Hepatology Clinical Studies

U-M Hepatology Program Join a Clinical Study

Clinical studies help to find better treatments and diagnostic tests that may benefit future patients. Some studies may provide participants early access to newer treatments.

  • the ability to be given a new intervention that may be better or have fewer side effects than their current treatment
  • gaining a better understanding of their disease or condition
  • additional advice, care, and support from trained clinical staff who understand the disease or condition

Partner with us as we advance medicine. Search our clinical studies below!

  • If you have any questions about one of our clinical studies, please contact the study coordinator, whose name appears at the end of the description of each study.

Acute Liver Failure

Acute liver failure and acute liver injury observational study

Enrollment status: OPEN

A multi-center NIH study initiated in 1997 is looking at acute liver failure and severe acute liver injury in adults. The aim of this study is to gather prospective demographic and clinical data on patients with acute liver failure and acute liver injury with varying etiologies.

Inclusion criteria

  • INR ≥ 1.5 with or without encephalopathy due to any cause

Informed consent may be obtained from a family member.

Blood and urine samples, clinical data, and survival will be obtained × 7 days.

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu


The use of PPIs, benzodiazepines, opiates, and anticonvulsants in patients with advanced liver disease

Enrollment status: OPEN

To support a multilevel intervention focused on achieving proper medication management for those at risk of developing decompensated liver disease.

  • Inclusion criteria
  • Adult (18+ years of age)
  • Able and willing to provide informed consent
  • Diagnosis of cirrhosis confirmed by one or more of the following:
    • Histology
    • Radiographic or elastographic evidence
    • Esophageal or gastric varices on endoscopy AND presence of chronic liver disease

Main exclusion criteria

  • Lack of fluency in spoken English
  • Unable or unwilling to provide consent
  • Severe cognitive impairment

Contacts for referrals or questions:

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu


ALF-MBT: 13C-methacetin breath test (MBT) for the prediction of outcome in acute liver failure (ALF)

Enrollment status: OPEN

To assess the safety and utility of the 13C-methacetin breath test system in predicting survival in adult patients with acute liver failure.

Inclusion criteria

  • Adult men or women (18–70 years of age)
  • Severe acute liver injury
  • INR ≥ 1.5
  • Presence of any degree of hepatic encephalopathy
  • Duration of illness <26 weeks
  • Enrolled in the Acute Liver Failure Study Group (ALFSG) registry

Informed consent may be obtained from a family member.

Test will be performed on Day 1, 2, 3, 5, and 7 of study enrollment.

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu

Cirrhosis

National Cancer Institute Early Detection Research Network (EDRN) Hepatocellular Carcinoma Early Detection Study (HEDS)

Enrollment status: CLOSED, follow-up ongoing

Primary objective

To determine the incidence rate and the performance of ultrasound, and the biomarkers, alpha-fetoprotein (AFP), AFP-L3%, and des-gamma carboxy-prothrombin (DCP), in detecting preclinical hepatocellular carcinoma (HCC), as well as evaluate the performance of novel biomarkers for the detection of preclinical HCC.

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥ 18 years of age
  • Diagnosis of cirrhosis based on:
    • Histology
    • US, MRI or CT showing cirrhotic appearing liver with splenomegaly and platelet count of <120 mm3
    • Elastography, done by ultrasound or MRI showing a cirrhotic liver
    • A FibroTest result of F4 (stage 4), indicating cirrhosis
    • Varices on endoscopy or an abdominal imaging test AND presence of chronic liver disease

Main exclusion criteria

  • Ongoing significant hepatic decompensation
  • Listed for liver transplant as “exception”
  • AIDS related diseases
  • Cancer history in last 5 years (excluding non-melanoma skin cancer)
  • Immunosuppressive therapy

Principal investigator: Neehar Parikh, MD, MS • ndparikh@med.umich.edu

Study coordinator: Austin Fobar, MS, MPH • afobar@med.umich.edu


PAL-LIVER study (PALiative Care for LIVER disease): Introducing palliative care (PC) within the treatment of end stage liver disease (ESLD): A cluster randomized controlled trial

Enrollment status: OPEN

Primary objective

To assess the comparative effectiveness of two Palliative Care Delivery models for patients with end stage liver disease on improving quality of life (QOL).

Main inclusion and exclusion criteria

Patients willing to participate will be asked to select a caregiver to participate in the study. A caregiver is defined as someone who knows the patient well and is involved in their routine medical care. A caregiver must consent and be willing to attend the initial intervention visit along with the patient.

