A Study of Controlled Lactulose Withdrawal
A Study of Controlled Lactulose Withdrawal
After resolution of the initial episode of hepatic encephalopathy (HE), lactulose is
 routinely continued indefinitely as maintenance therapy. Although widely used for this
 indication, lactulose has never been shown in randomized, controlled trials to be effective
 for preventing exacerbations of HE. Indeed, lactulose was found to be ineffective at
 preventing HE when administered prophylactically to patients undergoing portosystemic shunt
 insertion. While some patients may be lactulose dependent following an initial episode of HE,
 it is likely that most could have their lactulose discontinued with no adverse consequences.

 This goal is worth pursuing because lactulose is not innocuous. It has an unpleasant taste,
 and it routinely produces gastrointestinal symptoms, including bloating, gas and diarrhea. In
 high doses it can cause incontinence, dehydration and electrolyte derangements. Patients
 universally dislike taking lactulose and often are noncompliant with treatment. A recent
 trial showed that patients on lactulose had a substantial risk of hospital admissions due to
 lactulose-related complications and treatment non-compliance.
In this pilot study we propose to perform controlled lactulose withdrawal in selected
 patients with HE whose initial presentation follows a clearly defined, reversible
 precipitating event or those with stable, chronic HE. We hypothesize that a majority of these
 patients can be withdrawn from daily lactulose therapy without deterioration of cognitive
 function, and that lactulose withdrawal will improve symptoms and quality of life for these
 individuals. We propose to carry out a comprehensive battery of clinical, laboratory,
 microbiological and psychometric evaluations before and after lactulose withdrawal. We will
 closely follow changes in cognitive function and re-institute lactulose therapy at the first
 sign of clinical deterioration. Through multivariate analysis we propose to develop a model
 to discriminate between treatment dependent and treatment independent patients.
Inclusion Criteria:

 -  Diagnosis of hepatic cirrhosis based on biopsy, clinical and/or radiological findings.

 -  Stable HE (chronic): On daily lactulose for more than 6 months without hospitalization
 for HE within 3 months of enrollment.

 -  Treated with lactulose on a daily basis, with restoration of mental status to
 baseline.

 -  Lives with an adult individual who is willing to serve as a full-time caregiver.

 -  Able and willing to give informed consent.

 Exclusion Criteria:

 -  Use of antibiotics, including rifaximin.

 -  Patient without an adult caregiver.

 -  Pre-existing focal neurological deficits, seizures or other indication of structural
 neurological disorder.

 -  Actively abusing illicit drugs or alcohol.