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)

The human alcohol dehydrogenase 4 gene (ADH4) encodes the human pi-alcohol dehydrogenase (pi-ADH), which can contribute to ethanol metabolism at moderate and high concentrations of ethanol. There are no known structural variants of pi-ADH in humans. We report the first polymorphisms in the ADH4 gene, at three sites in the promoter: -192 bp, -159 bp and -75 bp, respectively. To determine whether these variations affected promoter function, different haplotypes of the ADH4 proximal promoter were subcloned into a luciferase reporter vector, and the relative promoter activity analysed in hepatoma cells. One of the three sites had a dramatic effect on promoter activity, while the others did not detectably affect activity. The -75A allele had promoter activity more than twice that of the -75C allele. Alcohol dehydrogenase activity is rate limiting for ethanol oxidation. We hypothesize that the different ADH4 alleles lead to different amounts of pi-ADH in liver, which affects the risk for alcoholism by modulating alcohol metabolism.
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PMID:Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene expression. 1020 39

Chronic infection with hepatitis B or C viruses is a common underlying condition in patients with hepatocellular carcinoma worldwide. We studied serum and liver tissue from a cohort of Alaska natives with hepatocellular carcinoma (HCC) for evidence of hepatitis B, C and G viral infection using conventional serological tests as well as the sensitive polymerase chain reaction. Evidence of HBV infection was found in 25 and possible HCV infection in two cases. Among the remaining 11 patients, four had a history of recent or remote alcoholism while seven had no recognizable risk factors for HCC. Only one was seropositive for HGV RNA and that was an individual with a history of alcoholism. Non-tumorous liver tissue was available for study in six of these seven cases. Histological features of chronic hepatitis were present in five. Thus, at least five of 38 (13%) Alaska natives with HCC appeared to have chronic hepatitis not related to HBV or HCV infection, suggesting the possibility of some form of previously unrecognized chronic liver disease predisposing to HCC.
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PMID:Hepatocellular carcinoma not related to hepatitis B virus infection among Alaska natives. 1052 71

Chronic alcoholism in patients with chronic hepatitis C hastens disease progression toward development of cirrhosis and hepatocellular carcinoma. Approximately 30% of alcoholic patients with liver disease are infected with the hepatitis C virus (HCV), the primary risk factor being a history of injection drug use. The histologic pattern in alcoholics is typically indistinguishable from nonalcoholic patients similarly infected with chronic hepatitis C. The mechanism(s) involved in alcohol-induced enhancement of chronic hepatitis C have not entirely been established but may involve increased viral replication, iron overload, and immune suppression. Still to be determined is the minimum amount of daily alcohol intake, if any, that can be ingested without enhancing progressive liver injury. However, chronic hepatitis C patients undergoing treatment with interferon must abstain from any alcohol intake, because the efficacy of interferon therapy is significantly lower in those who continue to drink. Future research efforts are needed in order to further delineate the epidemiology and pathogenesis of chronic hepatitis C in the alcoholic patient.
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PMID:The alcoholic patient with hepatitis C virus infection. 1065 67

In these last years the authors have devoted themselves to chronic alcoholism rehabilitation. They have studied 99 over 65 years old subjects. In these subjects gastrointestinal pathology alcohol correlated incidence has been studied. An abdominal echography and an esophagogastroduodenoscopy have been performed in all these subjects. In some subjects, on the guide line of these tests, the authors have put through more tests: hepatosplenic scintigraphy, hepatic biopsy, laparoscopy, colonoscopy. Statistic elaboration was performed by chi-square test. The conclusions of this study are: 1) the diagnostic importance of association between echography and scintigraphy; 2) the low prevalence of severe hepatic alcohol related lesions in the elderly; 3) the importance of alcohol in hepatocarcinoma etiopathogenesis; 4) the incidence and the importance of phlogistic and ulcerous gastroduodenal lesions in elderly alcoholics.
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PMID:[Alcohol-related liver diseases in the aged]. 1076 41

The effect of segmental transcatheter arterial chemoembolization (TAE) on serum amino acid levels and liver function were studied in 23 patients with HCC associated with hepatitis virus C (22 patients) or alcoholism (1 patient), with compensated liver cirrhosis (Child A 18 patients, Child B 5 patients). Serum levels of branched-chain amino acids (BCAA), tyrosine, branched-chain amino acids to tyrosine ratio (BTR), ammonia, total bilirubin and albumin, and prothrombin times were measured before and after TAE (24 h, 7 and 14 days). The BTR was increased significantly 24 h after TAE (p<0.001) and gradually decreased to pre-TAE levels. Serum tyrosine levels decreased at 24 h after TAE (p<0.005) and later increased. Serum BCAA levels increased slightly at 7days after TAE and were decreased at 14 days after TAE. This results indicated that the increased BTR was due primarily to the decreased tyrosine level at 24 h after TAE. Serum ammonia levels gradually decreased after TAE and the prothrombin time and serum levels of total bilirubin and albumin were not significantly changed. In this study, segmental TAE had little influence on liver function, and the BTR unexpectedly increased at 24 h after TAE. These results suggest that segmental TAE has minimal side effects and may have a beneficial effect on amino acid metabolism.
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PMID:Effect of segmental transcatheter arterial chemoembolization on branched chain amino acids and tyrosine ratio in patients with hepatocellular carcinoma. 1102 1