Inclusion criteria: Patients

  1. Age >18 years old
  2. Patient and Caregiver willing to sign informed consent
  3. Able to read/understand English
  4. Either of the following two clinical criteria:
    1. CTP Class B or C cirrhosis with one of the following (new or ongoing) within the prior 6 months from the date of consent:
      1. Ascites (requiring diuretics)
      2. Spontaneous bacterial peritonitis (SBP)
      3. Hepatic hydrothorax (requiring diuretics)
      4. Variceal bleed (with 1 or more recurrences)
      5. Overt hepatic encephalopathy (requiring medications)
      6. Type 2 hepatorenal syndrome
    2. Hepatocellular Cancer (HCC)
      1. Any BCLC (except Stage D) with CTP class B OR
      2. BCLC Stage C with CTP class A

Exclusion criteria: Patients

  1. Hepatologist-estimated life expectancy of less than 6 months
  2. Prior liver transplant
  3. MELD>30 at the time of enrollment
  4. Patients who, in the judgment of the investigator, are likely to undergo liver transplantation within 3 months of enrollment
  5. Lacks capacity to provide informed consent, including those with stage 2 HE or higher at the time of consent
  6. Patients who are already receiving, or who have received palliative care prior to study entry (within the past 1 year)

Inclusion criteria: Caregivers

  1. Identified caregiver of ESLD patients
  2. Age>18
  3. Able to read/understand English
  4. Providing direct care for at least >10 hours per week

Exclusion criteria: Caregivers

  1. Impaired cognitive function

Study design

This is a two-armed cluster randomized controlled trial (RCT). Randomization will take place at the level of clinical centers, and will be stratified by VA vs non-VA. Each arm will have 7 clinical centers. Standardized protocols (including visit agenda) will be followed at each of the clinical centers to maintain intervention fidelity across sites.

Model 1: Consultative PC (i.e., consultation with a board-certified or board-eligible PC specialist provider)

Model 2: Trained hepatologist-led PC intervention (i.e., hepatologist trained to deliver PC services)

The University of Michigan is a hepatologist-led site (Model 2).

All patients and caregivers participating in this study will receive palliative care intervention at an initial visit, followed by 1, 2, and 3 months. The intervention will comprise an approach to render palliative care, as taught to hepatologists through an on-line learning platform.  The elements of the intervention will follow a palliative care checklist, to include:

  1. Patient/caregiver understanding of diagnosis, illness, and prognosis
  2. Symptom assessment and management
  3. Psychosocial assessment and management
  4. Distress screening and management
  5. Discussion of goals of care
  6. Advanced directives

The intervention is delivered over the course of initial, 1, 2, and 3 month visits, each approximately one hour in duration.

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


Predictors and impact of hepatic encephalopathy

Enrollment status: CLOSED, follow-up ongoing

Primary objective

To determine the predictors of hepatic encephalopathy (HE) in people with cirrhosis followed for up to 3 years. We are evaluating the usefulness of new biomarkers and risk factors that may help to predict the development of HE. If we predict HE, something for which tools are currently lacking, this information could be used to develop preventive interventions 

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥ 18 years of age
  • Standard blood tests ordered by clinicians within 180 days of the date of consent
  • Diagnosis of cirrhosis based on one or more of the following:
    • Histology
    • Radiographic or elastographic evidence of cirrhosis
    • Esophageal or gastric varices on endoscopy AND presence of chronic liver disease

Main exclusion criteria

  • History of HE
  • Significant mobility limitations
  • Child–Pugh Class C
  • Significant co-morbid medical conditions with life expectancy less than 1 year
  • Prior liver transplant

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


What matters to patients with liver disease?

Enrollment status: OPEN

Primary objective

Cirrhosis is a chronic condition for which there is substantial value in efforts to prevent long-term, costly complications. These include ascites, variceal hemorrhage and, the most devastating, hepatic encephalopathy. Yet, no study to date has asked patients which are the most meaningful outcomes for them, limiting our power to tailor interventions and assess their benefits. We are evaluating several previously unevaluated dimensions of health state utility in patients with cirrhosis using a prospective, cross-sectional survey design via a structured patient interview.

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥ 18 years of age
  • Diagnosis of cirrhosis based on one or more of the following:
    • Histology
    • Radiographic or elastographic evidence of cirrhosis
    • Esophageal or gastric varices on endoscopy AND presence of chronic liver disease

Main exclusion criteria

  • Lack of fluency in spoken English
  • Unable or unwilling to provide consent
  • History of liver transplant
  • Severe cognitive impairment

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


Safety and efficacy of terlipressin in hepatorenal syndrome (HRS) type 1

Enrollment status: OPEN

Objective

This is a phase 3, randomized, double-blind, placebo-controlled, multicenter trial to confirm the safety and efficacy of terlipressin in subjects with hepatorenal syndrome (HRS) type 1. HRS type 1 is a rare condition that can occur in patients with cirrhosis, decompensated liver disease, and portal hypertension. HRS type 1 is characterized by rapid progressive renal injury and has a very poor prognosis with >80% mortality within 3 months. At present, there are no approved drug therapies for HRS type 1 in the United States or Canada. The only cure for HRS type 1 and the underlying end-stage cirrhosis is liver transplantation; however, many patients will not survive long enough to receive a liver transplant. Terlipressin is an investigational vasoconstrictive drug that may improve renal function in patients with HRS type 1. There is substantial data available from many published clinical investigations that provide compelling evidence of terlipressin's efficacy in patients with HRS type 1.

Michigan Medicine is one of sites that is actively enrolling subjects for this clinical trial. A total of 300 subjects are planned to be enrolled at about 70 sites in the United States and Canada. For more information about this trial, please see https://clinicaltrials.gov/ct/show/NCT02770716.

