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)

Chronic hepatitis B viral (HBV) infection greatly increases the risk for cirrhosis and hepatocellular carcinoma. HBV serologic testing is important for the identification of chronically infected individuals, who may benefit from antiviral treatment and regular monitoring for disease sequelae. Elevated rates of cirrhosis and hepatocellular carcinoma among Vietnamese American men can largely be attributed to high rates of chronic HBV infection. We surveyed 509 Vietnamese men aged 18-64 years in Seattle, Washington and examined sociodemographic and health care access factors associated with HBV serology testing. Nearly two-thirds (65%) reported past testing. The following were among those factors associated with HBV testing in bivariate comparisons: older age; short proportion of life in the US; low English fluency; private health insurance; identifying a regular source of medical care; reporting no long waits for medical appointments; and having access to interpreter services. The following were independently associated with HBV testing in multiple logistic regression analysis: older age; college education; low English fluency; private health insurance; having a regular medical provider; and reporting no long waits for medical appointments. Younger and less educated men, and those with difficulty accessing medical care may be at particular risk for never having had HBV testing. Programs to reduce HBV transmission and sequelae should make special effort to target these vulnerable Vietnamese Americans.
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PMID:Health care access and sociodemographic factors associated with hepatitis B testing in Vietnamese American men. 1679 29

Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.
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PMID:Lamivudine treatment in patients with chronic hepatitis B and cirrhosis. 1692 9

Chronic hepatitis B is an important public health problem worldwide. In Poland the incidence rate decreased from 40,0 (in the year 1990) to 3,86 (in 2004) per 100,000 inhabitants. The goal of anti-chronic hepatitis B therapy is to prevent the progression of liver disease to cirrhosis which may effect in development of liver failure or HCC. The aims of treatment are: reduction of HBV viral load and normalization of ALT activity. Among HBeAg positive patients important marker is the loss of e antigenemia followed by seroconversion to anti-HBe positivity. Lamivudine is an oral nucleoside analogue with strong antiviral activity against hepatitis B virus. The objective of this study was to analyse the efficacy of lamivudine treatment of chronic hepatitis B patients positive for hepatitis B e antigen (HBeAg). 224 patients were treated in Hospital of Infectious Diseases in Warsaw in the years 2001-2002. Patients were treated for 48 weeks with 100 mg lamivudine once daily (50 mg in case of renal failure). Results obtained at the end of therapy: loss of HBeAg was observed in 33,4% and seroconversion to anti-HBe in 15,1% patients, normalization of ALT activity was noticed in 53,4% patients, inhibition of HBV DNA replication was observed in 37,9% patients. The results are comparable with known randomized clinical trials.
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PMID:[Results of 48 weeks lamivudine treatment of patients with chronic hepatitis B and HBeAg (+)]. 1696 76

Although preventable by vaccination, hepatitis B infection is common, affecting more than 350 million individuals worldwide. Chronic hepatitis B infection is associated with the complications of chronic liver disease including cirrhosis and hepatocellular carcinoma. Current agents designed to target hepatitis B are hindered by the development of resistance, poor tolerability or limited efficacy and a demand for new agents and strategies continues. This review focuses on telbivudine, a novel agent in the fight against hepatitis B.
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PMID:Novel anti-hepatitis B agents: A focus on telbivudine. 1698 73

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.
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PMID:Natural course, therapeutic options and economic evaluation of therapies for chronic hepatitis B. 1704 Jan 14

Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.
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PMID:Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy. 1705 72

Chronic hepatitis B virus (HBV) infection is the most frequent risk factor for development of hepatocellular carcinoma (HCC) worldwide. Studies of the molecular genetics and pathophysiology of HCC suggest that there are significant differences in the allelic imbalance, genome copy number, and gene expression patterns of HBV-induced HCC as compared to HCCs from other causes, which are presumably reflected to differences in the mode of presentation and outcomes of HBV-induced HCCs. Unique features of HBV-induced carcinogenesis include the role of HBV DNA integration in carcinogenesis and the powerful synergism between HBV and dietary aflatoxins in the pathogenesis of HCC. A more complete understanding of the biology of HBV-induced HCCs may reveal well-defined differences in the molecular pathways that regulate growth of these HCCs and allow better-targeted approaches to prevention and therapy of HBV-induced HCCs. This review will attempt to summarize the current knowledge about carcinogenic pathways in HBV-induced HCCs, review the agents currently in development for targeted therapy of HCCs, and propose potentially novel approaches to therapy of HBV-induced HCC.
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PMID:Molecular targets for therapy of hepatitis B virus-induced hepatocellular carcinoma. 1710 69

