Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)
Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)
Hepatic Encephaopathy is a common complication occurring in patients with Liver cirrhosis.
 Patients usually develop mild confusion, sleep disturbance or obtundation. It occurs due to
 accumulation of excess ammonia in the brain, as the liver is unable to metabolize the
 ammonia. The common gold standard treatment recommended for patients with Hepatic
 Encephalopathy is Lactulose syrup. This is a non absorbable sugar, often combined with an
 antibiotic called Rifaxamine to treat this condition.

 Polyethylene glycol is in a class of medications called osmotic laxatives which works by
 causing water to be retained with the stool. PEG and lactulose, when used together, result in
 faster resolution of symptoms suggesting that PEG may be superior to standard lactulose
 therapy in these patients.

 Non-absorbable sugars like lactulose are associated with non-serious (mainly
 gastrointestinal) adverse events like diarrhea and bloating Hence, due to the side effect
 profile, newer drugs continue to be tested for treatment of Hepatic Encephalopathy.

 The aim of this research project is to compare the effect of PEG versus lactulose for
 treatment of HE in patients with liver cirrhosis. The investigators want to compare the
 resolution of HE as the main outcome. In addition, they will compare length of stay,
 non-serious (mainly gastrointestinal) adverse events, and 3 months outcome. The investigators
 hypothesize that rapid purgation of the gut using PEG may resolve HE more effectively than
 lactulose.
Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver cirrhosis
 manifested by mild confusion, sleep disturbance or obtundation. Lactulose treatment has long
 been the standard of care, which presumably acidifies stool and eradicates toxic metabolites.
 However a third of these patients with hepatic encephalopathy do not respond to this standard
 treatment and have refractory HE. Hence newer drugs with effective improvement in HE and
 better side effect profile are still being tested.

 Polyethylene glycol (PEG) is in a class of medications called osmotic laxatives which works
 by causing water to be retained with the stool. PEG and lactulose, when used together, result
 in rapid overt HE resolution within 24 hours compared to the standard-of-care lactulose,
 suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis
 hospitalized for acute HE.

 Rationale Non-absorbable disaccharides like lactulose are associated with non-serious (mainly
 gastrointestinal) adverse events like diarrhea and bloating, hence, due to the side effect
 profile, newer drugs continue to be tested for treatment of HE.

 Hypothesis and Aim The aim of this research project is to compare the effect of PEG with
 Lactulose for treatment of Hepatic Encephalopathy in patients with liver cirrhosis. The
 investigators want to compare the resolution of HE as the main outcome. In addition, they
 would compare length of stay, non-serious (mainly gastrointestinal) adverse events, and 3
 months outcome. The investigators hypothesize that rapid purgation of the gut using PEG may
 resolve HE more effectively than lactulose.

 These aims are original in that the investigators aim to test this hypothesis on a different
 patient population (South Asian), where the predominant cause of cirrhosis is due to viral
 hepatitis C and B. In addition,the investigators will also look at the effect of PEG v
 lactulose on 3 months outcome in this study.

 Significance The significance of this proposal is that if the investigators can prove the
 hypothesis, it will add to the currently limited evidence on use of PEG in treatment of HE in
 the world. PEG might have a better side effect profile when compared to lactulose. Based on
 current market pricing of lactulose, if PEG is found to have favorable outcome then it might
 be more cost effective as well. Hence PEG might be a useful alternative in 30% of those who
 don't respond to lactulose, if PEG shows favorable outcome.

 Objective Primary: To determine the effect of PEG versus Lactulose on resolution of HE in
 patients with liver cirrhosis during inpatient stay at 24 hours, 48 hours and 72 hours .

 Secondary: To determine the effect of Lactulose versus PEG on length of stay, and 3 months
 outcome in patients with liver cirrhosis.
Inclusion Criteria:

 1. All patients of 18-80 years admitted to Aga Khan University Hospital

 2. With Chronic liver disease: Chronic liver disease will be defined based on
 ultra-sonographic evidence of chronic liver disease including shrunken liver, dilated
 portal vein, splenomegaly.

 3. With Hepatic encephalopathy; Hepatic encephalopathy will be defined as the onset of
 disorientation or asterixis according to The International Society for Hepatic
 Encephalopathy and Nitrogen Metabolism consensus and will be assessed using HESA score

 4. Presence of first degree relative for consent (Next of kin)

 Exclusion Criteria:

 1. Allergy to PEG

 2. Bowel obstruction or perforation diagnosed clinically or on Xray

 3. Major psychiatric illness; on benzodiazepines

 4. Treated with locally acting antibiotics (rifaximin) in the previous 7 days;

 5. Active gastrointestinal tract bleeding

 6. Acute Liver failure:defined as coagulopathy (international normalized ratio >1.5) with
 any degree of AMS in the absence of underlying chronic liver disease (CLD)

 7. Female patients if pregnant or lactating