Inclusion criteria

  • Adult patients (outpatients and inpatients) >18 years of age at Michigan Medicine
  • Patients with chronic liver disease – cirrhosis + ascites
  • Patients with acute renal failure (worsening serum creatinine within last two weeks reaching 2.25 mg/dL or above)
  • No granular casts on urine microscopy, proteinuria < 500 mg/day
  • Able and willing to provide an informed consent

Exclusion criteria

  • Patients with renal failure caused by acute tubular necrosis (ATN), nephrotoxic drugs, or contrast-induced injury
  • Renal replacement therapy
  • Unable and unwilling to provide an informed consent

For full inclusion and exclusion criteria, please inquire.

Contact person:


Preferences of patients undergoing surveillance of hepatocellular carcinoma

Enrollment status: OPEN

Objective

Analyze patient perspective on various aspects of surveillance for and therapy of HCC through the use of conjoint methodology

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥ 18 years of age
  • Undergoing HCC surveillance due to cirrhosis or HBV diagnosis

Exclusion criteria

  • History of or current diagnosis of HCC
  • Active hepatic encephalopathy
  • No English
  • Dementia or other type of cognitive impairment

Principal investigator: Neehar Parikh, MD, MS • ndparikh@med.umich.edu

Study coordinator: Austin Fobar, MS, MPH • afobar@med.umich.edu

Drug-Induced Liver Injury

Idiosyncratic liver injury associated with drugs (ILIAD): A retrospective study

Enrollment status: OPEN

The goal of the ILIAD protocol is to create a database and bank of biological specimens (DNA, plasma, lymphocytes) from individuals with severe drug-induced liver injury (DILI) due to drugs, or herbal and dietary supplements (HDS) and complementary and alternative medications (CAM) after January 1, 1994. This study is funded by the NIH/NIDDK.

Study design

  • Telephone or personal interview of medical history surrounding DILI event
  • Single blood draw
  • Participant receives up to $100

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu


A multi-center, longitudinal study of drug-induced and complementary and alternative medication—induced liver injury

Enrollment status: OPEN

The goal of this multicenter NIH study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications (CAM) within 6 months of onset. Clinical data, blood, DNA, and urine will be collected from affected patients and matched controls for mechanistic and genetic studies.

Study design

  • All subjects have a baseline and 6-month follow-up visit at Michigan Medicine, which includes surveys, medical history, and blood and urine collection.
  • Patients with liver injury at 6 months return for 12-, 36-, and 48-month visits.

Costs

  • Costs of study lab tests provided by sponsor (NIDDK).
  • Subjects receive $50 for each completed study visit.

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu


For more information on drug-induced liver injury, see the following websites:

Drug-Induced Liver Injury Network: http://www.dilin.org

NIDDK LiverTox website: http://www.livertox.nih.gov/

Hepatitis B

NIH Hepatitis B Research Network

In September 2008, the NIH launched a Hepatitis B Research Network (http://www.hepbnet.org) comprised of 29 clinical centers (adult and pediatric), a data coordinating center, and an immunology laboratory. The University of Michigan is one of the clinical centers and Dr. Anna Lok chairs the network's steering committee.

This network conducts observational studies as well as clinical studies of new treatment strategies.

Hepatitis B Research Network — Observational Study

Enrollment status: CLOSED, follow-up ongoing

Objective

To study the pattern of hepatitis B in North America and the rates of transition through different phases of chronic HBV infection

Inclusion criteria

  • Adult patients with hepatitis B who are currently not on any antiviral therapy for hepatitis B (exception: pregnant women).

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu


Hepatitis B Research Network — Immune-Active Trial

Combination therapy of peginterferon alfa-2a and tenofovir versus tenofovir monotherapy in HBeAg-positive and HBeAg-negative chronic hepatitis B

Enrollment status: CLOSED, Follow-up ongoing

Objective

To compare the long-term efficacy of initial treatment with combination therapy consisting of peginterferon alfa-2a plus tenofovir DF versus tenofovir DF monotherapy.

Inclusion/exclusion criteria

  • Adults with chronic hepatitis B infection, slightly abnormal liver enzyme levels (ALT >45 IU/mL for males and >30 IU/mL for females), no or limited previous antiviral treatment.
  • Patients with cirrhosis can be included provided no liver failure
  • Normal kidney function, no major medical or psychosocial illnesses, can tolerate interferon

Study design

This is a randomized (1:1) trial comparing

  1. Tenofovir DF 300 mg daily for 192 weeks (4 years) and
  2. Peginterferon alfa-2a 180 µg weekly for 24 weeks plus tenofovir DF 300 mg daily for 192 weeks (4 years).

Note: The cost of medications, clinical evaluations, and tests associated with the study will be covered.

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu 


TARGET HBV: An observational study of patients undergoing therapy for chronic hepatitis B (HBV) infection

Enrollment status: OPEN

Objective

The purpose of this research is to learn more about people who have been diagnosed with hepatitis B and how they are managed in clinical practice.

