, extrapulmonary organ involvement including liver injury is reported., Although the underlying mechanism is not fully understood, it has been proposed that liver injury might be caused by either direct SARS-CoV-2 viral damage, or treatment toxicity, or severe systemic inflammatory and sepsis response. Liver injury incidence in critically ill patients with COVID-19 disease is as high as 80%.
The Acute Physiologic and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores are commonly used to assess disease severity and estimate mortality for critical illnesses. Increased APACHE II score in critically ill COVID-19 patients and increased SOFA in all hospitalized COVID-19 patients predicted increased mortality. The Model for End-Stage Liver Disease modified for Sodium concentration (MELD-Na) score is a prognostic tool for patients awaiting liver transplant that is also commonly applied to estimate mortality in acute liver failure patients. A study among general COVID-19 patients found that the MELD-Na score predicted mortality from renal failure; however, literature on MELD-Na predicting mortality for liver injury in COVID-19 patients is lacking.
There are limited data for the APACHE II, SOFA, and MELD-Na scores for COVID-19 disease. These scores have not been studied in critically ill COVID-19 patients with liver injury. Liver injury patients have high mortality, and it is important to have readily available tools for risk stratification. We study the association of the APACHE II, SOFA, and MELD-Na scores for mortality and length of stay (LOS) in critically ill COVID-19 patients with liver injury.
| Methods|| |
Study design and participants
This is a retrospective study with the inclusion criteria of (1) adults of age 18 years or greater, (2) confirmed COVID-19 infection, and (3) admitted to ICU-LC at a safety-net institution in a suburban New York City hospital from March 1, 2020, to May 15, 2020. Ethical approval was received from the hospital institutional review board. COVID-19-positive status was confirmed by a positive nasopharyngeal sample of real-time reverse transcription–polymerase chain reaction result for SARS-CoV-2. Liver injury was defined by the presence of elevated levels alanine transaminase 1.5-times normal range (above 60 U/L) or elevated total bilirubin above 1.1 mg/dL. ICU-LC was defined by supplemental oxygen requirement with fraction of inspired oxygen >55% (with or without invasive mechanical ventilation) or use of vasopressor medications (e.g., norepinephrine, phenylephrine, epinephrine, vasopressin, dobutamine, and dopamine). Patients who did not have liver injury were excluded from the study. All patients completed their hospital course as either discharged alive or deceased. This manuscript adheres to the STROBE guideline.
Demographic variables were age (years), sex (male and female), and race/ethnicity (Caucasian, African American, Hispanic and/or Latino, Asian [e.g., Chinese, Japanese, Korean], South Asian [e.g., Indian, Pakistani, Thai, Vietnamese], and Other). Comorbidities included history of alcohol abuse (former or current), obesity (body mass index ≥30.0 kg/m2), and Charlson Comorbidity Index (CCI), which includes a range of comorbid conditions of age, diabetes mellitus, renal disease, chronic obstructive pulmonary disease, history of myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular accident, dementia, solid tumor, leukemia, lymphoma, AIDS status, connective tissue disease, peptic ulcer disease, and chronic liver disease. The CCI predicts a 10-year survival rate based on a comorbidity burden out of 37 points.
Indicators for disease severity were the MELD-Na score (40 points total), APACHE II score (71 points total), SOFA score (24 points total), and invasive mechanical ventilation during hospitalization., APACHE II score was calculated during the first 24 h of admission to ICU-LC. MELD-Na score and SOFA score were calculated using characteristics available at any time during ICU-LC admission, including the first 24 h.
Treatment/management variables included the use of antimalarial therapy (hydroxychloroquine or chloroquine), any antibiotic, antiviral (remdesivir), vasopressor medication (i.e., norepinephrine, phenylephrine, epinephrine, vasopressin, dobutamine, and dopamine), interleukin inhibitors (anti-IL6 monoclonal antibodies such as tocilizumab), systemic corticosteroid therapy (i.e., prednisone, methylprednisolone, hydrocortisone, and dexamethasone), convalescent plasma from COVID-19 survivor donors, and therapeutic dosage of anticoagulant medications.
