Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [>/= 2 packs per day, odds ratio (OR)=2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (>/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.
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PMID:Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. 1069 21

A 68-year old mildly obese Caucasian man underwent hepatic resection for multinodular hepatocellular carcinoma which had developed in the left lobe of a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking, and serum markers of hepatitis B virus without virus genome in hepatocytes. The non tumoral liver was mildly fibrotic and iron overloaded (hepatic iron index: 1.6) with three types of iron-free lesions: (i) periportal clear hepatocyte foci, (ii) hyperplastic nodules and (iii) dysplastic or neoplastic nodules with well to moderately-differentiated hepatocellular carcinoma. The genetic investigation was negative for the C282Y and the H63D mutations of the HFE gene. This observation illustrates the multistep process of carcinogenesis in the non-cirrhotic liver and raises the question of i) the origin of this iron overload possibly linked to insulin resistance syndrome and ii) the role of iron as a co-carcinogen.
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PMID:[Premalignant lesions and hepatocellular carcinoma on non cirrhotic liver overloaded with iron]. 1108 32

In Japan, more than 90% of primary liver cancers consist of hepatocellular carcinoma (HCC), 80% of which is caused by chronic hepatitis C virus (HCV) infection, and the remaining 15% of which is caused by chronic hepatitis B virus (HBV) infection. The proportion of older patients among patients with HCC has been increasing in recent years because of the aging of the HCV-prevalent birth cohort born between 1925 and 1935. The cumulative risk of developing HCC among HCV carriers was estimated as 30% for males and 6% for females. Older age, being male, having a low platelet count, higher histological stage, genotype 1b, co-infection with HBV, heavy drinking and smoking increase the risk of developing HCC among patients with chronic HCV infection. Recent reports on the efficacy of interferon therapy on the incidence of HCC in Japanese patients with chronic hepatitis C demonstrate the importance of providing a screening system for chronic HCV infection and establishing a medical referral system so that patients undergo the appropriate therapy for the Japanese HCV carriers.
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PMID:[Epidemiology of primary liver cancer in Japan]. 1124 37

The alcohol-withdrawal syndrome is a well-known clinical situation, so does its treatment. However, new researches have shown that the risk of severe withdrawal manifestations increases proportionally with the number of previous detoxifications, according to a sensitisation stress model. As a consequence, special attention should be paid to patients with a clinical history of multiple alcohol detoxifications, even if they never previously had delirium tremens and/or comitiality. Even in the absence of characteristic neurologic lesions, long-lasting heavy drinking is associated with brain dysfunction, concerning mostly the frontal cortex. This is clinically associated to neuropsychological deficits, specifically disorders of working memory and the so-called "executive functions". These deficits have a dramatic importance, because they impair drastically the outcome of alcoholic patients after detoxification. In Belgium like in other countries, an increasing prevalence of hepatitis C is present in alcoholic patients. This is due probably to the increase of a former illegal drugs consumption in those patients. This association between alcoholism and hepatitis C is of major importance, because alcohol consumption increases the viral load and the risk of cirrhosis and hepatocarcinoma. Furthermore, alcohol reduces the response to interferon therapy.
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PMID:[Clinical and therapeutic aspects in the treatment of alcohol addiction]. 1242 55

Alcohol has been known to be associated with an increased risk of cancer. We investigated the characteristics of hepatocellular carcinoma (HCC) in heavy drinkers with negative serum markers for viral hepatitis (non-B, non-C) to determine whether ethanol enhances the development of HCC in Japanese patients with or without serum markers for viral hepatitis. Among the 432 HCC cases seen at our hospital between 1995 and 2000, 26 patients had negative serum markers (non-B, non-C) and were heavy drinkers. The mean patient age at the time of HCC diagnosis was [Formula: see text] years. The mean total ethanol intake was [Formula: see text] kg. Most of the patients also had liver cirrhosis (LC), although the frequency was significantly higher in non-B, non-C, heavy drinkers HCC cases than in non-B, non-C, non-alcoholic HCC cases. Among the hepatitis C virus (HCV)-positive cases, the mean age at the time of HCC diagnosis was lower in heavy drinkers; this trend was not seen in HBV-positive cases. In HCC cases with heavy drinking, a high frequency of gastrointestinal (oropharynx, esophagus, stomach, colon and anal) cancers was seen. As for the aldehyde dehydrogenase-2 (ALDH2) genotype, the frequency of normal homozygotes was 87.5% in heavy drinkers with HCC and the frequency of heterozygotes was 12.5%; the frequency of heterozygotes was 58.3% in alcoholics with esophageal cancer. More than half of the non-B, non-C, heavy drinkers HCC cases had a normal range of serum alpha-fetoprotein (AFP) levels. These results indicate that heavy drinking enhances HCV-related hepatocarcinogenesis. Whether or not ethanol is directly involved in hepatocarcinogenesis remains controversial, but LC may progress HCC in heavy drinkers even if their serum markers for HBV (including tissue) or HCV are negative. Therefore, close observation, including radiographic examinations, is recommended for non-B, non-C, heavy drinkers with LC. In HCV-positive cases, abstinence or a reduction in daily ethanol intake is recommended.
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PMID:Hepatocellular carcinoma in heavy drinkers with negative markers for viral hepatitis. 1504 Sep 57

