Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis

Study Overview
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Brief Summary
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The aim of the present study is to evaluate the efficacy and safety of pentoxifylline in the treatment of non-alcoholic steatohepatitis patients.

Detailed Description
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Nonalcoholic steatohepatitis(NASH) is the progressive form of Non-alcoholic fatty liver disease (NAFLD), is characterized by hepatocellular damage, inflammation, and liver fibrosis that can progress to cirrhosis, in 25% of patients, NAFLD progresses to NASH, which increases the risk for the development of cirrhosis, liver failure, and hepatocellular carcinoma. In patients with NASH, liver fibrosis is the main determinant of mortality. Pentoxifylline (PTX) is a xanthine derivative drug with a wide range of actions at the cellular and molecular level. PTX possess anti-inflammatory, antioxidant activities. PTX have potential role in improvement of NASH . Also, PTX inhibits a number of pro-inflammatory cytokines including interleukin-1, interleukin-6 and tumor necrosis factor (TNF-α ) which play an important role in the pathogenesis and progression of NASH.

Official Title
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Effectiveness and Safety of Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: pentoxifylline (Trental SR®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18- 60 years old. Both sexes Patients who have nonalcoholic steatohepatitis (NASH) will be diagnosed by clinical examination (obese, high body mass index). radiological criteria of fatty liver (abdominal ultrasonography). laboratory investigation (elevated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT). The ability to give informed consent Appropriate exclusion of other liver diseases Exclusion Criteria: 1- Patients with other diagnosed chronic liver diseases as viral hepatitis, metabolic and genetic disorders as Hemochromatosis, Wilson disease, autoimmune hepatitis and drug induced liver disease as well as patients with recent infection and those who refused to be entitled in the study. 2. Patients will be excluded if they had a history of past excessive alcohol drinking for a period longer than 2 years at any time in the past 10 years. 3. Patients also will be excluded if they take medications known to cause steatosis or taking medications that have shown benefits in previous NASH pilot studies, including vitamin E, , thiazolidinedione, and alpha-glucosidase inhibitors. 4. Patients with a history of hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, and theobromine) will be excluded, as well as those with a history of cerebral

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Clinical trial, parallel, randomized, prospective, controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pentoxifylline Group<br>25 patients will receive pentoxifylline (Trental SR®) 400 mg three times daily with their standard therapy for 6 months. | Drug: pentoxifylline (Trental SR®)<br>* 400 mg three times daily<br>|
| No Intervention: Control Group<br>25 patients will receive their standard therapy only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in liver aminotransferases(ALT and AST) | Difference between last and first measurements | 6 months compared to the baseline | 
| NAFLD fibrosis score (NFS) | Change in NAFLD fibrosis score (NFS) (lower score means better outcome). | 6 months compared to the baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Aspartate (AST) to Platelet Ratio Index (APRI) score: | Change in (APRI) score (lower score means better outcome). | 6 months compared to the baseline | 
| The Fibrosis-4 (FIB-4) values: | Change in (FIB-4) values (lower values means better outcome). | 6 months compared to the baseline | 
| Serum Alkaline Phosphatase level (ALP) | Change in ALP serum level as inflammatory markers of NASH | 6 months compared to the baseline | 
| Serum Gamma-glutamyl Transferase level (GGT) | Change in GGT serum level as inflammatory markers of NASH | 6 months compared to the baseline | 
| Serum total and direct bilirubin. | Change in levels of serum total and direct bilirubin. | 6 months compared to the baseline | 
| Waist circumference | Change in waist circumference | 6 months compared to the baseline | 
| Change in anthropometric measures | including BMI etc. | 6 months compared to the baseline | 
| Lipid profile | Change in serum lipids | 6 months compared to the baseline | 
| Glycated hemoglobin (HbA1C) | Change in HbA1C level for patients with T2DM | 6 months compared to the baseline | 
| Fasting blood glucose level | Change in fasting blood glucose for patients with T2DM | 6 months compared to the baseline | 
| Drugs adverse events | Assessment of safety by reporting any adverse events | 6 months compared to the baseline |