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Primary liver cancer (PLC) is a malignant disease which is difficult to detect in its early stages and has very poor prognosis. Although relatively uncommon among Caucasians it is one of the major malignancies in many countries throughout the world, particularly in sub-Saharan Africa and the Far East. It accounts for 65.5% of all malignant disease in men and 31% of malignant tumors in women among Shangaan blacks in South Africa (1). It is the third major cause of cancer death in males and the fourth among females in China (2); it ranked third and fifth in these groups, respectively, in Japan in 1983 (3). Of PLC, hepatocellular carcinoma (HCC) is the major histological type followed in frequency by cholangiocellular carcinoma-the ratio of HCC to cholangiocellular carcinoma varies from 5:l to nearly 401 (4). In other words, the major malignant killer in the high PLC incidence areas is HCC.A close association of HCC with cirrhosis, particularly the posthepatitic or macronodular variety, has long been known (5-7). This interrelationship, an enigma in the past, now seems explainable in part by the hepatocarcinogenic properties of hepatitis B virus infection (8, 9). However, some epidemiological data speak against the theory that this virus is the sole etiologic factor in HCC (10,ll). Besides food contamination by aflatoxins in the tropical and subtropical regions, chronic non-A, non-B hepatitis is one recent etiologic candidate in Japan where HCC incidence has more than doubled in the past 15 years despite a concomitant increase in hepatitis B virus seronegative cases (12). A recent study in Tokyo shows that 40% of patients with HCC now have a history of past blood transfusion (13). Because of frustrations due to late diagnosis and bad therapeutic results, Japanese gastroenterologists have pioneered clinical programs for the early detection of HCC. MASS SCREENING FOR ASYMPTOMATIC HCCIn the early 1970's, when serum a-fetoprotein (AFP) was still under investigation for its diagnostic significance in HCC, an attempt was made by Masseyeff and his group (14) in Senegal to screen normal people for the detection of early HCC. They used the AFP Ouchterlony test and screened 9,000 male workers three times a year for 2 years. AFP-positive HCC was found in three apparently healthy males. Unfortunately, in only 1 of the 3, the tumor was sufficiently small to permit surgical removal. In South Africa, the young blacks coming from Mozambique to work in gold mines near Johannesburg were the high risk group for developing HCC prior to the discontinuation of diplomatic relations between South Africa and Mozambique. Purves and his group (15) screened AFP in more than 5,000 such gold miners by radioimmunoassay (RIA) and more than 4,000 by immunodiffusion methods. This study was a complete failure and not a single asymptomatic black patient with cancer was found (15).After the founding of the People's Republic of China, the central government set out to determine the regional incidences of various cancers as a prime public health program....
Primary liver cancer (PLC) is a malignant disease which is difficult to detect in its early stages and has very poor prognosis. Although relatively uncommon among Caucasians it is one of the major malignancies in many countries throughout the world, particularly in sub-Saharan Africa and the Far East. It accounts for 65.5% of all malignant disease in men and 31% of malignant tumors in women among Shangaan blacks in South Africa (1). It is the third major cause of cancer death in males and the fourth among females in China (2); it ranked third and fifth in these groups, respectively, in Japan in 1983 (3). Of PLC, hepatocellular carcinoma (HCC) is the major histological type followed in frequency by cholangiocellular carcinoma-the ratio of HCC to cholangiocellular carcinoma varies from 5:l to nearly 401 (4). In other words, the major malignant killer in the high PLC incidence areas is HCC.A close association of HCC with cirrhosis, particularly the posthepatitic or macronodular variety, has long been known (5-7). This interrelationship, an enigma in the past, now seems explainable in part by the hepatocarcinogenic properties of hepatitis B virus infection (8, 9). However, some epidemiological data speak against the theory that this virus is the sole etiologic factor in HCC (10,ll). Besides food contamination by aflatoxins in the tropical and subtropical regions, chronic non-A, non-B hepatitis is one recent etiologic candidate in Japan where HCC incidence has more than doubled in the past 15 years despite a concomitant increase in hepatitis B virus seronegative cases (12). A recent study in Tokyo shows that 40% of patients with HCC now have a history of past blood transfusion (13). Because of frustrations due to late diagnosis and bad therapeutic results, Japanese gastroenterologists have pioneered clinical programs for the early detection of HCC. MASS SCREENING FOR ASYMPTOMATIC HCCIn the early 1970's, when serum a-fetoprotein (AFP) was still under investigation for its diagnostic significance in HCC, an attempt was made by Masseyeff and his group (14) in Senegal to screen normal people for the detection of early HCC. They used the AFP Ouchterlony test and screened 9,000 male workers three times a year for 2 years. AFP-positive HCC was found in three apparently healthy males. Unfortunately, in only 1 of the 3, the tumor was sufficiently small to permit surgical removal. In South Africa, the young blacks coming from Mozambique to work in gold mines near Johannesburg were the high risk group for developing HCC prior to the discontinuation of diplomatic relations between South Africa and Mozambique. Purves and his group (15) screened AFP in more than 5,000 such gold miners by radioimmunoassay (RIA) and more than 4,000 by immunodiffusion methods. This study was a complete failure and not a single asymptomatic black patient with cancer was found (15).After the founding of the People's Republic of China, the central government set out to determine the regional incidences of various cancers as a prime public health program....
The role of HBV and HCV in the course of primary liver cancer in patients who are negative for HBsAg has been debated. Using a combination of serological and polymerase chain reaction assays, we investigated the association between HCV and HBV infections and primary liver cancer in 24 HBsAg-negative patients living in France. The presence of HCV RNA and HBV DNA sequences was tested for in serum and in tumorous and nontumorous liver samples. Twelve patients had anti-HCV, and 11 patients had anti-HBs and/or anti-HBc. HCV RNA sequences were found in the serum samples of all anti-HCV-positive patients and none of the patients who were negative. Patients with HCV viremia had HCV RNA genomic sequences and presumed replicative intermediates in both tumorous and nontumorous specimens. Sequence analysis of a hypervariable region in the E2/NS1 gene of HCV showed significant variations between the viral molecules isolated from the nontumorous, tumorous and serum samples. This eliminated the hypothesis of the contamination of the tumor by nontumorous cells and serum particles and assessed that liver tumor cells did contain HCV RNA genomes. Eleven of 22 patients tested had HBV DNA in the serum; 5 patients were anti-HBc positive and anti-HBs positive. Patients with HBV viremia had HBV DNA sequences in both tumorous and nontumorous liver specimens. Selective loss of part of the HBV genome in the tumorous tissue of two of these patients suggested HBV DNA persistence in clonally expanded malignant cells. Only 4 of the 22 patients were negative for both viruses. Our results show that HBsAg-negative hepatocellular cancer in France is associated with chronic HBV or HCV infection and, in some cases, both; these findings are consistent with an etiological role for HBV and HCV in HCC that develops in cirrhotic patients living in areas of low prevalence.
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