Purpose of this study is to assess the therapeutic efficacy of L-alanine in improving
biological and histological findings by administrating 6-18g/day L-alanine for one year. We
will also assess the safety and toxicity profile of long-term administration of L-alanine.
- Males and females, age between 18 and 75
- Histological diagnosis of steatohepatitis with or without fibrosis made within one
year of entry
- Transaminase levels (ALT or AST) more than 1.5 times the upper normal limit on at
least two occasions with one assessment in three months or more prior to treatment of
- Previous and current alcohol consumption less than 20g per day by patient-provided
- Written informed consent specific for this protocol available prior to entry.
- Patients with diabetes and on stable medical management for six months prior to entry
and an anticipated stable program throughout the study will be eligible. Medications
that may be used include insulin, biguanides and sulfonylureas.
- Patients with congestive heart failure, hypertension and arrhythmia controlled by
medications and without cardiac episodes during the past 6 months will be eligible.
- Any causes for liver disease other than nonalcoholic steatohepatitis that are
confirmed by patient history, laboratory data, or histological data
- Decompensated liver disease based on laboratory data, or clinical manifestations
1. Hemoglobin <11.0g/dl for male, <10.0 g/dl for female
2. White blood cells <2000 /mm3
3. Platelet count <50,000/mm3
4. Prothrombin time >INR 1.5
5. Total Bilirubin >2.0 g/dl
6. Albumin <3.0/dl
7. The presence of ascites
8. The presence of bleeding varices
9. The presence of spontaneous encephalopathy
- Any previous experimental treatment of NASH within the past 3 months such as betaine,
thiazolidinediones, α-tocopherol, or UDCA
- Pre-existing diseases/situations that could interfere with the results or the
completion of this trial.
- Uncontrolled diabetes mellitus meeting following criteria in previous 3 months
1. Fasting blood sugar >200 mg/dl
2. Hemoglobin A1c >12%
- Renal or liver transplant patients
- Renal dysfunction in previous 3 months
a) CCr <50ml/min
- Severe cardiovascular dysfunction in previous 6 months
- Congestive heart failure
- Uncontrolled hypertension
- Uncontrolled arrhythmia
- Patients with hyperlipidemia on a medical program for control of lipids which has had
a change in drug treatment in the proceeding six months or with anticipated changes
in the year of the study.
- Chronic pulmonary disease such as COPD requiring corticosteroid therapy in previous 3
- Active autoimmune or immunologically mediated diseases including systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel diseases in previous 12
- Previous (in three years) or present malignant disease except for non-melanoma skin
- Untreated hyperthyroidism and hypothyroidism
- Substance abuse of oral, I.V., or inhaled drugs.
- If patients with history of substance abuse are considered as participants in this
trial, patients must have abstained from using the abused substance for at least one
- Patients receiving methadone within the past 6 months are also excluded.
- Any other conditions that would make the patients unsuitable for enrollment in the
opinion of the investigator in terms of interference in completing the trial and/or
results of trial.
- Pregnant women
- Unwillingness of patients and /or partner to use contraceptive during treatment and
for 3 months after discontinuation of treatment.