Hypoglycemia is Associated with Increased In-Hospital Mortality in Patients with Liver Cirrhosis; A Nationwide Study

Hypoglycemia is Associated with Increased In-Hospital Mortality in Patients with Liver Cirrhosis; Nationwide Study. Abstract Aim: Cirrhosis may cause dysregulation of glucose homeostasis due to abnormalities in metabolism and responses to changes in the blood glucose level. Cirrhotic patients may be more prone to hypoglycemia. Hypoglycemia is associated with poor outcomes in cirrhotic patients with sepsis and may indicate a greater severity of illness. This study aims to elucidate the effect of hypoglycemia on in-hospital mortality in cirrhotic patients. were calcul-ated. Diabetic patients were excluded from the study to rule out the possibility of iatrogenic hypoglycemia. Results: Out of 1,778,829 inpatients with cirrhosis, 31,615 had a diagnosis of hypoglycemia. Total hospital charges were significantly higher in the cirrhosis and hypoglycemia group compared to the non-hypoglycemia group. The mean length of stay (LOS) in the hypoglycemia group was significantly higher. Mortality, vasopressor usage, mechanical ventilation, cardiac arrest, and intensive care unit (ICU) admission were significantly higher in the hypoglycemia group compared to the non-hypoglycemia one. Conclusion: In patients with cirrhosis, hypoglycemia was associated with higher in-hospital mortality and rate of critical illness as suggested by elevated rates of ICU admission, mechanical ventilation, and vasopre-ssor use. These patients also had longer hospital LOS and higher total hospital charges. Hypoglycemia may reflect advanced liver disease or indicate early sepsis and potentially forbodes a prolonged, complicated hospital course.


Introduction
Chronic liver inflammation causes diffuse hepatic fibrosis which can eventually give rise to liver cirrhosis and subsequent liver failure [1]. Cirrhosis is the leading cause of liver-related death globally [2]. The liver regulates glucose homeostasis by controlling various pathways of glucose metabolism, including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis [3]. It functions as a reserve for carbohy-drates, storing glycogen from glucose in postprandial periods and releasing glucose during fasting periods [4]. Liver cell damage in cirrhosis can alter the liver's metabolism and affect the liver's ability to regulate the blood glucose level, thereby making cirrhotic patients prone to hypoglycemia. Hypoglycemia is not uncom-mon in cirrhotic patients. Nouel et al. reported hypo-glycemia in 15 out of 30 cirrhotic patients admitted with septicemia [5]. Moreover, hypoglycemia was associated with increased mortality in patients with liver cirrhosis [4,[6][7][8].
These findings indicate the important impact of hypoglycemia on patients with liver cirrhosis. In this retrospective United States (US) national inpatientbased population study, we evaluated the effect of hypoglycemia on in-hospital mortality as well as other in-hospital complications in patients with liver cirrhosis.

Data source
This was a retrospective cohort study of patients who states and covers more than 97% of the US population [9]. A 20% probability sample was collected and subsequently weighted to ensure that the selected population was nationally represent-ed.
Each admission in the database was assigned one principal diagnosis, up to 40 secondary diagnoses, and 25 procedures. These variables are defined via the International Classification of Disease, 10th  revision, and Clinical Modification (ICD-10-CM) codes. admission was defined as any patient who had cardiac arrest or needed vasopressors or mechanical ventil-ation. Figure 1 demonstrates the study population ( Figure 1).  (Table 3).

Total hospital charges and length of stay (LOS): Total hospital charges and the mean LOS
were significantly higher in the cirrhosis and hypoglycemia group compared to the cirrhosis without hypogl-ycemia. Mortality, vasopressor usage, mechanical ventilation, cardiac arrest and ICU admission were significantly higher in cirrhotic patients with hypoglycemia compared to cirrhotics without hypoglycemia (Table 2).

Other in-hospital complications:
Cirrhotic patients with hypoglycemia were more likely to need mechanical ventilation and vasopressors. Moreover, patients with cirrhosis and hypoglycemia had a higher chance of having cardiac arrest during hospitalization and to be admitted to the ICU. Tables 4, 5, 6 and 7 summarize these findings. Figure 2 demonstrates OR plots.

Discussion
In mg/dL. He also reported that blood glucose level < 100 mg/dL in cirrhotic patients with positive blood culture was associated with increased mortality [8]. Hypogly-cemia per se is associated with elevated mortality in the setting of sepsis, regardless of cirrhosis also being present [12][13][14]. Future studies could focus on the utility of adding hypoglycemia to calculations for risk stratification and prognosis including transplant priority in cirrhotic patients.
In our study, we found that hypoglycemia was associated with greater severity of illness, including cemia [14]. However, our data did not include diagnoses of hypoalbuminemia in the patient sample and thus we were unable to support this finding.
In keeping with the increased likelihood of acute complications related to cirrhosis, hypoglycemia was also associated with a longer length of stay and total hospital charges. This is likely related to the higher incidence of these complications and the additional resources required to manage them. Incorporating an understanding of prognostication in cirrhosis may be important for future development of healthcare policy and inpatient hospital resource utilization. Hypoglycemia was more likely to occur in females than males. Although this remains unclear, this discrepancy could be related to differences in sexhormone effects on liver physiology [16].
Furthermore, Black race was also associated with greater incidence of hypogly-cemia. It is possible that genetic, socioeconomic, and other demographic variables contribute to illness complications [17].
This study has several limitations which include the inability to categorize patients based on their MELD score which is used for prognostication and risk of short-term mortality in cirrhosis [18]. Our data may suggest that hypoglycemia tends to occur more frequently in patients with decompensated liver disease. Given that the MELD score correlates with degree of liver dysfunction, it is possible that hypoglycemia may correlate similarly [19]. Our study does not account for individuals who had a diagnosis of sepsis, and with the current data we may only hypo-