Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)

Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up

Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by the deposition of misfolded transthyretin protein within the myocardium. Current disease staging and follow-up strategies mainly rely on cardiac biomarkers and renal function; however, the systemic nature of ATTR suggests that additional organ involvement may provide valuable prognostic information.

The purpose of this prospective observational study is to investigate liver dysfunction and coagulation abnormalities in patients with wild-type or hereditary ATTR-CA and to evaluate their potential role as novel markers of disease severity and progression. Patients with ATTR-CA will be compared with an age-matched control population with non-amyloid hypertrophic cardiomyopathy.

Clinical, laboratory, echocardiographic, hepatic ultrasound, liver stiffness, and coagulation parameters will be assessed at baseline and during follow-up. The study will also evaluate changes in these parameters after 6 and 12 months of treatment with tafamidis.

The results may improve the understanding of cardio-hepatic interactions in ATTR-CA and identify new tools for disease staging and longitudinal monitoring.

Study Overview

• Status: Recruiting
• Conditions: Cardiomyopathies; Cardiac Amyloidosis; Transthyretin (TTR) Amyloid Cardiomyopathy; Wild-Type Transthyretin Cardiac Amyloidosis; Hereditary Transthyretin Amyloidosis (ATTRv)

Detailed Description

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure and left ventricular hypertrophy in older adults. Although several prognostic models have been developed for ATTR-CA, most currently available staging systems are based primarily on cardiac biomarkers and renal function. These approaches may not fully capture the systemic nature of the disease.

Emerging evidence suggests that liver dysfunction and coagulation abnormalities may represent underexplored manifestations of ATTR-CA. Liver involvement may result from direct amyloid deposition, chronic venous congestion related to heart failure, or a combination of both mechanisms. Similarly, alterations in coagulation pathways may reflect hepatic dysfunction and systemic disease burden.

LICA2025 is a single-center, prospective, observational study designed to evaluate biochemical and instrumental markers of liver function and coagulation in patients with wild-type or hereditary ATTR-CA followed at the University Hospital G. Martino of Messina, Italy. A control population with non-amyloid hypertrophic cardiomyopathy will be enrolled for comparison.

The primary objective is to compare liver and coagulation parameters between ATTR-CA patients and controls. Secondary objectives include evaluating the relationship between hepatic/coagulation abnormalities and cardiac disease severity, assessing changes after 6±1 and 12±1 months of tafamidis therapy, and exploring potential interactions between liver dysfunction and coagulation disturbances.

Participants will undergo clinical evaluation, laboratory testing, electrocardiography, transthoracic echocardiography, hepatic ultrasound, liver elastography (FibroScan), and coagulation assessment according to the study protocol. Follow-up evaluations will be performed at baseline, 6 months, and 12 months.

The study aims to identify novel biomarkers and imaging parameters that may improve disease staging, risk stratification, and longitudinal monitoring in transthyretin cardiac amyloidosis.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Luigi Colarusso, MD, PhD Candidate; Phone Number: +390902212341; Email: luigi.colarusso@polime.it

Study Locations

• Italy
  • Sicily
    • Messina, Sicily, Italy, 98124
      • Recruiting
      • AOU Policlinico G. Martino, UOC Cardiologia con UTIC
      • Contact: Luigi Colarusso, MD, PhD Candidate; Phone Number: +390902212341; Email: luigi.colarusso@polime.it
      • Sub-Investigator: Roberto Licordari, MD, PhD
      • Principal Investigator: Luigi Colarusso, MD, PhD Candidate

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) followed at the University Hospital G. Martino, Messina, Italy, and an age-matched control population with non-amyloid hypertrophic phenotype cardiomyopathy.

Description

Inclusion Criteria:

• Written informed consent obtained prior to study participation.
• Diagnosis of wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) according to current European recommendations.
• Ability to comply with study procedures and follow-up visits.

