This study is designed to study the pharmacokinetic (PK) and safety profiles of a single dose of efimosfermin alfa in participants with varying degrees of Hepatic Impairment (HI) (assessed by Child-Pugh score) due to steatotic liver disease, with and without significant alcohol consumption.

Inclusion Criteria:

• Between 18 years and 70 years of age inclusive

• Body Mass Index (BMI) within the range 23-40 kilogram per square meter (kg/m^2)

• Male or female participants

• Participant has liver cirrhosis with a grade of hepatic impairment that can be classified as a discrete Child-Pugh class. Participants must:

  • Have a clinical diagnosis of liver cirrhosis in the participant's medical history corroborated by previous liver biopsy, medical imaging or compatible biochemical profile, and

  • Be classed during Screening as one of the following Child-Pugh classes:

    • Child-Pugh B: Score 7-9 or
    • Child-Pugh C: Score 10-15

• Chronic (greater than [>] 6 months) HI which is currently stable (no acute episodes of illness within the previous 1 month prior to Screening (Visit 1) due to deterioration in hepatic function). Participants must also remain stable throughout the Screening period. Assessment of the stability of the participant's hepatic function will be determined by the investigator.

Exclusion Criteria:

• History of extrahepatic disorders possibly related to etiology of cirrhosis.
• History of cryoglobulinemia.
• Participants with Grade 3 ascites or refractory ascites.
• Participants with refractory encephalopathy or significant central nervous system disease
• History of gastric or esophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated with medication and/or surgical procedures.
• Other primary causes of liver disease. Steatotic liver disease must be the primary cause of liver disease.
• Clinically significant abnormalities affecting physical health in medical history, or on physical examination, that could interfere with or for which treatment could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study.
• Current, or history of known hepatocellular carcinoma (HCC).
• Participants with transjugular intrahepatic portosystemic shunt (TIPS) placement.
• Presence of hepatopulmonary or hepatorenal syndrome.
• Presence of primarily cholestatic liver diseases.
• Evidence of symptomatic or complicated cholecystitis.
• History of pancreatic injury, pancreatitis, or other pancreatic disease.
• History of liver transplantation, or active on the liver transplant waiting list.
• Participants with signs of active infection
• History of adrenal gland disease or using treatment that affects the hypothalamic-pituitary-adrenal axis.
• History of significant bone disease such as osteoporosis
• Psychosocial features that, in the opinion of the investigator, increase the likelihood of loss to follow-up.
• History or presence of drug abuse.
• Use of other investigational drugs at the time of screening, or within 5 half-lives or 30 days prior to study intervention, whichever was longer; or longer if required by local regulations
• Have previously taken efimosfermin alfa
• Participants with Alanine Aminotransferase (ALT) value >3 times (x) upper limit of normal (ULN)
• Participants with Aspartate aminotransferase (AST) value >=300 Units/Liter.
• Participants with estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology [CKD-Epi] 2021) <45 milliliter/minute/1.73 square meter (mL/min/1.73m^2).
• Average of triplicate QT interval corrected for heart rate using Fridericia formula (QTcF) >480 milliseconds (msec) (for male and female participants) at Screening
• For participants in the MASH with alcohol category, significant risk of withdrawal symptoms.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

open-label study