Using TIPS before sleeve gastrectomy to improve outcomes for people with cirrhosis and severe obesity

Inclusion Criteria

1. Is a candidate for general anesthesia
2. Is ≥18 and ≤70 years old at the time of signing the informed consent
3. Has a BMI ≥35 and ≤85 kg/m2 at the time of first study visit
4. Is eligible for metabolic surgery (SG) based on the ASMBS/IFSO 2022 guidelines \[39\]
5. Has insurance coverage for metabolic surgery
6. Patients who are currently receiving or have previously received anti-obesity medicines will be considered for participation
7. Liver cirrhosis as determined via liver biopsy or noninvasive liver disease assessment
8. CSPH as determined by HVPG of ≥ 10-12 mmHg, presence of esophagogastric varices, moderate-to-severe portal hypertensive gastropathy, dilated portal vein (\>13 mm), biphasic or reverse portal vein flow, enlarged paraumbilical veins, splenorenal collaterals, or dilated left and short gastric veins.
9. Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study.
10. Has a negative urine pregnancy test at the first visit and at the randomization visits for women of childbearing potential.
11. Women of childbearing age must agree to use reliable method of contraception for 2 years.

Exclusion Criteria

1. Prior bariatric and metabolic surgery of any kind

   • Reversed procedures such as gastric band or intragastric balloon that have been removed at least 3 months prior to the first study visit are allowed.
2. Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, biliary diversion, and complex trauma surgery
3. History of solid organ transplant
4. Severe pulmonary disease defined as FEV1 \< 50% of predicted value
5. Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
6. Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
7. Left ventricular ejection fraction \<25% at the time of screening
8. Myocardial infarction, unstable angina, stroke, heart surgery, coronary stent placement in the past 6 months
9. Presence of large hiatal hernia (\>7 cm)
10. Presence of erosive esophagitis (LA Grade C and D)
11. Presence of active Crohn's disease
12. Psychiatric disorders including (but not limited to) dementia, active psychosis, severe depression requiring 3 or more medications, history of suicide attempts, active alcohol, or substance abuse within the previous 12 months that in the opinion of the investigators could disqualify the patient from metabolic surgery
13. Pregnancy, the intention of becoming pregnant, or not using adequate contraceptive measures
14. Breastfeeding
15. Diagnosis of malignancy within the preceding 1 year, including intra- or extra-hepatic malignancy. This includes known hepatocellular carcinoma or evidence of OPTN-V lesion on imaging (except squamous cell and basal cell cancer of the skin).
16. Clinical judgment that life expectancy is less than 2 years
17. Use of investigational therapy within 3 months prior to signing the consent
18. Acute pancreatitis \< 90 days before screening
19. Portal vein thrombosis
20. Decompensated cirrhosis: moderate-to-large volume ascites, hepatic encephalopathy, or patients undergoing liver transplant evaluation.

    • We will include patients with prior variceal hemorrhage or small volume ascites
21. Total bilirubin \> 3 mg/dl within 1 month of screening
22. INR \> 1.7 within 1 month of screening
23. Platelets \<50,000 per microliter within 1 month of screening
24. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to the first study visit.

    • Defined as more than 14 units/week for females (\>1 drink per day) and more than 21 units/week for males (\>2 drinks per day) on average, where one unit of alcohol is equivalent to a 12-ounce beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor.
25. Chronic renal insufficiency with estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 or being on dialysis within 1 month of screening.
26. Known cases of Acquired Immune Deficiency Syndrome (AIDS)
27. Unable to understand the risks, benefits, and compliance requirements of study
28. Lack capacity to give informed consent
29. Plans to move outside the primary location of study (within 3-hour distance of Cleveland) within the next 6 months.
30. Previous participation in this trial and got randomized to one of the study groups but did not proceed.
31. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study