Inclusion criteria

  • Adult patients with hepatitis B who are on a stable antiviral therapy regimen for hepatitis B

Study design

  • Data extracted from medical records
  • Participants complete survey
  • No research-specific visits

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Christopher Foster, (734) 647-0236 • fostechj@med.umich.edu

Hepatitis C

DAA Salvage B16-439: A phase 3b, multi-center, randomized, open-label, pragmatic study of glecaprevir/pibrentasvir (G/P) +/- ribavirin for GT1 subjects with chronic hepatitis C previously treated with an NS5A inhibitor + sofosbuvir therapy

Sponsor: University of Florida / AbbVie

Enrollment status: CLOSED, follow-up ongoing

Objective

Safety and sustained virologic response rates of glecaprevir/pibrentasvir (G/P).

Inclusion criteria

  • Chronic hepatitis C genotype 1
  • Without cirrhosis or with compensated cirrhosis
  • Prior NS5A-inhibtor plus sofosbuvir +/- ribavirin treatment experience (eg, Harvoni®, Epclusa®, or Daklinza™ failure)

Exclusion criteria

  • Prior treatment with combination of protease inhibitor and NS5A inhibitor at any time (eg, Viekira™ or Zepatier® failure)
  • Significant medical illnesses or recent drug/alcohol abuse
  • Liver failure
  • Unable to comply with protocol and study visits

Study design

  • Eligible patients will be randomized to:
    • Arm A: G/P (300 mg /120 mg QD) for 12 weeks
    • Arm B: G/P (300 mg /120 mg QD) for 16 weeks
    • Arm C: G/P (300 mg /120 mg QD) + weight-based ribavirin for 12 weeks
    • Arm D: G/P (300 mg /120 mg QD) for 16 weeks
  • Arms A and B for patients without cirrhosis, and Arms C and D for those with compensated cirrhosis
  • Follow-up visits until 12 weeks after completion of treatment
  • Study medications and tests associated with the study will be covered by the sponsor

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza, (734) 615-3853 • sravanth@med.umich.edu


The PRIORITIZE Study: A pragmatic, randomized study of oral regimens for hepatitis C: Transforming decision-making for patients, providers, and stakeholders

Sponsor: University of Florida / Patient-Centered Outcomes Research Institute (PCORI)

Enrollment status: CLOSED, follow-up ongoing

Objective

PRIORITIZE will be able to compare the effectiveness of FDA-approved medicines for HCV, side effects reported by patients, treatment adherence, and to see if patients' liver disease improves or worsens after treatment.

Inclusion criteria

  • Chronic hepatitis C genotype 1
  • No cirrhosis or compensated cirrhosis
  • Harvoni® covered by patient's insurance

Exclusion criteria

  • Child B/C cirrhosis

Study design

  • Subjects will be randomly assigned to one of two FDA-approved oral medicines for hepatitis C: 1) Harvoni® or 2) Zepatier™.
  • Subjects randomized to Zepatier™ will receive drugs from the study sponsor while those randomized to Harvoni® will have drugs covered by insurance and usual co-pay applies.
  • Subjects will have up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (if subject provides additional consent).
  • Management during the course of treatment will be per standard of care and determined by the clinic liver doctor.
  • Subjects will complete questionnaires before HCV treatment, during, at the end and 1 and 3 years after treatment. Subjects will be compensated for their time and participation.

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Christopher Foster, (734) 647-0236 • fostechj@med.umich.edu 


Hepatitis C therapeutic registry and research network (HCV-TARGET) – a longitudinal, observational study

Sponsor: University of Florida, University of North Carolina

Enrollment status: CLOSED, follow-up ongoing

Eligibility criteria

  • Any HCV patient receiving direct-acting antiviral drug therapy

Objective

To collect and study information on patients with chronic hepatitis C virus who are being treated with direct-acting antiviral agents in a “real world” patient population to determine:

  • Effectiveness of these drugs in differing patient populations
  • Compare treatment durations in differing groups of patients
  • How best to manage side effects
  • Genetic variances in drug response
  • Drug-to-drug interactions
  • Patient education — group versus individual
  • Pharmacy usage
  • Drug resistance

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Christopher Foster, (734) 647-0236 • fostechj@med.umich.edu 

Hepatocellular Carcinoma

A 5-year longitudinal observational study of patients with hepatocellular carcinoma (TARGET–HCC)

Sponsor: TARGET PharmaSolutions

Enrollment status: OPEN

Objective

The goal of this research study is to observe the clinical course of patients diagnosed with HCC in a "real-life" setting. Researchers are interested in collecting information and blood/tissue samples in order to develop predictors of disease progression.

Inclusion criteria

  • Adult patients (age > 18 years) with any history of HCC diagnosed by imaging or pathology within the last 3 years

Exclusion criteria

  • None

Study design

  • Medical records will be collected from date of consent going back 3 years and forward 5 years from the date of consent.
  • Optional Patient-Reported Outcome Survey annually
  • Optional Biorepository Specimen Bank annually. Patients who agree to participate in the Biorepository Specimen Bank will be paid $25 for each blood draw.
  • Optional Post-Authorization Safety Study of Early Recurrence of Hepatocellular Carcinoma in HCV-Infected Patients after Direct-Acting Antiviral Therapy
    • This study will also look at data from a specific period of time for patients with hepatitis C following successful HCC treatment and compare information from those who get direct-acting antiviral drugs to treat their hepatitis C to those who do not get direct-acting antiviral drugs. People who have a specific type or degree of HCC and meet the sub-study requirements, including having hepatitis C, may be asked to participate.

