Optimizing Portal Hypertension With TIPS and Interval Metabolic Surgery for Advanced Liver Disease

Prior treatment

• 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.
• Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, biliary diversion, and complex trauma surgery
• 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
• Use of investigational therapy within 3 months prior to signing the consent
• Acute pancreatitis \< 90 days before screening
• 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
• 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.
• Previous participation in this trial and got randomized to one of the study groups but did not proceed.

Other illness

• History of solid organ transplant
• Severe pulmonary disease defined as FEV1 \< 50% of predicted value
• Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
• Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
• Myocardial infarction, unstable angina, stroke, heart surgery, coronary stent placement in the past 6 months
• Presence of active Crohn's disease
• 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).
• Portal vein thrombosis
• Known cases of Acquired Immune Deficiency Syndrome (AIDS)
• Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study

Lab values

• Left ventricular ejection fraction \<25% at the time of screening
• Total bilirubin \> 3 mg/dl within 1 month of screening
• INR \> 1.7 within 1 month of screening
• Platelets \<50,000 per microliter within 1 month of screening
• 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.

Other

• Presence of large hiatal hernia (\>7 cm)
• Presence of erosive esophagitis (LA Grade C and D)
• Pregnancy, the intention of becoming pregnant, or not using adequate contraceptive measures
• Breastfeeding
• Clinical judgment that life expectancy is less than 2 years
• Unable to understand the risks, benefits, and compliance requirements of study
• Lack capacity to give informed consent
• Plans to move outside the primary location of study (within 3-hour distance of Cleveland) within the next 6 months.

• Is a candidate for general anesthesia
• Is ≥18 and ≤70 years old at the time of signing the informed consent
• Has a BMI ≥35 and ≤85 kg/m2 at the time of first study visit
• Is eligible for metabolic surgery (SG) based on the ASMBS/IFSO 2022 guidelines \[39\]
• Has insurance coverage for metabolic surgery
• Patients who are currently receiving or have previously received anti-obesity medicines will be considered for participation
• Liver cirrhosis as determined via liver biopsy or noninvasive liver disease assessment
• 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.
• Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study.
• Has a negative urine pregnancy test at the first visit and at the randomization visits for women of childbearing potential.
• Women of childbearing age must agree to use reliable method of contraception for 2 years.