This study will evaluate the safety, feasibility, and preliminary effects of S-adenosyl-L-methionine (SAMe) compared with placebo in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Investigators will assess whether treatment is associated with changes in liver-related clinical measures, biologic markers, and other study outcomes relevant to disease progression. The goal of this study is to generate early data to determine whether SAMe should be studied further as a potential therapeutic strategy in patients with MASLD cirrhosis.

Patients with MASLD cirrhosis are at risk for progressive liver dysfunction and liver-related complications, and additional treatment strategies are needed. SAMe is a biologically relevant methyl donor with potential effects on liver metabolism, inflammation, and cellular injury pathways. In this study, eligible patients will be assigned to receive SAMe or placebo according to the study protocol. Investigators will evaluate safety, tolerability, study adherence, and changes in prespecified clinical and laboratory outcomes over the treatment period. Results from this study are intended to support the design of future trials and to clarify the potential role of SAMe in patients with MASLD cirrhosis.

Inclusion Criteria:

1. individuals 18 years old or above.

2. Understand the study procedures and able to provide informed consent.

3. Clinical diagnosis of MASLD per American Association for the Study of Liver Diseases (AASLD) guideline: Patients with hepatic steatosis identified by imaging or biopsy, AND have at least one of five cardiometabolic risk factors:

   (i) BMI ≥25 kg/m2 (23 kg/m2 for Asian) OR waist circumference >94 cm for male or >80 cm for female.

   (ii) Fasting serum glucose ≥5.6 mmol/L (100 mg/dL) OR 2-hour post-load glucose levels ≥7.8 mmol/L (140 mg/dL) OR HbA1c ≥5.7% (39 mg/dL) OR type 2 diabetes OR treatment for type 2 diabetes (iii) Blood pressure ≥130/85 mmHg OR specific antihypertensive drug treatment. (iv) Plasma triglycerides ≥1.7 mmol/L (150 mg/dL) OR lipid lowering treatment (v) Plasma HDL-cholesterol ≤1.0 mmol/L (40 mg/dL) for male or ≤1.3 mmol/L (50 mg/dL) for female OR lipid lowering treatment.

4. Current weekly intake of alcohol <210 g (7.41 oz) for male or weekly intake of alcohol <140 g (4.76 oz) for female, [1 oz/30 mL of alcohol is present in one 12 oz/360 mL beer, 4 oz/120 mL glass of wine, and a 1oz/30 mL measure of 40 proof (20%) alcohol]

5. Diagnosis of cirrhosis confirmed via histopathology OR at least two of the following measures:

   (i) Transient elastography (FibroScan® ≥ 12 kPa) (ii) Computed tomography (iii) MRI including MR elastography (stiffness ≥ 4.71 kPa) (iv) Abdominal Ultrasound

6. Patient had imaging for HCC screening (Ultrasound or MRI or CT) within 3 months prior to screening.

Exclusion Criteria:

1. Confirmed diagnosis of HCC prior to screening, any suspicious nodules identified prior or during screening must be followed with documentation of HCC negative confirmed prior to randomization.
2. History of other causes of liver disease, including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (primary biliary cholangitis, primary sclerosing cholangitis, or autoimmune hepatitis), drug-induced hepatotoxicity, Wilson's disease, iron overload, or alpha-1-antitrypsin deficiency.
3. Most recent serum creatinine >1.5 mg/dl within 3 months prior to screening.
4. Active infection with positive urine culture, blood culture, or pneumonia at screening.
5. History of gastrointestinal bleeding within the prior 28 days
6. History of liver transplantation.
7. Women who are pregnant or nursing at screening.
8. Significant systemic illness including chronic obstructive pulmonary disease, congestive heart failure, and renal failure that in the opinion of the investigator would preclude the patient from participating in the study or poses a significant risk of mortality during the study period, such as conditions that are interfering with the absorption, distribution, metabolism, or excretion of S-adenosyl-L-methionine (SAMe) such as those with gastric bypass surgery.
9. HIV infection or patients who are immunocompromised.
10. Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening.
11. Systemic antibiotic use or use of rifaximin for 10 days or more within the last 2 months prior to screening.
12. Actively taking investigational or over-the-counter SAMe within 28 days prior to screening.
13. Subjects with psychiatric illnesses such as bipolar disorders and Parkinson's disease as SAMe may interfere with the levels of anti-psychotic drugs and might interact with drugs and dietary supplements that increase levels of serotonin (a chemical produced by nerve cells), such as antidepressants, L-tryptophan, and St. John's wort.
14. Members from the same family of study participant.

Matched placebo tablets are identical in appearance and similar in odor to active SAMe tablets. Patients and care providers will remain blinded to treatment assignment. Investigators will use centralized randomization, and study product will be dispensed using coded lot numbers, with the treatment code maintained in a sealed unblinding record for use only if needed. At the end of the trial, patients will be asked whether they believed they received active treatment or placebo.