We collected information on involvement of the following organs: Glasgow Coma Score nadir during hospitalization for the neurological system, peak creatinine level (mg/dL) for the renal system, mean arterial pressure on admission (mmHg) for the cardiovascular system, peak total bilirubin level (mg/dL) for the gastrointestinal/liver system, peak blood glucose level (mg/dL) for the endocrine system, peak creatine kinase level (U/L) for the musculoskeletal system, and nadir white blood cell (k/mm3), and peak platelet level (k/mm3) for the hematologic system. Number of organs involved was defined as the sum of organs that were impaired or involved during admission. The primary outcome was mortality and the secondary outcome was LOS.
Continuous variables were analyzed with mean and standard deviation. Frequency and percentage were analyzed for categorical variables. The outcome variable of mortality was analyzed with multivariate logistic regression. The outcome variable of LOS was analyzed with multivariate linear regression. LOS was logarithmic transformed due to skewness. All P values were two-tailed. The data were analyzed with IBM SPSS Statistics version 26 (Armonk, NY, USA: IBM Corporation; 2019).
| Results|| |
A total of 368 patients met the inclusion criteria, and 77 patients were excluded. The remaining 291 patients were included in the study. [Table 1] shows the sample characteristics. For demographics, mean age was more than 61 years, less than one-third were female, and more than two-thirds were those from either African American or Hispanic race/ethnicity. For comorbidities, alcohol abuse was slightly above 5%, more than one third were obese, and mean CCI was 2.8 indicative of a 10-year survival rate based on the comorbidity burden between 21% and 96%. For disease severity variables, mean values were SOFA score = 4.7, a low SOFA score with <33% ICU mortality, MELD-Na score = 13.9, indicative of an estimated 90-day mortality of 1.9%–6%, and APACHE II score = 13.9, indicative of 15% ICU mortality. The two highest percentages for treatment management variables were antibiotics (99.0%) and antimalarial therapy (89.7%). The mean number of organs involved was 5.4. Mortality was 58.4% and mean LOS was 15.6 days.
[Table 2] shows the multivariate logistic regression analysis for mortality. Increased age, female sex, mechanical ventilation, and increased number of organs involved were each significantly associated with increased odds for mortality. Alcohol abuse, increased SOFA score, convalescent plasma, and anticoagulant were each significantly associated with decreased odds for mortality. However, the disease severity variables of MELD-Na score and APACHE II score were each not associated with mortality.
[Table 3] shows the multivariate linear regression analysis for LOS. Alcohol abuse, antibiotic, steroid, and convalescent plasma were each significantly associated with increased LOS. Increased age was significantly associated with decreased LOS. The disease severity variables of SOFA score, MELD-Na score, and APACHE II score were each not associated with LOS.
| Discussion|| |
Our study found that increased age and female sex were significantly associated with increased mortality. Two-thirds of participants were Hispanic or African-American; we did not find an association between race/ethnicity with mortality or LOS. Alcohol abuse, which is an important risk factor for liver disease, showed decreased odds for mortality. The disease severity variables of mechanical ventilation and total number of organs involved were significantly associated with increased mortality. However, neither MELD-Na score nor APACHE II score were significantly associated with mortality or LOS. Increased SOFA score was significantly associated with decreased odds for mortality. Patients managed with convalescent plasma and anticoagulant medications had significantly decreased odds for mortality, but only convalescent plasma showed a significant association with increased LOS. Antibiotic therapy and steroid medications were each significantly associated with increased LOS. Obesity and the CCI were not associated with mortality or LOS.
In our study, increased age was associated with increased odds for mortality and with decreased LOS. This is consistent with the literature showing increase age as a risk factor for mortality in critically ill COVID-19 patients, and is associated with decreased LOS as these patients rapidly decompensated resulting in a shorter hospital course. We found no association of race/ethnicity with mortality or LOS. The data on race/ethnicity and mortality are conflicting with study showing increased mortality and severe COVID-19 disease in Hispanics and African-Americans, while other do not show any association. Some even report higher mortality risk in Caucasians. To our knowledge, there are no other studies examining an association between race/ethnicity and severe COVID-19 disease with liver injury.
