Liver Cirrhosis Network Cohort Study (LCN-C)

Liver Cirrhosis Network (LCN) Cohort Study is an observational study designed to identify risk factors and develop prediction models for risk of decompensation in adults with liver cirrhosis. LCN Cohort Study involves multiple institutions and an anticipated 1200 participants. Enrolled participants will have study visits every 6 months (180 days), with opportunities to complete specific visit components via telehealth or remotely. Visits will include collection of questionnaire data and the in-person visits will include questionnaires, physical exams, imaging, and sample collection.

Study Overview

• Status: Active, not recruiting
• Conditions: Cirrhosis; Autoimmune Hepatitis; Cirrhosis, Liver; Cirrhosis Due to Hepatitis B; Cirrhosis Due to Hepatitis C; Cirrhosis Early; Cirrhosis Advanced; Cirrhosis Infectious; Cirrhosis Alcoholic; Cirrhosis, Biliary; Cirrhosis Cryptogenic; Cirrhosis Due to Primary Sclerosing Cholangitis

• Study Type: Observational
• Enrollment (Actual): 1222

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92035
      • University of California San Diego NAFLD Research Center
    • Los Angeles, California, United States, 90033
      • LAC + USC Medical Center
    • Los Angeles, California, United States, 90033
      • Keck Medical Center of USC
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
    • San Francisco, California, United States, 94110
      • UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
  • Florida
    • Miami, Florida, United States, 33122
      • University of Miami Health System
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian/Weill Cornell
    • New York, New York, United States, 10031
      • Columbia University Iriving School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Liver Center
  • Ohio
    • Cleveland, Ohio, United States, 44192
      • Cleveland Clinic
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • Central Virginia Veterans Healthcare System

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

The study will include participants with cirrhosis of the liver.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Willing to provide samples at baseline
• Cirrhosis

Where Cirrhosis is defined as:

1. At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis OR
2. At least 2 of the following:

1. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past year 2. Liver stiffness: VCTE within one year prior to consent or during Screening ≥12.5 kPa or MRE within one year prior to consent or during Screening ≥5 kPa 3. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening 4. Either: FIB-4>2.67 or platelets <150/mL within 6 months prior to consent or during Screening 5. >5 years METAVIR stage 4 fibrosis or Ishak stage 5-6

Exclusion Criteria:

• Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence
• Known prior solid organ transplant or bone marrow transplant
• Current participation in active medication treatment trials at the time of consent for LCN Cohort Study
• Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits
• Bariatric surgery in the last 180 days prior to consent
• Known history of fontan procedure-associated liver disease (FALD)
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol
• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ)
• Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis with 90 days prior to consent
• Documented cardiac cirrhosis
• Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax (including trace ascites discovered at screening not requiring intervention), hepatic encephalopathy or variceal bleeding. If a patient has had a history of decompensation, they must have been off any medications to treat decompensation for at least 365 days. Refer to the MOP for clarifying details on evaluating eligibility for patients with a history of prior decompensation.
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• Current model for end-stage liver disease (MELD-Na) cut off ≥ 15*
• Current Child-Turcotte-Pugh (CTP) B or C*
• Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR)
• Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy*
• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2X upper limit of normal (ULN) within 90 days prior to consent or during Screening*

• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 90 days prior to consent or during Screening*

  • Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 90 days prior to consent, it does not need to be re-done for eligibility.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-decompensation	Time-to-decompensation, defined as any of the following events: Ascites: definite as determined by adjudication; Hepatic Encephalopathy (HE): definite or highly likely as determined by adjudication; Portal hypertensive upper gastrointestinal (GI) bleeding: definite as determined by adjudication	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of decompensations	Number of decompensations (treated as a count variable in analyses)	3 years
All-cause mortality	All-cause mortality (treated as time-to-event in analyses)	3 years
All-cause hospitalizations	All-cause hospitalizations (treated as a count variable in analyses)	3 years
Number of liver-related hospitalizations	Liver-related hospitalizations (treated as a count variable in analyses)	3 years
Time to liver transplantation	Liver transplantation (treated as time-to-event in analyses)	3 years
Time to development of hepatocellular carcinoma (HCC)	Development of HCC (treated as time-to-event in analyses)	3 years
Time to development of portal and/or mesenteric vein thrombosis	Development of portal and/or mesenteric vein thrombosis (treated as time-to-event in analyses)	3 years
Change in liver stiffness as measured by vibration-controlled transient elastography (VCTE)	Liver stiffness as measured by VCTE (treated as continuous measure in analyses)	3 years
Degree of fibrosis as measured by fibrosis-4 index (FIB-4)	Degree of fibrosis as measured by FIB-4 (treated as continuous measure in analyses)	3 years
Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1)	Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1) relevant "T-scores," a continuous measure. T-scores are normalized to the population and are centered at 50 with anticipated standard deviation of 10. A higher score means better "health."	3 years
Change in cognitive function as measured by Stroop Test	Change in cognitive function as measured by Stroop Test (treated as continuous measure in analyses). Measured as time to complete the test. A higher score means longer time to complete, which means more impaired function. Minimum score is 0, and there is no maximum score.	3 years
Change in frailty as measured by the Liver Frailty Index	Change in frailty as measured by the Liver Frailty Index (treated as continuous measure in analyses). A higher score means the participant is more frail. The score is based on grip strength, number of chair stands per second, and balance time. https://liverfrailtyindex.ucsf.edu/ Maximum score of 6, and there is no minimum score.	3 years
Adjudicated liver-related mortality	Adjudicated liver-related mortality (treated as time-to-event in analyses)	3 years

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Cancer Institute (NCI); Mayo Clinic; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of California, San Diego; University of Miami; Columbia University; University of Michigan; The Cleveland Clinic; Duke University; University of Southern California; Weill Medical College of Cornell University; University of California, San Francisco; Virginia Commonwealth University; LAC+USC Medical Center; Central Virginia Veterans Healthcare System
• Investigators: Principal Investigator: Abigail Smith, Northwestern University

Publications and helpful links

General Publications

• Tapper EB, Goldberg D, Parikh ND, Terrault NA, Welch N, Sharpton S, Hameed B, Khalili M, Stolz A, Verna EC, Brown RS Jr, Sanyal AJ, VanWagner L, Ladner DP, Moylan CA, Diehl AM, Jones PD, Loomba R, Dasarathy S, Simonetto DA, Shah VH, Bajaj JS; LCN Study Group. The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints. Am J Gastroenterol. 2025 Mar 1;120(3):570-575. doi: 10.14309/ajg.0000000000002953. Epub 2024 Jul 17.

Helpful Links

• Information about the study

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Estimated): October 24, 2030
• Study Completion (Estimated): October 24, 2030

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NASH; Nonalcoholic steatohepatitis; Cirrhosis; Liver; Nonalcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Bile Duct Diseases; Hepatitis, Chronic; Cholestasis, Intrahepatic; Cholestasis; Hepatitis; Fatty Liver; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Pathological Conditions, Signs and Symptoms; Fibrosis; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Liver Cirrhosis, Biliary; Hepatitis, Autoimmune; Liver Cirrhosis, Alcoholic; Cirrhosis, Cryptogenic
• Other Study ID Numbers: LCN Cohort Study; 1U24DK130164-01 (U.S. NIH Grant/Contract); Pro00064389 (Other Identifier: Advarra, Inc.); 5U01DK130177-02 (U.S. NIH Grant/Contract); 5U01DK130197-02 (U.S. NIH Grant/Contract); 5U01DK130185-02 (U.S. NIH Grant/Contract); 5U01DK130180-02 (U.S. NIH Grant/Contract); 5U01DK130221-02 (U.S. NIH Grant/Contract); 5U01DK130134-02 (U.S. NIH Grant/Contract); 5U01DK130168-02 (U.S. NIH Grant/Contract); 5U01DK130190-02 (U.S. NIH Grant/Contract); 5U01DK130113-02 (U.S. NIH Grant/Contract); 5U01DK130181-02 (U.S. NIH Grant/Contract); 5U24DK130164-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Dataset with National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No