Role of Bilirubin Molecular Species in Hepatic Encephalopathy and Acute-on-chronic Liver Failure

Overview

It has been identified that impaired liver function, as occurs in patients with liver cirrhosis, prevents proper conjugation of glucuronic acid with bilirubin; as a result, unconjugated bilirubin accumulates in the blood, and conjugated bilirubin is markedly altered to form diglucuronides or monoglucuronides. However, in the development and progress of acute-on-chronic liver failure (ACLF) there is not enough information about these processes and the possible concentration levels that they can take. Also Hepatic encephalopathy (HE) is a reversible complication, but with a high mortality rate in patients with acute or chronic liver failure, as well as a consequence of the formation of portosystemic shunts.

Liver cirrhosis is a pathological diagnosis characterized by diffuse fibrosis, severe alteration of intrahepatic arterial and venous flow, portal hypertension, and, ultimately, liver failure. The prevalence of liver cirrhosis in the Mexican population depends on various factors, including gender, ethnic groups, and geographic regions, in addition to the nature, frequency, and time of acquisition of the main risk factors for cirrhosis, such as the hepatitis B virus, hepatitis C virus (HCV) in addition to non-alcoholic steatohepatitis, non-alcoholic fatty liver or alcoholic liver disease. Liver cirrhosis has been classified as decompensated or compensated. Decompensated liver cirrhosis occurs when there is gradual progression over months causing liver and extrahepatic organ failure. On the other hand, if it appears suddenly, in a short-term deterioration for days or several weeks after the defined triggering disease, it is known as Acute-on-chronic liver failure (ACLF). ACLF is a syndrome characterized by acute and severe liver abnormalities as a result of different types of lesions present in patients with underlying chronic liver disease or cirrhosis, but unlike decompensated cirrhosis, it has a high short-term mortality. It is important to determine the prognosis of patients with ACLF, in a short period of time, in order to act appropriately and reduce the use of temporary liver support or liver transplantation, an important variable that is included in various scores that assess liver function in different scenarios such as the Child-Pugh score and Model for End-stage Liver Disease (MELD) systems. Among liver cirrhosis complications, there is the Hepatic encephalopathy (HE) involves a wide range of neurocognitive and psychiatric abnormalities that can range from subclinical neurological deficits and disturbances in attention to coma. Diagnosis of hepatic encephalopathy can be made using the West Haven (WH) criteria, which are clinical criteria that evaluate the degree of neurological deterioration and divide hepatic encephalopathy into 5 grades (from grade 0 to grade 4), with grades 3 and 4 having a worse prognosis. In addition to these criteria, it can be diagnose based on psychometric tests such as the Portosystemic- Encephalopathy- Syndrome test (PSE) and psychophysiological tests, such as the Critical flicker frequency (CFF). Despite the existence of this evidence and the WH criteria, there is no quantitative parameter that can be used to diagnose the hepatic encephalopathy. In addition, although the quantification of ammonia levels is carried out in multiple centers as part of the protocol for diagnosing HE, there are numerous studies showing that ammonia levels cannot be used to diagnose or rule out the presence of HE.