In our study, female sex was associated with increased odds for mortality. Male gender is associated with increased risk for severe disease and death in COVID-19. However, a systematic review of liver injury in COVID-19 did not find any association of gender with mortality. Furthermore, another study reported incidence of liver injury in COVID-19 was higher among female patients irrespective of COVID-19 disease severity. A possible explanation for our finding is that nonalcoholic steatohepatitis (NASH), a form of Non-Alcoholic Liver Disease (NAFLD), has a high prevalence among females over 50-year-old, particularly those of Hispanic ethnicity. Our sample included those from Hispanic race/ethnicity and those over 50-year-old. Although the implications of COVID-19 in NAFLD have not been investigated, some suggest that these patients may be particularly vulnerable to the increased cytokine production and inflammatory manifestations associated with COVID-19. Future studies should investigate the association of NAFLD and COVID-19 severity.
Alcohol abuse was associated with decreased odds for mortality. Although some hypothesize that alcohol consumption has a negative role in COVID-19 pathogenesis due to upregulation of systemic chemokines and inflammatory markers, there are still mixed data regarding alcohol consumption and its association with COVID-19 infection and mortality. A large prospective cohort study found that nonalcohol drinkers had a higher association for COVID-19 infection. However, another study showed that alcohol users were more likely to test positive for COVID-19, but they did not find an association with mortality or severe COVID-19 disease. There is an alcohol-induced anti-inflammatory state that is based on an initial and transient inhibitory effect of acute alcohol consumption on monocytes and macrophages which later may develop into a pro-inflammatory state in chronic alcoholics due to repeated alcohol exposure. The impact of alcohol on monocyte/macrophage polarization may induce a shift towards M2-type anti-inflammatory macrophages predominance that have tissue repair capacity over M1-type pro-inflammatory cells that can cause tissue damage. We believe that our study finding of decreased mortality in alcohol abusers in critically ill COVID-19 patients with liver injury occurred because our study was looking at short-term in-hospital mortality where these patients might have been protected by the initial anti-inflammatory effects of acute alcohol consumption. Furthermore, as our sample of alcohol abusers was small, it is possible that our finding may not reflect the true impact.
There was no association with mortality or LOS for APACHE II score, whereas increased SOFA score was associated with decreased odds for mortality, and no association for LOS in critically ill COVID-19 patients with liver injury was found. Standardized scoring systems such as SOFA and APACHE II are widely utilized as estimators of mortality in critically ill patients. Higher APACHE II scores were associated with increased mortality in critically ill COVID-19 patients. However, a study reporting both SOFA and APACHE II scores in COVID-19 patients, found that higher SOFA score was associated with increased odds for mortality but did not find an association for APACHE II score. The mean APACHE II score in our sample was approximately 14 points, which is similar to the study that did not find an association for mortality. In contrast to earlier studies,, we found that increased SOFA score was associated with decreased odds for mortality. Our mean SOFA score was approximately 5 points, which is lower than the mean SOFA scores found in studies associated with increased mortality in COVID-19. It is possible that a relatively lower SOFA score is associated with the converse of decreased mortality. Additionally, SOFA score can be calculated at different times during ICU admission, including upon admission, on a daily basis throughout ICU admission, only using the worst values during ICU admission, or as a mean value from daily scoring. In our study, we calculated the SOFA score from the earliest available values within 24 h of ICU admission. This may have had an impact on our findings because ICU admission SOFA score may not be reflective of the COVID-19 patient's prognosis over time. It is also possible that the SOFA and APACHE II scores may not be useful predictive tools for mortality and LOS in critically ill COVID 19 patients with liver injury.
