Liver Cirrhosis, Portal Hypertension Related to Cirrhosis
Conditions
Keywords
Liver Cirrhosis, Portal Hypertension, Simvastatin
Brief summary
This prospective open-label parallel pilot clinical study evaluated the efficacy and safety of physiologically based pharmacokinetic (PBPK)-guided simvastatin dosing in Child-Pugh A and B cirrhotic patients with portal hypertension over a 3-month period. Twenty-two patients were enrolled following screening, and portal hemodynamic, laboratory, and safety parameters were assessed.
Detailed description
This was a prospective, open-label, parallel interventional clinical study conducted over a three-month period in Egyptian cirrhotic patients with portal hypertension. Thirty patients were screened for eligibility. Eight patients were excluded as they did not meet the predefined inclusion criteria. A total of 22 patients were enrolled and completed the study. Adult patients aged ≥18 years with confirmed liver cirrhosis and portal hypertension without a history of variceal bleeding were eligible for inclusion. Patients with severe renal impairment, pregnancy, known hypersensitivity to statins, active malignancy within the previous two years, or recent use of strong CYP3A4 inhibitors were excluded. Patients were stratified according to Child-Pugh (CP) classification into CP class A and CP class B groups. Simvastatin doses were determined using physiologically based pharmacokinetic (PBPK) modeling via the Simcyp® Simulator to account for hepatic impairment-related changes in drug exposure. CP class A patients received simvastatin 15 mg once daily, while CP class B patients received simvastatin 5 mg once daily. Clinical evaluation included Doppler ultrasonographic assessment of portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, and hepatic artery resistive index. Laboratory investigations included liver function tests (ALT, AST, total bilirubin, and serum albumin), renal function tests (serum creatinine and BUN), complete blood count, and creatine kinase for safety monitoring. Patients were followed monthly throughout the 3-month study period, with systematic documentation of adverse events.
Interventions
DRUGSimvastatin 15 mg
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.
DRUGSimvastatin 5 mg
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.
Sponsors
Kafrelsheikh University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients aged ≥ 18 years * Confirmed diagnosis of liver cirrhosis (clinical, laboratory, or imaging evidence) * Evidence of portal hypertension (clinical findings and/or Doppler ultrasound measurements) * No previous history of variceal bleeding * Child-Pugh class A or B
Exclusion criteria
* Active hepatocellular carcinoma * Severe renal impairment (eGFR \< 30 mL/min/1.73 m²) * Baseline creatine kinase (CK) \> 3 × upper limit of normal * Known hypersensitivity to simvastatin * Current therapy with strong CYP3A4 inhibitors * Any active malignancy in the last 2 years * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Portal Vein Diameter (mm) | 3 months | Portal vein diameter will be measured as a Doppler ultrasound parameter to evaluate changes related to portal hypertension |
| Change in Portal Vein Velocity (cm/s) | 3 months | Portal vein velocity will be assessed as an indicator reflecting changes in portal hypertension |
| Change in Hepatic Artery Resistance Index (HARI) | 3 months | The Hepatic Artery Resistance Index will be measured as a Doppler-based marker associated with changes in portal hypertension |
| Change in Congestion Index (CI) (cm/ [cm/s2]) | 3 months | The congestion index will be evaluated as a Doppler-derived surrogate marker for portal hypertension severity |
| Change in Modified Vascular Liver Index (MVLI) (cm/s) | 3 months | MVLI will be measured as part of the Doppler assessment reflecting changes in portal hypertension |
| Change in Platelet Count (×10⁹/L) | 3 months | Platelet count will be assessed as a hematologic surrogate marker associated with portal hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse effects related to Simvastatin | 3 months | Adverse effects will be monitored throughout the study period, including clinical evaluation and laboratory investigations such as liver function tests (ALT, AST), creatine kinase (CK), and documentation of any muscle-related or gastrointestinal symptoms. |
Countries
Egypt
Contacts
PRINCIPAL_INVESTIGATORNaira Galal, BSc in Pharmacy
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
STUDY_DIRECTORNoha Mahmoud El-khodary, PhD
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Outcome results
None listed