Predicting Outcomes in Nonalcoholic Steatohepatitis With Advanced Fibrosis

Nonalcoholic Steatohepatitis (NASH) is a condition with increased amount of fat, inflammation and scarring in the liver. In compensated cirrhosis, the liver is coping with this damage and maintaining its important functions. Decompensation occurs when the liver becomes unable to perform all of its functions adequately. Variceal hemorrhage (bleeding from abnormal vessels in the liver called varices), Ascites (abnormal build-up of fluid in the abdomen), and Encephalopathy (brain confusion as a result of the liver not being able to get rid of toxic substances) are three symptoms of liver decompensation.

The purpose of this research study is to investigate better ways to routinely monitor the condition of patients with NASH with compensated cirrhosis and to better pinpoint the development of decompensation in the livers of these patients.

Study Overview

• Status: Recruiting
• Conditions: Nonalcoholic Steatohepatitis
• Intervention / Treatment: Other: Standard of care

Detailed Description

This clinical research study is done to investigate better ways to routinely monitor the condition of patients with Nonalcoholic Steatohepatitis (NASH) with compensated cirrhosis. The purpose of this study is to better pinpoint the development of decompensation in the livers of these patients (some symptoms are variceal hemorrhage, ascites, and encephalopathy, defined below).

NASH is a condition with increased amount of fat, inflammation and scarring in the liver. In compensated cirrhosis, the liver is coping with this damage and maintaining its important functions. Decompensation occurs when the liver becomes unable to perform all of its functions adequately. Variceal hemorrhage (bleeding from abnormal vessels in the liver called varices), Ascites (abnormal build-up of fluid in the abdomen), and Encephalopathy (brain confusion as a result of the liver not being able to get rid of toxic substances) are three symptoms of liver decompensation.

Aside from current routine procedures including blood draws, this study will check to see how effectively adding three additional procedures will help predict development of liver decompensation. These additional procedures are Spleen Stiffness Measurement (SSM) during a special liver ultrasound called a Fibroscan, an imagining scan called Magnetic Resonance Imagining (MRI) using a contrast agent called Gadoxetate Sodium to highlight cirrhosis, and an MRI scan called metabophenotype, which examines muscle composition of the liver.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Mohammad S Siddiqui, MD; Phone Number: 804-828-4060; Email: mohammad.siddiqui@vcuhealth.org

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Christopher Kigongo; Phone Number: 507-266-1998; Email: Kigongo.Christopher@mayo.edu
      • Contact: Mia Mahmoud; Phone Number: 507-284-0361; Email: Mahmoud.Mia@mayo.edu
      • Principal Investigator: Manal F. Abdelmalek, MD
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Mohammad Siddiqui, MD; Phone Number: 804-828-4060; Email: mohammad.siddiqui@vcuhealth.org
      • Principal Investigator: Mohammad Siddiqui, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with presence of NAFLD associated cirrhosis.

Description

Inclusion Criteria:

Adult patients with presence of NAFLD associated cirrhosis.

• Cirrhosis: biopsy confirmed or Agile F (F4) score > 0.45

• NAFLD as an etiology of liver disease will be determined based on presence of any of the following:

  • Biopsy showing >5% steatosis or
  • CAP > 280 dB/m or MR-PDFF>5%
  • If CAP < 280 dB/m or MR-PDFF <5%, then must have type 2 diabetes and or 2 or more features of metabolic syndrome for 5 years (cryptogenic cirrhosis)

Exclusion Criteria:

• Refusal to consent
• Alcohol use > 14/21 gm/week cutoff
• Other causes of chronic liver disease
• MELD > 12
• Hepatic and extrahepatic cancers expected to limit life expectancy < 2 yrs
• prior hepatic resections, TIPS, splenic embolization
• prior decompensation events
• inability to fit into MRI (failed hula-hoop test)
• general contraindication for MRI contrast (GFR < 30 ml/min)
• contraindications for MRI
• pregnancy
• acute kidney injury
• reduced kidney function (GFR <30ml/min)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
nonalcoholic steatohepatitis (NASH); Adult patients nonalcoholic steatohepatitis (NASH)	Other: Standard of care; Participants will receive the standard of care for their condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of deaths	Number of deaths will be determined from death records and patient charts.	Up to 2 years
Incidents of variceal hemorrhage	Number of participants showing bleeding from abnormal vessels in the liver called varices will be assessed using an endoscopy exam.	Up to 2 years
Incidents of ascites	Number of participants with experiencing abnormal build-up of fluid in the abdomen will be assessed using a clinical exam including an ultrasound graded per clinical standards.	Up to 2 years
Hepatic Encephalopathy (HE)	Number of grade 2, 3, or 4 HE events will be assessed by clinician during exams.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model For End-Stage Liver Disease (MELD) score	Number of participants with MELD scores greater than 15	Up to 2 years
Hepatocellular cancer (HCC)	Number of participants with HCC	Up to 2 years

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Mohammad S Siddiqui, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: HM20024296; 1R01DK129564 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No