Precancerous Changes in the Liver Screening and Prevention

Cirrhosis itself is a precancerous condition but the magnitude of the risk varies with aetiology, i.e. it is high with HBV and HCV but low with alcohol. Sustained proliferation of liver cells consequent upon chronic hepatitis B and C or the daily ingestion of a hepatoxic agent such as alcohol over many years seems to be the most likely mechanism of carcinogenesis as it predisposes the cell to accumulate DNA abnormalities. Proliferation prevents the repair of any damage to DNA and it is then 'fixed' and transmitted to the progeny. The 'right' combination of sites of damage that results in neoplastic transformation is a rare event, hence it takes time for the tumour to develop.

In addition, several microscopic and architectural abnormalities have been described and assigned a pre-cancerous role (Anthony, 1994). Cellular changes such as large-cell dysplasia (meaning liver cells with enlarged, hyperchromatic, polyploid nuclei) have been held to be associated with an increased risk of malignant change for many years, especially in studies from Africa, Italy and France. Structurally abnormal and often large liver nodules in cirrhosis have been termed macroregenerative nodule, adenomatous hyperplasia and dysplastic nodule (Figure 2). These, especially when associated with cytological atypia (nuclear enlargement, prominent nucleoli, increased nucleo-cytoplasmic ratio), acinar, gland-like structures, nodules within nodules, and growth into areas of fibrosis, have been held to be directly precancerous lesions. Small-cell dysplasia has also been described in these nodules. However, dysplastic nodules may be difficult to distinguish from early, small hepatocellular carcinomas.

It must be pointed out that hepatocellular carcinoma does not always develop from cirrhosis with or without large nodules and dysplastic changes and, therefore, these abnormalities do not constitute obligate and exclusive pathways of liver carcinogenesis in humans. They are clinically useful, however, as they indicate an increased risk and the need for close supervision, which allows early intervention before overt development of tumours in cir-rhotic patients (Okuda, 1993; Schafer and Sorrell, 1999; Hirohashi et al., 2000).

The best preventive measure for hepatocellular carcinoma is elimination of the causative agent (primary prevention). Vaccination against HBV is highly effective in reducing chronic infection with this virus and has resulted in a reduction of tumour incidence in countries with nation-wide programmes such as Taiwan. A vaccine against HCV is not yet available but the virus has now been eliminated from blood used for transfusion by screening of donors. It is also possible to reduce exposure to aflatoxin by improving conditions of food storage. However, hundreds of millions of people remain for whom such measures are too late.

Secondary prevention means the identification of individuals considered to be at highest risk. In practice, this means those with cirrhosis due to chronic infection with HBV and HCV and large nodular lesions with or without

Figure 2 The interior of a cirrhotic 'dysplastic' nodule. Liver cell plates vary in thickness, their arrangement is disorganized and those in the middle of the field show nuclear enlargement.

dysplastic changes. The most effective means are regular ultrasound examination and estimation of serum levels of «-fetoprotein, the role of repeat liver biopsies being more controversial. Individuals with early, small tumours can then successfully be treated by surgery: resection or transplantation.

Body Detox Made Easy

Body Detox Made Easy

What exactly is a detox routine? Basically a detox routine is an all-natural method of cleansing yourbr body by giving it the time and conditions it needs to rebuild and heal from the damages of daily life and the foods you eat and other substances you intake. There are many different types of known detox routines.

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