Prevalence of Alpha-1 Antitrypsin Deficiency in Non-Cirrhotic Liver Cancer

Prevalence of Alpha-1 Antitrypsin Deficiency in a Cohort of Hepatocellular Carcinoma on Non-Cirrhotic Liver Without Identified Etiologies

Patients with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease, have a 20- to 50-fold higher risk of developing primary liver cancer (PLC), such as hepatocellular carcinoma (HCC), in both cirrhotic and non-cirrhotic livers, highlighting AATD as a potential oncogenic factor. Therefore, our aim is to evaluate the association between AATD and HCC in patients with a non-cirrhotic liver and no known predisposition

The two most common pathogenic AATD variants, PiS and PiZ, will be identified using the multiplex digital PCR (dPCR) system in a French cohort of 71 patients who developed HCC in a non-cirrhotic liver without known risk factors for HCC

Inclusion Criteria:

1. Adult patients (≥18 years of age).

2. Histopathologically confirmed diagnosis of hepatocellular carcinoma (HCC).

3. Normal liver or chronic liver disease with minimal to moderate fibrosis in non-tumoral tissue.

4. Signed informed consent obtained prior to participation.

5. No other known etiology or risk factors for liver disease, including:

   • Alcohol-related liver disease
   • Metabolic-associated steatohepatitis (MASH)
   • Viral hepatitis infections
   • Hemochromatosis

Exclusion Criteria:

1. Minor patients (<18 years of age).

2. HCC diagnosis not established according to standard histopathological criteria.

3. Liver with chronic liver disease showing advanced fibrosis in non-tumoral tissue.

4. No signed informed consent prior to participation.

5. Presence of other identified etiologies or known risk factors for liver disease, including:

   • Alcohol-related liver disease
   • Metabolic-associated steatohepatitis (MASH)
   • Viral hepatitis infections
   • Hemochromatosi