Alcohol, Gut Leakiness, & Liver Disease

Inclusion criteria

There are 4 different categories of participants that were used for recruitment:

Healthy controls

• Subjects must have a normal physical exam
• No GI complaints
• No known liver disease
• Normal liver function tests (ALT, AST, bilirubin, alkaline phosphatase, serum albumin)
• Consume no more than a moderate amount of alcohol (NIAAA definition [1 ]).
• These subjects should not be daily drinkers (< 3x / week) and should typically drink < 3 drinks per occasion.

Alcoholics

• Subjects should fulfill NIAAA criteria for at-risk drinking & alcohol abuse or dependence & DSM-IV criteria for alcoholism
• Each must have consumed alcohol regularly for at least the past 3 mos but must be sober for 3-7 day post-binge at the time of sugar test (except for group 7)
• Have a total regular heavy drinking history of at least 10 y (except for Group 6) the minimal period of time required for the development of ALD.

These are the different alcoholic groups and their specific inclusion criteria:

ALCOHOLICS WITHOUT LIVER DISEASE

• no clinical evidence of ALD on physical examination
• serum bilirubin or ALT or AST less than 1.25X normal
• sobriety must be <7 days at the time of sugar test.

ALCOHOLICS WITH LIVER DISEASE

• These subjects will have 1 of 3 possible grades of LD severity (mild, moderate, severe) & have either clinical evidence of LD (hepatomegaly, splenomegaly, and esophageal varices), or serum bilirubin or ALT or AST more than 1.5X normal.
• If liver biopsy or CT or ultrasound is available, there should be histological evidence of LD (alcoholic hepatitis or cirrhosis) or radiological evidence of LD (cirrhotic liver, splenomegaly, varices)
• Their sobriety must be <7 days at the time of the sugar test.

ALCOHOLICS WITH SHORT-TERM Drinking

• These subjects should fulfill the criteria of alcohol abuse
• have sobriety <7 days at the time of urine collection, but the duration of their heavy drinking must be <5 years
• They must not have any liver disease (negative serology) due to non-EtOH causes or clinical evidence of
• cirrhosis. Here, liver enzyme levels are not inclusion/exclusion criteria; but since the duration of EtOH abuse (<5 y) is too short for the development of cirrhosis, it is expected that none will have sustained elevated liver enzymes.

SOBER ALCOHOLICS WITH LD .

• Criteria is the same as Alcholics with liver disease but last drink was >7 days from the study enrollment.

Subjects with Non-alcoholic liver disease

• Criteria for LD are similar to those outlined for alcoholics with liver disease subjects except that drinking history should be similar to that of healthy volunteers. Subjects after liver transplant.
• These subjects must have successful liver transplantation at least 6 mos prior to the study and are on stable doses of immunosuppression for 3 mos.

Exclusion criteria

• Unreliable drinking history (to rule out closet drinkers or pretenders).
• Subjects must clearly fulfill the criteria either of "alcoholism" or of "on-drinker".
• Subjects with a drinking history of 5-9 years duration are excluded since this period is not short enough to preclude cirrhosis nor long enough to cause ALD in most subjects.
• Significant renal impairment (creatinine>l.2 mg/dL
• Diseases that affect GI motility such as scleroderma.
• insulin-requiring diabetes &/or uncontrolled diabetes (Hgb-Alc>8%)
• Clinically significant dehydration.
• clinically detectable ascites
• Significant peripheral edema
• Sepsis
• Clinically significant cardiac failure
• Regular daily use of medications that may affect intestinal permeability such as NSAIDS or intestinal motility (e.g. metoclopramide).
• Alcoholics positive for other markers of LD such as smooth muscle antibody, hepatitis B surface antigen, hepatitis C antibody or hemochromatosis
• Inability to sign an informed consent form
• Patients with low platelet count (<80k), uncorrectable prolonged PT (>15 sec), history of bleeding will be excluded from aspirin tests