Pentoxiphylline and Vitamin E Versus Vitamin E in Patients With Non- Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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120 patients of biopsy proven NASH will be randomized into two groups. Cases group will receive combination of pentoxiphylline and Vitamin E, and control group will receive only Vitamin E.

Detailed Description
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The investigators plan to randomise 120 patients of biopsy proven NASH into cases and control groups. Baseline investigations: Clinical characteristics Age Gender Anthropometry (BMI, waist circumference, waist- hip ratio, triceps skin fold thickness, mid arm circumference) Alcohol intake should be nil Laboratory characteristics Hemogram, INR, KFT LFT (especially ALT, GGT) , APRI (AST to platelet ratio) Fasting Lipid Profile Other possible etiologies of liver disease (viral markers, ferritin, ANA, IgG, ceruloplasmin ) HOMA-IR (II) Serum uric acid levels Liver stiffness Fibroscan MR elastography Radiological characteristics USG abdomen Variceal status by UGI endoscopy Alpha fetoprotein Pro- inflammatory markers TNF-alpha, IL-6, adiponectin, leptin and osteopontin Liver biopsy and NAS score

Official Title
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A Randomized Controlled Project to Study the Efficacy of Combined Pentoxiphylline and Vitamin E Versus Vitamin E in Patients With Non- Alcoholic Steatohepatitis

Conditions
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Non Alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: pentoxiphylline and Vitamin E
* Drug: Vitamin E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 years Persistently abnormal ALT >1.2 times upper limit of normal Histological evidence of NASH/cirrhosis on liver biopsy. ( The minimal criteria for diagnosis of NASH included the presence of lobular inflammation and either ballooning of cells or perisinusoidal or pericellular fibrosis in Zone 3 of the hepatic acinus) Exclusion Criteria: A known case of Type 2 diabetes mellitus on treatment Alcohol intake of more than 40gm / week If they had evidence of cirrhosis with significant portal hypertension Ongoing total parenteral nutrition/ jejunal-ileal bypass Other known liver disease (Hepatitis A to E, autoimmune liver disease, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis) Medication like estrogens, amiodarone, MTx, tamoxifen, ATT Pregnancy or lactation Hypersensitivity to methylxanthines (e.g., caffeine, theophylline, theobromine ) Recent retinal/cerebral hemorrhage Acute myocardial infarction or severe cardiac arrhythmias Impaired renal function Hypothyroidism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pentoxiphylline and Vitamin E<br> | Drug: pentoxiphylline and Vitamin E<br>* Patients in cases group (Group 1) will receive pentoxiphylline (PTX) 400 mg thrice daily and vitamin E 800 IU/day.<br>|
| Active Comparator: Vitamin E<br> | Drug: Vitamin E<br>* Patients in control group will receive vitamin E 800 IU/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| histological outcome in the form of improvement or non- progression in hepatocyte injury and fibrosis (NAS score). |  | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response in form of anthropometry , HOMA-IR, fasting lipid profiles, biochemical response in form of normalization of ALT and AST levels and reduction in uric |  | 3 Months |