Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels.

Cedera Hati Hipoksik Prediktor Komplikasi Akut Utama Pasien Infark Miokard di Unit Rawat Intensif Koroner Rumah Sakit Cipto Mangunkusumo

Pendahuluan. Major adverse cardiac event (MACE) adalah komplikasi akut utama yang terjadi pada pasien infark miokard, meliputi gagal jantung akut, syok kardiogenik, dan aritmia fatal. Diperlukan biomarker yang akurat, mudah dilakukan, dan cost-effective untuk memprediksi MACE dan kematian. Cedera hati hipoksik atau HLI (hypoxic liver injury) adalah salah satu biomarker potensial menggunakan kadar enzim hati transaminase (serum glutamic-oxaloacetic transaminase/SGOT) sebagai parameter. Penelitian ini bertujuan untuk mengetahui peran HLI sebagai prediktor MACE pada pasien infark miokard tanpa gambaran EKG elevasi segmen ST (NSTEMI).Metode. Penelitian ini merupakan penelitian potong lintang dengan luaran berupa MACE dan kohort retrospektif dengan keluaran kematian selama masa perawatan. Populasi penelitian adalah semua pasien NSTEMI yang menjalani perawatan di ICCU Rumah Sakit Cipto Mangunkusumo (RSCM). Sampel penelitian adalah pasien NSTEMI yang menjalani perawatan di ICCU RSCM pada tahun 2006-2016 dan memenuhi kriteria penelitian. Penentuan titik potong HLI berdasarkan kadar SGOT yang dapat memprediksi MACE dan kematian dihitung dengan kurva ROC. Analisis multivariat dilakukan menggunakan regresi logistik untuk mendapatkan nilai prevalence odds ratio (POR) terhadap MACE dengan memasukkan kovariat. Analisis bivariat mengenai sintasan pasien terhadap kematian dilakukan dengan menggunakan kurva Kaplan-Meier dan diuji dengan log-rank.Hasil. Sebanyak 277 subjek diikutsertakan pada penelitian ini. Proporsi subjek dengan MACE pada penelitian ini adalah 51,3% (gagal jantung akut 48,4%, aritmia fatal 6,5%, syok kardiogenik 7,2%) dan angka kematian sebesar 6,13%. Median nilai SGOT adalah 35 U/L pada seluruh subjek, 40 (rentang 8-2062) U/L pada subjek dengan MACE dan 31 (rentang 6-1642) U/L pada subjek tanpa MACE (p = 0,003). Nilai titik potong yang diambil untuk memprediksi MACE adalah 101,0 U/L (sensitivitas 21,8%; spesifisitas 89,6%; POR 2,727 (IK 95%: 1,306-5,696), p = 0,006). Pada analisis multivariat tidak didapatkan hubungan yang bermakna antara HLI dengan MACE. Nilai titik potong untuk memprediksi kesintasan terhadap kematian adalah 99,0 U/L (sensitivitas 23,5%; spesifisitas 83,8%; likelihood ratio +1,46). Tidak didapatkan perbedaan kesintasan yang bermakna antara subjek dengan nilai HLI di bawah dan di atas titik potong kadar SGOT.Simpulan. Cedera hati hipoksik (HLI) tidak dapat digunakan untuk memprediksi MACE pada pasien NSTEMI kecuali dikombinasikan dengan variabel lain. Tidak terdapat perbedaan kesintasan yang bermakna antara subjek dengan atau tanpa HLI. Kata Kunci: Cedera hati hipoksik, Infark miokard, Kesintasan, MACE, NSTEMI, SGOTHypoxic Liver Injury as Predictor of Major Adverse Cardiac Events in Acute Myocardial Infarction patients admitted to Intensive Coroner Care Unit of Cipto Mangunkusumo National General HospitalIntroduction. Major adverse cardiac events (MACE) is a complicating myocard infarctwhich consist of acute heart failure, cardiogenic shock, and fatal arrhytmia. An accurate, easy and cost-effective biomarker is needed to predict MACE and mortality in patients with myocard infarct. Hypoxic liver injury (HLI) is a potential biomarker using serum glutamic-oxaloacetic transaminase (SGOT) level as the parameter. This study is aimed to discover HLI’s role in predicting MACE in non ST elevation myocard infarct (NSTEMI).Methods. This study was designed as cross sectional to predict MACE and prospective cohort for survival analysis. Study population was all NSTEMI patients admitted to ICCU of Cipto Mangunkusumo Hospital and study sample were NSTEMI patients admitted to ICCU of Cipto Mangunkusumo Hospital that meets all criteria during 2006-2016. Cut-off level of SGOT for HLI to predict MACE and mortality was analyzed using ROC curve and AUC. Survival analysis was done using Kaplan Meier curve and the difference was tested with log-rank. Results. A total of 277 subjects were included in this study. Incidence of MACE in this study was 51.3% (acute heart failure 48.4%, fatal arrhytmia 6.5%, and cardiogenic shock 7.2%).The mortality rate was 6.13%. The median of SGOT level on all subject was 35 U/L, 40 (range 8-2062) U/L in subjects with MACE and 31 (range 6-1642) U/L in subjects without MACE (p = 0.003). Cut-off level for SGOT used to predict MACE was 101 U/L (sensitivity 21.8%; specificity 89.6%; POR 2.727 (CI 95% 1.306-5.696), p = 0.006). In multivariate analysis, HLI was insignificantly related to MACE. Cut-off level for SGOT used to predict survival was 99 U/L (sensitivity 23.5%; specificity 83.8%; likelihood ratio +1.46). There were no significant difference of survival between groups with HLI level below and above the cut-off SGOT level. Conclusion. Hypoxic liver injury (HLI) cannot be used to predict MACE in NSTEMI patients unless combined with other variables. There is no significant difference of survival between subjects with or without HLI.