Exclusion Criteria:

• Age younger than 18 years.
• Severe liver dysfunction due to causes other than amyloidosis.
• Inability to comply with study procedures because of language barriers, cognitive impairment, or severe psychiatric disorders.
• Comorbidities associated with life expectancy less than 12 months.
• Active alcohol or substance abuse.
• For coagulation analyses: congenital coagulation disorders, thrombotic disorders, active malignancy, or sepsis.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ATTR-CA Patients; Patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) diagnosed according to current European recommendations and followed at the University Hospital G. Martino, Messina. Participants will undergo clinical, laboratory, echocardiographic, hepatic ultrasound, liver elastography, and coagulation assessments at baseline and during follow-up.
Hypertrophic Phenotype Controls; Age-matched patients with non-amyloid hypertrophic phenotype cardiomyopathy serving as a control population. Participants will undergo the same clinical, laboratory, echocardiographic, hepatic, and coagulation evaluations as the ATTR-CA group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Stiffness Measured by Transient Elastography (FibroScan)	Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.	Baseline, 6 Months, 12 Months
Controlled Attenuation Parameter (CAP) Measured by FibroScan	Controlled attenuation parameter (CAP) measured by FibroScan as an instrumental measure of hepatic steatosis, expressed in decibels per meter (dB/m), compared between patients with ATTR-CA and controls.	Baseline, 6 months, 12 months
Serum Aspartate Aminotransferase (AST/GOT)	Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.	Baseline, 6 months, 12 months
Serum Alanine Aminotransferase (ALT/GPT)	Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Gamma-Glutamyl Transferase (GGT)	Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Alkaline Phosphatase (ALP)	Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Bile Acids	Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Total Bilirubin (mg/dL)	Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Direct Bilirubin (mg/dL)	Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Albumin (g/dL)	Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Gamma Globulins (g/dL)	Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Immunoglobulin M (IgM) (g/L)	Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Serum Ferritin (ng/mL)	Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Anti-Mitochondrial Antibodies	U/ml	baseline, 6 months, 12 months
Fibrosis-4 (FIB-4) Index	FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Portal Vein Diameter Assessed by Liver Ultrasound	Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)	Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Spleen Diameter Assessed by Ultrasound (mm)	Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Prothrombin Time (PT) (s)	Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Activated Partial Thromboplastin Time (aPTT) (s)	Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
International Normalized Ratio (INR)	International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Plasma Fibrinogen	Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Fibrin/Fibrinogen Degradation Products	Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	Baseline, 6 months, 12 months
D-Dimer	D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Alpha-2-Antiplasmin	Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Antithrombin	Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Plasminogen	Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Thrombin-Antithrombin Complex	Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex	Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Prothrombin Fragment 1+2	Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Coagulation Factor X	Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
von Willebrand Factor Antigen	von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 (PAI-1)	Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.	baseline, 6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)	Correlation between liver stiffness measured by FibroScan (kPa) and plasma NT-proBNP concentration (ng/L) in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)	Correlation between liver stiffness measured by FibroScan (kPa) and interventricular septal thickness expressed in mm measured by transthoracic echocardiography in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)	Correlation between liver stiffness measured by FibroScan (kPa) and Global Longitudinal Strain (expressed in %) measured by transthoracic echocardiography in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)	Correlation between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L) measured by standard laboratory testing in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Change in Liver Stiffness During Disease-Modifying Treatment	Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.	Baseline, 6±1 months, and 12±1 months
Change in Controlled Attenuation Parameter During Disease-Modifying Treatment	Change in controlled attenuation parameter (CAP) measured by FibroScan and expressed in dB/m from baseline to 6±1 months and 12±1 months after treatment initiation.	Baseline, 6±1 months, and 12±1 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2	Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Correlation Between FIB-4 Index and Prothrombin Fragment 1+2	Correlation between FIB-4 and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline
Correlation Between Liver Stiffness and Fibrinogen	Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma fibrinogen concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.	Baseline

Collaborators and Investigators

• Sponsor: University of Messina
• Collaborators: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
• Investigators: Study Chair: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino; Principal Investigator: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: June 12, 2026
• First Submitted That Met QC Criteria: August 10, 2026
• First Posted (Actual): August 14, 2026

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Hemostasis; Biomarkers; Echocardiography; Liver Dysfunction; ATTR; Fibroscan; Transthyretin Amyloidosis; Cardiac Amyloidosis; Tafamidis; Liver Stiffness; Acoramidis; Coagulation Disorder; Disease Staging; ATTR-CA; Hepatic Congestion; Cardiohepatic Syndrome; Wild-Type ATTR; Hereditary ATTR
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Digestive System Diseases; Hematologic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Hemorrhagic Disorders; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Heart Failure; Liver Diseases; Cardiomyopathies; Hemostatic Disorders; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related
• Other Study ID Numbers: CEL Messina Prot. 28-25; Delibera n. 63/2026 (Other Identifier: AOU Policlinico G. Martino)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The decision regarding IPD sharing has not yet been finalized. Any future data sharing will be considered in accordance with applicable ethical approvals, participant consent, institutional policies, and data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No