MELD-Na score was not associated with mortality or LOS. The utility of the MELD-Na score to predict mortality in patients with cirrhosis admitted to the ICU, liver transplant patients, and in patients with acute-on-chronic liver failure is widely described.,, Prior studies have found that MELD score predicts prognosis in COVID-19 patients with cirrhosis, acute-on-chronic liver failure, and for liver transplant candidates.,, While these studies on MELD score investigated patients with chronic liver diseases, limited studies focus on the MELD score in acute liver injury patients. One study classified acute liver injury severity in COVID-19 by MELD score and found higher mortality in the high MELD score group. We used the MELD-Na score, which includes serum Na, because it improves the predictive accuracy of mortality in acute liver disease. We are aware of only one study on MELD-Na score and its association with increased mortality in COVID-19 which was performed on 107 hospitalized COVID-19 patients and did not adjust for confounding variables or specifically investigate critically ill COVID-19 patients with liver injury. Our study included a larger sample size and focused on critically ill COVID-19 patients with acute liver injury. The mean MELD-Na score for our sample was approximately 14 points which represents the lowest mortality range. Our sample had a reduced comorbidity burden demonstrated by our low CCI score which also includes liver cirrhosis. We propose that this reduced comorbidity burden was associated with a lower MELD-Na score and thus no association with mortality and LOS.
Our SOFA, APACHE II, and MELD-Na scores were each not associated with LOS. Previous research reports that COVID-19 patients who die during their admission have a shorter LOS. As most of our patients (58%) died, we believe that this high mortality negated any association with increased LOS. This finding is supported by other studies on sepsis in ICU that showed increased SOFA and APACHE II scores were not associated with mortality and LOS.
In our study, liver injury adjusted for all other organ involvement was associated with increased mortality. Dysfunction of individual organ systems is commonly associated with a worse prognosis in COVID-19 patients., To our knowledge, the association of liver injury with mortality adjusted for all other organ dysfunction has not been previously reported.
We found that mechanical ventilation during hospitalization was associated with increased odds for mortality. This is consistent with literature reporting higher mortality rates in critically ill COVID-19 patients., A study performed in critically ill patients requiring invasive mechanical ventilation with liver injury versus noncritically ill COVID-19 patients with liver injury also found that the critically ill COVID-19 patients had higher odds for mortality. Our findings are consisted with this study.
Convalescent plasma and therapeutic anticoagulant treatments were associated with decreased odds for mortality. This is similar to other studies conducted in critically ill COVID-19 patients. We found that convalescent plasma, steroid, and antibiotic treatments were each associated with increased LOS. Patients receiving these treatments were required to stay in-hospital for a longer time to complete the course of treatment.
In our study CCI and obesity were not associated with mortality. There are studies for both CCI and obesity indicating that both a higher CCI and obesity are associated with increased mortality in COVID-19 patients,, while other studies did not find that association., A potential explanation for this finding for CCI is that it does not incorporate NAFLD/NASH, and therefore CCI may fail to capture patients at potential risk for severe COVID-19 disease with liver injury. It is possible that CCI is not a useful predictor for mortality or severity of disease for critically ill COVID-19 patients with liver injury. For obesity, a study that found an association for obesity and mortality in COVID-19 patients with liver injury did not adjust for any covariates. Our study adjusted for many covariates. We believe that obesity is not independently associated with mortality in critically ill COVID-19 patients with liver injury.
There are several study limitations. First, our study was performed in a single center, safety-net hospital, with a large minority population that may not be representative of the general US population. However, predominance of racial/ethnic minorities in our study provides a good perspective on the impact of COVID-19 among these racial/ethnic groups. Second, the retrospective nature of our study prevents any causative analysis. Third, we chose SOFA score variables early during ICU admission. There are different approaches of collecting SOFA variables and therefore it is possible that a more targeted approach is needed for the application of SOFA score in critically ill COVID-19 patients with liver injury.
| Conclusions|| |
Liver injury adjusted for all other organ involvement was strongly associated with increased mortality in critically ill COVID-19 patients. We found that neither APACHE II score nor MELD-Na score were useful tools for predicting mortality or LOS in critically ill COVID-19 patients with liver injury. We found that increased SOFA score was associated with decreased odds for mortality. We suggest that the novel nature of the COVID19 disease that is constantly evolving necessitates new scoring systems or modification of existing scoring systems to better predict outcomes in critically ill COVID-19 patients with liver injury.
Research quality and ethics statement
This study was approved by the Institutional Review Board/Ethics Committee at Nassau Health Care Corporation (Approval # 20–324; Approval date May 15, 2020). The authors followed the applicable EQUATOR Network (http://www.equator-network.org/) guideline, specifically the STROBE guideline, for this research project.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]