Environmental, Metabolic and Nutritional Factors of Hepatocellular Carcinoma in Cirrhotic Patients

CIRCE: Environmental, Metabolic and Nutritional Factors of Hepatocellular Carcinoma in Cirrhotic Patients

Available data do not allow carcinogenesis mechanisms in cirrhotic patients to be well understood in absence of studies taking into account all recognised factors. A large scale clinical, biochemical and molecular studies is potentially relevant to the understanding of nutrition, physical activity, body weight metabolic syndrome whatever the etiology of underlying cirrhosis. It will open new perspectives :

• in prevention of hepatocellular carcinoma development in cirrhotic patients through dietary counselling and therapeutics of metabolic syndrome,
• in early screening of hepatocellular carcinoma in cirrhotic patients through spectroscopic technology and later proteomic study resulting in an improvement of hepatocellular carcinoma prognosis.

Inclusion Criteria:

Cases and controls will be males and females aged 35 or older, and will give an informed consent to participate in the study.

* Hepatocellular carcinoma case:

All hepatocellular carcinoma cases evolving in cirrhotic liver, whatever the etiology of cirrhosis, will be included. Criteria for the diagnosis of hepatocellular carcinoma will be those defined by the European Association for Study of the Liver (EASL) (Bruix J, J Hepatol 2001):

Focal hepatic lesions ≥ 2cm in diameter:

• alpha-fetoprotein (AFP) < 400 ng/ml: nodules have to be identified by at least two coincident morphologic examinations (abdominal US, angiography, CT or MRI) with arterial hypervascularisation in at least one of the imaging modalities
• AFP > 400 ng/ml: lesion seen in a single imaging modality

Focal hepatic lesions < 2 cm in diameter:

• lesions 1 to 2 cm in diameter:use of fine-needle aspiration with biopsy
• lesions < 1 cm: serial abdominal US every 3 months until the lesion exceeds 1 cm in size so that biopsy becomes possible. Such cases will be included after diagnosis confirmation.

Whatever the size of focal lesions, the diagnosis of cirrhosis will be made according to the same criteria as in the cirrhotic group control.

* Cirrhotic control patients:

All patients with cirrhosis, whatever its etiology, will be included. The diagnosis of cirrhosis will rely on:

Histological confirmation by liver biopsy or in the absence of biopsy:

• in patients free of portal thrombosis at Doppler imaging, on the presence of portal hypertension ascertained by biological (tricytopenia), morphologic (abdominal US, CT or MRI), hepatic venous pressure measurement or upper endoscopy (mosaic gastropathy, varices).
• in patients with portal thrombosis, on the presence of portal hypertension associated with: Clinical (hepatomegaly with clinical evidence of hepatocellular failure: spider naevi, palmar erythema, white mails, gynecomastia) or morphological signs of cirrhosis (enlarged liver, nodular surface, sharp lower edge).

And/or biological signs of hepatocellular failure (TP<70%, low albuminemia) And/or sinusoidal block assessed by liver venous gradient > 18mmHG In the present state of knowledge, a fibrotest value at 4 or a fibroscan value > 12.5 kilopascal.

Without any other clinical or biological signs will be considered as diagnosis criteria of cirrhosis only for chronic viral C hepatitis.

The lack of hepatocellular carcinoma in cirrhotic patients at inclusion will be assessed through good quality imaging examinations (abdominal US, CT scan or MRI) and AFP below 100 ng/ml.

Exclusion Criteria:

• age under 35 of year
• other cancer in evolution
• HIV infection
• Major somatic pr psychiatric illness not compatible with the inclusion in the study
• No hepatocellular carcinoma primary liver cancer.