Chronic hepatitis B virus (HBV) infection is a serious health issue worldwide. The presence of HBV replication markers--hepatitis B e antigen (HBeAg) or HBV DNA--is associated with continuing hepatitis activity or intermittent hepatitis flares and subsequent disease progression, including hepatic decompensation and development of liver cirrhosis or hepatocellular carcinoma (HCC). Long-term (>10 years) prospective studies in patients >30 years of age have shown that HBeAg seropositivity is associated with increased risk of disease progression, and the risk of cirrhosis and HCC begins to increase at an HBV DNA level of 10(4) copies/ml. Therefore, elimination of HBV, or at least sustained or maintained suppression of HBV, is the key to reducing hepatitis and thereby halting or preventing disease progression. Therapy with interferon-alpha or a direct antiviral agent has been shown to reduce the risk of cirrhosis and prevent further disease worsening. In both the woodchuck hepatitis model and in HBV patients, maintained suppression of HBV replication by a direct antiviral agent may reduce the progression to HCC. However, the efficacy of current antiviral therapy is still far from satisfactory. The ability to achieve a high rate of sustained or maintained HBV suppression with a low risk of drug resistance would be the ultimate goal in the treatment of chronic HBV infection.
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PMID:Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy. 1731 Aug 11

Chronic hepatitis B continues to be a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. Nucleos(t)ide analogues have proven to be effective in controlling the disease and perhaps decreasing the incidence of hepatocellular carcinoma. However, development of drug resistance is a major limitation to their long-term effectiveness. Understanding the mechanisms of drug resistance are important for designing new agents and devising strategies to manage and prevent the development of antiviral drug resistance. The development of resistance is determined by an interplay of viral, host, and drug characteristics Homology of the HBV polymerase to the human immunodeficiency virus-1 reverse transcriptase has allowed predictions to be made on the effect mutations have on HBV polymerase structure. In vitro functional studies provide complementary information. Several broad principles on the mechanism of resistance have emerged from these studies. First, most of the primary mutations cluster in the vicinity of the incoming nucleotide and act by directly affecting the position or stability of the bound substrate, template, or primer. In contrast, secondary mutations tend to occur away from the nucleotide-binding pocket. Finally, the structural and functional consequences of mutations are quite variable among the different agents. This paper reviews the key mutations and mechanisms associated with resistance to the nucleos(t)ide analogues approved for clinical use and discuss new targets for drug development.
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PMID:Drug targets and molecular mechanisms of drug resistance in chronic hepatitis B. 1740 58

Chronic hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC), and the HBV X (HBx) gene plays a critical role in the molecular pathogenesis of HBV-related HCC. We have investigated whether there are particular HBx gene mutations associated with HCC in patients from southern China. The HBx gene was examined in 51 paraffin-embedded tumor tissue samples from patients with HCC and 25 serum samples from the HBV carrier by nested polymerase chain reaction (PCR), single-stranded conformational polymorphism and heteroduplex analysis. The HBx genes with potentially important mutations from tumor tissue samples were cloned, sequenced and aligned with the published HBx gene sequence. HBV genotypes in tumor tissue samples were analyzed by nested PCR. Analyses of HBx gene polymorphism showed that 31.3% of HBx gene fragments in tumor tissue samples had a special pattern. A common deletion at nt 382-400 of the HBx gene accompanied by 29 point mutations was detected in four randomly selected tumor tissue samples with this pattern which caused a frame-shift in the HBx open reading frame with a new stop codon at nt 1818, resulting in an HBx polypeptide chain truncated at the C end in these cases. Among the four randomly selected samples, three were HBV genotype B, and one was not detected by our present assay. In another tumor tissue sample, amplification of the full-length HBx gene yielded a shorter fragment. Sequencing of this fragment revealed a 264 bp deletion between nt 1577 and 1840 of the HBV gene. These results suggest that HBx gene mutation occurs frequently in HCC samples, and the deletion at nt 382-400 of the HBx gene might play a role in carcinogenesis of HCC in southern China.
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PMID:Polymorphism analyses of hepatitis B virus X gene in hepatocellular carcinoma patients from southern China. 1741 81


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