Therapeutic Efficacy of Oral PEG3350 Plus Lactulose Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Single Blind Prospective Randomized Controlled Study

Therapeutic Efficacy of oral PEG3350 plus Lactulose Versus Lactulose alone in Patients of Acute on Chronic Liver Failure with Overt Hepatic Encephalopathy: A Single Blind Prospective Randomized Controlled Study

INTRODUCTION:

Hepatic encephalopathy (HE) refers to syndrome observed in patients with cirrhosis exhibiting clinical manifestations of mild to severe cognitive dysfunction (neuropsychiatric abnormalities) characterised by alterations in sleep pattern, sudden behavioural changes & personality changes along with altered cognition, or coma. The basic pathophysiology involved in development of potentially reversible neuropsychiatric abnormalities associated with HE are not clearly understood but ammonia generation by gut microbiota is considered as significant contributing factor. HE is categorized into overt hepatic encephalopathy (OHE) and minimal hepatic encephalopathy (MHE). Previous studies have reported the incidence of OHE and MHE to be 30-45% and 60-80% respectively in patients suffering from cirrhosis .

In the present study, we propose to assess the efficacy of an ammonia reducing therapy utilisisng PEG 3350 in patients with Acute on Chronic Liver Failure (ACLF).

Hepatic encephalopathy in Acute on Chronic Liver Failure (ACLF) The syndrome of acute on chronic liver failure is a recently described clinical entity. The defining criterion for acute-on-chronic liver failure (ACLF) takes into consideration the existence of hepatic encephalopathy (HE) within 4 weeks. In Asia, the following definition has been suggested: "acute hepatic insult manifesting as jaundice (serum bilirubin level ≥5 mg/dl) and coagulopathy (international normalized ratio ≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease" . In the West, experts proposed to define ACLF as "an acute deterioration of liver function in patients with cirrhosis which is usually associated with a precipitating event and results in the failure of one or more organs and high short-term mortality". This definition is on the basis of the European Association for the Study of the Liver (EASL)-Chronic Liver Failure (CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC)" study which established diagnostic criteria for ACLF in hospitalized patients who had an acute decompensation (AD) of cirrhosis . In ACLF, hyperammonemia, systemic inflammatory state mediated by various cytokines which includes sepsis/SIRS, bacterial translocation, insulin resistance resulting in hyperglycemia and oxidant induced injury, in addition modulation by glutaminase gene alteration along with alterations in cerebral hemodynamics appear to be crucial factors in the pathogenesis of encephalopathy.Various studies have explored the potential of bacterial infections, hyponatremia, alcohol intake and factors responsible for systemic inflammation in HE. HE is diagnosed after excluding other causes of altered cognition such as metabolic, neurological and psychiatric conditions. Clinical features of HE in ACLF patients are very much similar to those with HE in acute liver failure (ALF). The clear correlation of serum ammonia levels, systemic inflammation and outcome of HE in ACLF patients is not well understood .