Chronic hepatitis C is the leading cause of decompensated liver disease requiring liver transplantation and a major cause of hepatocellular carcinoma (HCC). In liver clinic series, about 20% of those chronically infected with hepatitis C virus (HCV) develop cirrhosis over 20 years. From epidemiological data, however, it is clear that certain subgroups of patients are more likely to develop liver-related complications than others. Both host and viral factors have been implicated in individual susceptibility to adverse outcomes. The impact of host factors, such as alcoholism, is now well defined, and viral factors, such as genotype and viral load, appear to be less influential than previously considered. Coinfections with HIV, hepatitis A virus (HAV) and hepatitis B virus (HBV) may influence the rate of fibrotic progression and the subsequent development of complications in patients with chronic hepatitis C. The stage of fibrosis on biopsy and biochemical markers, such as a low serum albumin, can help identify patients who are more likely to develop complications. The role of the immune system in modifying the course of HCV is only now being defined. This editorial explores the role of host and viral factors in the development of liver-related complications in HCV-infected individuals.
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PMID:Predictors of liver-related complications in patients with chronic hepatitis C. 1120 65

Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of treatment. Therapy must include correction of nutritional deficiencies, while taking into account changes of nutritional requirements. Methionine is normally activated to S-adenosylmethionine (SAMe). However, in liver disease, the corresponding enzyme is depressed. The resulting deficiencies can be attenuated by the administration of SAMe but not by methionine. Similarly, phosphatidylethanolamine methyltransferase activity is depressed, but the lacking phosphatidylcholine (PC) can be administrated as polyenylphosphatidylcholine (PPC). Chronic ethanol consumption increases CYP2E1, resulting in increased generation of toxic acetaldehyde and free radicals, tolerance to ethanol and other drugs, and multiple ethanol-drug interactions. Experimentally, PPC opposes CYP2E1 induction and fibrosis. Alcoholism and hepatitis C infection commonly co-exist, with acceleration of fibrosis, cirrhosis, and hepatocellular carcinoma. PPC is being tested clinically as a corresponding antifibrotic agent. Available antiviral agents are contraindicated in the alcoholic. Anti-inflammatory agents, such as steroids, may be selectively useful. Finally, anticraving agents, such as naltrexone or acamprosate, should be part of therapy.
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PMID:Liver diseases by alcohol and hepatitis C: early detection and new insights in pathogenesis lead to improved treatment. 1126 19

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Samuel W. French and R. J. Mayer. The presentations were (1) The ubiquitin-proteasome 26s pathway in liver cell protein turnover: Effect of alcohol and drugs, by Samuel W. French and F. Bardag-Gorce; (2) The role of CYP2E1 phosphorylation and degradation pathway in the induction of the enzyme, by Magnus Ingelman-Sundberg; (3) Role of proteasome in the proteolysis of oxidized proteins in experimental chronic alcoholism, by Helen Rouach; (4) Alcohol, proteolysis and liver cancer, by R. J. Mayer; (5) Effect of ethanol feeding on the ATP-ubiquitin-proteasome pathway in the liver cell, by F. Bardag-Gorce; (6) Novel mechanisms and targets for intracellular transport of CYP2E1, by E. Neve; and (7) Gankyrin, an oncoprotein commonly over expressed in hepatoma, by H. Higashitsuji.
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PMID:The ubiquitin-proteasome 26s pathway in liver cell protein turnover: effect of ethanol and drugs. 1139 Oct 75

Alcoholic cirrhosis is a major public health issue in France. The prevalence of alcoholic cirrhosis and the number of potential candidates for liver transplantation is unknown but certainly underestimated. Despite physicians' ethical reserves concerning this self-inflicted disease and the public's misgivings, liver transplantation for alcoholic cirrhosis can provide survival rates comparable with those observed for other chronic liver diseases. in this indication, liver transplantation if often associated with a low risk of acute rejection and a high rate cancer of the upper respiratory and digestive tracts. The risk of recurrent alcoholism after liver transplantation is also a major problem. Its prevalence varies from 10 to 50%, depending on the assessment criteria, and the rate recurrent risk for the liver graft (alcohol intake>40 g/d) is to the order of 10%. These figures illustrate the importance of careful management and support for these patients. At least 6 months weaning from alcohol is a commonly accepted selection criterion for transplantation candidates. Criteria for liver transplantation generally include patients aged under 65 years, weaned for more than 6 months, with Child C cirrhosis or less, uncontrollable digestive tract hemorrhage, spontaneous severe infection, hepatorenal syndrome, hepatopulmonary syndrome, or multifocal hepatocellular carcinoma if the largest nodule measures less than 3 cm. Acute alcoholic hepatitis is a severe disease, fatal in 50% of the cases, and resistant tot corticosteroid therapy. Liver transplantation in this subpopulation of often young patient who have not achieved weaning merits further evaluation.
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PMID:[Liver transplantation for alcoholic liver disease]. 1147 Oct 4

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies provide a proof of principle that specific inhibition of gene expression can be used to mimic the protective effects afforded by the ALDH2-2 phenotype.
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PMID:Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense mechanism results in an aversion to ethanol. 1153 26


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