Hepatocellular carcinoma - a preventable disease

liver411

--------------------------------------------------------------------------------



Hepatocellular carcinoma - a preventable disease



--------------------------------------------------------------------------------



Date: Fri, 23 Nov 2001 04:22:19 -0500



Subject: Hepatocellular carcinoma - a preventable disease



--------------------------------------------------------------------------------









Hepatocellular carcinoma - a preventable disease.

Gatro-hepa web

by Monica Acalovschi, 09 November 2001



Hepatocellular carcinoma (HCC) is one of the major cancers in the world, with an estimated 500,000 to 1 million new cases a year.



It ranks fifth place in incidence among all cancers, and causes substantial morbidity and mortality.



The reported survival rates for untreated symptomatic HCC vary from 0% at 4 months, to 1% at 2 years. With such a poor survival, it is possible to assimilate HCC incidence with mortality rates.



The incidence rates vary considerably by area, by country, or even within the same country. The high-risk populations are clustered in sub-Saharan Africa (where liver cancer is the most common cancer), China, and South-East Asia.



In Europe, HCC incidence is intermediate in eastern and southern countries, and low in western and northern regions. A rising incidence of HCC in both high- and low-incidence areas has been shown over the last two decades.



The geographic differences in HCC prevalence are mainly due to the

predominant etiologic factors: aflatoxins, hepatitis B virus (HBV), and

hepatitis C virus (HCV). About 80% of HCCs are related to HBV and HCV infection.



While HBV infection rate is decreasing among HCC patients, hepatitis C

infection has increased in liver cancer patients in Western countries and in Japan.





Primary prevention of HCC



The prognosis of HCC is somber, and it represents a major scourge in

developing Third World countries. It is encouraging to think that the

majority of cases could be prevented by the widespread use of hepatitis B vaccines and the development of intervention programs against aflatoxin contamination of foodstuffs.



To control hepatitis B, Taiwan launched a nationwide vaccination program in 1984. Over 10 years, this program reduced the HBsAg carrier rate in children from 10% to less than 1%. This was achieved by interrupting perinatal and early horizontal transmission of HBV. Hence, the subsequent development of chronic liver disease was reduced.



Since the incidence of HCC in Taiwan peaks in the sixth decade of life, it may take 40 years or longer to see an overall decrease in the rate of HCC as a result of the vaccination program. However, 6-10 years after the initiation of the hepatitis B mass-vaccination program, HCC incidence declined significantly in children [1].



Similar measures are important and urgent in areas with a high incidence of HBV infection and HCC. Anti-HBV vaccine is considered as the first anticancer vaccine with a widespread use. It has already been introduced into the national programs in China and South-East Asia, Egypt and the Middle East, Eastern and Western Europe, the United States, and Canada.



Treatment with interferon could also prevent the development of HCC in patients with chronic viral hepatitis C. There is an increasing number of trials indicating that IFN-alpha treatment might reduce the incidence of HCC in patients with chronic viral C hepatitis and compensated cirrhosis [2][3][4]. HCC incidence has been found to decrease in patients who responded to alpha-interferon, as compared to non-responders. It also decreased in non-responders, as compared to patients not treated.



The incidence of HCC may be further reduced by eliminating aflatoxins from the food supply in areas of the world where agricultural products are stored under conditions that favor growth of A. flavus and A. parasiticus. Extensive quality control measures are required to minimize levels in finished products. Protection through modulation of aflatoxin metabolism has also been suggested.



A recent Phase II trial, conducted in China, demonstrated that intermittent or sustained administration of oltipraz, an inducer of Phase 2 metabolizing enzymes, significantly increased biomarkers of aflatoxin detoxification [5]. This approach seems to be feasible as a chemopreventive strategy in populations at high risk for HCC.



With the development of new and more effective antiviral therapies, and the implementation of preventive approaches, it is highly likely that the incidence of one of the most common and devastating tumors in the world can be reduced.





Secondary prevention of HCC



The objective of both screening and surveillance programs is to detect a disease at a stage when intervention may significantly improve the natural course and outcome, and to reduce disease-specific mortality.



Join the debate! Click here to post your comments about this Soapbox Speech.



Considering the criteria by which the screening/surveillance programs can be judged, liver cancer is suitable for such a program, because:



The disease is common and has substantial mortality and morbidity.

The target population (cirrhotics, HbsAg carriers) is easily identifiable,

and the physicians do accept that screening is necessary and that the

population will answer the call for screening. The screening tests (alpha-fetoprotein, ultrasound) have a low morbidity and a high sensitivity and specificity, and are acceptable to the target

population. Finally, and most importantly, there must be an acceptable and effective therapy.



The clinical effectiveness of the screening and surveillance programs

relies on the establishment of early diagnosis, provided that effective

treatments are available. Screening becomes more difficult when the patient is old or the liver is diseased, and cancer treatment may not prolong patient survival.



The possibility of lead-time bias is raised by a study conducted in the

USA. It was found that only a small improvement in survival of HCC patients occurred between 1977 and 1996, and the benefit was restricted to the first year following cancer diagnosis [6].



Despite the lack of evidence of benefit in reducing mortality,

screening/surveillance for HCC has become accepted practice by

hepatologists worldwide, particularly in patients with cirrhosis. The best approach must be to find small HCCs and to study the optimal treatment of these lesions through randomized controlled therapy trials. Encouragingly, a very recent study showed a longer survival in patients with liver cirrhosis who were kept under surveillance compared with patients who were not. [7].





References



Chang M.H., Chen C.J., Lai M.S. et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. New Engl J Med 1997, 336, 1855-9.

NishiguchiS, Kuroki T, Nakatani S et al. Randomised trial of effects of

interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995, 346, 1051-5.

International Interferon-alpha Hepatocellular Carcinoma Study Group. Effect of interferon-alpha on progression of cirrhosis to hepatocellular

carcinoma: a retrospective cohort study. Lancet 1998, 351, 1535-9.

Nishiguchi S, Shiomi S, Nakatani S et al. Prevention of hepatocellular

carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 2001, 357, 196-7.

Wang JS, Shen X, He X et al. Protective alterations in phase 1 and phase 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China. J Natl Cancer Inst 1999, 91, 347-54.

El-Serag HB, Mason AC, Key C. Trends in survival of patients with

hepatocellular carcinoma between 1977 and 1996 in the United States.

Hepatology 2001, 33, 62-5.

Bolondi L, Sofia S, Siringo S et al. Surveillance program