Alcoholic fatty liver is the earliest and most common response of the liver to alcohol in heavy alcohol use, and it may be a precursor of more severe forms of liver injury. We and colleagues in our laboratory found that in two rat hepatoma cell lines, H4IIEC3 and McA-RH7777, ethanol markedly induced transcription of a sterol regulatory element-binding protein (SREBP)-regulated promoter through increased levels of mature SREBP-1 protein. Whereas inhibition of ethanol oxidation by 4-methylpyrazole blocked the effect, the aldehyde dehydrogenase inhibitor cyanamide enhanced the effect of ethanol in the hepatoma cells, supporting the idea that the effect is likely mediated by acetaldehyde. Consistent with these in vitro findings, consumption of a low-fat diet with ethanol by mice for 4 weeks resulted in a significant increase in the abundance of the mature (active) form of hepatic SREBP-1. Activation of SREBP-1 by ethanol feeding was associated with increased expression of lipogenic genes as well as the accumulation of triglyceride in the livers. Taken together, these findings seem to indicate that metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 and that this effect of ethanol may contribute to the development of alcoholic fatty liver. We and colleagues in our laboratory further studied the mechanisms of ethanol activation of SREBP-1 by identifying a new target of ethanol, adenosine 5'-monophosphate (AMP)-activated protein kinase. Our study results demonstrated that the effect of ethanol on SREBP-regulated promoter activation was mediated, at least in part, through inhibition of AMP-activated protein kinase. Consistent with this hypothesis, chronic ethanol feeding (4 weeks) resulted in a significantly reduced activity and protein level of AMP-activated protein kinase and increased acetyl coenzyme A carboxylase activity in the mouse livers.
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PMID:Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins. 1567 Jun 64

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming >or=3 "go"s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 "go"s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.
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PMID:Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. 1618 78

Injection drug use remains the predominant mode of transmission of hepatitis C virus (HCV) infection. Growing numbers of persons who have been chronically infected with HCV for 20 or more years are coming to medical attention and are at risk for serious complications of chronic infection, including cirrhosis and hepatocellular carcinoma. Factors linked with the development of advanced fibrosis and cirrhosis include age at infection, duration of infection, heavy alcohol use, coinfections with HIV or hepatitis B virus, and male sex. Emerging risk factors for disease progression include steatosis, insulin resistance (and factors associated with the metabolic syndrome), and host genetics.
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PMID:The changing epidemiology and natural history of hepatitis C virus infection. 1716 13

Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. A limited number of cohort and case-control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers, but mostly without consideration of hepatitis virus infection. In the present case-control study, we recruited 209 incident HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), all of whom were aged 40-79 years and residents of Saga Prefecture, Japan. A questionnaire survey elicited information on coffee use during the last 1-2 years and 10 years before, and plasma hepatitis B surface antigen and antibodies to hepatitis C virus were tested for all but community controls. After adjustment for sex, age, heavy alcohol use, smoking status and hepatitis virus markers (except for community controls), coffee use during the last 1-2 years was associated with a decreased risk against any control group. For coffee use 10 years before, comparison between HCC cases and either community controls or CLD patients revealed a decreased risk; adjusted odds ratios for occasional use, 1-2 cups/day and > or =3 cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001), respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend = 0.05), respectively, against CLD patients. These results suggest that coffee may protect against the development of HCC, yet further elaborate studies (hopefully, intervention studies) are warranted to corroborate these findings.
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PMID:Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case-control study in Japan. 1723 38

Emerging epidemiologic data suggest that cigarette smoking may increase the risk of hepatocellular carcinoma (HCC), yet considerable controversies (e.g. inconsistent dose-response relationships) still exist with this association. We examined whether smoking was associated with HCC risk in a case-control study including 209 incident HCC cases and two different control groups (256 hospital controls and 381 patients with chronic liver disease [CLD] without HCC). Comparison of HCC cases with CLD patients, but not with hospital controls, demonstrated a significantly increased risk of HCC for current smokers. After adjustment for sex, age, heavy drinking history and hepatitis virus markers, odds ratios (and 95% confidence intervals) for former and current smokers relative to never smokers were 1.0 (0.6-1.7) and 2.5 (1.4-4.6), respectively, against CLD patients, as compared with 0.8 (0.3-2.3) and 1.8 (0.6-5.1), respectively, against hospital controls. In terms of pack-years during lifetime, dose-response relationship was not evident against either control group (P trend = 0.43), but it became clearer for more recent cigarette use among CLD patients. For example, regarding cumulative cigarette consumption during the last 5 years, adjusted odds ratios (and 95% confidence intervals) for 1-4 and 5+ pack-years relative to no use were 1.9 (1.1-3.6) and 2.8 (1.5-5.2) (P trend = 0.003), respectively. These results suggest that cigarette smoking may play a crucial role in the late stage of HCC development and that CLD patients may benefit from their earliest smoking cessation.
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PMID:Case-control study on cigarette smoking and the risk of hepatocellular carcinoma among Japanese. 1795 90


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