Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During induction of hepatocellular carcinoma (HCC) in rats with 3'MeDAB (3'methyl-dimethyl-aminoazobenzene) and Aflatoxin B1 alpha-foetoprotein (AFP) could already be demonstrated in the serum in the early phase of carcinogen administration. In this period the liver showed livercell necrosis but no tumour formation. The AFP level in the induction phase was correlated with the degree of livercell necrosis. The detection of AFP during the induction period is of importance as it is followed by a high frequency of liver tumours in later phases. The AFP concentration in the tumour phase was not related in any histological feature of the tumour; however, the mean AFP concentration in cases of HCC combined with cirrhosis was much higher than in cases of HCC without cirrhosis. Some rats with HCC showed AFP-negative sera, but AFP-positive bile.
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PMID:Alpha-foetoprotein during chemically induced hepatocellular carcinoma in rats. 8 43

The carcinogenicity of aflatoxin B1 (AFB1) has been under evaluation in nonhuman primates for the past 13 years. A total of 47 Old World monkeys, chiefly rhesus and cynomolgus, have received AFB1 i.p. (0.125 to 0.25 mg/kg) and/or p.o. (0.1 to 0.8 mg/kg) for 2 months or longer, and 12 are currently alive and without evidence of tumor. Thirteen of the 35 monkeys necropsied to date (37%) developed one or more malignant neoplasms, yielding an overall tumor incidence of 28%. Five of the neoplasms were primary liver tumors (2 hepatocellular carcinomas and 3 hemangioendothelial sarcomas), and 2 cases of osteogenic sarcoma were found. Other tumors diagnosed were 6 carcinomas of the gall bladder or bile duct, 3 tumors of the pancreas or its ducts, and one papillary Grade I carcinoma of the urinary bladder. The tumors developed in animals receiving an average total AFB1 dose of 709 mg (range, 99 to 1354 mg) for an average of 114 months (range, 47 to 147 months). Fifteen of the 22 necropsied monkeys (68%) without tumor showed histological evidence of liver damage, including toxic hepatitis, cirrhosis, and hyperplastic liver nodules. These animals had received an average total AFB1 dose of 363 mg (range, 0.35 to 1368 mg) for an average of 55 months (range, 2 to 141 months). Our results indicate that AFB1 is a potent hepatotoxin and carcinogen in nonhuman primates and further support the hypothesis that humans exposed to this substance may be at risk of developing cancer.
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PMID:Induction of osteogenic sarcomas and tumors of the hepatobiliary system in nonhuman primates with aflatoxin B1. 11 76

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.
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PMID:Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. 17 84

In the past 5 years we have observed 27 children at the age from 3 days to 8 years who died on the encephalic syndrome with fatty degeneration of the viscera (Reye). According to the morphological changes in the liver and to the clinical course, we have divided our cases into 3 groups. In the first group there were 20 children who died within 2-10 days after the first symptoms of the disease appeared. In their liver diffuse fatty degeneration was found. In the second group there were 3 children who died within 1-2 months after the acute onset of the disease. In their liver fibrosis with bile duct proliferation and steatosis were found. In the third group there were 4 children who died within 2-4 months after the first symptoms. Their liver showed cirrhosis. The bacteriological and virological investigations in all cases were negative, but in the most of them direct contacts with viral infections were proved. In the liver specimens of the children in all 3 groups the presence of aflatoxin B1 chromatographically and spectrophotometrically was found. The source of the intoxication in 5 cases was aflatoxin contaminated milk food. Our observations of 2 - 3 - days old newborns with the morphological changes similar to that of Reye's syndrome seems to support our hypothesis about the possibility of the intrauterine intoxication. We suggest that aflatoxin represents an important factor in the etiology of this syndrome and a high risk for human health.
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PMID:Aflatoxin and encephalopathy with fatty degeneration of viscera (Reye). 61 46

Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B1 or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. In aflatoxin B1- and M1-treated rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiation-promotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepatotoxicity in rats treated with CCl4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of alpha-fetoprotein or ferritin, nor was there a correlation with alpha-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal EH in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.
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PMID:Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury. 133 49

The etiological problems concerning, in France, hepatocellular carcinoma (HCC) developed on liver cirrhosis, are studied in this work through 130 personal cases followed up during the last decade. These 130 cases of HCC are divided in five groups according to apparent etiology: alcoholic (63 p. cent), B virus, (15.3 p. cent), cryptogenetic (11.5 p. cent), hemochromatosic (7.6 p. cent), autoimmune (2.3 p. cent). A review of these cases according to recent publications shows an evidence underestimated for years: we mean the important role played in France by HBV (and probably HCV) not only in chronic cirrhogen hepatitis, but even more in cancerisation of cirrhosis in general whatever is the apparent etiology. This role, unsuspected when biological investigations are limited to serological markers of HBV, is demonstrated by implementing more sophistical technics (molecular hybridation and genic amplification). But it is very unlikely that this role is exclusive and one must recognize that viral "focalisation" of recent publications has a tendancy to hide other causes of HCC and primarily the toxicological etiology in a wide sense. This etiology is in fact indubitable, already in tropical areas, where the role of mycotoxins and particularly of aflatoxin B1 is very well demonstrated, even in areas of very high incidence of HBV. In low incidence areas, such as France, the specific carcinogenic role of alcohol cannot be excluded, neither the role of numerous experimental hepato-carcinogens, very much studied 15 years ago and may be incorrectly forgotten in our days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Current etiological problems, in France, posed by primary liver cancer after cirrhosis. Personal observations of 130 cases]. 166 25

