Effect of Dietary and Life Style Modification on Post Liver Transplant Obesity

This study is designed to be an interventional, prospective, randomized, case-control
clinical trial. Procedures will be done in Starzl Transplant Institute and Center for Liver
disease, Kaufmann building, UPMC.

Subjects selected to participate in this study, are adult liver transplant recipients who had
undergone one liver transplantation during 6 months before the time of inclusion. They must
be able to communicate in English (to be able to independently follow directives and record
their activities in recall diaries). Patients will be excluded from the study if they are
under 18 years old, refuse to give a written consent to participate in the study, have
received liver graft more than 6 months before time of inclusion, have psychological or
nervous disorders, have cardiovascular or musculoskeletal health problems interfering with
basic physical activity, or have any manifestation of hepatic failure such as ascites and
hepatic encephalopathy. Patients will be removed from the study if they develop intolerance
to the dietary and physical recommendations (e.g. remarkable fatigue).

Verifying the eligibility of patients for participation in the study will be done through
reviewing data in medical history, physical examination and investigations included in the
patients' medical records. Complete blood count, liver function tests, fasting glucose and
lipid profile, imaging and histopathologic investigations, abdominal imaging, pathology
reports of liver biopsy, stress ECG, echocardiography. These tests are performed for standard
of care.

Subjects will be randomly grouped into groups by simple randomization method. One of the
investigators will randomly pick one folded paper out of a plastic bag that contains folded
papers labeled on the folded side with the number of the group.

The first group (Group 1) will include the control subjects. They will receive one session of
dietary and behavioral education. The second group (Group 2) will be the interventional
group. They will receive a weight management and life style modification program similar to
what has been previously described (Kelley et al. 2004). The program will be presented by a
registered dietitian at UPMC". It consists of up to 6 weekly sessions of nutritional and
physical exercise education. These initial sessions will concentrate on lifestyle
modifications program including healthy food selections, emphasizing reduced fat consumption
(<=30% of daily calories) and restriction of proteins to create a daily negative energy
balance of ~500 kcal/day. Participants will be encouraged to start with 10 minutes of outdoor
or at home physical activity such as walking or cycling then gradually increase the activity
duration up to 30 minutes daily. The dietitian will provide each subject with diary for daily
recording of dietary intake and physical activity respectively. Following the initial 6-week
program patients will attend follow up session every 6 months for 5 years for dietary and
behavioral education and to check dietary and physical activity diaries, reinforce and
encourage compliance with dietary and physical exercise recommendations, answer questions and
address problems. Patients will be required to attend at least 60% of the follow up sessions
on site with face to face education. Attempts will be made to schedule these sessions on the
same day of their regular clinical follow up to facilitate compliance. Up to 40% of monthly
follow up sessions may be provided on the phone for patients who cannot attend on site
because of travel restraints. The dietitian will call the candidate within few days after the
missing appointment to check and encourage compliance, check for changes in weight. Each
session will be held for up to 1 hour at the health education room of center for liver
diseases. All sessions will be with a registered dietitian.

Additional 5 cc of blood will be taken at routine blood draws done twice in the first month
then every 6 months for 5 years. The total blood volume withdrawn from each subject in both
study groups is 60 cc. Blood will be spinned down, then serum will be banked in -80° Celsius
freezer. These banked serum will be used in future research work aiming to assess activity of
inflammatory and fibrotic markers such as tumor necrosis factor alpha, interleukin 6, leptin,
and adiponectin.

Stool samples will be taken from all patients before study intervention and every 12 weeks
afterwards. Stool samples will be stored at -80 degree Celsius freezer for future PCR study
of fecal microflra.

Jennifer Steel will assess stress for the study candidates through specific questionnaire
before start of intervention of the study and every 12 weeks afterwards.

The following data will be collected every 6 months during follow up visits for both groups;
anthropometric indices of obesity such as measurements of weight, height (for BMI
calculation), waist circumference, hip circumference, skin fold thickness and mid-arm
circumference, survival rate, morbidity events such as cardiovascular or cerbrovascular
events, diabetes and hypertension. For the control group, anthropometric measures will be
obtained from them when they return for their routine clinic visits. Midarm circumference and
triceps skin fold thickness will be measured to the nearest 1 cm, on the left arm midway
between the tip of the acromion and the tip of olecranon. Skinfold thicknesses will be
measured at triceps (Oppert et al. 2002). Waist circumference will be measured midway between
iliac crest and lowest rib margin, and hip circumference at the level of the greater
trochanters (Han et al. 2001).

Histological scores of necro-inflammation (Ishak score) and steatosis (Dixon's scale) of the
implanted liver will be assessed at 1 year post transplant. All pathological evaluation will
be done on parts (allocated for the research purpose) of biopsies obtained as deemed
necessary for routine care by clinical providers (e.g. at 1 year post liver transplant) and
will be conducted by the same pathologist blinded to the experimental protocol.

Data will be compared between the 2 groups by Chi square test and student t test . Assuming a
rate of obesity in the control group of 50% and a 50% reduction of obesity incidence in the
interventional group, we estimate that a sample size of 58 per group is needed to detect the
difference with 80% confidence and a p value < 0.05. A p< 0.05 will be considered
significant.

Inclusion Criteria:

- Adult liver transplant recipients

- Those who have undergone one liver transplantation during 3 months before the time of
inclusion.

- Ability to communicate in English (to be able to independently follow directives and
record their activities in recall diaries).

Exclusion Criteria:

- Patients under 18 years old

- refusal to give a written consent to participate in the study

- Those who received liver graft more than 3 months before time of inclusion

- Significant cardiovascular or musculoskeletal health problems interfering with basic
physical activity

- Any manifestations of hepatic failure such as ascites and hepatic encephalopathy

- Patients will be removed from the study if they develop intolerance to the dietary and
physical recommendations (e.g. remarkable fatigue).