Comparing the Effects of Vitamin E, Ursodeoxycholic Acid and Pentoxyfylline on Egyptian Non-alcoholic Steatohepatitis (NASH) Patients

Kafrelsheikh University

Status and phase: Completed; Phase 4

Conditions: Nonalcoholic Steatohepatitis (NASH)

Treatments: Drug: Ursodeoxycholic acid; Drug: Vitamin E; Drug: Pentoxifylline

Study type: Interventional

Funder types: Other

Identifiers

NCT04977661

154569224578

Details and patient eligibility

About

We conducted a 3-month, randomized, single-blind study in 102 Egyptian NASH patients who were divided into three groups; group 1 included 34 patients received Vit. E 400 mg twice a day, group 2 included 34 patients received UDCA 250 mg twice a day and group 3 included 34 patients received PTX 400 mg twice daily for 3 months. The following parameters were measured both before and after intervention intake; liver aminotransferases (AST, ALT), cytokine and chemokine (IL6 and CCL2/MPC-1), albumin, total bilirubin, direct bilirubin, total cholesterol, triglyceride, LDL, HDL.

Full description

This was a 3-month, prospective, randomized, and single blind study. Participants were recruited from the outpatient clinic and hepatology, gastroenterology and infectious diseases department at Kafrelsheikh University Hospital between February 2020 and January 2021. Two-hundred and five Egyptian patients diagnosed with NAFLD with potential clinical inclusion criteria were invited for a screening session to determine their eligibility for the study. Patients were enrolled in the study if they are > 18 years old, had evidence for NASH; persistently elevated alanine aminotransferase (ALT) >1.5 times the upper limit of normal), imaging (ultrasound) showing fatty infiltration, and histological evidence of NASH after biopsy (macrovascular steatosis, ballooning degeneration of hepatocytes, scattered lobular inflammation and apoptotic bodies).One hundred and forty-six patients were excluded from the study either because they did not meet the inclusion criteria (n = 135) or refused to enroll in the study (n =11). Qualifying participants (n = 102) were randomly assigned to one of the three treatment groups using a computer-generated randomization sequence. Group I (n = 34) received 400 IU Vitamin E (Vitamin E 400 IU®, MEPACO Pharmaceutical Company, Sharqia, Egypt) twice daily for 3 months. Group II (n =34) received 250 mg Ursodeoxycholic acid (Ursofalk 250 mg®, MINAPHARM Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months. Group III (n = 34) received 400 mg sustained release (SR) Film-Coated Tablets of pentoxifylline (Trental 400 mg®, SANOFI Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months. Patients were followed up every week to ensure compliance, drug adherence and to report side effects or drop out from the study.The following parameters were measured both before and after intervention intake; liver aminotransferases (AST, ALT), cytokine and chemokine (IL6 and CCL2/MPC-1), albumin, total bilirubin, direct bilirubin, total cholesterol, triglyceride, LDL, HDL.

Enrollment: 102 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients were enrolled in the study

  1. if they are > 18 years old
  2. had evidence for NASH; persistently elevated alanine aminotransferase (ALT) >1.5 times the upper limit of normal)
  3. imaging (ultrasound) showing fatty infiltration, and histological evidence of NASH after biopsy (macrovascular steatosis, ballooning degeneration of hepatocytes, scattered lobular inflammation and apoptotic bodies).

Exclusion criteria

• Patients were ruled out if they had

  1. history of alcohol dependence
  2. treatment with drugs known to induce NASH (e.g. amiodarone, calcium channel blocker, tamoxifen, oral anticoagulation, methotrexate , steroids and estrogen)
  3. positive serologic markers for known chronic liver diseases (hepatitis B surface antigen, anti-hepatitis C virus antibody antinuclear antibody)
  4. human immunodeficiency virus (HIV) infection
  5. Diabetes
  6. decompensated liver disease defined as serum bilirubin level >1 mg/dL, albumin level ˂3.5 g/dL, and international normalized ratio (INR) ≥1.7.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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102 participants in 3 patient groups

Group1

Active Comparator group

Description:

Group I (n = 34) received 400 IU Vitamin E (Vitamin E 400 IU®, MEPACO Pharmaceutical Company, Sharqia, Egypt) twice daily for 3 month

Treatment:

Drug: Vitamin E

Group2

Active Comparator group

Description:

Group II (n =34) received 250 mg Ursodeoxycholic acid (Ursofalk 250 mg®, MINAPHARM Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months

Treatment:

Drug: Ursodeoxycholic acid

Group3

Active Comparator group

Description:

Group III (n = 34) received 400 mg sustained release (SR) Film-Coated Tablets of pentoxifylline (Trental 400 mg®, SANOFI Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months

Treatment:

Drug: Pentoxifylline