A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study]

Completed

Brief Summary: This is a retrospective study in adult patients with cirrhosis and grade 3 or 4 HE (West Haven Criteria) to evaluate the effectiveness and safety of lactulose retention enema in the treatment of deep grade HE (West Haven Criteria). The study will be conducted retrospectively in a multi center of a multispecialty tertiary care hospital in India, in which lactulose retention enema is the mainstay of management of cirrhotic patients with grade 3 or 4 HE (West Haven criteria). Dosing of lactulose retention enema in this study will be done according to the dosing described for rectal administration of lactulose (India): 300ml of lactulose mixed with 700ml of potable water to be used as a retention enema; the enema is to be retained for 30-60 minutes and repeated every 4-6 hours until the patient is able to take oral medication. This treatment regime is also the standard protocol of management of deep grade HE (West Haven criteria) in the study centers. The standard treatment protocol of deep grade HE (West Haven criteria) of the study centers will also ensure that all known contraindications of lactulose will be respected before administration of lactulose retention enema to the study patients. The retrospective hospital records of the patient population of interest within the past 6 months will be identified, and these records will be used to collect data required for analysis.

Detailed Description: Data to be collected:

Data that would be collected for the study as part of retrospective chart review:

1. Patient demographics: age, gender, weight

2. Medical history

3. Etiology of cirrhosis (alcohol abuse, hepatitis, autoimmune, cryptogenic, other)

4. Diagnosis of cirrhosis

5. History of previous HE (if yes, the number of episodes in the past)

6. Grade of HE (as per the West-Haven criteria) at admission, 24 hrs and 48 hours post treatment with lactulose

7. Precipitating factor(s) of HE (Dehydration, GI bleeding, protein overload, constipation, infection, others)

8. Dose and duration of lactulose enema

9. Treatment given for precipitating factors

10. Laboratory data on haemoglobin, platelet, bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, sodium, potassium, and blood ammonia

11. Complete reversal of deep-grade HE (\< Grade 2 as per West-Haven criteria) (yes/no)

12. Time to complete reversal of deep-grade HE

13. Number of days in hospital

14. Adverse drug reaction experienced by the patient

15. Complications experienced by the patient

16. Other pharmacovigilance relevant information (OPRI)

Recruitment & Eligibility

Inclusion Criteria

Patients aged between 18 and 65 years of either gender.
Patients admitted to the hospital with liver cirrhosis and grade 3 or grade 4 (West Haven Criteria) HE
Patients treated with lactulose retention enema within 48 hours of onset of grade 3 or 4 (West Haven Criteria) HE

Exclusion Criteria

Patients treated with agents other than lactulose retention enema for grade 3 or 4 (West Haven Criteria) HE.
Patients who had significant concomitant diseases that could impair or contribute to the impairment of consciousness
Patients who had a major neuropsychiatric illness
Patients who had a contraindication to lactulose, including Hypersensitivity to the active substance or to any of the ingredients; Galactosaemia; Gastrointestinal obstruction, digestive perforation or risk of digestive perforation

Primary Outcome Measures

Name	Time	Method
Complete Reversal	48 hrs	Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema

Secondary Outcome Measures

Name	Time	Method
Time to Complete Reversal	up to 48 hrs	Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema
Mortality	within 48 hrs	Mortality in patients treated with lactulose retention enema
Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours	HE Grade shift at 24 hrs and HE Grade shift at 48 hrs	Grade shift at 24 and 48 hours - from baseline to 24 and 48 hours post administration of lactulose retention enema. Complete reversal of deep grade HE is defined as subjects having HE grade=\<grade 2 as per West-Haven criteria where grade 0 is Normal, Grade 1 is Mild lack of awareness, Grade 2 is Lethargic, Grade 3 is Somnolent but arousable and Grade 4 is Coma