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)

Liver carcinogenesis is associated with striking changes in the integrin repertoire of hepatocytes, including the overexpression of the laminin and collagen receptors alpha1beta1 and the de novo induction of the laminin receptor alpha6beta1. Our aim was to analyze the role of pro-inflammatory cytokines, interferons and fibrogenic cytokines TGF-beta and FGF2 in the regulation of the expression of beta1 integrins by neoplastic hepatocytes. The 2 human hepatocellular cell lines HepG2 and Hep3B were used as models. Integrin expression was assessed by qualitative methods (immunocytochemistry, Western blotting) and semi-quantitative techniques (FACS, cellular ELISA), before and after stimulation by TNFalpha, IL1-beta, TGF-beta, FGF2, interferon gamma and interferon alpha-2b. HepG2 and Hep3B constitutively expressed alpha1, alpha2, alpha6 and beta1 chains. A 24 to 48-hr stimulation with pro-inflammatory cytokines, TGF-beta and FGF2 induced a significant increase in the concentrations of all integrin chains. The maximum induction was registered for beta1 chain, which presented increases amounting up to 3, 4 and 7 times the control values in the presence of, respectively, TNF alpha/IL1-beta, TGF-beta and FGF2. Interferons had no direct effect on integrin expression and partially antagonized the effects of TNF alpha and TGF-beta. The increased concentrations of integrin chains were associated with an increased membrane expression of the corresponding dimers and with an increased adhesion of stimulated hepatocytes to laminin, which was antagonized by neutralizing anti-beta1 and anti-alpha6 antibodies. Finally, anti-alpha6 antibody inhibited the migration of HepG2 and Hep3B cells in reconstituted basement membrane. Our results suggest that the stimulation of alpha6beta1 integrin expression in hepatocarcinoma cells is essential for cell adhesion and migration.
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PMID:alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration. 1050 89

Hepatitis C is the commonest form of chronic viral hepatitis in most western countries. A significant proportion of patients develop cirrhosis, hepatic failure and hepatocellular carcinoma. The results of controlled trials have shown that interferon alpha is an effective treatment for hepatitis C. Treatment results in normalization of elevated transaminase levels in up to 50% of patients, although only 15-25% of patients have a sustained response. Recent studies have shown that iron influences the response of chronic hepatitis C to treatment and the natural history of hepatitis C. The mechanisms responsible for the effects of iron are not clear but emerging data suggest that the cellular location of iron within the liver lobule and the subsequent effects on immune function are likely to be critical determinants for these effects. It is likely that therapies for chronic hepatitis C which either remove iron or interfere with the action of iron at the cellular level may not only prove useful clinically but may also elucidate further the mechanisms of cellular injury in this disease.
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PMID:Hepatitis C and iron. 1053 73

A 67-year-old man with hepatitis C virus infection and histological features of chronic active hepatitis was treated with human recombinant interferon alpha-2b. He responded successfully to interferon with normalization of serum alanine aminotransferase and continuous eradication of hepatitis C virus. However, 4.5 years after the end of interferon therapy, hepatocellular carcinoma, 20 mm in diameter, was detected by routine ultrasonographic screening. The patient underwent surgical treatment for resection of the hepatocellular carcinoma. The non-cancerous liver tissue was histologically normal. This suggests that patients who have shown a complete response to interferon therapy for chronic hepatitis C should be followed up closely.
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PMID:Case report: Occurrence of hepatocellular carcinoma 4.5 years after successful treatment with virus clearance for chronic hepatitis C. 1053 62