Principal investigator

Contact person


Blood Sample Collection to Evaluate Biomarkers for Hepatocellular Carcinoma

Sponsor: Exact Sciences

Enrollment Status: OPEN

Objective

The primary objective of this study is to obtain de-identified, clinically characterized whole blood specimens for use in developing and evaluating the performance of new biomarker assays for detection of hepatocellular carcinoma (HCC).

Inclusion Criteria

  • HCC Subjects
    • Subject has a recent (within 6 months of enrollment) untreated clinically diagnosed hepatocellular carcinoma as defined by ≥1 cm lesion exhibiting arterial phase hyperenhancement in combination with washout appearance and/or capsule by 4 phase CT scan or multiphase contrast enhanced MRI or biopsy is positive for HCC.
  • Control
    • Non-cancer subject undergoing routine imaging surveillance for HCC
    • Definitive lack of HCC within 3 months prior to enrollment as defined by negative imaging, for HCC.
      • Control Group 1 - negative by ultrasound
      • Control Group 2 - negative by CT or MRI

Exclusion Criteria

  • Known cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers).
  • Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
  • Prior or current treatment with sorafenib, regorafenib, or other treatment indicated for HCC.
  • Any HCC treatment prior to enrollment/blood sample collection (e.g., surgery, ablation, embolization, pharmacotherapy, radiotherapy, liver transplant or other treatment indicated for HCC).
  • IV contrast (e.g. CT and MRI) within 1 day [or 24 hours] of blood collection.
  • Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
  • Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
  • Individual has a condition the Investigator believes would interfere with his or her ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.

Study Design

Subjects with untreated hepatocellular carcinoma (HCC) and subjects undergoing HCC surveillance will be enrolled and have blood samples collected. Subjects undergoing HCC surveillance will be followed for up to 6 months. Another blood sample will be collected at the 6-month visit which will be scheduled no longer than 6 months from enrollment.

Principal Investigator

Contact Person


Michigan Hepatocellular Carcinoma Early Detection Study

Enrollment status: OPEN

Objective

The aim of this study is to create an ongoing biorepository of longitudinally collected biospecimens from a cohort of cirrhosis patients, that will form a reference set to be used for future biomarker validation research.

Inclusion Criteria

  • Age ≥ 18 years of age
  • Ultrasound or other imaging within 6 months prior to consent showing no liver mass
  • Diagnosis of cirrhosis based on history of hepatic decompensation, histology, imaging, or elastography

Exclusion Criteria

  • Clinical evidence of significant hepatic decompensation:
    • Refractory ascites requiring paracentesis
    • Overt encephalopathy requiring lactulose or rifaximin
    • Hepatorenal syndrome
    • Child Class C
  • History of HCC
  • Significant co-morbid medical conditions with life expectancy less than one year
  • Cancer history within the last 2 years (excluding non-melanoma skin cancer)
  • Prior solid organ transplant

Study Design

  • Blood samples will be collected on the day of consent, at 6 months, and yearly thereafter.
  • If a liver biopsy is indicated for clinical care, any surplus tissue specimen will be collected.
  • Alcohol and tobacco questionnaire will be administered at baseline, and an Audit-C questionnaire will be administered at follow-up visits.

Principal investigator

Study coordinator


Biorepository of Blood and Liver Tumor Tissue Samples

Enrollment status: OPEN

Objective

The aim of this study is to create an ongoing biorepository of blood samples and liver tumor tissue to help identify protein and genetic signatures that may improve diagnostic and prognostic capabilities in patients with liver cancers.

Inclusion Criteria

  • Patients with hepatocellular carcinoma or colorectal metastases to the liver (patients with CRC metastases eligible if they received prior systemic chemotherapy or resection of primary tumor); ages 18-99

Exclusion Criteria

  • None

Study Design

  • Blood samples will on the day of consent, at 6 months and yearly thereafter.
  • We will measure QOL using the PROMIS Global Health Scale and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) instrument (Appendix 3.) The Global Health Scale is derived from the PROMIS assessment center and provides a 10-item assessment of global health related QOL within the 7 days of assessment.

Principal Investigator

Contact Person

Liver Transplant

Improving Kidney Outcomes in Liver Transplant Recipients

HUM00115731 & HUM00119820

Enrollment status: OPEN

Objective

Liver transplantation (LT) is the standard of care for decompensated cirrhosis. These patients are at a higher risk of developing chronic kidney disease after LT associated with high morbidity, mortality and healthcare costs. Patient-level interventions directed at risk factors have shown to improve health outcomes in chronic diseases. The feasibility of these interventions in improving patient outcomes has not been studied among LT recipients. Our overarching goal is to improve kidney outcomes among liver transplant recipients. The aims of this study are to assess the knowledge of chronic kidney disease knowledge among liver transplant recipients and examine the effect of personalized intervention(s) targeting the risk factors for chronic kidney disease on kidney function.

