The goal of this clinical study is to understand whether the study drugs, semaglutide (SEMA) with the fixed-dose combination (FDC) of cilofexor/firsocostat (CILO/FIR), cause fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants with cirrhosis due to NASH.

Key Inclusion Criteria:

• Liver biopsy consistent with cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH) in the opinion of the central reader. In individuals who have never had a liver biopsy, a screening liver biopsy may be performed.

• Screening laboratory parameters as determined by the study central laboratory:

  • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
  • Hemoglobin A1c (HbA1c) ≤ 10%
  • International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
  • Platelet count ≥ 125,000/µL
  • Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
  • Serum albumin ≥ 3.5 g/dL
  • Serum alkaline phosphatase (ALP) ≤ 2 x ULN

• Body mass index (BMI) ≥ 23 kg/m^2 at screening.

Key Exclusion Criteria:

• Prior history of decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal bleeding.

• Child-Pugh (CP) score > 6 at screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation.

• Model for End-stage Liver Disease (MELD) score > 12 at screening, unless due to an alternative etiology such as therapeutic anticoagulation.

• Other causes of liver disease based on medical history and/or central reader review of liver histology, including but not limited to: alcoholic liver disease, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency.

• Chronic hepatitis B virus (HBV) infection (HBsAg positive), or Chronic hepatitis C virus (HCV) infection (HCV antibody and HCV ribonucleic acid (RNA) positive). Individuals cured of HCV infection less than 2 years prior to the screening visit are not eligible.

• History of liver transplantation.

• Current or prior history of hepatocellular carcinoma (HCC).

• Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol (1 unit is equivalent to 12 ounce (oz)/360 mL of beer, a 4 oz/120 mL glass of wine, or 1 oz/30 mL of hard liquor).

  • For individuals on vitamin E regimen ≥ 800 IU/day, or pioglitazone, dose must be stable, in the opinion of the investigator for at least 180 days prior to the historical or screening liver biopsy.
  • For individuals on medications for diabetes, dose must be stable, in the opinion of the investigator, for at least 90 days prior to the historical or screening liver biopsy.

• History of type 1 diabetes.

• Treatment with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the period from 90 days prior to the screening visit and for individuals with a qualifying historical liver biopsy, for 90 days prior to the date of the historical liver biopsy.

• For individuals who have not completed a series of an authorized coronavirus disease 2019 (COVID-19) vaccination regimen prior to screening, a positive result for COVID-19 on severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) test.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.