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 30 days after clinically indicated systematic oral cleansing and interventions as well as 3-month hospitalizations post-cleaning.

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

Patients with cirrhosis and healthy controls will undergo dental examination and subsequent dental cleaning if necessary.

Relative change in serum endotoxin levels using LAL (limulus amebocyte lysate) assay will be measured before/after cleaning and between groups

Relative change in PHES battery (total standard deviations above normal performance)and EncephalApp Stroop values (seconds taken) will be measured before/after cleaning and between groups

Relative change in pg/ml of serum IL-6 (interleukin), IL-1b (interleukin) using ELISA assays will be measured before/after cleaning and between groups

All-cause, liver-related and elective hospitalizations at 3 months will be studied and compared between groups

Relative change in microbial composition using 16SrRNA multi-tagged sequencing in stool and saliva will be measured before/after cleaning and between groups

Inclusion criteria: Cirrhotic subjects: Age 21-75 years Able to give informed consent Cirrhosis diagnosed using biopsy or suggestive radiological features or endoscopic evidence of varices in a subject with chronic liver disease Healthy controls: Age 21-75 years Able to give informed consent Without chronic diseases Exclusion Criteria: Exclusions for all subjects (will be done at the screening visit at both clinics) Current use of absorbable antibiotics (use of antibiotics within 4 weeks) Diagnosed with severe chronic or aggressive forms of periodontitis based on American Academy of Periodontology Classification (5) Presence of more than 2 severe cavitated caries lesions Presence of oral soft-tissue lesions such as ulcers Presence of abscesses Unclear diagnosis of cirrhosis (for cirrhotics) Edentulous or less than 20 natural teeth Smoking, oral tobacco and alcohol abuse within 3 months Prisoners Pregnant women INR(international normalized ratio) >1.5 Platelet count <50,000 Diagnosed bleeding disorders Patients on anti-coagulation Patients who will otherwise be eligible for prophylactic antibiotics before dental cleaning Last dental cleaning within 3 months of study.