Testosterone Replacement in Non-alcoholic Steatohepatitis (TEREPINS) (TEREPINS)

This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hypogonadism, testosterone replacement therapy Read More

Inclusion Criteria:

• Abnormal serum ALT on >2 occasions over at least 3 months, despite standard lifestyle advice when appropriate, in regard to moderation of alcohol intake, weight reduction and exercise.
• Negative serological tests for hepatitis Bs ag and C antibody.
• Alcohol consumption >21 units per week for no more than 2 week in the last year and for no more than 3 months of the past 5 years, assessed using a lifetime alcohol consumption questionnaire.
• Liver biopsy, performed as part of clinical management within 6 months of recruitment, which shows all of: (a) steatosis (Kleiner grade 2 or 3); (b) NASH (combined intralobular inflammation and hepatocyte ballooning score of >1); (c) fibrosis Ishak stage <4; and (d) no evidence to suggest another major liver disease.
• Hypotestosteronaemia, defined by total serum testosterone <11 nmol/L . Investigators predict that this will include about 25% of men with NAFLD as defined above.

Exclusion Criteria:

• Inability to give informed consent.
• Age <18 or >75 years.
• Symptomatic sexual dysfunction.
• Cirrhosis either on baseline liver biopsy (Ishak score 5-6) or suggested by presence of varices, by ultrasound (small shrunken liver, ascites, splenomegaly) or by liver decompensation (encephalopathy, abnormal serum direct bilirubin, albumin or prothrombin time).
• Space occupying lesion on ultrasound with any suspicion of malignancy.
• Evidence of other chronic liver diseases pace occupying lesion on ultrasound with any suspicion of malignancy.
• Prostatic nodule or mass on PR examination unless full urological examination rules our prostate cancer
• Serum PSA or alpha feta protein above the age-specific normal range
• Carcinoma of male breast
• Taking medications (amiodarone, anti-retrovirals, sodium alproate, corticosteroids, tamoxifen) the previous 3 months (known to improve steatosis).
• Diabetes or hyperlipidaemia, where therapy has been changed within the last 12 months or with suboptimal control anticipating the need for change in therapy during the study.
• Severe or complicated obesity, likely requiring bariatric surgery in next 2 years.
• LH/FSH levels, raising the possibility of primary pituitary disease.
• Subject trying to or hoping to conceive within next 18 months.
• Haematocrit of >0.54
• History of any of the following: Sleep apnoea, breast or prostate or liver cancer, congestive heart failure, chronic renal failure (serum creatinine >150), severe chronic obstructive airways disease, uncontrolled hypertension epilepsy depression or migraine.
• Severe co morbidity likely in the opinion of the investigators to reduce life expectancy to <10 years.
• Hypersensitivity to active agent or to any of the excipients.
• On long-term warfarin or heparin-based anticoagulant therapy. Treatment with antiplatelet agents will not be an exclusion criterion, however, these will be omitted at the time of liver biopsies, as per normal clinical practice.