Hepatocellular carcinoma (HCC), the most frequent malignant tumour of the liver, is the commonest cancer occurring in males in the world. The annual incidence of the disease worldwide is estimated to be one million cases. There are variations in its geographical distribution. It tops the list of malignancies amongst males in sub-saharan Africa; it is the second most common cancer in Southeast Asia, including Hong Kong, and ranks third amongst males in China. It is relatively rare in America, Europe North Africa, and the Middle East. During the last 15 years, epidemiologic and laboratory investigations have established a strong and specific association between chronic hepatitis B virus (HBV) infection and HCC. Hepatic cirrhosis is another major aetiologic factor incriminated. In areas with a low incidence of HCC, cirrhosis due to alcohol may be a relatively more important predisposing factor. Chronic non-A, non-B hepatitis (NANBH) infection has now been incriminated as a cause of HCC, especially in Japan. Other environmental factors, particularly chemical carcinogens such as Aflatoxin, smoking, genetic predisposition and sex hormones may also act to promote hepatocarcinogenesis. The exact mechanisms of neoplastic transformation, however, are still far from understood. The following factors are discussed in detail: 1. HBV infection 2. Cirrhosis 3. NANBH infection 4. Aflatoxin B1 5. Cigarette smoking 6. Alcohol A number of less important associated diseases are also listed in Table I. At the end of this paper, a tentative scheme for hepatocarcinogenesis has been proposed and the methods for prevention is discussed in light of the risk factors considered.
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PMID:Hepatocarcinogenesis. 216 75

Although primary liver carcinoma is one of the most common forms of malignancy in most parts of Africa and the Far East, recent reports indicate that the incidence of primary liver cancer has been increasing in Western countries. Our retrospective study is in agreement with this suggestion. From 28,311 autopsies performed at the Department of Pathology in Hradec Kralove from 1951 to 1978, 91 primary liver carcinomas were found. The increase was apparent in the period 1971 to 1978: 0.53% compared to 0.22% in the period 1951 to 1970. Of the 91 cases, 68 were in association with cirrhosis. In 6 of 17 liver samples, aflatoxin B1 was proved. Some authors suggest that the increase of liver cancer is related to the increase of cirrhosis. Other authors note a striking association of tumors with HBAg. The increase of cirrhosis has not been confirmed in our study. We assume that the carcinogenic mechanism is more complex and that the determinating factor might be an interaction of HB infection and some of the environmental carcinogenic factors, e.g., aflatoxin.
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PMID:Hepatocellular carcinoma (a 28-year necropsy review). 217 90

We examined the roles of the hepatitis B virus and aflatoxin B1 in the development of primary hepatocellular carcinoma (PHC) in a cohort of 7917 men aged 25 to 64 yr old in southern Guangxi, China, where the incidence of PHC is among the highest in the world. After accumulating 30,188 man-yr of observation, 149 deaths were observed, 76 (51%) of which were due to PHC. Ninety-one% (69 of 76) of PHC deaths were hepatitis B surface antigen (HBsAg) positive at enrollment into the study in contrast to 23% of all members of the cohort (RR = 38.6). Three of the four patients who died of liver cirrhosis also were HBsAg positive at enrollment. There was no association between HBsAg positivity state and other causes of death. Within the cohort, there was a 3.5-fold difference in PHC mortality by place of residence. When estimated aflatoxin B1 levels in the subpopulations were plotted against the corresponding mortality rates of PHC, a positive and almost perfectly linear relationship was observed. On the other hand, no significant association was observed when the prevalence of HBsAg positivity in the subpopulations was compared with their corresponding rates of PHC mortality.
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PMID:Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. 253 5

In an attempt to determine the effect of aflatoxin B1 (AFB) intoxication on livers with duck hepatitis B virus (DHBV) infection, domestic ducks were given 0.1 mg of AFB/kg body weight twice a week for a maximum period of 54 weeks employing various experimental designs. The ducks were infected with DHBV by i.v. inoculation of DHBV-positive sera within 24 h posthatch. The livers were examined histologically, immunohistochemically, and ultrastructurally, and the livers and sera were examined by molecular hybridization for DHBV DNA. AFB administration induced hepatocellular necrosis and marked biliary cell proliferation of the periportal areas, and finally liver cirrhosis. On short-term administration, the hepatocytes of DHBV-infected livers revealed a marked increase in incomplete particles of DHBV by immunostaining and electron microscopy, as compared to those without its administration. Long-term AFB administration provoked frequent nodular or cirrhotic changes. There was no significant increase in frequency of these changes in DHBV-positive ducks as compared to DHBV-negative ones. AFB administration induced hepatocellular carcinoma (HCC) in one DHBV-positive duck and in two DHBV-negative ducks. The HCC and cirrhotic livers revealed extrachromosomal but no integrated form of DHBV DNA by Southern blot hybridization analysis. Immunostaining demonstrated a heterogeneous distribution of DHBV from area to area in nodular and cirrhotic livers. Thus, AFB intoxication provoked various liver disorders independent of DHBV infection, and neither a cocarcinogenic effect of AFB and DHBV nor integration of viral DNA into the genome of neoplastic and nonneoplastic tissues was observed in the present experiments. Generally speaking, DHBV infection did not appear to accelerate hepatic disorders induced by AFB intoxication. However, AFB administration altered the DHBV in the liver in terms of its amount and distribution.
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PMID:Influence of aflatoxin B1 intoxication on duck livers with duck hepatitis B virus infection. 312 65


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