Prognostic Role of Ammonia in Patients With Cirrhosis

Abstract

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in patients with cirrhosis and acute decompensation is unknown. The aims of this study were to determine the relationship between ammonia levels and severity of HE and its association with organ dysfunction and short‐term mortality. We identified 498 patients from two institutions as part of prospective observational studies in patients with cirrhosis. Plasma ammonia levels were measured on admission and Chronic Liver Failure‐Sequential Organ Failure Assessment criteria were used to determine the presence of organ failures. The 28‐day patient survival was determined. Receiver operating characteristic analysis was used to identify the cutoff points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. The 28‐day mortality was 43.4%. Plasma ammonia correlated with severity of HE (P < 0.001), was significantly higher in nonsurvivors (93 [73‐121] versus 67 [55‐89] µmol/L, P < 0.001), and was an independent predictor of 28‐day mortality (hazard ratio, 1.009, P < 0.001). An ammonia level of 79.5 µmol/L had sensitivity of 68.1% and specificity of 67.4% for predicting 28‐day mortality. An ammonia level of ≥79.5 µmol/L was associated with a higher frequency of organ failures (liver [P = 0.004], coagulation [P < 0.001], kidney [P = 0.004], and respiratory [P < 0.001]). Lack of improvement in baseline ammonia at day 5 was associated with high mortality (70.6%). Conclusion: Ammonia level correlates with not only the severity of HE but also the failure of other organs and is an independent risk factor for mortality; lack of improvement in ammonia level is associated with high risk of death, making it an important biomarker and a therapeutic target.

Ammonia

“…A reduction in ammonia level was associated with improved survival, confirming it as a potential therapeutic target. Classically in urea cycle disorders ammonia levels above 200 μmol/L were considered a poor prognostic factor [18], but in this study in cirrhotics even ≥79.5 μmol/L was associated with increased mortality, indicating an additional role of ammonia in dictating clinical outcomes [11].…”

“…Early studies had shown a correlation of levels of ammonia and worsening HE up to two times the upper limit of normality [6]. Further studies have not only cemented this correlation but have shown a more intricate relationship [10,11]. It can predict the risk and frequency of HE episodes [12].…”

“…Classically, there was a clear distinction of the harmful effects of the ammonia in acute liver failure due to the osmotic component [13] and in lesser degree in chronic liver disease, stating that ammonia in cirrhosis increased morbidity and not mortality. But newer studies and prospective analysis shows that it can be harmful in similar way, increasing mortality [11]. Further studies are needed to corroborate both the utility and prognostic value of ammonia in the setting of chronic liver disease.…”

Letter to Editor: Prognostic Role of Ammonia in Patients With Cirrhosis

“…Acute-on-chronic liver failure (ACLF) is characterized by high shortterm mortality, and outcomes depend on the type of organ failure. (1,2) The study by Shalimar et al (3) is a welcome addition to the literature regarding hyperammonemia and prognosis in cirrhosis, acute decompensation, or ACLF. The authors studied the relation of serum ammonia with hepatic encephalopathy, organ failure, and mortality in a cohort of 498 patients.…”

“…In this context, a plethora of parameters have already been identified that seem to improve preoperative risk assessment of patients undergoing liver resection. (2)(3)(4)(5) Indeed, the combination of preoperative liver function assessment might be beneficial to further characterize patients' risk for adverse postoperative outcome. However, the central aim of the presented study was to define a preoperative parameter that is easily assessable and highly standardized to provide a reliable and internationally available tool.…”