Hepatitis B virus (HBV) infection is a worldwide public health problem. In France, 150,000 individuals are infected with the HBV. Although many are asymptomatic carriers, about 30% have chronic hepatitis, a condition associated with a risk of cirrhosis and hepatocellular carcinoma. Antiviral treatments, most notably interferon alpha, probably modify the natural history of hepatitis B, decreasing the risk of hepatocellular carcinoma and increasing survival. Nucleoside analogs, particularly lamivudine, have also demonstrated potent antiviral activity, which should however be weighed against the increasing risk over time of mutation development in the YMDD region of the DNA polymerase reverse transcriptase. Antiviral therapy monitoring should include clinical safety evaluations and periodic laboratory tests including blood cell counts, transaminase activities, and serum DNA levels. The improving results provided by antiviral drugs should not deflect attention away from the importance of large-scale hepatitis B immunization of neonates, which has been shown to decrease the incidence of hepatocellular carcinoma in areas with high levels of hepatitis B endemicity.
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PMID:[Hepatitis B: epidemiology, natural history, biology, treatment monitoring]. 1060 72

In the great majority of patients, hepatitis C virus (HCV) infection is not self-limiting. Approximately 70% to 85% of patients exposed to HCV will go on to develop chronic hepatitis. Among those who undergo treatment with interferon alpha, only 15% to 20% can be expected to respond to a 12- to 18-month course of therapy. With the addition of ribavirin to interferon monotherapy, the likelihood of sustained response (defined as normal alanine aminotransferase levels and negative HCV RNA persisting 6 months after the end of therapy) increases to approximately 40%. The fact remains, however, that there is still a substantial proportion of patients who will fail to respond to treatment. Without viral eradication, cirrhosis and hepatocellular carcinoma persist as long-term risks. Several options are available for the treatment of patients who fail to respond to interferon monotherapy. These include interferon dose escalation, whether by administering higher doses or administering them more frequently; changing to a different form of interferon; retreatment with a combination of interferon and ribavirin; adjunctive therapies, of which the best studied is phlebotomy to decrease hepatic iron stores; use of long-term, low-dose "maintenance"-type therapy; and watchful waiting with frequent follow-up. In the absence of long-term, large-scale clinical trials to support these modalities, physicians must exercise their best clinical judgment and individualize treatment to suit the patient's condition, needs, and preferences.
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PMID:Available options for treatment of interferon nonresponders. 1065 61

Depressive or psychotic symptoms are a well known side-effect of interferon alpha (INF-alpha). Therefore, the questions arises whether a chronic psychosis should be considered a contraindication for the treatment of active hepatitis C with INF-alpha. We report on a 38-year-old woman with a chronic schizophrenic psychosis, who acquired chronic aggressive hepatitis C. Considering the young age of the woman, the potential risk of developing a hepatocellular carcinoma and the result of the liver biopsy, treatment with interferon alpha 2 b (3x5 million IU/week) was started. The patient was seen three times a week, her psychiatric condition was monitored using the positive and negative symptoms score (PANSS). No signs of psychotic or depressive symptoms appeared during INF-alpha therapy. During the first 6 months the liver enzymes dropped slowly but the virus load was increasing. After adding ribavirin to the therapy, the liver enzymes dropped again, and the PCR carried out 9 months after initiation and 6 months after the end of the 12 months INF-alpha treatment did not detect any virus RNA. This positive result should encourage prospective studies including patients with these two diagnoses on whether patients benefit from INF-alpha.
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PMID:Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha? 1076 23

Chronic hepatitis C (CHC) is a major health problem worldwide, with approximately 200 million affected individuals and a significant rate of progression to end-stage cirrhosis and hepatocellular carcinoma (HCC). If hepatitis C virus (HCV) infection is left untreated in the population, then the number of liver-related deaths will soon double and the need for liver transplantation may increase to five times that seen today. Available therapies for CHC are restricted to interferon alpha (IFN alpha) monotherapy and to the combination of IFN alpha and ribavirin. Despite their high cost and side effects, both of these therapies have proved to be cost effective, particularly combination therapy. IFN alpha monotherapy for one year can induce sustained response (SR) rates of approximately 10% in naive patients infected with HCV genotype 1, and above 50% in those infected with other genotypes. Combination therapy can double or even triple the rate of SR in genotype 1 infections and may further increase the SR rate in the other HCV genotypes. Combination therapy has also been proven to be effective in approximately 50% of relapsed responders to IFN alpha monotherapy. In clinical practice, the decision to treat should be individualized and tailored on the basis of several virus- and host-related factors, particularly the grade and stage of liver disease, HCV genotype and levels of viremia. Appropriate monitoring of therapy by careful clinical evaluation, liver biochemistry and serum HCV RNA testing is mandatory. IFN alpha therapy may also prove to be effective in reducing the rate of HCC development in CHC regardless of whether a virological response is achieved, but this remains to be established.
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PMID:Why and how to treat chronic hepatitis C. 1093 5

