Liver Cirrhosis Network Cohort Study

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) Metavirstage 4 fibrosis; Ishak Stage 5-6 fibrosis OR

2. At least 2 of the following:

3. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilicalvein within the past year 2. Liver stiffness: VCTE within one year prior to consentor during Screening ≥12.5 kPa or MRE within one year prior to consent or duringScreening ≥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 METAVIRstage 4 fibrosis or Ishak stage 5-6

Exclusion Criteria:

• Known and documented prior or current hepatocellular carcinoma (HCC) orcholangiocarcinoma

• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrogradetransvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of timeof occurrence

• Known prior solid organ transplant or bone marrow transplant

• Current participation in active medication treatment trials at the time of consentfor LCN Cohort Study

• Prisoners or individuals with more than 180 days incarceration pending due todifficulty 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 theinvestigator, would make the participant unsuitable for the study or interfere withor prevent follow-up per protocol

• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestiveheart failure (CHF), current chronic obstructive pulmonary disease (COPD) on homeoxygen, current known active malignancy besides non-melanomatous skin cancer orcarcinoma in situ)

• Documented history of acute alcohol-associated hepatitis (according to NIAAAcriteria as described in the MOP) in the 180 days prior to consent

• Documented current or continued signs and symptoms of acute Wilson disease (acuteliver failure, acute neurological deficits, hemolysis)

• In patients with primary sclerosing cholangitis (PSC): Current active cholangitiswith 90 days prior to consent

• Documented cardiac cirrhosis

• Known recent (within the last 365 days) or present hepatic decompensation withascites/hydrothorax (including trace ascites discovered at screening not requiringintervention), hepatic encephalopathy or variceal bleeding. If a patient has had ahistory of decompensation, they must have been off any medications to treatdecompensation for at least 365 days. Refer to the MOP for clarifying details onevaluating eligibility for patients with a history of prior decompensation.

• Known or documented habitual non-adherence to previous research studies or medicalprocedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consentor 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 ongoingadherence on suppressive therapy*

• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2Xupper 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 90days prior to consent or during Screening*

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