Inclusion criteria

  • Adult patients >18 years of age (out-patients and in-patients) at the University of Michigan
  • Patients who have received liver transplants between 2005 and 2016
  • Patients who are at least 3 months after transplant
  • Able and willing to provide an informed consent

Exclusion criteria

  • Unable and unwilling to provide an informed consent

For full inclusion and exclusion criteria, please inquire.

Contact Persons

Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH)

Intercept 747-304: A phase 3, double-blind, randomized, placebo-controlled, multicenter study to evaluate the efficacy and safety of obeticholic acid in subjects with compensated cirrhosis due to nonalcoholic steatohepatitis

Sponsor: Intercept Pharmaceuticals

Enrollment status: OPEN 

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03439254

Objective

The sponsor is conducting this study to find out how safe and effective the investigational drug obeticholic acid (also known as OCA) may be in improving compensated cirrhosis caused by nonalcoholic steatohepatitis (also known as NASH).

Inclusion criteria

  • Adults
  • Confirmed diagnosis of NASH with fibrosis score of 4 based on NASH-CRN

Exclusion criteria

  • Other liver disease
  • Current or past history of decompensated cirrhosis
  • Varices on EGD

Study design

  • Eligible patients will be randomized 1:1:1 to receive OCA 10 mg daily, OCA 10 mg to 25 mg daily, or placebo for 1-year.
  • There will be an optional 1-year open-label extension afterward. Everyone will receive OCA at that time.
  • Compensation provided

Principal Investigator: Hari Conjeevaram, MD

Contact person: Elizabeth Wu, (734) 764-4048 or elizwu@med.umich.edu


SARO.16.005: A phase 2, prospective, multicenter, double-blind, randomized study of saroglitazar magnesium 1 mg, 2mg or 4 mg versus placebo in patients with nonalcoholic fatty liver disease and/or nonalcoholic steatohepatitis

Sponsor: Zydus Discovery DMCC

Enrollment status: CLOSED, follow-up ongoing

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03061721

Objective

To investigate the effect of a 16-week treatment regimen of saroglitazar magnesium 1 mg, 2 mg or 4 mg on serum alanine aminotransferase (ALT) levels in patients with nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).

Inclusion Criteria

  • Adults, 18 to 75 years of age
  • Confirmed diagnosis of NAFLD established either by imaging (ultrasound, CT scan or MRI) or liver biopsy showing NASH
  • ALT level of ≥50 U/L

Exclusion criteria

  • Consumption of > 3 units of alcohol per day if male and > 2 units of alcohol per day if female 
  • Presence of alternative causes of fatty liver
  • History of other chronic liver disease
  • Patient has known cirrhosis
  • Type 1 diabetes
  • Poorly controlled type 2 diabetes 

Study design

  • Eligible patients will be randomized 1:1:1:1 to receive saroglitazar magnesium 1 mg daily, saroglitazar magnesium 2 mg daily, saroglitazar magnesium 4 mg daily or placebo for 16 weeks

Principal Investigator: Hari Conjeevaram, MD

Contact person: Elizabeth Wu, (734) 764-4048 or elizwu@med.umich.edu


A 5-year longitudinal observational study of patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (TARGET-NASH)

Sponsor: TARGET PharmaSolutions

Enrollment status: OPEN

Objective

The goal of this research study is to observe any treatment for NAFLD/NASH in a large number of people in a "real-life" setting. Researchers are interested in observing how lifestyle changes, counseling, or other treatments work in patients who are treated by their doctors in routine practice.

Inclusion criteria

  • NAFLD diagnosed by imaging
  • NASH diagnosed by liver biopsy OR by imaging + elevated ALT + 1 or more of the following: obesity, type 2 diabetes, dyslipidemia

Exclusion criteria

  • Other chronic liver disease, including alcohol-induced liver disease
  • Current participation in another NASH registry or clinical trial

Study design

  • Patients will be followed for up to 5 years. Medical records will be collected
  • Optional Patient Reported Outcome Survey annually
  • Optional Biorepository Specimen Bank annually. Patients who agree to participate in the Biorepository Specimen Bank will be paid $25 for each blood draw.

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Christopher Foster, (734) 647-0236 or fostechj@med.umich.edu


University of Michigan–Peking University Joint Initiative

Role of visceral adiposity in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in lean versus obese patients: A comparative study between patients at University of Michigan Health System versus Peking University Health Science Center

Enrollment status: CLOSED, follow-up ongoing

Objective

To use a novel technique, analytic morphomics, to quantify visceral adipose tissue, ectopic adipose tissue and quality of fat in lean persons with NAFLD versus lean persons with no NAFLD and obese persons with NAFLD to understand why some lean persons develop fatty liver and to understand the role of fat in the abdomen on development of fatty liver.