So far seven hepatotropic viruses were identified. They are described by letters A,B,C,D,E, G and TTV. The virus of hepatitis F is so far speculative. Virus of hepatitis A and E are transmitted by the orofaecal route and cause only acute hepatitis. The remaining hepatotropic viruses are transmitted by the parenteral route and have a longer incubation period than viruses A and E. The infection with the virus of hepatitis B develops into the chronic stage in about 10% and that of virus C in 50-90%. At least one third of chronic carriers of the virus of hepatitis B or C develop within 10-20 years liver cirrhosis or hepatocellular carcinoma. The objective of therapeutic regimes is eradication of the viruses or at least arrest or retarding of the activity of the disease. Corticoids are not used. The basis of therapeutic regimes is interferon alpha or lamivudine in hepatitis B and interferon alpha with ribavirine in hepatitis C. There is a permanent therapeutic response only in cca 40-50%. Active immunisation is possible against virus of hepatitis A and B. The virus of hepatitis D is a false virus, i.e. a so-called virold, and the cause is a super- or co-infection with the virus of hepatitis B. In this country it is practically not encountered, similarly as the virus of hepatitis E. The assembled findings on virus of hepatitis G are not applied so far very much in practice.
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PMID:[Characteristics of still unknown hepatotropic viruses and a clinical picture of the disease]. 1122 77

The hepatitis C virus (HCV) causes an acute but very often chronic liver disease. An estimated 3% of the world population is chronically infected with HCV. Chronic hepatitis C is the major cause of cirrhosis and hepatocellular carcinoma (HCC), which most often lead to liver transplantation. HCV is a single-stranded enveloped RNA virus; it belongs to the flaviviridae family. The virus has been classified into six genotypes, some of which are distributed worldwide, others of which are confined to more restricted areas. The genotype is an independent predictor of response to antiviral treatment. Blood transfusion was a major risk factor for acquiring HCV infection before donor screening for surrogate marker testing for non-A, non-B (NANB) hepatitis began in the mid-1980s, followed by screening for antibody to HCV in 1990. Today, intravenous drug use and high-risk sexual activity are the most frequently identified risk factors associated with HCV infection. The prevalence of people with unknown HCV infection worldwide is high, so it is necessary to screen people with risk factors. The treatment of patients with chronic HCV infection who have not been treated previously should consist of interferon alpha (IFN-alpha) and ribavirin.
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PMID:Hepatitis C virus infection: 10 years after the discovery of the virus. 1139 24

Hepatitis C virus (HCV) infection often progresses to chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma. Chronic hepatitis C infection is a leading cause of chronic liver disease and the most common indication for liver transplantation. Combination therapy of interferon alpha and ribavirin is currently the standard regimen for chronic hepatitis C. This combination can achieve viral clearance in approximately 40% of patients, and improve histology and prognosis. The most cost-effective approach to guide duration of combination therapy is HCV genotyping. Cost effectiveness cannot be improved further by taking other well-defined predictive factors for sustained virological response into account. Recent insights into HCV kinetics and the correlation between initial viral decline and sustained virological response will allow us to optimize and individually tailor antiviral treatment Individualized treatment according to the initial viral decline, together with further improvements in drugs (e.g. by long-acting pegylated interferons), will have new impact on antiviral efficacy and cost effectiveness.
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PMID:What is (cost) effective in patients with chronic hepatitis C virus infection? 1139 25


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