Oral Gut Liver Axis in Cirrhosis

This will be a prospective study of cirrhotics and healthy controls comparing their oral
microbiota, endotoxemia and systemic inflammation at baseline and at 10 and 30 days after
clinically indicated systematic oral cleansing and interventions as well as 3-month
hospitalizations post-cleaning.

The investigators will recruit cirrhotic subjects and age- matched healthy controls from the
hepatology clinics. Subjects will be informed regarding the study and will give the
investigators a written informed consent.

After informed consent and evaluation of eligibility, subjects will be asked to complete an
oral health questionnaire and sample collection during the recruitment visit. Patients will
then be scheduled for a dental exam during a separate screening visit up to 7 days after this
recruitment visit at the Dental Clinics.

At this time patients will undergo cognitive testing consisting of a validated cognitive
battery of PHES (psychometric hepatic encephalopathy score) and EncephalApp stroop. In
addition, they will undergo Sickness Impact Profile (a quality of life questionnaire).

During dental exam which will be done during screening visit, the subject will undergo
comprehensive oral evaluation which will include dental xrays (as needed) which are part of
the study, periodontal examination (determination of pocket depth, clinical attachment
levels, bleeding on probing, plaque index) and recording of caries and oral soft tissue
lesions. Dental cleaning is part of the study protocol and not intended to fully treat the
patient's periodontal and dental diseases. Therefore no follow-up dental visits will be
scheduled in the dental clinics after completion of dental cleansing.

The patients who do not qualify for the study will be informed of the findings by the dental
professionals and subsequently the patients need to make arrangements for their dental
treatment needs.

The study will include cirrhotic patients with/without hepatic encephalopathy. Subjects will
then be scheduled for dental cleaning which could occur over 1 or 2 visits as determined
during the screening exam.

Before the initiation of oral therapy, plaque and gingival crevicular samples will be
collected for microbiota. The subjects will receive deep dental cleanings (scaling and root
planing) and oral hygiene instructions as per clinical indication.

Subjects will then be followed at day 10 for clinical exam and day 30 at which point stool,
saliva and blood samples for the similar analyses as before will be collected. There will be
no more dental examinations after the initial assessment and treatment. We will repeat the
cognitive testing at day 30 using alternate forms of the same cognitive tests and also repeat
quality of life testing at day 30 .

The investigators will also follow them for up to 3 months post-cleaning for hospitalizations
using active chart review and follow-up

Inclusion criteria:

Cirrhotic subjects:

1. Age 21-75 years

2. Able to give informed consent

3. Cirrhosis diagnosed using biopsy or suggestive radiological features or endoscopic
evidence of varices in a subject with chronic liver disease

Healthy controls:

1. Age 21-75 years

2. Able to give informed consent

3. Without chronic diseases

Exclusion Criteria:

Exclusions for all subjects (will be done at the screening visit at both clinics)

1. Current use of absorbable antibiotics (use of antibiotics within 4 weeks)

2. Diagnosed with severe chronic or aggressive forms of periodontitis based on American
Academy of Periodontology Classification (5)

3. Presence of more than 2 severe cavitated caries lesions

4. Presence of oral soft-tissue lesions such as ulcers

5. Presence of abscesses

6. Unclear diagnosis of cirrhosis (for cirrhotics)

7. Edentulous or less than 20 natural teeth

8. Smoking, oral tobacco and alcohol abuse within 3 months

9. Prisoners

10. Pregnant women

11. INR(international normalized ratio) >1.5

12. Platelet count <50,000

13. Diagnosed bleeding disorders

14. Patients on anti-coagulation

15. Patients who will otherwise be eligible for prophylactic antibiotics before dental
cleaning

16. Last dental cleaning within 3 months of study.