Inclusion criteria

  • Adults 18+ with nonalcoholic fatty liver disease

Exclusion criteria

  • Other causes of liver disease (hepatitis B, hepatitis C, alcohol, etc)
  • Other causes of fat in the liver
  • History or plans to undergo bariatric surgery
  • Current use of weight reduction medications
  • Liver failure or liver cancer
  • Women who are pregnant

Study design

  • Subjects will undergo a thin slice CT scan to capture images of the abdomen and to apply analytic morphomics (special computer analysis) to measure quantity and quality of fat in abdomen
  • Subjects will give blood samples to test for markers of fatty liver, glucose and lipid levels
  • Subjects will complete 3 diet recalls
  • Compensation provided

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Sravanthi Kaza, (734) 615-3853 or sravanth@med.umich.edu


A randomized controlled pilot trial of a structured mobile technology based lifestyle program vs usual care for patients with nonalcoholic fatty liver disease

Enrollment status: OPEN

Objective

The aim of this study is to compare the effectiveness of usual care to a mobile technology based lifestyle intervention on change in liver and metabolic related parameters. Additionally, the study aims to identify predictors associated with reduction in hepatic steatosis and weight loss.

This is a structured mobile technology (Fitbit)-based study of NAFLD patients evaluated and managed in the Michigan Medicine Hepatology Clinic. Clinical data collection and surveys will be administered during a routine clinic visit or during an elective research visit through the clinical research center at baseline, at 6 months and 12 months follow-up visits. Patients in the intervention arm will receive the Fitbit during their baseline clinic visit and patients in the usual care arm will receive the Fitbit during their 6-month follow-up visit. The Fitbit will be used to track physical activity of patients in both arms for a total of 6 months each. During their Fitbit trial, patients will also be provided with personalized weekly feedback on step count.

Inclusion criteria

  • Adult patients over 18 years old
  • Diagnosis of NAFLD or nonalcoholic steatohepatitis (NASH)
  • Ability to communicate in English as primary language
  • Able to give informed consent
  • Must be able to participate in basic physical activity (i.e., regular walking)

Exclusion criteria

  • Significant alcohol use (defined based on clinical diagnosis or report of >7 drinks per week in women and >14 drinks per week in men)
  • Co-existing liver disease, such as viral hepatitis B or C, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, Wilson disease, or alcohol-related liver disease.
  • Evidence of hepatic decompensation (past or present), including variceal bleeding, ascites, hepatic encephalopathy, or hepatocellular carcinoma
  • Inability to make dietary modifications due to significant medical co-morbidity (including but not limited to severe, uncontrolled diabetes)

Principal investigator: Monica Tincopa, MD, MSc, tincopa@med.umich.edu

Contact person: Haila Asefa, (734) 232-0284 or asefa@med.umich.edu


Nonalcoholic Fatty Liver Disease Blood and Tissue Repository

Enrollment status: OPEN

Objective

The aim of the study is to develop a repository of blood (plasma and serum), liver tissue and clinical information from patients who are diagnosed with NAFLD or NASH. The samples will be stored indefinitely and utilized for future research to better understand clinical phenotypes of NAFLD/NASH, and better predict disease progression, as well as guide the management of future patients

Inclusion criteria

  • Adult patients over 18 years old
  • Ability to communicate in English as a primary language
  • Diagnosis of NAFLD or NASH

Exclusion criteria

  • Significant alcohol use (defined based on clinical diagnosis or report of >7 drinks per week in women and >14 drinks per week in men)
  • Co-existing liver disease, such as viral hepatitis B or C, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, Wilson disease, or alcohol-related liver disease.
  • Current or prior history of decompensated cirrhosis: variceal bleeding, ascites, hepatic encephalopathy, or hepatocellular carcinoma
  • Medications known to cause hepatic steatosis or other alternative causes of hepatic steatosis: mediations include steroids, tamoxifen, amiodarone, certain highly active anti-retroviral therapy (HAART), valproate, methotrexate.
  • Active substance abuse or psychiatric disease
  • Current participation in pharmacological clinical trial for NAFLD/NASH. Those with prior participation are eligible.
  • Pregnancy

Principal investigator: Monica Tincopa, MD, MSc, tincopa@med.umich.edu

Contact person: Haila Asefa, (734) 232-0284 or asefah@med.umich.edu

Primary Biliary Cholangitis (PBC)

A phase 2, prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium in patients with primary biliary cholangitis (PBC)

Sponsor: Zydus Discovery DMCC

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03112681

Enrollment status: OPEN

Objective

The sponsor is conducting this study to evaluate the safety, tolerability, and efficacy of the investigational drug saroglitazar magnesium in patients with PBC. This drug is labelled investigational because it has not been approved by the Food and Drug Administration (FDA) for the treatment of PBC 

Inclusion

  • Adults, between 18-75 years of age
  • Patients on therapeutic doses of ursodeoxycholic acid (UDCA) for ≥12 months and stable therapy for ≥3 months prior to enrollment or Patients who are unable to tolerate UDCA, and did not receive UDCA for at least 3 months from the date of screening
  • History of confirmed primary biliary cholangitis diagnosis as demonstrated by the presence of at least two of the following three diagnostic factors:
    1. History of elevated alkaline phosphatase levels for at least 6 months prior to Screening Visit 1
    2. Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
    3. Liver biopsy consistent with PBC

