Carvedilol and Alverine in Portal Hypertension

Prior treatment

• Those who have taken alverine, papaverine, or their derivatives (such as papaverine hydrochloride preparations, trimebutine maleate, etc.) within 4 weeks before enrollment;
• Those who have undergone transjugular intrahepatic portosystemic shunt (TIPS) or other interventional treatments affecting portal pressure (including splenic embolization, splenic microwave treatment, etc.) or liver transplantation;
• Those who have had overt hepatic encephalopathy, esophageal and gastric variceal bleeding within 2 weeks before enrollment; those who have undergone endoscopic treatment for esophageal and gastric varices within 1 week before enrollment or are planned for endoscopic treatment;
• Those who have used somatostatin and its analogs, vasopressin, terlipressin, dopamine, norepinephrine, and other vasoactive drugs within 1 week before enrollment;
• Those with a history of heavy alcohol consumption within 12 weeks before enrollment and cannot abstain from alcohol during the study period (equivalent ethanol intake of ≥30 g/day for males and ≥20 g/day for females);
• Presence of thrombosis in the portal venous system (including portal vein, splenic vein, superior mesenteric vein, etc.) and cavernous transformation of the portal vein; those with a history of portal venous system thrombosis who have no definite thrombosis detected in the portal venous system within 2 weeks before enrollment may be included;
• HBV DNA or HCV RNA \> the lower limit of detection; patients with active hepatitis C receiving antiviral treatment; those who have received anti-HBV treatment for less than 24 weeks;
• Those with uncontrollable current infections (pulmonary infections, abdominal infections, HIV, etc.) within 4 weeks before enrollment;
• Those who have participated in other drug trials within 4 weeks before enrollment;

Other illness

• Those with poorly controlled hypertension, diabetes, or other severe heart, lung diseases;
• Those diagnosed or suspected to have malignant tumors, including liver cancer;
• Known allergies to alverine, papaverine, or their derivatives (such as papaverine hydrochloride preparations, trimebutine maleate, etc.), or simethicone, or carvedilol; patients with contraindications to carvedilol: New York Heart Association Class IV decompensated heart failure requiring intravenous inotropic agents; asthma, chronic obstructive pulmonary disease (COPD) with bronchospasm; second- or third-degree atrioventricular block, severe bradycardia (heart rate less than 50 beats per minute), sick sinus syndrome (including sinoatrial block); cardiogenic shock; severe hypotension (systolic blood pressure less than 85 mmHg);

Lab values

• Serum total bilirubin levels ≥3×ULN (for patients with autoimmune liver disease, serum total bilirubin levels ≥5×ULN), or serum sodium levels \<125 mmol/L, or white blood cell count \<1×10\^9/L, or platelet count \<30×10\^9/L, or International Normalized Ratio (INR) \>1.8; or serum creatinine ≥1.2×ULN;

Other

• Those with glaucoma;
• Those with mental abnormalities;
• Pregnant or breastfeeding women, or women who do not rule out the possibility of pregnancy;
• Other reasons the investigator deems unsuitable for participation.

• Ages 18 to 80 years old (inclusive), no gender restrictions;
• Patients with liver cirrhosis diagnosed by clinical, laboratory, imaging examinations, and/or liver biopsy;
• Treated with carvedilol at a dose of up to 15 mg/day or at a lower dose that is the maximum tolerated for at least 3 months, with HVPG≥12 mmHg and ≤20 mmHg;
• Agree to participate and sign the informed consent form.