Exclusion

  • Consumption of >3 units of alcohol per day (>21 units per week) if male and >2 units of alcohol per day (>14 units per week) if female
  • Other liver disease
  • Cirrhosis with complications

Study Design

  • Eligible subjects will be randomized 1:1:1 to one of three treatment groups: either 2 mg saroglitazar magnesium, 4 mg saroglitazar magnesium, or placebo for treatment period of 16 weeks
  • The duration of the study will be approximately 26 weeks including: screening period, treatment period, and safety follow-up period 

Principal investigator: Frederick Askari, MD faskari@med.umich.edu

Contact person: Elizabeth Wu, (734) 764-4048 or elizwu@med.umich.edu


TARGET PBC

A 5-year longitudinal observational study of patients with primary biliary cholangitis

Enrollment status: OPENS in July 2019

Objective

The purpose of this research is to learn more about people who have been diagnosed with primary biliary cholangitis and how they are managed in clinical practice.

Inclusion criteria

  • Adult patients who are being treated or managed for primary biliary cholangitis

Study design

  • Data extracted from medical records
  • Participants complete optional surveys and annual blood sample
  • No research-specific visits

Principal investigator: Anna Lok, MD aslok@med.umich.edu

Contact person: Christopher Foster: (734) 647-0236 or fostechj@med.umich.edu

Blood, Tissue, and Urine Repositories

Liver Disease Blood and Tissue Repository

Enrollment status: OPEN

Objective

The main objective of the Liver Disease Blood and Tissue Repository is to facilitate clinical and translational research. The repository of blood samples (plasma and serum), liver tissue samples, and urine samples will be used by clinical and translational researchers to answer questions related to the pathophysiology and clinical outcomes of chronic liver disease. The samples will be used to evaluate the utility of available markers for the diagnosis and prognosis of various liver diseases, including fatty liver, viral hepatitis, and liver cancer, and to discover new biomarkers, such as biomarkers for liver fibrosis and liver cancer. We hope these studies will help us to better predict disease severity and progression of chronic liver disease and guide the management of patients in the future.

Inclusion criteria

  • All adult patients >18 years of age (out-patients and in-patients) undergoing a liver biopsy at the University of Michigan.
  • Patients with all liver diseases (acute or chronic) will be enrolled, including patients who are post-liver transplant.
  • Able and willing to provide an informed consent.

Exclusion criteria

  • Unable and unwilling to provide an informed consent.

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Sravanthi Kaza, (734) 615-3853 or sravanth@med.umich.edu


Liver Transplant Blood and Urine Repository

HUM00100527

Enrollment status: OPEN

Objective

The rapid development of genomics, proteomics, and metabolomics have significantly increased the potential for productive translational research in transplantation, and many current research protocols in solid organ transplantation utilize blood and urinary specimens, in an effort to establish relationships between biologic markers, histological findings, and clinical outcomes. The main objective of the Liver Transplant Blood and Urine Repository is to facilitate clinical and translational research to utilize blood, cells and urine from patients who are candidates or have received a transplanted liver along with relevant medical record information to study clinical outcome and to discover new pathways and biomarkers to predict disease progression and guide future management.

Inclusion criteria

  • Living or deceased donor liver transplant candidates and recipients.
  • Male or female, 18 years or older.
  • Subject must be able to understand and provide informed consent.

Exclusion criteria

  • Recipients of multiple organ transplants, with the exception of simultaneous liver and kidney transplants.
  • Unable and unwilling to provide an informed consent.

For full inclusion and exclusion criteria, please contact the research staff.

Contact persons

Wilson Disease

A phase 3, randomized, rater-blinded, multicentre study to evaluate the efficacy and safety of ALXN1840 administered for 48 weeks versus standard of care in patients with Wilson disease aged 12 and older, with an extension phase of up to 60 months

Sponsor: Wilson Therapeutics AB

Enrollment status: OPEN

Study description

The purpose of the clinical study is to evaluate the safety and effectiveness of an investigational medication (ALXN1840) compared to standard-of-care treatment in patients with Wilson disease. This medication is considered "investigational" because it has not been approved by the Food and Drug Administration (FDA) to treat Wilson disease. ALXN1840 has the potential to address the unmet needs in Wilson disease by possibly reducing the amount of copper buildup in the body.

Eligibility

You may be eligible to participate in the clinical study if you meet the following criteria:

  • Aged 12 years or older
  • Established diagnosis of Wilson Disease
  • Have normal or elevated free copper blood levels
  • Have hepatic or neurological symptoms, or both
  • Are in otherwise good health
  • Willing to undergo at least a 48-hour washout from current Wilson Disease treatments if you receive the investigational medication

Study design

If you are eligible and agree to participate in the study, you will be randomly assigned to receive either treatment with ALXN1840 or regular standard of care treatment. Once the treatment period is completed, study participants may choose to receive ALXN1840 for up to an additional 60 months.

Principal investigator: Fred Askari, MD, PhD faskari@med.umich.edu

Study coordinator: Elizabeth Wu, (734) 764-4048 or elizwu@med.umich.edu